digoxin and Arrhythmias--Cardiac

Atrial flutter (AFL) in pediatric patients is a rare condition as the physical dimensions of the immature heart are inadequate to support the arrhythmia. This low incidence makes it difficult for patients in this particular setting to be studied. AFL accounts for 30% of fetal tachyarrhythmias, 11% to 18% of neonatal tachyarrhythmias, and 8% of supraventricular tachyarrhythmias in children older than 1 year of age. Transesophageal overdrive pacing can be used, instead, with lower success rate (60%-70%). The recommended drugs are digoxin which can decrease the ventricular rate until the spontaneous interruption of the AFL. Digoxin can be combined with flecainide or amiodarone in case of failure.

Topics: Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Flutter; Child; Child, Preschool; Digoxin; Flecainide; Humans; Infant, Newborn; Tachycardia

Atrial flutter (AFL) is a supraventricular tachyarrhythmia. In the ECG tracing, it is marked by a fast, irregular atrial activity of 280-500 beats per minute. AFL is known to be a rare and also life-threatening rhythm disorder both at the fetus and neonatal period. AFL may result in circulatory failure, and in a more severe form, it may lead to a non-immune fetal hydrops. However, with early prenatal diagnosis and proper treatment, the majority of AFL cases show a good prognosis.. We report a case of a neonate who was born at 34 weeks of gestational age by C-section because of risk for birth asphyxia, based on abnormal CTG tracing, which had no characteristic rhythms for fetal decelerations. A third day his heart rate was 220/bpm. ECG has shown supraventricular tachycardia with narrow QRS. The administration of adenosine resulted in the obvious appearance of "sawtooth wave" typical for AFL. Arrhythmia was resistant to the therapy of amiodaron. Then cardioversion was performed and the rhythm converted to normal.. As neonatal AFL might be resistant to conventional pharmacotherapy, one needs to remember about the possibility of electrical cardioversion in the pediatric cardiology referral center. Moreover, CTG monitoring is of limited use because it does not record fetal heart rhythms > 200/min and echocardiography at the reference center is practically the only method to monitor the condition of the fetus with abnormal rapid heart rhythm.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Flutter; Child; Digoxin; Electric Countershock; Female; Humans; Infant, Newborn; Pregnancy

Digoxin is the oldest known treatment for heart failure (HF) and has been demonstrated to reduce admissions for worsening heart failure in a large randomized trial recruiting patients in sinus rhythm with heart failure and ejection fraction <45%. This study forms the basis for current international guidelines recommending that digoxin should be considered in patients with symptomatic HF despite optimal doses of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and mineralocorticoid receptor antagonists in addition to device therapy, if indicated. However, digoxin predates mortality reducing HF therapies, and this article reviews the historical and recent data.. Multiple PubMed searches were performed including, but not limited to, the search terms "digoxin," "heart failure," "efficacy," "treatment," "side-effects," "morbidity," "mortality," and "arrythmia." Articles were excluded if not relevant, not in English or without abstract. Reference lists of relevant articles were manually searched for further references. Due to the large number of articles retrieved, a selection was reviewed based on the authors' best judgement.. Three randomized controlled trials and three large contemporary observational reports of digoxin therapy in heart failure and sinus rhythm were retrieved. Other studies were noted that included patients with heart failure and atrial fibrillation, which were also reviewed.. Definitive randomized evidence of digoxin efficacy as add-on therapy in HF is lacking because most landmark trials of modern HF disease modifying agents postdate the randomized studies of digoxin. Furthermore, questions remain regarding the optimum dose of digoxin and there are signals that digoxin may be harmful in some patients with HF. All contemporary data for digoxin in HF are derived from observational studies and the findings are conflicting. Despite two centuries of experience using cardiac glycosides to treat HF, fundamental questions regarding the efficacy and safety of digoxin in HF remain unanswered.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiotonic Agents; Digitalis; Digoxin; Heart Failure; Humans; Risk Assessment; Risk Factors; Treatment Outcome

The incidence of cardiac arrhythmias is estimated et 1.2 per 1000 pregnancies, usually in the third trimester and 50% of them are asymptomatic. They may appear for the first time in pregnancy or have a recurring character An important risk factor related to their appearance is the presence of structural heart disease, which complicates < 1% of pregnancies. Generally the symptoms are mild and the treatment is not necessary but in some cases pharmacotherapy is necessary Pharmacotherapy must be a compromise between the potentially adverse effects of drugs on the fetus and the beneficial effects on the cardiovascular system of the mother. Due to the development of cardiac surgery many women with heart defects reach reproductive age and become pregnant. Therefore this problem will be faced more and more often in clinical practice. In addition to pharmacological methods some cardiac arrhythmias may require urgent, life-saving procedures. External electrical cardioversion is associated with the application of certain amount of energy via two electrodes placed on the thorax. It is used to treat hemodynamically unstable supraventricular tachycardias, including atrial fibrillation and atrial flutter Also in hemodynamically stable patients in whom drug therapy was ineffective elective electrical cardioversion can be use to convert cardiac arrhythmia to sinus rhythm. We present a case of a 33 years old patient with congenital heart disease surgically corrected in childhood who had first incident of atrial flutter in pregnancy. Arrhytmia occured in 26th week of gestation. The patient was hemodynamically stable and did not approve electrical cardioversion as a method of treatment therefore pharmacotherapy was started. Heart rate was controled with metoprolol and digoxin, warfarin was used to anticoagulation. Calcium and potassium were also given. Described therapy did not convert atrial flutter to sinus rhythm therefore in 33rd week of gestation after patient's approval electrical cardioversion was performed. Before cardioversion transesophageal echocardiogram was made to exclude the presence of thrombus inside atria. Energy of 50J was applied and sinus rhythm was restored. Cardiotocography during and after cardioversion did not show any significant fetal heart rate changes. Further pregnancy and puerperium were uneventful. Case report and review of the literature about cardiac arrhytmias and methods of its treatment especially in pregnant women. Analysis of medical do

Topics: Adult; Anti-Arrhythmia Agents; Anticoagulants; Arrhythmias, Cardiac; Digoxin; Electric Countershock; Female; Heart Rate, Fetal; Humans; Metoprolol; Pregnancy; Pregnancy Complications, Cardiovascular; Thromboembolism; Warfarin

A 53-year-old woman presented with digitalis toxicity caused by acute overdose that manifested as atrial tachycardia with block, sinus pauses, and competing AV junctional rhythm with atrial fibrillation. Patient admitted to overdosing with digoxin 15-20 h before presentation with intent to commit suicide. Serum digoxin level was 35.6 ng/ml and renal function was normal. Patient was treated with 1,040 mg of digoxin-specific antibody Fab fragment with prompt resolution of arrhythmias and restoration of sinus rhythm. Four hours after digoxin antibody administration, serum digoxin level declined to 0.2 ng/ml. Eighteen hours after treatment with Fab fragment, patient developed premature ventricular complexes, atrial tachycardia with and without atrioventricular block, and non-sustained ventricular tachycardia followed by ventricular fibrillation from which she was successfully resuscitated. Electrocardiogram showed no evidence of acute myocardial infarction, and emergent coronary angiogram did not reveal significant coronary artery disease. Repeat digoxin level was 20.4 ng/ml. A diagnosis of recrudescent digoxin toxicity was made and the patient was treated with one session of plasma exchange with resolution of arrhythmias. Immediately after plasma exchange, digoxin level decreased to 10.4 ng/ml, and after 10 h, the level further decreased to 6.6 ng/ml. The following day, digoxin level had decreased to 2.9 ng/ml. Our experience with this case would suggest that plasma exchange should be considered as a treatment modality for recrudescent digoxin toxicity.

Topics: Arrhythmias, Cardiac; Digoxin; Electrocardiography; Female; Humans; Middle Aged; Plasma Exchange; Recurrence; Suicide, Attempted; Treatment Outcome

Digitalis toxicity produces a toxidrome characterized by gastrointestinal, neurologic, electrolyte, and nonspecific cardiac manifestations. Chronic toxicity remains much more difficult to recognize compared with an acute presentation because of the nonspecific manifestations; therefore, serum glycoside levels are essential for diagnosis in this population. The mainstay of management continues to be rapid toxidrome identification followed by digoxin-specific antibody fragment therapy with supportive care. Several controversies still remain, including therapy for patients dependent on hemodialysis, appropriateness of calcium therapy for hyperkalemia, ideal agents for arrhythmia therapy, and the potential utility of plasmapheresis for removal of bound digoxin-antibody fragment complexes.

Topics: Anti-Arrhythmia Agents; Antidotes; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Drug Overdose; Humans; Hyperkalemia

The objective of this review is to characterize the mechanisms, risk factors, and offending pharmacotherapeutic agents that may cause drug-induced arrhythmias in critically ill patients. PubMed, other databases, and citation review were used to identify relevant published literature. The authors independently selected studies based on relevance to the topic. Numerous drugs have the potential to cause drug-induced arrhythmias. Drugs commonly administered to critically ill patients are capable of precipitating arrhythmias and include antiarrhythmics, antianginals, antiemetics, gastrointestinal stimulants, antibacterials, narcotics, antipsychotics, inotropes, digoxin, anesthetic agents, bronchodilators, and drugs that cause electrolyte imbalances and bradyarrhythmias. Drug-induced arrhythmias are insidious but prevalent. Critically ill patients frequently experience drug-induced arrhythmias; however, enhanced appreciation for this adverse event has the potential to improve prevention, treatment, patient safety, and outcomes in this patient population.

Topics: Anesthetics, Inhalation; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Bradycardia; Bronchodilator Agents; Cardiotonic Agents; Critical Care; Digoxin; Drug-Related Side Effects and Adverse Reactions; Humans; Long QT Syndrome; Risk Factors; Torsades de Pointes; Water-Electrolyte Balance

Poisoning due to deliberate self-harm with the seeds of yellow oleander (Thevetia peruviana) results in significant morbidity and mortality each year in South Asia. Yellow oleander seeds contain highly toxic cardiac glycosides including thevetins A and B and neriifolin. A wide variety of bradyarrhythmias and tachyarrhythmias occur following ingestion. Important epidemiological and clinical differences exist between poisoning due to yellow oleander and digoxin; yellow oleander poisoning is commonly seen in younger patients without preexisting illness or comorbidity. Assessment and initial management. Initial assessment and management is similar to other poisonings. No definite criteria are available for risk stratification. Continuous ECG monitoring for at least 24 h is necessary to detect arrhythmias; longer monitoring is appropriate in patients with severe poisoning. Supportive care. Correction of dehydration with normal saline is necessary, and antiemetics are used to control severe vomiting. Electrolytes. Hypokalemia worsens toxicity due to digitalis glycosides, and hyperkalemia is life-threatening. Both must be corrected. Hyperkalemia is due to extracellular shift of potassium rather than an increase in total body potassium and is best treated with insulin-dextrose infusion. Intravenous calcium increases the risk of cardiac arrhythmias and is not recommended in treating hyperkalemia. Oral or rectal administration of sodium polystyrene sulfonate resin may result in hypokalemia when used together with digoxin-specific antibody fragments. Unlike digoxin toxicity, serum magnesium concentrations are less likely to be affected in yellow oleander poisoning. The effect of magnesium concentrations on toxicity and outcome is not known. Hypomagnesaemia should be corrected as it can worsen cardiac glycoside toxicity. Gastric decontamination. The place of emesis induction and gastric lavage has not been investigated, although they are used in practice. Gastric decontamination by the use of single dose and multiple doses of activated charcoal has been evaluated in two randomized controlled trials, with contradictory results. Methodological differences (severity of poisoning in recruited patients, duration of treatment, compliance) between the two trials, together with differences in mortality rates in control groups, have led to much controversy. No firm recommendation for or against the use of multiple doses of activated charcoal can be made at present, and furthe. Digoxin-specific antibody fragments remain the only proven therapy for yellow oleander poisoning. Further studies are needed to determine the place of activated charcoal, the benefits or risks of atropine and isoprenaline, the place and choice of antiarrhythmics, and the effect of intravenous magnesium in yellow oleander poisoning.

Topics: Antibodies, Blocking; Antidotes; Antiemetics; Arrhythmias, Cardiac; Blood Pressure; Charcoal; Digoxin; Electrocardiography; Emetics; Fluid Therapy; Humans; Nerium; Ondansetron; Plant Poisoning; Potassium; Resuscitation; Therapeutic Irrigation; Water-Electrolyte Imbalance

Chronic heart failure (CHF) is common, and increases in incidence and prevalence with age. There are compelling data demonstrating reduced mortality and hospitalizations with adrenergic blockade in older patients with CHF. Despite this, many older patients remain undertreated. The aim of the present article is to review the potential mechanisms of the benefits of adrenergic blockade in CHF and the clinical data available from the large randomized studies, focusing particularly on older patients.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Carbazoles; Carvedilol; Chronic Disease; Comorbidity; Digoxin; Heart Failure; Humans; Propanolamines; Ventricular Dysfunction, Left; Ventricular Remodeling

Individuals vary widely in their responses to therapy with most drugs. Indeed, responses to antiarrhythmic drugs are so highly variable that study of the underlying mechanisms has elucidated important lessons for understanding variable responses to drug therapy in general. Variability in drug response may reflect variability in the relationship between a drug dose and the concentrations of the drug and metabolite(s) at relevant target sites; this is termed pharmacokinetic variability. Another mechanism is that individuals vary in their response to identical exposures to a drug (pharmacodynamic variability). In this case, there may be variability in the target molecule(s) with which a drug interacts or, more generally, in the broad biological context in which the drug-target interaction occurs. Variants (polymorphisms and mutations) in the genes that encode proteins that are important for pharmacokinetics or for pharmacodynamics have now been described as important contributors to variable drug actions, including proarrhythmia, and these are described in this review. However, the translation of pharmacogenetics into clinical practice has been slow. To this end, the creation of large, well-characterised DNA databases and appropriate control groups, as well as large prospective trials to evaluate the impact of genetic variation on drug therapy, may hasten the impact of pharmacogenetics and pharmacogenomics in terms of delivering personalised drug therapy and to avoid therapeutic failure and serious side effects.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Arylamine N-Acetyltransferase; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cytochrome P-450 CYP2D6; Digoxin; Humans; Long QT Syndrome; Personal Health Services; Pharmacogenetics; Polymorphism, Genetic; Potassium Channels; Propafenone; Risk Factors; Sodium Channel Blockers; Sodium Channels; Torsades de Pointes

Digoxin therapy has no effect on mortality in heart failure. Digoxin may be useful for maintaining clinical stability and exercise capacity in patients with symptomatic heart failure. Digoxin appears to be of most benefit in patients with severe heart failure, cardiomegaly and a third heart sound. Digoxin should be used as a second-line drug after diuretics, angiotensin-converting enzyme inhibitors and beta-blockers in patients with congestive heart failure who are in sinus rhythm. Digoxin should be used as a first-line drug in patients with congestive heart failure who are in atrial fibrillation. ARRHYTHMIAS: Digoxin has a limited, but useful, role, either alone or in combination with other agents such as beta-blockers, diltiazem or verapamil, in achieving satisfactory resting ventricular rate control in patients with chronic atrial fibrillation. In patients who lead a predominantly sedentary lifestyle (perhaps particularly in those who are elderly), digoxin alone may be the agent of choice.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Heart Failure; Humans

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Clinical Trials as Topic; Digoxin; Drug Interactions; Electrophysiology; Heart; Humans; Potassium Channels; Quinidine; Sodium Channels

It has for years been a matter of debate whether digoxin may/should be used in chronic heart failure with sinus rhythm. Interest in digoxin was renewed when it was found that the substance had a vagotonic as well as a sympatholytic effect in heart failure patients. A recent clinical trial led to the conclusion that although digoxin had no effect on the mortality among heart failure patients, it did lead to a reduction of the number of hospital admissions, particularly because of heart failure (indicating reduced morbidity and deceleration of the progression of the disease). Many heart failure patients continue to have symptoms in spite of treatment with diuretics and ACE inhibitors. As only few alternatives are available, many physicians in the near future will go on using digoxin in these patients- and as the recent study shows, rightly so.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Clinical Trials as Topic; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged

Atrial fibrillation represents a common and challenging arrhythmia. A rational approach to management of the individual case depends on careful assessment of the temporal of the arrhythmia, any associated cardiovascular disease, and any particular features suggesting the advisability or risks of any particular treatment regimen. The nature of an arrhythmia and of individual patient factors change over time, requiring a flexible approach to long-term treatment that may be defined only after months or years. While new treatment options such as catheter ablation techniques and implantable atrial defibrillators are being tested, old therapies (e.g., low-dose amiodarone) are undergoing reappraisal. Increasing recognition of the dangers of antiarrhythmic therapy used to maintain sinus rhythm is focusing attention on nonpharmacologic methods. All patients with persistent atrial fibrillation merit serious consideration for direct current cardioversion before accepting that atrial fibrillation is permanent, and many patients may benefit from more than one attempt to restore and maintain sinus rhythm.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Calcium Channel Blockers; Catheter Ablation; Digoxin; Electric Countershock; Flecainide; Heart Failure; Heart Rate; Heart Ventricles; Humans; Quinidine; Sinoatrial Node; Thromboembolism; Time Factors

Topics: Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiotonic Agents; Defibrillators, Implantable; Digoxin; Diuretics; Female; Heart Conduction System; Heart Failure; Humans; Male; Prognosis; Vasodilator Agents

Topics: Adrenergic beta-Antagonists; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Catheter Ablation; Cerebrovascular Disorders; Defibrillators, Implantable; Digoxin; Electrophysiology; Heart; Heart Failure; Humans

Significant digitalis toxicity, although uncommon, is a medical emergency. Recognition of the problem and good supportive care (eg, administration of activated charcoal and binding resins, correction of potassium levels, restoration of heart rhythm) are the cornerstones of treatment. If indicated, immunotherapy with digoxin immune Fab (Digibind) is a valuable and effective tool.

Topics: Arrhythmias, Cardiac; Charcoal; Digitalis Glycosides; Digoxin; Emergencies; Humans; Hypokalemia; Immunoglobulin Fab Fragments; Poisoning

This meta-analysis was performed to determine the efficacy of digoxin, verapamil, and beta-adrenoceptor blockers as prophylaxis against supraventricular arrhythmias (SVAs) after coronary artery bypass graft surgery (CABG). Randomized control trials were included if the electrocardiographic monitoring technique was clearly defined and extended through at least the first 3 postoperative days. Twenty-four of 69 identified studies were included in the final analysis. A summary odds ratio (OR) of the likelihood of developing SVAs after CABG in the treatment versus control groups was calculated. The pooled mean ventricular rate during SVA in patients who developed such an arrhythmia was also calculated. Neither digoxin nor verapamil reduced the likelihood of SVAs after CABG (digoxin: OR = 0.97, 95% confidence interval [CI] = 0.62-1.49; verapamil: OR = 0.91, CI = 0.57-1.46). The likelihood of developing an SVA in patients treated with beta-blockers was markedly decreased compared with controls (OR = 0.28, CI = 0.21-0.36). The pooled ventricular rate when SVAs did occur was significantly lower in each of the treatment groups. Prophylactic beta-adrenoceptor blockers had a protective effect against the development of SVAs in a select population of patients undergoing CABG. No such beneficial effect was demonstrated for digoxin or verapamil. All three classes of agents reduced the ventricular rate in patients who developed the arrhythmia, although the ventricular rate reduction was not clinically optimal.

Topics: Adrenergic beta-Antagonists; Arrhythmias, Cardiac; Coronary Artery Bypass; Digoxin; Humans; Meta-Analysis as Topic; Odds Ratio; Verapamil

Topics: Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Drug Interactions; Drug Therapy, Combination; Humans; Potassium; Procainamide; Propranolol; Quinidine; Verapamil

Topics: Arrhythmias, Cardiac; Causality; Digoxin; Humans; Risk Factors

Moricizine is well absorbed after oral administration and undergoes extensive first-pass metabolism. The drug has a large apparent volume of distribution (approximately 4 liters/kg), exhibits extensive plasma protein binding (approximately 95%) and produces at least 30 metabolites. Indirect evidence indicates that some of those metabolites may be pharmacologically active. The elimination half-life of moricizine is 2 to 6 hours, but its duration of antiarrhythmic action is much longer suggesting active metabolites. Moricizine induces its own metabolism with no change in pharmacologic effect. It also induces the metabolism of theophylline and specific pathways of antipyrine. Cimetidine reduces metabolism of moricizine but does not alter its pharmacologic effects. This observation provides further support for the hypothesis that the metabolites of moricizine contribute to the pharmacologic actions during therapy and indicate that plasma level monitoring is not likely to be of value. There are no known clinically significant pharmacokinetic interactions between moricizine and digoxin, warfarin or propranolol. Excessive prolongation of the PR interval has been seen in some patients receiving both digoxin and moricizine, probably due to additive electrophysiologic effects of the 2 drugs.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cimetidine; Clinical Trials as Topic; Digoxin; Drug Interactions; Humans; Moricizine; Phenothiazines; Propranolol; Theophylline; Warfarin

The place of digoxin in the pediatric cardiologist's armamentarium remains uncertain. As an antiarrhythmic, its use in the Wolff-Parkinson-White syndrome is obsolete, but it remains useful in the treatment of the chronic atrial fibrillation seen in some patients postoperatively and in children with dilated cardiomyopathy. The efficacy of digoxin in heart failure is unproven. There is some evidence of improvement in non invasive left ventricular contractile indices in neonates and infants, but it is unclear whether this is associated with sustained clinical improvement. There is even less evidence of its effectiveness in the older child. Whilst the measurement of any effect will undoubtedly be difficult, the time has come for double-blind, placebo-controlled trials in selected groups of patients. These should be designed not only to test the notion that digoxin does not improve ventricular function, but also to embrace the possibility that its administration may result in clinical improvement over and above that following diuretics alone. An absence of proof of efficacy must be distinguished from no efficacy--more data are needed.

Topics: Arrhythmias, Cardiac; Child; Child, Preschool; Digoxin; Heart Defects, Congenital; Heart Failure; Humans; Infant

The history of the discovery of endogenous digoxin-like factor (EDF) is described and the role played by the substance in blood circulation regulation, in the pathogenesis of arterial hypertension is discussed. The authors provide their own data (both experimental and clinical ones) concerned with EDF participation in the pathogenesis of early ventricular fibrillations in acute myocardial ischemia. Experiments on rats demonstrated that myocardial infarction (MI) is marked by a negative linear correlation between the intensity of ventricular fibrillations and the activity of Na,K-ATPase of intact red blood cells (r = -0.84) that mirrors the content of circulating EDF. Administration to the animals of digoxin antibodies binding EDF resulted in the antiarrhythmic effect and in the recovery of the enzyme activity. The patients demonstrated, within the first day of MI, a 76-percent inhibition of the activity of Na,K-ATPase of red blood cells. A correlation was discovered between the enzyme activity and the capacity of protein-free supernatants of blood plasma for inhibiting Na,K-ATPase, which indicates the presence of circulating EDF in blood plasma.

Topics: Acute Disease; Animals; Arrhythmias, Cardiac; Blood Circulation; Blood Proteins; Cardenolides; Coronary Disease; Digoxin; Female; Humans; Male; Middle Aged; Ouabain; Rats; Rats, Inbred Strains; Saponins; Sodium-Potassium-Exchanging ATPase

Digitalis glycosides have a narrow margin between therapeutic and toxic levels. Although the incidence of digitalis toxicity appears to be decreasing, continuation of digoxin therapy in the face of overt toxicity carries a substantial risk of life-threatening cardiac rhythm disturbances. This review will focus primarily on toxicity produced by digoxin and discuss the mechanisms, clinical manifestations, and current management of digitalis toxicity. The appropriate methodology for measurement and interpretation of serum digoxin levels is emphasized. The varied cardiac dysrhythmias induced by digoxin are detailed and their specific management outlined. Immunological (antibody) treatment has now been established and approved for the therapy of advanced, life-threatening digitalis toxicity and the multicenter trial of digitalis antibodies is described. Proper understanding of the pharmacokinetics of digitalis glycosides and careful followup of digitalis treated patients for early evidence of toxicity should help to decrease further the prevalence of toxic reactions.

Topics: Arrhythmias, Cardiac; Digitoxin; Digoxin; Humans; Poisoning

Positive inotropic agents are used to improve the impaired cardiac contractility that characterizes chronic heart failure. Digitalis is the traditional drug given for this purpose. However, there is controversy about the effectiveness of digitalis in chronic heart failure. Analysis of the available data indicates the efficacy of digoxin in mild heart failure (i.e., New York Heart Association functional classes I and II) and the relative lack of efficacy in advanced heart failure (i.e., NYHA functional class IV). Further, digoxin can be stopped in a substantial number of patients without recurrence of congestive heart failure. In selected patients whose condition no longer responds to digoxin, the long-term administration of dobutamine may be an effective alternative approach.

Topics: Adult; Aged; Arrhythmias, Cardiac; Cardiac Glycosides; Cardiotonic Agents; Digitalis Glycosides; Digoxin; Dobutamine; Dose-Response Relationship, Drug; Double-Blind Method; Follow-Up Studies; Heart Failure; Hemodynamics; Humans; Infusions, Parenteral; Middle Aged; Myocardial Contraction; Random Allocation; Risk; Sodium-Potassium-Exchanging ATPase; Stroke Volume

Topics: Animals; Arrhythmias, Cardiac; Cattle; Coronary Circulation; Digitalis Glycosides; Digoxin; Guinea Pigs; In Vitro Techniques; Myocardium; Ouabain; Sodium-Potassium-Exchanging ATPase; Swine; Vasoconstriction

The frequency of ventricular arrhythmias increases with age. Several factors make elderly people more prone to antiarrhythmic drug toxicity. Familiarity with the changes in the pharmacokinetics and pharmacodynamics of antiarrhythmic agents may reduce or prevent adverse response in this patient population.

Topics: Aged; Amiodarone; Anilides; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Bretylium Compounds; Digoxin; Disopyramide; Encainide; Flecainide; Humans; Lidocaine; Mexiletine; Piperidines; Procainamide; Propranolol; Quinidine; Tocainide; Verapamil

Topics: Adolescent; Adult; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Biological Availability; Cardiopulmonary Bypass; Child; Child, Preschool; Digoxin; Drug Interactions; Female; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Absorption; Kinetics; Maternal-Fetal Exchange; Pregnancy

Topics: Animals; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Drug Interactions; Drug Tolerance; Electric Countershock; Heart; Humans; Immunoglobulin Fab Fragments; Immunoglobulin G; Kinetics; Myocardial Infarction; Phenytoin; Potassium Chloride

Digitalis glycosides continue to place high on the list of prescribed drugs. Digoxin is 8th on prescriptions written in the United States in 1980, digitoxin 16th, and digitalis leaf 23rd. There is little doubt that most physicians continue to believe these drugs are useful. The application of more definite indications, smaller doses, and the recognition of the role of pharmacokinetics and drug interactions make use of the glycosides more challenging than ever before in 1985.

Topics: Administration, Oral; Adrenergic beta-Antagonists; Age Factors; Anti-Arrhythmia Agents; Antihypertensive Agents; Arrhythmias, Cardiac; Biological Availability; Bretylium Tosylate; Deslanoside; Digitalis Glycosides; Digitoxin; Digoxin; Dose-Response Relationship, Drug; Drug Interactions; Heart Failure; Humans; Injections, Intramuscular; Injections, Intravenous; Intestinal Absorption; Kidney Failure, Chronic; Lidocaine; Metabolic Clearance Rate; Myocardial Infarction; Obesity; Phenytoin; Potassium; Pulmonary Heart Disease; Thyroid Diseases

The principal causes of digitalis toxicity are overdose, reduced volume of distribution, reduced renal elimination, and increased myocardial sensitivity. The metabolic mechanism of digitalis toxicity is intense inhibition of sarcolemma Na-K ATPase, which leads to increases of intracellular Na+ and Ca2+ and arrhythmogenic membrane ionic currents. A variety of cellular electrophysiologic effects and effects on the nervous system are responsible for the array of clinical arrhythmias seen during digitalis toxicity, i.e., sinus bradycardia, atrioventricular block, nonparoxysmal atrioventricular junctional tachycardia, and ventricular tachycardia.

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Drug Interactions; Humans; Myocardial Infarction; Quinidine

Topics: Anti-Arrhythmia Agents; Arrhythmia, Sinus; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Cardiac Pacing, Artificial; Child; Child, Preschool; Digoxin; Electrocardiography; Electrophysiology; Heart Block; Humans; Infant; Mitral Valve Prolapse; Pacemaker, Artificial; Tachycardia

Topics: Angina Pectoris; Arrhythmias, Cardiac; Calcium Channel Blockers; Coronary Vasospasm; Digoxin; Diltiazem; Heart Block; Heart Diseases; Heart Rate; Humans; Hypertension; Nifedipine; Verapamil

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Biotransformation; Coumarins; Digoxin; Drug Synergism; Female; Fetal Growth Retardation; Fetus; Heparin; Humans; Infant, Newborn; Milk, Human; Pacemaker, Artificial; Pregnancy; Pregnancy Complications, Cardiovascular; Procainamide; Quinidine; Verapamil

Topics: Absorption; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Heart; Humans; Kinetics; Male; Nifedipine; Probability; Verapamil

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Drug Interactions; Electrocardiography; Heart Conduction System; Humans; Kinetics; Quinidine

Topics: Arrhythmias, Cardiac; Digoxin; Drug Synergism; Heart Diseases; Humans; Poisoning; Potassium; Vision Tests

Topics: Arrhythmias, Cardiac; Blood Pressure; Creatine Kinase; Digitalis Glycosides; Digitoxin; Digoxin; Diuretics; Heart Failure; Humans; Myocardial Contraction; Myocardial Infarction; Oxygen Consumption

Basic considerations in biotransformation and pharmacodynamics are presented as a basis for understanding clinical usage. The role of polarity in determining a given glycoside's duration of action and extent of biotransformation is emphasized. The pharmacokinetics are summarized emphasizing the fact that digoxin is not completely absorbed by oral administration. The important relationship of serum digoxin levels to myocardial content and apparently to myocardial response is reviewed. This relationship and the development of precise methods for measurement of digoxin in serum provide the clinician with accurate means to assess myocardial tolerance for digoxin under diverse clinical circumstances. This review includes discussion of methods of digitalization, appropriate use of serum levels, apparent and real resistance to digoxin, and apparent and real sensitivity to digoxin. The limitations of serum levels as a precise guide to toxicity are analyzed. Finally, new developments in use of immunologic therapy for digoxin intoxication are presented.

Topics: Arrhythmias, Cardiac; Biological Availability; Biotransformation; Digitoxin; Digoxin; Dose-Response Relationship, Drug; Humans; Middle Aged; Myocardium

The use of digitalis in pulmonary heart disease has been a topic of great interest for a number of years. The physician's decision to use or not to use digitalis in pulmonary disease has often been an emotional rather than a reasoned one. The diagnostic difficulties from a clinical point of view in separation of pulmonary from cardiac symptoms and findings have also been confusing. The fact that small doses of digitalis may have an inotropic effect on the cardiac muscle has been a difficult concept for many physicians to adopt. On the other hand, the larger doses of digitalis that are often necessary to control the ventricular response in supraventricular arrhythmias sometimes gives rise to confusion. We shall attempt to review the subject in detail and examine indications, contraindications, toxicity, dosage, assessment of benefit, and role of digitalis serum levels in patient management.

Topics: Arrhythmias, Cardiac; Body Weight; Digitalis Glycosides; Digoxin; Humans; Pulmonary Heart Disease

Topics: Arrhythmias, Cardiac; Delirium; Depression; Digitalis Glycosides; Digitoxin; Digoxin; Hallucinations; Heart Failure; Humans; Vision Disorders

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Heart Failure; Humans; Kidney Failure, Chronic; Poisoning; Vision Disorders

Topics: Arrhythmias, Cardiac; Body Fluids; Digoxin; Heart Failure; Humans; Methods

Recent reports of treatment of massive digoxin overdosage have emphasized the success of medical therapy. This report describes a fatal outcome to this problem despite aggressive medical management, including pervenous cardiac pacing and draws attention to deficiencies in current treatment of a serious problem.

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Humans; Lidocaine; Male; Phenytoin; Procainamide; Suicide, Attempted; Urination

Topics: Animals; Arrhythmias, Cardiac; Coronary Disease; Digitalis Glycosides; Digoxin; Humans; Hypertension; Kidney; Myocardium; Oxygen Consumption

Topics: Angina Pectoris; Arrhythmias, Cardiac; Biological Availability; Cardiac Glycosides; Central Nervous System Diseases; Digitoxin; Digoxin; Endocrine System Diseases; Gastrointestinal Diseases; Heart Failure; Humans; Hypersensitivity; Hypertension; Intestinal Absorption; Myocardial Infarction; Preoperative Care

Topics: Arrhythmias, Cardiac; Body Weight; Cardiac Glycosides; Digitoxin; Digoxin; Humans; Intestinal Absorption; Methods; Strophanthins

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Diuretics; Dogs; Haplorhini; Heart Failure; Humans; Magnesium; Magnesium Deficiency; Potassium

Topics: Aged; Anti-Arrhythmia Agents; Arrhythmia, Sinus; Arrhythmias, Cardiac; Atrial Fibrillation; Atropine; Bradycardia; Digitalis Glycosides; Digoxin; Heart Block; Heart Ventricles; Humans; Infant; Isoproterenol; Lidocaine; Phenytoin; Potassium; Procainamide; Propranolol; Quinidine; Tachycardia; Tachycardia, Paroxysmal

Cardiovascular diseases and their treatment in the aged are discussed under the headings of ischemic heart disease, hypertension, cardiac failure (with special reference to the use of diuretics and digoxin), infective carditis and thyroid disorders. Advanced age modifies the approach to treatment; the choice of drugs and the dosage must be adjusted accordingly. Possible drug interactions should also be considered. A rehabilitation program is of great benefit for many elderly cardiac patients. It should be planned individually and involve psychologic and environmental factors as well as medical therapy. After successful treatment of the acute episode, even the aged patient can undertake rewarding activities in his remaining lifetime.

Topics: Adrenergic beta-Antagonists; Aged; Anti-Bacterial Agents; Arrhythmias, Cardiac; Benzothiadiazines; Cardiac Rehabilitation; Cardiac Surgical Procedures; Cardiovascular Diseases; Coronary Disease; Delayed-Action Preparations; Digoxin; Diuretics; Endocarditis; Female; Heart Failure; Humans; Hypertension; Hypertension, Malignant; Hyperthyroidism; Hypothyroidism; Isosorbide Dinitrate; Male; Methyldopa; Middle Aged; Nitroglycerin; Sodium Chloride Symporter Inhibitors

Antibodies to digitalis glycosides have been elicited in experimental animals and have been utilized in the development of rapid, sensitive, specific and convenient radioimmunoassay methods for the clinical measurement of digoxin and other cardiac glycosides in man. The use of these assay methods has supplemented earlier studies with radiolabeled digitalis preparations and has made it possible to obtain much new information concerning factors which may contribute to the well known patient to patient variability in digitalis dosage requirements and in sensitivity to the toxic effects of cardiac glycosides. In some patients with a poor clinical response to digitalis, the finding of a serum concentration which is relatively low for the dose prescribed may suggest that true digitalis resistance is not present and may raise questions of poor patient compliance, tablet inadequacies, intestinal malabsorption, increased metabolic degradation or hyperthyroidism; if the cause of the low serum level cannot be identified or corrected, serial serum measurements should enable safe and rational upward adjustment of dosage. In some patients with digitalis toxicity, the finding of a serum level which is relativity high for the dose prescribed may suggest that the patient is not sensitive to digitalis but rather is excreting it slowly; in such instances in elderly patients (with decreased glomerular filtration rates) and in patients with renal disease, serial digitalis measurements are useful adjuncts to clinical observation in determining optimal digitalis dosage schedules. A knowledge of serum digitalis concentrations should enable us to develop sound principles for a more rational approach to the clinical administration of cardiac glycosides, especially in patients with unusually high dosage requirements or with unusual sensitivity to relatively small doses of digitalis.

Topics: Animals; Antibodies; Antibodies, Anti-Idiotypic; Arrhythmias, Cardiac; Biological Availability; Cardiomyopathies; Cattle; Cooperative Behavior; Digitalis Glycosides; Digoxin; Drug Interactions; Drug Resistance; Humans; Infant; Intestinal Absorption; Malabsorption Syndromes; Radioimmunoassay; Tablets; Tachycardia; Tritium

Topics: Administration, Oral; Animals; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Cardiac Catheterization; Cardiac Surgical Procedures; Coronary Disease; Depression, Chemical; Digitalis; Digoxin; Heart; Heart Diseases; Humans; Injections, Intravenous; Ouabain; Phenytoin; Plants, Medicinal; Plants, Toxic; Ventricular Fibrillation

Topics: Age Factors; Arrhythmias, Cardiac; Child; Child, Preschool; Chlorothiazide; Diet, Sodium-Restricted; Digitalis Glycosides; Digoxin; Diuretics; Ethacrynic Acid; Furosemide; Heart Block; Heart Defects, Congenital; Heart Failure; Heart Septal Defects, Ventricular; Humans; Infant; Infant, Newborn; Organomercury Compounds; Pacemaker, Artificial; Phenytoin; Procainamide; Propranolol; Quinidine; Tetralogy of Fallot; Transposition of Great Vessels

Topics: Administration, Oral; Adult; Arrhythmias, Cardiac; Body Weight; Digoxin; Dose-Response Relationship, Drug; Humans; Kidney; Male; Thyroid Diseases

Topics: Aluminum Hydroxide; Arrhythmias, Cardiac; Biopharmaceutics; Digoxin; Dose-Response Relationship, Drug; Drug Evaluation; Drug Interactions; Drug Therapy, Combination; Folic Acid; Half-Life; Humans; Intestinal Absorption; Phenytoin; Research Design; Tetracycline; Therapeutic Equivalency; Time Factors

Topics: Action Potentials; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Bradycardia; Digitalis Glycosides; Digoxin; Fever; Heart Atria; Heart Block; Humans; Hypotension; Lung Diseases, Obstructive; Methoxamine; Pacemaker, Artificial; Procainamide; Propranolol; Pulmonary Embolism; Quinidine; Tachycardia; Tachycardia, Paroxysmal; Ventricular Fibrillation

Topics: Animals; Antibodies; Antibody Formation; Arrhythmias, Cardiac; Biological Assay; Cattle; Cross Reactions; Digitoxin; Digoxin; Dogs; Immunoglobulin G; Ouabain; Papain; Protein Binding; Rabbits; Serum Albumin, Bovine; Sheep; Species Specificity; Structure-Activity Relationship; Time Factors; Tritium

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Atrioventricular Node; Diagnosis, Differential; Digitalis Glycosides; Digitoxin; Digoxin; Heart Diseases; Heart Rate; Heart Ventricles; Humans; Myocardium; Poisoning; Radioimmunoassay

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrioventricular Node; Digitalis Glycosides; Digoxin; Diuretics; Electrocardiography; Fatigue; Female; Gastrointestinal Diseases; Glucose; Heart Block; Humans; Lidocaine; Male; Middle Aged; Phenytoin; Poisoning; Potassium; Procainamide; Saliva; Tachycardia; Time Factors; Vision Disorders

Topics: Adenosine Triphosphatases; Arrhythmias, Cardiac; Digitalis Glycosides; Digitoxin; Digoxin; Heart; Heart Failure; Heart Rate; Humans; Kidney Diseases; Kinetics; Lanatosides; Lidocaine; Myocardium; Pacemaker, Artificial; Phenytoin; Potassium; Procainamide; Propranolol; Quinidine; Thyroid Diseases

Topics: Arrhythmias, Cardiac; Biopharmaceutics; Digitalis Glycosides; Digitoxin; Digoxin; Half-Life; Heart; Humans; Lanatosides; Ouabain; Structure-Activity Relationship; Vascular Resistance

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Coronary Disease; Digitalis Glycosides; Digitoxin; Digoxin; Heart Failure; Humans; Tachycardia, Paroxysmal

Topics: Acute Kidney Injury; Administration, Oral; Arrhythmias, Cardiac; Digitoxin; Digoxin; Drug Interactions; Electric Countershock; Half-Life; Humans; Injections, Intramuscular; Injections, Intravenous; Liver Diseases; Malabsorption Syndromes; Pharmaceutical Vehicles; Phenytoin; Potassium; Thyroid Diseases

Topics: Animals; Antibodies; Arrhythmias, Cardiac; Cardiac Glycosides; Digoxin; Erythrocytes; Haptens; Heart; Heart Rate; Humans; Immunoglobulin G; Immunotherapy; Kidney Cortex; Myocardium; Poisoning; Rabbits

Topics: Arrhythmias, Cardiac; Bradycardia; Cardiac Complexes, Premature; Child; Child, Preschool; Deafness; Digoxin; Electric Countershock; Electrocardiography; Female; Heart Failure; Heart Ventricles; Humans; Infant; Infant, Newborn; Lidocaine; Male; Propranolol; Tachycardia; Ventricular Fibrillation; Wolff-Parkinson-White Syndrome

Topics: Adenosine Triphosphatases; Aged; Arrhythmias, Cardiac; Cell Membrane; Chromatography, Gas; Digitalis Glycosides; Digitoxin; Digoxin; Erythrocytes; Evaluation Studies as Topic; Humans; Kidney Diseases; Potassium; Radioimmunoassay; Radioisotope Dilution Technique; Radioisotopes; Rubidium; Sodium; Tritium

Topics: Adrenergic beta-Antagonists; Anesthetics; Anticholesteremic Agents; Arrhythmias, Cardiac; Cathartics; Digitalis Glycosides; Digitoxin; Digoxin; Diuretics; Drug Interactions; Heart Conduction System; Heart Rate; Humans; Intestinal Absorption; Ion Exchange Resins; Lidocaine; Liver Circulation; Phenobarbital; Phenytoin; Potassium; Protein Binding

Topics: Action Potentials; Adult; Aged; Arrhythmias, Cardiac; Cardiac Output; Cardiac Volume; Digitalis; Digitalis Glycosides; Digoxin; Electrocardiography; Female; Heart Conduction System; Heart Rate; Humans; Male; Membrane Potentials; Middle Aged; Mitochondria, Muscle; Muscle Contraction; Ouabain; Plants, Medicinal; Plants, Toxic; Refractory Period, Electrophysiological; Sarcoplasmic Reticulum; Stimulation, Chemical

Topics: Adenosine Triphosphatases; Animals; Arrhythmias, Cardiac; Calcium; Cardiac Glycosides; Cats; Cell Membrane; Chemical Phenomena; Chemistry; Digitalis Glycosides; Digitoxin; Digoxin; Heart; Heart Rate; Humans; Membrane Potentials; Mitochondria, Muscle; Potassium; Radioimmunoassay; Serum Albumin; Sodium; Venous Pressure

Topics: Arrhythmias, Cardiac; Creatinine; Digitoxin; Digoxin; Heart Failure; Humans; Intestinal Absorption; Protein Binding; Time Factors

Topics: Age Factors; Arrhythmias, Cardiac; Calcium; Child; Coronary Care Units; Digitalis Glycosides; Digoxin; Electric Countershock; Electrocardiography; Endocrine System Diseases; Heart Diseases; Heart Failure; Heart Rate; Heart Valve Diseases; Humans; Kidney Failure, Chronic; Liver Diseases; Lung Diseases; Magnesium; Obesity; Ouabain; Poisoning; Potassium; Psychophysiologic Disorders; Pulmonary Heart Disease; Thyroid Diseases; Time Factors

Topics: Arrhythmias, Cardiac; Digoxin; Gastrointestinal Diseases; Heart Failure; Humans; Injections; Tablets

Digoxin provides symptomatic relief in patients with systolic heart failure, yet it has potential proarrhythmic mechanisms and has not been formally studied in patients with cardiac resynchronization therapy-defibrillators (CRT-Ds). We evaluated the association between digoxin use and appropriate tachyarrhythmia therapy in patients with CRT-D with advanced heart failure, analyzing the incidence of appropriate device therapies and overall survival in 350 consecutive primary prevention recipients with CRT-D with baseline left ventricular ejection fraction (LVEF) ≤35%, non-right bundle-branch block native QRS complex ≥120 ms, New York Heart Association III to IV heart failure, and significant coronary artery disease. Digoxin was prescribed in 162 patients (46%) at discharge from CRT-D implant. Over 48 ± 32 months of follow-up, 59 patients (17%) received ≥1 appropriate shock. Digoxin therapy was associated with shorter time to first shock in intention-to-treat (corrected hazard ratio 2.18, 95% confidence interval 1.23 to 3.87, p = 0.007) and on-treatment analysis (corrected hazard ratio 2.27, 95% confidence interval 1.27 to 4.07, p = 0.006). Patients prescribed digoxin had a lower baseline LVEF, and digoxin therapy was associated with increased risk of shocks only in patients with LVEF <22% (median); there was no increased risk in patients with LVEF ≥22%. Overall survival and incidence of antitachycardia pacing were similar regardless of digoxin therapy. In conclusion, digoxin therapy is associated with increased likelihood of appropriate CRT-D shocks for rapid ventricular arrhythmias in primary prevention patients with coronary artery disease, and this risk appears to be most evident in patients with more severe baseline LV dysfunction. Digoxin use should be reexamined prospectively in patients with CRT-D.

Topics: Aged; Arrhythmias, Cardiac; Cardiac Resynchronization Therapy; Cardiotonic Agents; Coronary Artery Disease; Death, Sudden, Cardiac; Defibrillators, Implantable; Digoxin; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Primary Prevention; Prospective Studies; Stroke Volume; Treatment Outcome; Ventricular Function, Left

Fimasartan (BR-A-657) is an angiotensin II receptor antagonist, recently approved as an antihypertensive agent.. This study aimed to investigate whether administration of fimasartan has an effect on the steady-state pharmacokinetics of digoxin.. An open-label, two-period, two-treatment, single-sequence, crossover study was conducted in 14 healthy male volunteers. On the first day of each 7-day treatment period, subjects received a loading dose of digoxin 0.5 mg, either alone or together with fimasartan 240 mg in the morning, followed by an additional dose of digoxin 0.25 mg after 6 h. On the subsequent 6 days, digoxin 0.25 mg, either alone or with fimasartan 240 mg was administered once daily. Serial blood samples for pharmacokinetics were collected up to 24 h after the last administration in each period.. The geometric mean ratio and 90% confidence intervals (CI) for the Cmax,ss and AUCτ,ss of digoxin (with/without fimasartan) were 1.307 (1.123 - 1.520) and 1.087 (1.015 - 1.165), respectively. Study medications were well-tolerated without serious adverse events or clinically meaningful changes.. Coadministration of fimasartan with digoxin does not result in clinically significant changes of digoxin pharmacokinetics at steady-state in healthy subjects.

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Area Under Curve; Arrhythmias, Cardiac; Biphenyl Compounds; Cardiotonic Agents; Cross-Over Studies; Digoxin; Female; Heart Failure; Humans; Male; Pyrimidines; Tetrazoles; Young Adult

For out-of-hospital cardiac arrest (OHCA) to be predicted and prevented, it is imperative the healthcare system has access to those vulnerable before the event occurs. We aimed to determine the extent of contact to the healthcare system before OHCA.. All patients in Denmark with a registered OHCA June 1, 2001-December 31, 2005 were matched on age and sex with 10 random controls from the entire Danish population. We estimated the association with OHCA by conditional logistic regression analyses, and we determined the proportion of patients in contact with the healthcare system before OHCA from hospital admissions or claimed prescriptions.. We identified 12,089 patients with an OHCA. Of these, 62% (7548) and 85% (10,312) were in contact with the healthcare system up to 30 days and 1 year before OHCA, respectively. Association with OHCA up to 30 days before the event pertained to myocardial infarction (odds ratio (OR)=6.4, 95% confidence interval (CI): 4.7-8.6)); heart failure (OR=5.1, CI: 4.1-6.3); ischemic heart disease (OR=1.9, CI: 1.6-2.4); and cardiac dysrhythmia (OR=1.8, CI: 1.4-2.2). Concomitant pharmacotherapy up to 30 days before OHCA with the strongest association was: corticosteroids (systemic) (OR=2.7, CI: 2.5-3.0), bronchial dilators (OR=2.5, CI: 2.3-2.7), anti-psychotic medication (OR=2.1, CI: 1.9-2.3), and digoxin (OR=2.1, CI: 2.0-2.3). Similar results were found for associations up to 1 year before OHCA.. Contrary to general belief, the majority of OHCA patients are in contact with the healthcare system shortly before OHCA.

Topics: Adrenal Cortex Hormones; Aged; Antipsychotic Agents; Arrhythmias, Cardiac; Bronchodilator Agents; Denmark; Digoxin; Female; Health Behavior; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Out-of-Hospital Cardiac Arrest; Patient Admission; Regression Analysis

To evaluate the efficacy and safety of a step-by-step fixed dose of specific immunotherapy protocol in case of severe digoxin poisoning in an open uncontrolled prospective study.. Twenty consecutive patients were admitted because of severe digoxin poisoning. The inclusion criteria were: digoxin overdose and either life-threatening arrhythmia; high-degree atrioventricular block, ventricular arrhythmia, or bradycardia less than 50 bpm and hyperkalaemia (>5.5 mmol/l). A two-step protocol of antidigoxin antibodies treatment was carried out. At admission, every patient received two vials of specific Fab-fragments. If after 1 h following infusion ECG signs regressed, no more treatment was given. If ECG signs did not regress, patients were given two more vials. At inclusion and 6 h after immunotherapy, clinical (cardiac rhythm, ECG records) and biological (serum digoxin concentration, potassium) findings were recorded.. Patients had a median (interquartile range) age of 83 (75-90) years. Four patients had acute poisoning and 16 chronic overdoses. Eleven patients showed ventricular arrhythmia, and five had high-degree atrioventricular block. Seventy percent of the patients needed only the first step. Significant decreases were observed in the number of cardiac dysrhythmia (16 vs. three patients), in the median (interquartile range) of serum digoxin concentration [5 microg/l (3.8-6.2) vs. 0.4 microg/l (0.3-2.2)] and in serum potassium [4.6 mmol/l (4.1-5.5) vs. 3.85 mmol/l (3.7-4.55)] before and after immunotherapy. The digoxin-related mortality was 5%.. This protocol of step-by-step digoxin-specific immunotherapy seems to be as effective as the equimolar treatment, and there was significant cost reduction in case of acute poisoning.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Clinical Protocols; Digoxin; Drug Overdose; Electrocardiography; Emergencies; Female; Humans; Immunoglobulin Fab Fragments; Immunologic Factors; Male; Prospective Studies

Implantable cardioverter defibrillator (ICD) therapy with backup ventricular pacing increases survival in patients with life-threatening ventricular arrhythmias. Most currently implanted ICD devices provide dual-chamber pacing therapy. The most common comorbid cause for mortality in this population is congestive heart failure.. To determine the efficacy of dual-chamber pacing compared with backup ventricular pacing in patients with standard indications for ICD implantation but without indications for antibradycardia pacing.. The Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial, a single-blind, parallel-group, randomized clinical trial.. A total of 506 patients with indications for ICD therapy were enrolled between October 2000 and September 2002 at 37 US centers. All patients had a left ventricular ejection fraction (LVEF) of 40% or less, no indication for antibradycardia pacemaker therapy, and no persistent atrial arrhythmias.. All patients had an ICD with dual-chamber, rate-responsive pacing capability implanted. Patients were randomly assigned to have the ICDs programmed to ventricular backup pacing at 40/min (VVI-40; n = 256) or dual-chamber rate-responsive pacing at 70/min (DDDR-70; n = 250). Maximal tolerated medical therapy for left ventricular dysfunction, including angiotensin-converting enzyme inhibitors and beta-blockers, was prescribed to all patients.. Composite end point of time to death or first hospitalization for congestive heart failure.. One-year survival free of the composite end point was 83.9% for patients treated with VVI-40 compared with 73.3% for patients treated with DDDR-70 (relative hazard, 1.61; 95% confidence interval [CI], 1.06-2.44). The components of the composite end point, mortality of 6.5% for VVI-40 vs 10.1% for DDDR-70 (relative hazard, 1.61; 95% CI, 0.84-3.09) and hospitalization for congestive heart failure of 13.3% for VVI-40 vs 22.6% for DDDR-70 (relative hazard, 1.54; 95% CI, 0.97-2.46), also trended in favor of VVI-40 programming.. For patients with standard indications for ICD therapy, no indication for cardiac pacing, and an LVEF of 40% or less, dual-chamber pacing offers no clinical advantage over ventricular backup pacing and may be detrimental by increasing the combined end point of death or hospitalization for heart failure.

Topics: Adrenergic beta-Antagonists; Aged; Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Anticoagulants; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Cardiovascular Agents; Catheter Ablation; Defibrillators, Implantable; Digoxin; Diuretics; Female; Heart Failure; Humans; Male; Middle Aged; Pacemaker, Artificial; Single-Blind Method; Survival Analysis; Tachycardia, Ventricular; Ventricular Dysfunction, Left; Warfarin

The role of cardiac glycosides in treating patients with chronic heart failure and normal sinus rhythm remains controversial. We studied the effect of digoxin on mortality and hospitalization in a randomized, double-blind clinical trial.. In the main trial, patients with a left ventricular ejection fraction of 0.45 or less were randomly assigned to digoxin (3397 patients) or placebo (3403 patients) in addition to diuretics and angiotensin-converting-enzyme inhibitors (median dose of digoxin, 0.25 mg per day; average follow-up, 37 months). In an ancillary trial of patients with ejection fractions greater than 0.45, 492 patients were randomly assigned to digoxin and 496 to placebo.. In the main trial, mortality was unaffected. There were 1181 deaths (34.8 percent) with digoxin and 1194 deaths (35.1 percent) with placebo (risk ratio when digoxin was compared with placebo, 0.99; 95 percent confidence interval, 0.91 to 1.07; P=0.80). In the digoxin group, there was a trend toward a decrease in the risk of death attributed to worsening heart failure (risk ratio, 0.88; 95 percent confidence interval, 0.77 to 1.01; P=0.06). There were 6 percent fewer hospitalizations overall in that group than in the placebo group, and fewer patients were hospitalized for worsening heart failure (26.8 percent vs. 34.7 percent; risk ratio, 0.72; 95 percent confidence interval, 0.66 to 0.79; P<0.001). In the ancillary trial, the findings regarding the primary combined outcome of death or hospitalization due to worsening heart failure were consistent with the results of the main trial.. Digoxin did not reduce overall mortality, but it reduced the rate of hospitalization both overall and for worsening heart failure. These findings define more precisely the role of digoxin in the management of chronic heart failure.

Topics: Aged; Arrhythmias, Cardiac; Cardiotonic Agents; Cardiovascular Diseases; Digoxin; Double-Blind Method; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Stroke Volume; Treatment Outcome

This prospective study was designed to determine whether diltiazem is superior to digoxin for the prophylaxis of supraventricular dysrhythmias (SVD) after pneumonectomy or extrapleural pneumonectomy (EPP) and to assess the influence of these drugs on perioperative cardiac function.. Seventy consecutive patients without previous SVD were randomly allocated immediately after pneumonectomy or EPP to receive diltiazem (n = 35) or digoxin (n = 35). Diltiazem-treated patients received a slow intravenous loading dose of 20 mg, followed by 10 mg intravenously every 4 hours for 24 to 36 hours, then 180 to 240 mg orally daily for 1 month. Digoxin-treated patients received a 1-mg intravenous loading in the first 24 to 36 hours, then 0.125 to 0.25 mg orally daily for 1 month. A concurrent prospective cohort of 40 patients without previous SVD, who did not participate in the study and underwent pneumonectomy or EPP without prophylaxis, served as a comparison group for SVD occurrence. Serial Doppler echocardiograms were performed to assess cardiac function and all patients were continuously monitored with Holter recorders for 3 days. Data were analyzed by intent-to-treat.. In patients undergoing standard or intrapericardial pneumonectomy, diltiazem prevented the overall incidence of postoperative SVD when compared with digoxin, 0 of 21 patients versus 8 of 25 patients, respectively, p < 0.005. When EPP patients were included in the analysis, diltiazem decreased the incidence of all SVD from 11 of 35 patients (31%) to 5 of 35 patients (14%) when compared with digoxin, p = 0.09. Digoxin-treated patients had a similar incidence of all SVD (31%) as concurrent controls (11 of 40 patients [28%]). The two treated groups did not differ in right or left atrial size, left ventricular ejection fraction, or right heart pressure. When all patients were combined, those in whom SVD developed were significantly older (65 +/- 12 years versus 55 +/- 11 years, p = 0.004) and had a longer median hospital stay (9 versus 6 days, p = 0.03), when compared with those in whom SVD did not develop, respectively. The subset of patients undergoing EPP had a greater incidence of atrial fibrillation and electrocardiographic changes suggestive of postoperative pericarditis than all other pneumonectomy patients.. Diltiazem was both safe and more effective than digoxin in reducing the overall incidence of SVD after standard or intrapericardial pneumonectomy. Digoxin therapy had no effect on the incidence of postoperative SVD and is not recommended for prophylaxis of SVD. Dysrhythmias after pneumonectomy or EPP occur in older patients and are associated with a greater length of hospital stay.

Topics: Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Calcium Channel Blockers; Digoxin; Diltiazem; Echocardiography, Doppler; Female; Heart; Humans; Lung Neoplasms; Male; Middle Aged; Pleural Neoplasms; Pneumonectomy; Prospective Studies; Treatment Outcome; Ventricular Pressure

Controversy surrounds the safety of digoxin use in patients recovering from acute myocardial infarction. Previous observations yielded contradictory conclusions. To determine whether digoxin therapy is associated with increased mortality in patients recovering from acute myocardial infarction, we analyzed data from 1731 survivors of acute myocardial infarction enrolled in the Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT), from which patients with severe heart failure were excluded. At the time of hospital discharge, 175 patients (10%) were taking digoxin. Mortality over 1 year after infarction was significantly higher in patients treated with digoxin than in patients who were not receiving digoxin [27 of 175 (15%) vs. 60 of 1556 (4%); p < 0.0001]. Digoxin administration was associated with increased mortality in several subsets of patients. Since patients treated with digoxin had baseline characteristics predictive of mortality more frequently than their counterparts, we adjusted for these differences. Multivariate analysis performed by the Cox proportional hazards model identified treatment with digoxin as an independent determinant associated with increased death during the first year after myocardial infarction [relative risk (RR) 2.8; 90% confidence interval (CI) 1.8-4.2]. Subgroup multivariate analysis indicated digoxin as an independent predictor of first year death in 464 patients who developed heart failure during their hospital stay (RR 2.3; 90% CI 1.3-4.0), as well as among 1267 patients who did not (RR 3.4; 90% CI 1.7-6.9). The present study suggests a significant excess mortality associated with digoxin therapy after myocardial infarction. The increased mortality risk may be related to unidentified variables associated with the severity of disease in patients treated with digoxin. However, our findings raise concern that the administration of digoxin may contribute to increased mortality in survivors of acute myocardial infarction.

Topics: Acute Disease; Adrenergic beta-Antagonists; Aged; Arrhythmias, Cardiac; Cardiotonic Agents; Digoxin; Double-Blind Method; Electrocardiography, Ambulatory; Female; Humans; Israel; Male; Middle Aged; Myocardial Infarction; Regression Analysis; Risk; Survivors

In this study 24-h Holter electrocardiographic recordings were used to measure the effects of an angiotensin converting enzyme inhibitor, enalapril given for 4 weeks, on the frequency of cardiac arrhythmias in 24 patients (14 patients had enalapril, 30 patients had placebo) with congestive heart failure (New York Heart Association Functional Class 3) receiving maintenance therapy with digoxin and furosemide. Although the placebo group had no change in the frequence of arrhythmias, enalapril-treated patients showed significant decrease in the frequency of premature ventricular complexes couplet, bigemine VPS and ventricular tachycardia. Moreover, it was observed that six cases of atrial fibrillation returned to sinus rhythm. During enalapril treatment, some patients experienced increased serum potassium levels, but there was no change in serum digoxin levels. We also observed echocardiographic improvement in left ventricular function as well as clinical symptoms of congestive heart failure. Finally we observed that there was an antiarrhythmic effect of enalapril in congestive heart failure. We thought that the antiarrhythmic effect of enalapril in congestive heart failure was probably due to hemodynamic improvement.

Topics: Aged; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Digoxin; Double-Blind Method; Electrocardiography, Ambulatory; Enalapril; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Myocardial Contraction; Placebos; Potassium; Tachycardia, Ventricular; Ventricular Function, Left

Prophylactic digitalization is still recommended after open lung surgery in order to prevent cardiac arrhythmias in the postoperative period. Since a beneficial effect of this potentially harmful medication is only poorly documented, we conducted a prospective randomized trial. Patients undergoing elective open lung surgery were divided into two groups one of which received digoxin postoperatively, the other not. Randomization was performed independently in three groups with regard to the extent of surgery, i.e. pneumonectomies in patients of any age, (bi-)lobectomies in patients > 50 and other (less extended) operations in patients > 60. Patients who were either too young for either group or who had already taken digoxin before surgery were followed separately. Monitoring was performed continuously in the ICU and conventional ECG was registered after 24, 48 and 72 hours and weekly until dismission.--Cardiac arrhythmias are very frequent in the early postoperative period with a maximum between the third and the fifth postoperative day. Any kind of arrhythmias were present in 19 of 30 patients (63%) compared to 14 of 35 patients (40%) in the control group. Symptomatic arrhythmias that needed treatment occurred in 11.4% of the control group, but in 33.3% of the patients with prophylactic digitalization. We therefore conclude that a general prophylactic digitalization after open lung surgery is not indicated, but that arrhythmias should be treated individually.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Digoxin; Dose-Response Relationship, Drug; Drug Administration Schedule; Electrocardiography, Ambulatory; Female; Humans; Lung Diseases; Male; Middle Aged; Pneumonectomy; Postoperative Complications; Premedication; Prospective Studies; Thoracotomy

Topics: Adult; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Double-Blind Method; Drug Combinations; Female; Heart Rate; Humans; Magnesium; Male; Middle Aged; Placebos; Prospective Studies; Tachycardia, Ventricular; Time Factors; Ventricular Function

A prospective controlled randomized clinical study of 50 patients undergoing total thoracic oesophagectomy by one surgical team is described, in which one group of patients was given prophylactic digoxin and the other was not. The incidence of cardiac dysrhythmia in each group was compared. Fourteen (56%) of 25 patients digitalized, compared to 16 (64%) of 25 patients not digitalized, suffered cardiac dysrhythmia, with a total incidence of 30 patients (60%). The first onset of dysrhythmia occurred within 48 h in 89% of the patients who suffered this complication. These results indicate a high incidence of cardiac dysrhythmia in patients undergoing this operative procedure, which is not significantly reduced by prophylactic digitalization and which is likely to occur within 2 days of surgery.

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Esophagectomy; Humans; Middle Aged; Premedication; Prospective Studies

A prospective, controlled, randomized study of 80 patients undergoing esophageal operations was undertaken, in which one group of patients was given digoxin and the other was not. The incidence of cardiac dysrhythmia was compared in each group. Twenty-six patients underwent operation for benign disease. Equal numbers were digitalized or not and no dysrhythmias occurred. Fifty-four patients underwent operation for malignant disease. Of 26 in the group digitalized, 12 suffered dysrhythmia (46%). Of 28 not digitalized, 9 suffered dysrhythmia (32%). Overall, 39% of patients with malignant disease suffered a dysrhythmia compared with none with benign disease (p < 0.002 by chi 2).

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Esophageal Diseases; Esophageal Neoplasms; Female; Humans; Intraoperative Complications; Male; Postoperative Complications; Premedication; Thoracotomy

Lisinopril 5-20 mg once daily was compared with digoxin 0.125-0.375 mg once daily in a double-blind, randomized, parallel-group study involving 217 patients with mild-to-moderate heart failure (New York Heart Association [NYHA] grades II-III) who were maintained on optimized diuretic therapy. After 6 weeks of treatment, digoxin and lisinopril had increased exercise duration by 18 seconds (p = 0.015) and 32 seconds (p = 0.0007), respectively, versus the baseline run-in period. The difference between treatments was not statistically significant (p = 0.1343). After 12 weeks, digoxin and lisinopril had increased exercise duration by 29 seconds and 51 seconds, respectively. The effect of digoxin compared with the baseline value was not significant but that for lisinopril was (p = 0.0027). The difference between treatments approached statistical significance (p = 0.0813). There was no difference between lisinopril and digoxin with regard to their effects on the frequency of ventricular ectopic counts, couplets, or nonsustained ventricular tachycardia. Blood pressures were not significantly different between treatments, although both systolic and diastolic blood pressure were consistently lower in the lisinopril group throughout randomized treatment. The proportions of patients demonstrating an improvement in NYHA grading were similar for both lisinopril and digoxin. Both treatments had similar effects on the symptoms of heart failure. Both drugs appeared to be equally well tolerated with a similar frequency of adverse events reported for both drugs (30% for lisinopril vs 29% for digoxin). Withdrawals from treatment were of a similar frequency for both treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Blood Pressure; Digoxin; Dipeptides; Diuretics; Double-Blind Method; Electrocardiography, Ambulatory; Exercise Test; Female; Heart Failure; Humans; Lisinopril; Male; Middle Aged; Physical Exertion; Placebos

The prognosis of heart failure patients is poor and as many as half of the deaths are sudden and thereby presumably attributable to arrhythmias. In the present study the effect of traditional therapy of mild heart failure with digoxin on arrhythmias was compared with the effect of xamoterol, a cardioselective beta 1 partial agonist, which has in addition beta-blocking properties at higher levels of sympathetic tone. Fifteen patients (NYHA class II-III) were included in the study. After a two-week baseline period they were randomized to digoxin or xamoterol for four weeks followed by a two-week washout and another four weeks of crossover therapy. Heart rate, blood pressure, and the number of complex ventricular premature beats remained essentially unchanged with digoxin. With xamoterol heart rate increased from 86 to 93 (ns) but was significantly higher during the night in comparison with digoxin. The number of ventricular premature beats decreased from 186 +/- 317 to 110 +/- 137 and increased to 130 +/- 175 after treatment. The number of runs decreased from 11 +/- 35 to 2.7 +/- 5 and increased to 5.6 +/- 9 after therapy. In conclusion, no significant effect of digoxin or xamoterol on ventricular arrhythmias was found. However, xamoterol showed a tendency to reduce simple and complex ventricular arrhythmias in patients with mild to moderate heart failure.

Topics: Adrenergic beta-Agonists; Analysis of Variance; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Double-Blind Method; Electrocardiography, Ambulatory; Female; Heart Failure; Humans; Male; Middle Aged; Propanolamines; Time Factors; Xamoterol

The efficacy and safety of intravenous flecainide to convert recent-onset atrial fibrillation (AF) (present for greater than or equal to 30 minutes and less than or equal to 72 hours and a ventricular response greater than or equal to 120 beats/min) was investigated. A total of 102 patients without severe heart or circulatory failure were randomized to receive either intravenous flecainide (2 mg/kg, maximum dose 150 mg; 51 patients) or placebo (51 patients) in a double-blind trial. Digoxin (500 micrograms intravenously) was administered to all patients who had not previously been receiving digoxin. The electrocardiogram was monitored continuously during the study. In 29 (57%) patients stable sinus rhythm was restored within 1 hour after flecainide and in only 7 (14%) given placebo (chi square 18.9; p = 0.000013; odds ratio 8.3; 95% confidence interval 2.9-24.8). Reversion to sinus rhythm within 1 hour after starting the trial medication was considered a pretrial end point and likely to be due to a drug effect. At the end of the 6-hour monitoring period, 34 patients (67%) in the flecainide group were in sinus rhythm whereas only 18 (35%) in the placebo group had reverted (chi square 8.83, p = 0.003; odds ratio 3.67; 95% confidence interval 1.5-9.1). Significant hypotension, although short lived, was more common in the flecainide group. One patient given flecainide developed torsades de pointes and was successfully electrically cardioverted. Flecainide is useful for the management of recent-onset AF both for control of the ventricular response and conversion to sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Double-Blind Method; Drug Evaluation; Female; Flecainide; Humans; Hypotension; Male; Middle Aged; Monitoring, Physiologic; Time Factors

Prophylactic digoxin is widely used in patients undergoing pulmonary surgery to prevent or control cardiac arrhythmias, but whether it is helpful or not is uncertain.. An open, controlled randomised prospective clinical study of 111 patients was undertaken to compare the incidence of cardiac arrhythmias in the 58 patients who received preoperative digoxin and the 53 who did not.. Cardiac arrhythmia occurred in half (29/58) of those given prophylactic digoxin and in 36% (19/53) of those who were not. The overall incidence of arrhythmia was 43%, with no statistically significant difference between the groups.. Cardiac arrhythmias remain an important complication of pulmonary surgery and the incidence is not reduced by prophylactic digoxin.

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Humans; Incidence; Intraoperative Complications; Lung; Middle Aged; Postoperative Period; Prospective Studies

Because life-threatening digitalis intoxication is unusual in children, treatment with digoxin-specific-antibody Fab fragments (Fab) has rarely been reported. We describe the efficacy of Fab in the treatment of children with severe digitalis intoxication.. Twenty-nine children with intoxication due to digoxin (28) or digitoxin (1) received Fab at 21 participating hospitals between 1974 and 1986. Data were gathered about the patients' medical illnesses, doses and serum concentrations of digitalis, responses to Fab therapy, and outcomes.. In the infants and young children with acute digoxin intoxication, the digoxin doses ranged from 0.30 to 0.96 mg per kilogram of body weight; two adolescents had severe intoxication after doses of only 0.20 and 0.26 mg per kilogram. The serum digoxin concentrations ranged from 3.0 to greater than 100 ng per milliliter (mean, 13.8). Atrioventricular block (present in 22 patients [76 percent]) was the most common sign of toxicity. All the patients in this series had severe disturbances of cardiac rhythm, hyperkalemia (mean serum potassium concentration, 5.4 mmol per liter), or both. In 27 patients (93 percent), digitalis toxicity resolved after the administration of Fab. Of the 19 patients for whom data were available on the timing of the response to Fab, 15 responded within 180 minutes. Three patients required retreatment with Fab. Seven died of complications unrelated to the administration of Fab.. We recommend that Fab be used in the treatment of digitalis poisoning in infants and young children who have ingested greater than or equal to 0.3 mg of digoxin per kilogram, who have underlying heart disease, or who have a serum digoxin concentration of greater than or equal to 6.4 nmol per liter (greater than or equal to 5.0 ng per milliliter) in the elimination phase; and who also have a life-threatening arrhythmia, hemodynamic instability, hyperkalemia, or rapidly progressive toxicity. Adolescents, who are more sensitive to the toxic effects of digoxin than younger children, may require treatment with Fab after ingesting lower doses.

Topics: Acute Disease; Adolescent; Arrhythmias, Cardiac; Child, Preschool; Digitoxin; Digoxin; Female; Heart Block; Heart Diseases; Humans; Hyperkalemia; Immunoglobulin Fab Fragments; Infant; Infant, Newborn; Male; Poisoning

In 25 patients whose chronic congestive heart failure (CHF) had recently worsened to New York Heart Association class IV, pimobendan (5 to 20 mg/day) was added to maximum conventional therapy consisting of digoxin, diuretics, angiotensin-converting enzyme inhibitors, coumadin derivatives to prevent thromboembolic complications, and amiodarone to suppress serious ventricular rhythm disturbances. CHF was fatal in less than 1 month in five patients (two had shown some initial improvement). The other 20 had sustained improvement by at least one functional class, interrupted by episodes of CHF that usually responded to intravenous therapy. Median survival was 12 months (range 10 days to greater than 3 years); five patients died suddenly, 12 died of intractable CHF, and two died of other causes. Six patients were alive 3 years after the onset of treatment with pimobendan. Add-on therapy with pimobendan produced a sustained improvement in many patients with severe CHF that was no longer responding to a combination of digoxin, diuretics, and angiotensin-converting enzyme inhibitors.

Topics: Aged; Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Digoxin; Diuretics; Female; Heart Failure; Humans; Male; Pyridazines; Survival Analysis; Vasodilator Agents

The study was designed to evaluate the safety of ibopamine (3,4-diisobutyryl ester of N-methyldopamine. SB(-)-505. Inopamil; CAS 66195-31-1) for the chronic treatment of congestive heart failure. It was conducted as a comparative cohort survey, versus digitalis. A third cohort was made with patients who received both drugs in association. Any differences between cohorts at baseline were dealt with by identifying explanatory variables with linear discriminant analysis and by performing multivariate statistical analysis by Cox's proportional hazard model. During 16 months, 3.330 patients were enrolled and then followed-up for a median time of 1 year. Baseline characteristics are reported as well as follow-up results on mortality, disease progression, anginal episodes, arrhythmias, need for cointervention and other undesired on-therapy events. Results pointing to efficacy are consistent with the favourable results from controlled randomized double blind medium--long term clinical trials. In addition, data from the present study do indeed provide strong evidence on the safety of long-term treatment with ibopamine. At variance with inotropic agents ibopamine did not increase mortality. The results rather suggest that long-term treatment with ibopamine affords an increase in survival and a delay in the progression of the disease, without adverse effects on cardiac rhythm and myocardial oxygen balance, and with a general improvement in the patients' quality of life.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angina Pectoris; Arrhythmias, Cardiac; Blood Pressure; Cardiotonic Agents; Deoxyepinephrine; Digoxin; Drug Prescriptions; Drug Therapy, Combination; Electrocardiography; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Product Surveillance, Postmarketing; Prognosis; Risk Factors

Cardiac arrhythmias are known complications of thoracic operations. The prophylactic value of flecainide administered as a constant-rate, intravenous infusion (0.15 mg.kg-1.h-1) after a loading dose (2 mg.kg-1) was compared with digoxin (10 micrograms.kg-1 for 12 hours, then 0.25 mg.24 h-1) in a randomized study in 30 patients using Holter monitoring during the first 72 hours after operation. Drug monitoring was performed every day to keep a serum level of flecainide of 200 to 600 ng.mL-1 and a digoxin level of 0.8 to 2 ng.mL-1. Failure, defined as the appearance of atrial fibrillation or flutter or the development of complex ventricular arrhythmias (Lown IVb and V), was observed in one patient in the flecainide group (7%) and in 7 patients in the digoxin group (47%) (p less than 0.05). It is concluded that flecainide is more efficient than digoxin in preventing and treating cardiac arrhythmias after thoracic operations. At the dosage used side effects related to flecainide or digoxin were not observed.

Topics: Arrhythmias, Cardiac; Digoxin; Electrocardiography, Ambulatory; Flecainide; Humans; Lung; Postoperative Complications; Thoracic Surgery

In a randomized single-blind cross-over trial, the efficacy of digoxin, angiotensin-converting enzyme (ACE) inhibition by quinapril, and their combination on exercise tolerance, heart size (echocardiography), and neurohumoral systems was investigated in 19 outpatients with congestive heart failure (CHF) New York Heart Association functional class II and sinus rhythm. Baseline therapy consisted of 25 mg hydrochlorothiazide and remained unchanged. After treatment with quinapril, exercise tolerance significantly increased (606 vs. 644 s, 2 p less than 0.03) and left ventricular end-diastolic dimension (63 vs. 58 mm, 2 p less than 0.03), mean arterial blood pressure (MABP, 100 vs. 92 mm Hg, 2 p less than 0.03) and plasma norepinephrine (NE) levels (378 vs. 323 pg/ml, 2 p less than 0.03) were significantly reduced. Digoxin increased resting systolic blood pressure (SBP 133 vs. 142 mm Hg, 2 p less than 0.03). Combined administration of both drugs significantly increased fractional shortening (24 vs. 28%, 2 p less than 0.03), reflecting the positive inotropic action of digoxin in combination with afterload reduction. However, there was no further increase in exercise tolerance. Our data suggest that early administration of ACE inhibitors may be beneficial in patients with mild CHF and sinus rhythm, although the magnitude of improvement was less substantial than that reported for patients with more severe CHF.

Topics: Adult; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Digoxin; Drug Therapy, Combination; Exercise Test; Female; Follow-Up Studies; Heart Failure; Humans; Hydrochlorothiazide; Isoquinolines; Male; Middle Aged; Norepinephrine; Peptidyl-Dipeptidase A; Quinapril; Randomized Controlled Trials as Topic; Renin; Single-Blind Method; Tetrahydroisoquinolines

In 50 patients with chronic congestive heart failure (CCHF, III or IV class), aged 62.8 +/- 9.1 years, who were treated with digoxin (Dx) and furosemide (F) (investigation A), continuous 24-hour ecg registration was performed according to Holter. Next, this treatment was extended by two-week administration of nifedipine (N) or isosorbide dinitrate (S) (investigation B), followed by one-month addition of captopril (Cp) (investigation C). During the last two weeks Dx, F, N or Dx, F, S were administered with Cp being withdrawn (investigation D). At the end of each stage of the treatment ecg registration was repeated according to Holter. At the same time, during the investigation A there were performed determinations of blood serum sodium, potassium and digoxin concentrations, two-dimensional echocardiography and evaluation of submaximal exercise tolerance. In 96 per cent of patients with CCHF, treated with Dx and F, cardiac rhythm disturbances were found. In 53.3 per cent life-threatening ventricular arrhythmias occurred, including unstable ventricular tachycardia in 11.1 per cent of patients. Addition of N or S to the classical treatment did not decrease either patient number or amounts of cardiac rhythm disturbances in individual classes according to Lown. Also Cp did not affect numbers of patients with cardiac rhythm disturbances, but it decreased numbers of patients with life-threatening ventricular arrhythmias from 53.3 per cent to 28.9 per cent (from 24/45 to 13/45). At the same time, Cp significantly decreased numbers of ventricular arrhythmias in class 3 and 4a (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Atrial Fibrillation; Captopril; Cardiac Output; Coronary Disease; Digoxin; Drug Therapy, Combination; Electrocardiography; Exercise Test; Female; Furosemide; Heart Block; Heart Failure; Heart Valve Diseases; Heart Ventricles; Humans; Isosorbide; Male; Middle Aged; Nifedipine; Tachycardia; Vasodilator Agents

A prospective, controlled, randomized clinical study of 140 patients undergoing elective thoracic operations over a period of 1 year in a regional referral unit was performed in which one group received digoxin and the other did not. The incidence of cardiac arrhythmia was compared in each group. Overall mortality was 5.7%. There was no significant difference in incidence of cardiac arrhythmia in each group, and we conclude that the prophylactic use of digoxin in elective thoracic operations should be revised.

Topics: Age Factors; Aged; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Humans; Incidence; Middle Aged; Oxygen; Pneumonectomy; Potassium; Premedication; Prospective Studies; Randomized Controlled Trials as Topic; Thoracotomy; Time Factors

Moricizine is well absorbed after oral administration and undergoes extensive first-pass metabolism. The drug has a large apparent volume of distribution (approximately 4 liters/kg), exhibits extensive plasma protein binding (approximately 95%) and produces at least 30 metabolites. Indirect evidence indicates that some of those metabolites may be pharmacologically active. The elimination half-life of moricizine is 2 to 6 hours, but its duration of antiarrhythmic action is much longer suggesting active metabolites. Moricizine induces its own metabolism with no change in pharmacologic effect. It also induces the metabolism of theophylline and specific pathways of antipyrine. Cimetidine reduces metabolism of moricizine but does not alter its pharmacologic effects. This observation provides further support for the hypothesis that the metabolites of moricizine contribute to the pharmacologic actions during therapy and indicate that plasma level monitoring is not likely to be of value. There are no known clinically significant pharmacokinetic interactions between moricizine and digoxin, warfarin or propranolol. Excessive prolongation of the PR interval has been seen in some patients receiving both digoxin and moricizine, probably due to additive electrophysiologic effects of the 2 drugs.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cimetidine; Clinical Trials as Topic; Digoxin; Drug Interactions; Humans; Moricizine; Phenothiazines; Propranolol; Theophylline; Warfarin

The antiarrhythmic efficacy of intravenous flecainide and intravenous digoxin was assessed in 29 patients (26 men), aged 43 to 73 (63 +/- 7) years who developed atrial arrhythmias in the first 96 hours after coronary artery bypass grafting. Twenty-seven had atrial fibrillation and 2 had atrial flutter. Patients were entered into the study if the arrhythmia persisted for at least 15 minutes with a ventricular rate greater than 120 beats/min. Fifteen patients were randomized to flecainide (group 1) and 14 to digoxin (group 2). Flecainide was given as a bolus of 1 mg/kg over 10 minutes followed by an infusion of 1.5 mg/kg/hr for 1 hour and then 0.25 mg/kg/hr for the rest of the study period (24 hours). Digoxin was given as 3 bolus doses (0.5 mg followed after 6 and 12 hours by 0.25 mg). In both groups, 10 mg of verapamil was given intravenously after 45 minutes if the arrhythmia persisted with a mean ventricular rate greater than 100 beats/min. The antiarrhythmic efficacy was assessed by 24-hour Holter monitoring and frequent 15-second rhythm strips. Within 45 minutes control of arrhythmia, which was maintained for the rest of the study period, was achieved in 10 of 15 patients in group 1 and 2 of 14 in group 2 (p less than 0.01). Nine of 15 reverted to sinus rhythm in group 1 compared to 0 of 14 in group 2 and 1 of 15 remained in arrhythmia with a controlled ventricular rate in group 1 compared to 2 of 14 in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Arrhythmias, Cardiac; Coronary Artery Bypass; Digoxin; Drug Therapy, Combination; Female; Flecainide; Hemodynamics; Humans; Male; Middle Aged; Random Allocation; Verapamil

The substitution of digoxin with ibopamine, a new inotropic and vasodilating agent, was evaluated in a multicenter study in 58 patients with mild-to-moderate congestive heart failure, stabilized on diuretics, and digoxin therapy. The study was a parallel, double-blind, randomized trial of four weeks duration in which half of the group continued the pre-study medication (diuretics and digoxin) and half of the group was treated with diuretics and ibopamine (100 mg, three times a day). At baseline evaluation, the two groups were similar for age, sex, underlying cardiac disease, duration of congestive heart failure, symptom score, cardiothoracic ratio, echocardiographic parameters of left ventricular function and exercise tolerance as measured by bicycle ergometry. After four weeks, no clinical deterioration was found in the patients treated with ibopamine in any measured parameter. There were two deaths during the study: a sudden death and one following an acute myocardial infarction. Both patients were on digoxin. This study suggests that in patients with mild-to-moderate congestive heart failure, ibopamine therapy may effectively and safely substitute digoxin therapy for up to four weeks, representing an option for patients requiring inotropic support but are at risk for potential digoxin toxicity.

Topics: Adult; Aged; Arrhythmias, Cardiac; Deoxyepinephrine; Digoxin; Dopamine; Echocardiography; Exercise Test; Female; Heart Failure; Heart Ventricles; Humans; Male; Middle Aged

Fifty six adult patients were randomised to treatment with flecainide (group 1, n = 29) or a combination of digoxin and disopyramide (group 2, n = 27) for acute atrial fibrillation and flutter after cardiac surgery. Intravenous flecainide was given as a 2 mg/kg bolus over 20 minutes followed by an infusion (0.2 mg/kg per hour) for 12 hours. Group 2 were given digoxin (0.75 mg) intravenously followed two hours later by an intravenous bolus of disopyramide (2 mg/kg) and an infusion (0.4 mg/kg per hour) for 10 hours. Within 12 hours sinus rhythm was restored in 86% of the group 1 (25 patients) and 89% of the group 2 (24 patients). The median time to reversion was significantly shorter in group 1 (80 minutes, range 30-180 minutes) than group 2 (220 minutes, range 138-523 minutes). None of the patients in group 1 and four of the patients in group 2 had transient relapses into atrial fibrillation during the 12 hours of intravenous treatment. There were five late relapses in group 1 and seven in group 2 during subsequent oral treatment. Two group 1 patients and two group 2 patients showed adverse drug effects. Intractable ventricular arrhythmias occurred after five days of oral treatment in one patient (group 1) who had poor left ventricular function, hepatic impairment, and toxic concentrations of drugs at the time of death. Flecainide was as effective as the combination of digoxin and disopyramide and it acted significantly faster and was associated with fewer relapses. Monitoring of blood concentrations of flecainide is essential in patients with poor left ventricular function and hepatic impairment.

Topics: Acute Disease; Aged; Arrhythmias, Cardiac; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Clinical Trials as Topic; Digoxin; Disopyramide; Drug Therapy, Combination; Female; Flecainide; Humans; Male; Middle Aged; Postoperative Complications; Random Allocation

A method is presented for choosing an additive constant c when transforming data x to y = log(x + c). The method preserves Type I error probability and power in ANOVA under the assumption that the x + c for some c are log-normally distributed. The method has advantages similar to those of rank transformations--namely, it is easy to use and is resistant to extreme observations. Since the special case c----infinity corresponds in ANOVA to y = x, the method is a useful generalization of least squares.

Topics: Analysis of Variance; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Clinical Trials as Topic; Digoxin; Double-Blind Method; Drug Therapy; Hair; Heart Ventricles; Humans; Research Design; Skin

Intravenous digoxin, 1 mg, was administered over 8 hours to 10 cardiac patients with left ventricular (LV) dysfunction after coronary artery bypass grafting. The cardiovascular effects of digoxin were monitored over 20 hours by indwelling pulmonary artery and radial artery lines and were compared with those of a control group of 10 patients who had normal postoperative LV function. Digoxin administration produced an increased cardiac index and mean arterial blood pressure within 2 hours. Within 4 hours after digoxin administration pulmonary artery wedge pressure in patients receiving digoxin was significantly lower than in control patients. At 16 hours there was a significant increase in both the LV stroke work and LV stroke work index in patients receiving digoxin vs control patients. Two patients receiving digoxin and 3 control patients had changes in cardiac rhythm during the study. Thus, digoxin can be safely administered to postoperative patients with LV dysfunction and is an acceptable inotropic agent.

Topics: Arrhythmias, Cardiac; Cardiovascular System; Clinical Trials as Topic; Coronary Artery Bypass; Digoxin; Heart; Heart Diseases; Heart Ventricles; Humans; Male; Middle Aged; Pulmonary Wedge Pressure; Time Factors

The potential for pharmacokinetic drug interaction between ethmozine (moricizine HCl), a phenothiazine class I antiarrhythmic investigational drug, and digoxin was evaluated in 13 cardiac patients with normal renal function. Antiarrhythmic therapy was initiated in patients with potentially lethal (nonlife-threatening) ventricular arrhythmias (greater than 30 ventricular ectopic beats [VEB]/hr) who were receiving maintenance digoxin therapy for congestive heart failure and/or atrial fibrillation. Serum digoxin concentrations of patients were measured frequently by radioimmunoassay and plasma ethmozine concentrations by high-performance liquid chromatographic methods. Patients entered a short-term (4 weeks) single-blind, placebo controlled ethmozine protocol with an option to receive long-term (1 to 6 months) open-label maintenance ethmozine therapy. Ambulatory ECGs (48 hour) used to assess antiarrhythmic efficacy of ethmozine during each week of the short-term protocol showed that 77% of patients demonstrated greater than 90% mean hourly frequency suppression of all forms of ventricular ectopy. Serum digoxin concentrations during short-term ethmozine dosing showed a nonsignificant (p greater than 0.05) increase of 10% to 15% (mean 0.91 ng/ml to 1.13 ng/ml). The short-term protocol serum digoxin levels correlated closely with serum digoxin concentrations during placebo therapy (1st week, r = 0.90; 2nd week, r = 0.87). Serum digoxin concentrations were not significantly different (p greater than 0.05) from placebo values at the end of 1, 3, and 6 months of maintenance ethmozine therapy. Thus, we conclude that ethmozine administered in an antiarrhythmic efficacious dosage (10 mg/kg/day) showed no important clinical or statistically significant change in serum digoxin concentrations of cardiac patients with normal renal function.

Topics: Adult; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Cardiac Complexes, Premature; Clinical Trials as Topic; Digoxin; Drug Interactions; Female; Heart Failure; Humans; Kinetics; Male; Middle Aged; Moricizine; Phenothiazines

The antiarrhythmic efficacy and safety of oral encainide hydrochloride and quinidine sulfate were compared in a nine center double-blind crossover study in 187 outpatients with benign or potentially lethal ventricular arrhythmias. Patients with at least 30 premature ventricular complexes/h were randomized to receive either encainide, 25 mg four times/day, or quinidine, 200 mg four times/day, for 2 weeks. These doses were continued for another 2 weeks if a 75% or greater reduction in premature ventricular complexes was observed. If this reduction was not seen, encainide was increased to 50 mg four times/day or quinidine to 400 mg four times/day for an additional 2 weeks. Both drugs produced a statistically significant reduction in premature ventricular complex frequency compared with baseline values. Encainide produced a statistically significant greater mean reduction in total premature ventricular complexes than did quinidine during the initial dose phase and after dose adjustment. More patients required dose increases of quinidine (60%) than of encainide (51%). Early discontinuation of treatment resulting in advancement to the next study period occurred in 12 patients taking encainide and 38 patients taking quinidine (p less than 0.05). PR and QRS intervals increased significantly during encainide treatment, as did QTc and JT intervals during quinidine treatment. No adverse reactions resulted from these electrocardiographic changes. Adverse reactions were more common with quinidine than with encainide.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Anilides; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Clinical Trials as Topic; Digoxin; Double-Blind Method; Drug Interactions; Electrocardiography; Encainide; Female; Humans; Male; Middle Aged; Quinidine; Random Allocation

The effect of the postoperative administration of digoxin to patients undergoing coronary artery bypass surgery on the incidence of supraventricular arrhythmias was studied. Patients were randomly assigned to a control group (n = 51) or digoxin group (n = 47) on a prospective basis. Patient characteristics were similar in both groups, and no patients were receiving digoxin therapy preoperatively or other antiarrhythmic medications. All patients had normal systolic ejection fractions, renal function, and hepatic function. Eight patients (16%) in the control group developed postoperative arrhythmias while seven patients (15%) in the digoxin group developed supraventricular arrhythmias. This difference was not significant. Two patients in the digoxin group developed digoxin-induced arrhythmias, and two other patients experienced digoxin-related nausea and vomiting, which were resolved with discontinuation of the drug. The postoperative administration of digoxin to patients undergoing coronary artery bypass surgery had no effect on the incidence of supraventricular arrhythmias. The prophylactic use of digoxin therapy in this patient population is not recommended unless there is a history of arrhythmias responsive to digoxin therapy.

Topics: Adult; Aged; Angina Pectoris; Arrhythmias, Cardiac; Coronary Artery Bypass; Digoxin; Female; Humans; Male; Middle Aged

This study compares the effects of digoxin, placebo and ibopamine (SB-7505), the orally active 3,4-diisobutyryl ester of N-methyl-dopamine, on exercise tolerance and cardiac rhythm of 14 patients whose left ventricular heart failure (end-diastolic pressure, 26.3 +/- 5.9 mmHg; ejection fraction, 0.42 +/- 0.10%) depended on a previous myocardial infarction. Patients were admitted to the study while on chronic oral digoxin treatment (serum levels between 1.1 and 1.9 ng/ml). Placebo instead of digoxin was given for the following month. Thereafter ibopamine 50 mg t.i.d. for one month was given. A sequence of one-month treatments with digoxin, placebo and ibopamine was repeated, then ibopamine was administered continuously for the next two months. The concurrent treatment (diuretics in all patients, nitroderivates in twelve, calcium antagonists in two) remained unchanged during the observation period. Symptoms-limited exercise tests and 24-h Holter recordings were obtained at admission, at the end of each one-month treatment and at the end of the observation period. Two patients developed unstable angina without increase of serum creatine phosphokinase while on ibopamine and were withdrawn. Out of the 12 patients that concluded the trial, one required supplementary doses of diuretic at the end of the second period on placebo. The results obtained during the trial suggest that: a) therapeutic plasma levels of digoxin have no deleterious effect on cardiac rhythm nor significantly increase exercise tolerance as compared with placebo; b) diuretics and nitrates appear to sustain the clinical stability of these patients as a group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Arrhythmias, Cardiac; Cardiotonic Agents; Deoxyepinephrine; Digoxin; Dopamine; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Myocardial Infarction; Physical Exertion

Twenty-four-hour Holter electrocardiographic recordings were used to measure the effects of a converting-enzyme inhibitor, enalapril, given for 12 weeks, on the frequency of cardiac arrhythmias in 10 patients with congestive heart failure (New York Heart Association functional class II to III) receiving maintenance therapy with digoxin and furosemide. Nine patients were given placebo, and both study groups were conducted in a double-blind, parallel manner. The placebo group had no change in the frequency of arrhythmias, whereas enalapril-treated patients showed a significant decrease in the frequency of premature ventricular complexes, ventricular couplets and ventricular tachycardia. A minor, nonsignificant reduction in atrial premature complexes was seen in patients who received enalapril. Compared with placebo patients, those who received enalapril had an increase in plasma potassium levels of 0.33 mmol/liter, a decrease in plasma digoxin, and decreases in pulmonary artery wedge, mean pulmonary artery and right atrial pressures. However, none of these indexes were correlated with the concomitant decline in cardiac arrhythmias. It is concluded that enalapril reduces the frequency of ventricular arrhythmias in congestive heart failure, although the underlying mechanisms are not known.

Topics: Adult; Aged; Arrhythmias, Cardiac; Blood Pressure; Digoxin; Dipeptides; Electrocardiography; Enalapril; Female; Furosemide; Heart Failure; Heart Ventricles; Humans; Male; Middle Aged; Pulmonary Wedge Pressure

After aorta-coronary bypass grafting, 164 consecutive patients were randomized to receive propranolol 5 mg every 6 hours orally (n = 82) or to serve as control subjects (n = 82). All patients were receiving beta blockers preoperatively. There were no significant differences between the two groups. The incidence of sustained supraventricular (nonsinus) tachyarrhythmias was 23% in the control group and 9.8% in the treated group (p = 0.02). The incidence of ventricular arrhythmias was 15% in the control group and 2.4% in the treated group (p = 0.005). The overall difference in clinically important arrhythmias was 38% in the control group and 12.2% in the treated group (p = 0.0002). We conclude that low-dose oral propranolol in patients who were receiving beta blockers preoperatively is effective in reducing the incidence of clinically important arrhythmias occurring after aorta-coronary bypass grafting.

Topics: Aged; Arrhythmias, Cardiac; Blood Pressure; Coronary Artery Bypass; Digoxin; Female; Heart Rate; Humans; Male; Middle Aged; Preoperative Care; Propranolol; Random Allocation

Topics: Administration, Oral; Aged; Alprenolol; Arrhythmias, Cardiac; Blood Pressure; Clinical Trials as Topic; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Heart Rate; Humans; Injections, Intravenous; Middle Aged; Myocardial Infarction; Random Allocation; Time Factors

The effectiveness of oral propafenone in treating ventricular premature complexes (VPCs) was assessed with a single-blind dose-ranging trial followed by a double-blind, randomized, crossover comparison of propafenone and placebo. Patients subsequently were treated with propafenone for up to 24 months. During dose ranging, the average of individual percent suppressions was 83% at the largest dose (300 mg/8 hours). During the double-blind trial, the effectiveness of propafenone was confirmed, with 7 of 12 patients achieving greater than or equal to 80% reduction in VPCs (p less than 0.05 versus double-blind placebo study). Propafenone was also effective in controlling couplets and nonsustained ventricular tachycardia. Seven patients were treated with propafenone for 24 months, during which effectiveness continued, with mean suppression ranging from 67 to 79% (p less than 0.05 versus initial single-blind placebo). Propafenone prolonged PR and QRS intervals by 16 and 18%, respectively; these prolongations continued during long-term therapy. Propafenone increased serum digoxin levels in 5 of 5 patients (mean increase 83%). Cardiovascular side effects included congestive heart failure (1 patient) and conduction abnormalities (3 patients). Thus, propafenone was effective in the treatment of total and repetitive VPCs. Side effects were few, but congestive heart failure, conduction disturbances and increases in serum digoxin were observed.

Topics: Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Clinical Trials as Topic; Digoxin; Double-Blind Method; Electrocardiography; Female; Heart Ventricles; Humans; Kinetics; Male; Middle Aged; Propafenone; Propiophenones; Random Allocation

Ninety patients undergoing coronary bypass surgery were studied prospectively by bedside and subsequent ambulatory electrocardiographic monitoring to investigate the incidence, possible causes, and prevention of atrial fibrillation. Patients with good left ventricular function were divided randomly into a control group or groups treated with digoxin or propranolol. In the control group the incidence of atrial fibrillation was 27% and of significant ventricular extrasystoles 3%. Propranolol reduced the incidence of atrial fibrillation (14.8%), whereas digoxin had no effect and increased the incidence of ventricular extrasystoles. Age, sex, severity of symptoms, cardiomegaly, heart failure, previous myocardial infarction, and number of grafts did not affect the result. The operative myocardial ischaemic time was related to the occurrence of atrial fibrillation. There was also a significant relation between atrial fibrillation and bundle branch block. Atrial fibrillation is common after coronary artery grafting; it may be due to diffuse myocardial ischaemia or hypothermic injury. The incidence may be reduced by beta blockade.

Topics: Adult; Aged; Arrhythmias, Cardiac; Bundle-Branch Block; Coronary Artery Bypass; Coronary Disease; Digoxin; Female; Humans; Male; Middle Aged; Propranolol; Time Factors

The ventricular antiarrhythmic properties of oral digoxin were examined in 13 patients with chronic ventricular ectopy using serial 24-hour electrocardiographic monitoring. Mean premature ventricular complex frequency (per 1,000 normal beats) decreased from 56 +/- 47 during the placebo period to 40 +/- 27 (p = not significant [NS]) and 25 +/- 17 (p less than 0.05) during daily administration of digoxin, 0.25 and 0.375 mg. Digoxin had no significant effect on the qualitative occurrence of complex ventricular arrhythmia patterns (multiformity, bigeminy, couplets, ventricular tachycardia). Radionuclide left ventricular (LV) ejection fraction was measured during the placebo period. Seven patients had normal (ejection fraction greater than 50%) and 6 abnormal global LV performance. In the normal group, the mean premature ventricular complex frequency decreased from 69 +/- 58 to 20 +/- 18 (p less than 0.05) and the mean couplet frequency decreased from 0.59 +/- 0.85 to 0.07 +/- 0.06 (p less than 0.04) during the placebo and 0.375 mg digoxin dosing periods, respectively. In contrast, no significant changes in either variable occurred after digoxin in subjects with depressed LV function. This study indicates that oral digoxin is moderately effective in suppressing premature ventricular complexes, and that its effects are greatest in patients with normal overall LV performance.

Topics: Administration, Oral; Aged; Arrhythmias, Cardiac; Clinical Trials as Topic; Digoxin; Electrocardiography; Heart Ventricles; Humans; Middle Aged; Stroke Volume

Supraventricular arrhythmias continue to complicate the postoperative course of patients undergoing myocardial revascularization. In a previous study, we showed a decrease in arrhythmias if patients were given digitalis prior to operation. Since that time we have made two changes-- propranolol is no longer discontinued prior to operation and cold hyperkalemic cardioplegic solution is routinely used. To assess the affect of these changes on arrhythmias, we repeated the previous study. One hundred twenty patients all receiving preoperative and postoperative propranolol were randomized into a control group and a digitalis-treated group. The incidence of supraventricular arrhythmia postoperatively was 21.4% in the control group and 3.1% in the digitalis group (p less than 0.005). Therefore, we continue to advise preoperative digitalization in patients requiring coronary artery bypass and continue to maintain beta blocker and digitalis therapy in the postoperative period.

Topics: Arrhythmias, Cardiac; Clinical Trials as Topic; Coronary Artery Bypass; Digoxin; Female; Humans; Male; Middle Aged; Postoperative Complications; Premedication; Propranolol; Random Allocation

The effects of oral digoxin and placebo in 41 geriatric in-patients were compared using a randomized, double-blind, cross-over method. The patients were in sinus rhythm or had atrial fibrillation. The observation period was two months on digoxin or placebo. Patients with symptoms of cardiac failure at rest or during light physical activity, X-ray signs of pulmonary congestion, proven need of digoxin therapy following earlier withdrawal, atrial fibrillation with a ventricular rate greater than 95 beats/min and patients in whom digitalis intoxication was suspected were excluded from the study. Five (14%) of 37 patients deteriorated during the placebo phase. Four of these developed rapid atrial fibrillation and one patient developed sinus tachycardia and symptoms of heart failure.

Topics: Aged; Arrhythmias, Cardiac; Clinical Trials as Topic; Digoxin; Double-Blind Method; Female; Heart Failure; Homes for the Aged; Humans; Male; Middle Aged; Random Allocation

The effects of oral digoxin on symptoms, arrhythmias, exercise tolerance and echocardiographic function in primary mitral leaflet prolapse were studied in 23 patients using a double-blind crossover protocol. Digoxin reduced the incidence and severity of chest pain compared with both the control (P = 0.0002) and placebo (P = 0.0005) periods. We found a high (83%) incidence of predominantly minor arrhythmias on continuous ambulatory monitoring. Digoxin favourably affected the incidence of frequent supraventricular ectopic beats and supraventricular tachycardia but was associated with a significant number (P less than 0.0025) of asymptomatic bradyarrhythmias. In patients with frequent ventricular ectopics, digoxin had no consistent effect. No difference in exercise tolerance between treatment periods was found on maximal treadmill stress testing, but digoxin administration resulted in an increase in echocardiographic mean circumferential fibre shortening velocity (P less than 0.01) and fractional shortening percent (P less than 0.01). This study demonstrates the efficacy of oral digoxin therapy in ameliorating chest pain in patients with primary mitral leaflet prolapse and suggests a favourable effect on supraventricular arrhythmias in such patients.

Topics: Administration, Oral; Adolescent; Adult; Arrhythmias, Cardiac; Clinical Trials as Topic; Digoxin; Double-Blind Method; Echocardiography; Electrocardiography; Female; Humans; Male; Middle Aged; Mitral Valve Prolapse; Pain; Physical Exertion; Random Allocation

Although quinidine and digoxin are frequently given together, it has only recently become apparent that serum digoxin concentration may rise during quinidine treatment. A prospective study was performed to compare the effects of quinidine and disopyramide in patients receiving maintenance digoxin therapy. During quinidine administration serum digoxin concentration rose by more than 50% in seven of nine patients (the mean concentration rising from 1.43 +/- 0.20 to 2.61 +/- 0.43 nmol/l, P < 0.005). During the disopyramide treatment a small rise in serum digoxin was noted (mean 1.3 +/- 0.16 to 1.5 +/- 0.19 nmol/l, P < 0.05). We suggest that digoxin doses should be reduced immediately prior to commencing quinidine therapy in patients already receiving adequate maintenance digoxin, and patients should be followed carefully for evidence of digoxin toxicity. Disopyramide appears a suitable alternative anti-arrhythmic drug to quinidine in patients on maintenance digoxin.

Topics: Adult; Aged; Arrhythmias, Cardiac; Digoxin; Disopyramide; Drug Interactions; Female; Humans; Male; Metabolic Clearance Rate; Middle Aged; Pyridines; Quinidine; Syncope

One hundred and twenty patients undergoing aortocoronary bypass procedures were randomly placed into control and digitalized groups. All were initially in normal sinus rhythm and without evidence of congestive heart failure. Supraventricular arrhythmias occurred in 17 of 66 controls and in only three of 54 digitalized patients (P less than 0.01). There was no evidence of digitals toxicity. Based on this evidence we recommend prophylactic digitalization for patients having aortocoronary bypass operations.

Topics: Arrhythmias, Cardiac; Coronary Artery Bypass; Coronary Disease; Digoxin; Female; Humans; Male; Middle Aged; Postoperative Complications

The results are reported from the observations on the activity of the semi-synthetic preparation beta-Methyl-Digoxin in 60 patients with chronic cardiac insufficiency. The conclusions are based on the data, obtained by a series of clinical and instrumental examinations, electro- and balistocardiography included, measurements of venous pressure, etc. The high efficiency and good tolerance of the preparation is stressed upon. It is stressed to be especially suitable for the treatment of patients with bradycardic form of chronic heart decompensation as well as in the treatment of cardiac cirrhosis.

Topics: Adult; Aged; Arrhythmias, Cardiac; Ballistocardiography; Bulgaria; Chronic Disease; Clinical Trials as Topic; Digoxin; Drug Evaluation; Electrocardiography; Female; Heart Diseases; Humans; Male; Middle Aged

The haemodynamic effects of N, N-bis(phenyl-carbamoylmethyl) dimethylammonium chloride (QX-572) in man were studied. A controlled study was performed to rule out a possible influence of the catheterization procedure as such on the results. Ten patients with mild to moderate aortic regurgitation were studied: based on clinical data the patients were divided into 2 groups of 5. Randomly it was decided that one group should constitute a control group receiving saline while the second group received QX-572 , MG/KG BODY WEIGHT. In both groups the administration was performed as a slow intravenous infusion during 30 minutes. Heart rate, pressures in brachial artery and right atrium, cardiac output, stroke volume, and systemic vascular resistance were determined before, during, and up to 30 minutes after completion of placebo or QX-572. These variable remained stable in the control group while QX-572 produced an increase in heart rate most pronounced at the end of the infusion period. A transient decrease in systolic and mean brachial artery pressure during the infusion, and during the same period a decrease in right atrial pressure. Cardiac output and systemic vascular resistance were unchanged by QX-572 but they were not measured during the infusion when the changes in pressures were most pronounced. QX-572 was thought to act as a peripheral vasodilator during the infusion. Left ventricular contractility was studied by means of pressure curves obtained from a catheter tip manometer placed in the left ventricle. The first derivative of the isovolumic left ventricular pressure at the highest level (45mmHg) common to all patients was used (dp/dt-45). No significant difference could be observed when comparing mean changes of dp/dt-45 for the two groups. In the control group there was a slight but significant increase in dp/dt-45 during the time of observation. In the QX-572 group the results varied between individuals. Two of the patients differed from all other patients in the control and QX-572 groups showing a decrease in dp/dt-45 which, when most pronounced at the end of the infusion period, was -31 and -28 per cent of the preinfusion levels, respectively. This decrease probably reflects reduction of contractility. It was concluded that QX-572 in a dose of 8 mg/kg body weight did not have any major haemodynamic drawbacks.

Topics: Adult; Anti-Arrhythmia Agents; Aortic Valve Insufficiency; Arrhythmias, Cardiac; Blood Pressure; Brachial Artery; Carbamates; Cardiac Output; Clinical Trials as Topic; Digitoxin; Digoxin; Female; Heart Atria; Heart Rate; Heart Ventricles; Hemodynamics; Humans; Infusions, Parenteral; Male; Middle Aged; Placebos; Quaternary Ammonium Compounds; Vascular Resistance

Seven patients with chronic or recurrent supraventricular tachyarrhythmias were selected for a trial of antazoline therapy because sinus rhythm or a controlled ventricular response could not be achieved with quinidine, procainamide, digitalis or propranolol. Sinus rhythm was established by either intravenous administration of antazoline or direct-current countershock, and has been maintained in all for 4 to 16 months by oral administration of antazoline. Side effects were minor. Antazoline is a sufficiently promising antiarrhythmic agent to warrant large-scale controlled studies.

Topics: Adolescent; Adult; Aged; Antazoline; Arrhythmias, Cardiac; Chronic Disease; Clinical Trials as Topic; Digoxin; Drug Evaluation; Female; Humans; Imidazoles; Male; Middle Aged; Procainamide; Propranolol; Quinidine; Recurrence

The bioavailability of various formulations of digoxin was assessed after single and multiple doses in a series of crossover studies in human volunteers. Digoxin tablets that were 97% dissolved in 1 hr in vitro were not significantly better absorbed than tablets with a dissolution rate of 78%. A solution given in capsule form had greater bioavailability than tablets of 97% dissolution rate; serum and urinary glycoside levels after 0.4 mg doses of the encapsulated solution were similar to those attained after 0.5 mg doses of tablets with dissolution rates of 78% and 97%. The bioavailability of the solution in capsule form exceeded that of equal doses of the same solution given as a liquid or that of a standard elixir. No increase in gastrointestinal or cardiac toxicity was detected. Inter- and intrasubject variation in bioavailability was not decreased. Above a certain level, dissolution rate is no longer the limiting factor in digoxin absorption. The mechanism of the enhanced bioavailability of concentrated liquid digoxin in capsule form remains to be determined. Such a preparation deserves further consideration as a possible replacement for digoxin tablets.

Topics: Adult; Arrhythmias, Cardiac; Biological Availability; Capsules; Clinical Trials as Topic; Digoxin; Electrocardiography; Female; Humans; Male; Solutions; Tablets; Time Factors

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Creatinine; Digitalis; Digoxin; Dyspnea; Edema; Female; Heart Failure; Humans; Male; Middle Aged; New York; Phytotherapy; Placebos; Plants, Medicinal; Plants, Toxic; Respiratory Insufficiency; Skilled Nursing Facilities; Time Factors

Topics: Adult; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzothiadiazines; Digoxin; Disopyramide; Diuretics; Electrocardiography; Female; Humans; Male; Methyldopa; Middle Aged; Placebos; Potassium Chloride; Pyridines; Sodium Chloride Symporter Inhibitors; Tachycardia

Topics: Adult; Aged; Arrhythmias, Cardiac; Clinical Trials as Topic; Coronary Disease; Digoxin; Evaluation Studies as Topic; Heart Diseases; Heart Failure; Humans; Middle Aged; Time Factors

Topics: Administration, Oral; Adult; Aged; Arrhythmias, Cardiac; Clinical Trials as Topic; Digoxin; Humans; Time Factors

Seven types of digoxin 0.25 mg tablet in common use in the United Kingdom were administered to a total of 38 patients. Significant differences were found in the mean plasma digoxin levels and in the control of atrial fibrillation achieved with these brands. There was a close correlation between the dissolution rate of the tablets and the plasma digoxin levels. Measurement of in-vitro dissolution rate appears to be a valid method of ensuring that different tablets of digoxin are of equal efficacy. However, in some patients absorption of the drug is markedly sensitive to changes in dissolution rate and new pharmacopoeal standards should not be defined until very rapidly-dissolving formulations have been studied.

Topics: Administration, Oral; Arrhythmias, Cardiac; Creatinine; Digoxin; Female; Humans; Male; Middle Aged; Radioimmunoassay; Solubility; Tablets; Therapeutic Equivalency; Time Factors; United Kingdom; Urea

Topics: Acute Disease; Adult; Amitriptyline; Arrhythmias, Cardiac; Clinical Trials as Topic; Death, Sudden; Depression; Digoxin; Electrocardiography; Heart; Humans; Imipramine; Middle Aged

Topics: Adenosine Triphosphatases; Animals; Arrhythmias, Cardiac; Binding Sites; Brain; Cardiac Glycosides; Chemistry, Clinical; Clinical Trials as Topic; Digitalis Glycosides; Digitoxin; Digoxin; Guinea Pigs; Humans; Immunoassay; Methods; Ouabain; Potassium; Radionuclide Imaging; Sodium; Tritium; Tromethamine

Topics: Arrhythmias, Cardiac; Cardiac Glycosides; Digoxin; Electrocardiography; Humans; Intestinal Absorption; Isomerism; Male

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Drug Interactions; Heart Failure; Humans; Methods; Phenytoin

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Berlin; Digoxin; Heart Block; Heart Failure; Humans; Myocardial Infarction; Myocardium; Oxygen Consumption; Tachycardia; Ventricular Fibrillation

Digoxin is a cardiac glycoside obtained from the leaves of the foxglove plant, Digitalis lanata. Several studies have described the safety of digoxin including various life-threatening events, notably cardiac arrhythmias. Early identification of high-risk patients and subsequent initiation of the utmost medical care are associated with a better prognosis. The assessment of serum digoxin levels, which is not always convenient, is the only tool used to evaluate the severity of digoxin exposure. However, the feasibility of this tool, particularly in resource-restricted countries, remains unclear. Therefore, the current study aimed to establish and validate a feasible alternative tool, a bedside nomogram, to identify pediatric patients diagnosed with acute digoxin intoxication who are at risk of developing serious arrhythmias. This was a two-phase, multicenter, retrospective study. The prevalence of serious arrhythmias was approximately 17%. Patients diagnosed with serious arrhythmias showed significantly higher serum digoxin, random blood glucose, and potassium levels but lower sodium, magnesium, and hemoglobin levels. Serious arrhythmias were associated with significantly lower P-R intervals, shorter QTc intervals, and more frequent digoxin effects (p < 0.05). The proposed nomogram showed that combining age and initial random blood glucose, sodium, and potassium levels could predict the future incidence of serious arrhythmia with an accuracy of 96.2% (sensitivity = 94.4%, specificity = 96.5%), an area under the curve (AUC) of 0.977, and p < 0.001. Validation of the proposed nomogram yielded an AUC for the nomogram probability of approximately 81%, and the AUC for the predicted probability using the developed model was 98.3%, indicating that both the validated model and the developed nomogram were significant predictors of serious arrhythmia. The utility of using the four-factor nomogram to determine the risk of serious arrhythmia in children exposed to an overdose of digoxin is comparable, if not superior, to the serum digoxin level.

Topics: Arrhythmias, Cardiac; Blood Glucose; Child; Digoxin; Humans; Nomograms; Potassium; Retrospective Studies; Sodium

Prognosis of fetuses with hydrops and tachyarrhythmia has been portrayed as poor in most published reports. This might lead to biased counselling, unnecessary caesarean section, preterm delivery, and even termination of pregnancy.. To evaluate contemporary fetal and postnatal outcomes of hydropic fetuses with fetal tachyarrhythmia when it is treated effectively and monitored systematically.. This is a retrospective review of a single centre experience at the University Hospital of Wales over a 20-year period. All fetuses received high doses of flecainide and digoxin combination treatment. Tachycardia response rate, time to arrhythmia and hydrops resolution, fetal and postnatal morbidity, and mortality rates were analysed.. Twenty fetuses were diagnosed with hydrops fetalis and received treatment. The mechanism of fetal tachyarrhythmia was supraventricular tachycardia in thirteen and atrial flutter in eight cases. Among the 20 fetuses treated, the overall tachycardia response rate was 90% (18/20) with the restoration of sinus rhythm in 85% (17/20) of the cases. The median time to restore sinus rhythm or to rate control of the arrhythmia was 1.5 days (range 12 hours to 13 days). Hydrops resolved in 17 of the 20 fetuses, with a median time of 12 days (range 3-21 days). Four fetuses went into spontaneous preterm birth and one fetus was delivered early due to worsening hydrops. No significant neurological morbidity was observed in surviving neonates and infants on clinical examination. There was one postnatal death due to respiratory complications of prematurity in the non-responsive supraventricular tachycardia case.. High-dose flecainide and digoxin combination offers effective treatment strategy in fetuses with hydrops and tachyarrhythmia with favourable outcomes. This study may guide more realistic counselling for pregnancies complicated by tachyarrhythmia and hydrops.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cesarean Section; Digoxin; Female; Fetal Diseases; Flecainide; Heart Failure; Humans; Hydrops Fetalis; Infant, Newborn; Pregnancy; Premature Birth; Retrospective Studies; Tachycardia; Tachycardia, Supraventricular

Arrhythmias are common in single ventricle patients though their effect on outcomes during stage I palliation (S1P) is unclear.. The authors sought to study associated risks for arrhythmia in patients undergoing S1P for single ventricle disease and evaluate the outcome of arrhythmias and their treatment strategies on survival.. Retrospective patient, surgical, medication, and arrhythmia data were obtained from the NPC-QIC (National Pediatric Cardiology Quality Improvement Collaborative) database. Bivariate analysis of variables associated with arrhythmias, as well as those associated with survival, was performed at the time of stage II palliation. Appropriate variables were included in multivariate modeling.. Of the 2,048 patients included in the study, 36% had arrhythmia noted during their S1P hospitalization, with supraventricular tachycardia (12%) and focal atrial tachycardia (11%) the most common. At S1P discharge, 11% of patients were on an antiarrhythmic medication. Arrhythmias were associated with lower survival and increased hospital length of stay. Heterotaxy syndrome, younger age at S1P, male sex, and additional anomalies were associated with increased risk of arrhythmia in multivariable modeling (P ≤ 0.01). Arrhythmia and female sex were associated with increased mortality, whereas antiarrhythmic medication and digoxin use were associated with decreased mortality (P ≤ 0.003, model area under the curve = 0.79). The use of antiarrhythmic medications within the subcohort of arrhythmia patients was also associated with decreased risk of mortality (P < 0.0001; odds ratio: 2.0-7.2).. Arrhythmias are common during admission for S1P and associated with poor outcomes. The use of antiarrhythmic medications may improve survival, though future studies are needed.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Child; Digoxin; Female; Heart Ventricles; Humans; Hypoplastic Left Heart Syndrome; Male; Retrospective Studies; Treatment Outcome

Topics: Adult; Arrhythmias, Cardiac; Counseling; Digoxin; Electrocardiography; Female; Humans; Seeds; Thevetia

Although digoxin poisoning has declined in the past decades, it still has deleterious outcomes. The hallmark of serious life-threatening arrhythmias remains challenging due to its non-specific initial presentation. Therefore, this study aimed to evaluate the initial predictive factors for recurrent serious arrhythmias and the need for temporary pacing in acute digoxin-poisoned patients. This retrospective cohort study included all patients with acute digoxin poisoning admitted to Tanta University Poison Control Center from 2017 to 2020. Demographic and toxicological data, poisoning severity score (PSS), laboratory investigations, and serial ECG monitoring data were documented. Patients were divided according to their age into a childhood group and adolescence & adulthood group. Each age group was divided into two subgroups according to the presence of recurrent serious arrhythmias. Patient outcomes, including intensive care unit admission, temporary pacing, and in-hospital mortality were recorded. A percentage of 37.34% (n = 31) of the included patients had recurrent serious arrhythmias in both groups. Recurrent serious arrhythmias groups had significantly low heart rate, prolonged PR interval, high PSS, Mobitz II dysrhythmias, elevated serum digoxin, serum potassium and serum creatinine, and increased adverse outcomes compared to other groups. Logistic regression analysis showed that only serum digoxin and potassium levels were significant independent predictors of recurrent serious arrhythmias and temporary pacing. Serum digoxin level had an excellent discriminatory power with the best sensitivity and specificity, followed by serum potassium level in both groups. Thus, monitoring serum digoxin and potassium levels is essential in all patients with acute digoxin poisoning, especially with limited Fab availability.

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Biomarkers; Child, Preschool; Digoxin; Egypt; Electrocardiography; Female; Heart Rate; Humans; Infant; Male; Poison Control Centers; Potassium; Predictive Value of Tests; Prognosis; Recurrence; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Young Adult

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Diseases; Digoxin; Humans

Fetal arrhythmias are common, and they may resolve spontaneously in majority of the cases. Sustained fetal arrhythmias associated with major structural heart disorders, hydrops fetalis, and fetal heart failure warrant intrauterine pharmaceutical conversion of heart rhythm or early pacemaker implant in order to avoid fetal demise. Fetal atrial flutter (AF) and supraventricular tachycardia (SVT) resemble in terms of the effects of intrauterine therapies. Digoxin is more suitable for rhythm conversion of fetal AF and SVT in fetuses free of hydrops fetalis, while sotalol shows better effects for those with hydrops fetalis. In fetal cases of atrioventricular blocks, an etiological treatment for the maternal antibody exposure by steroids could be an alternative remedy. In this article, the clinical diagnosis and treatment of fetal arrhythmias are presented, and advantages and disadvantages of antiarrhythmic agents for fetal arrhythmias are compared.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Female; Humans; Hydrops Fetalis; Pregnancy; Sotalol; Tachycardia, Supraventricular

The most appropriate choice of pharmacological treatment of heart rhythm disorders occurring in patients with chronic obstructive pulmonary disease (COPD) and cardiovascular comorbidity is often a topic of debate between pulmonologists and cardiologists in clinical practice, although numerous studies and clinical trials have demonstrated evidence to support the use of selective beta-blockers (BBs) in these patients.. To examine the difference in the number of exacerbations in patients treated with a combination of verapamil and digoxin or BB alone in patients with different COPD stages.. The study included 68 patients (n = 68) diagnosed with COPD who were followed-up during a 12-month period, and the number of exacerbations were analyzed. The patients were divided into two groups according to the stage of COPD: GOLD II (moderate), and GOLD III (severe), and in each group a subdivision was established in relation to the use of either a combination of verapamil and digoxin or the use of BBs alone in pharmacological treatment. The inclusion criteria for patients were defined as following: a) established diagnosis of COPD according to present or deteriorated relevant clinical symptoms and signs, b) the ejection fraction (EF) of a left ventricle (LV) >35%, and c) spirometric cut-points classified as GOLD II (FEV1 / FVC <0.7, FEV1 predicted 50-80%), or GOLD III (FEV1/FVC <0.7, FEV1 predicted 30-50%) stage of the COPD. The exclusion criteria were EF of LV <35% and a lethal outcome during a follow-up period (2 patients were encountered). Exacerbation was defined as functional deterioration of the COPD symptoms verified by spirometric functional testing, frequency of hospitalizations according to GOLD stage assignment or verified clinical symptoms deterioration.. Regardless the pharmacological treatment, there is a statistically significant increase in the number of COPD exacerbations, in a 12-month period follow-up, in the GOLD III group (severe) compared to the GOLD II group (moderate). In the group of patients taking verapamil and digoxin, a two-tailed t-test was used to analyze the results between the GOLD II and GOLD III stage groups, p = 0.01, and 2. In the group of patients taking BBs, a two-tailed t-test was also used to analyze the results between the GOLD II and GOLD III stage groups, p = 0.003). Within the COPD GOLD II stage group, there appears to be no statistically significant difference in the number of exacerbations between the patients taking verapamil and digoxin (n = 24) and the patients taking BBs alone (n = 15), although, in patients taking BBs alone, there appears to be a trend towards a decrease in the exacerbations compared to the number of exacerbations in patients taking verapamil and digoxin (p = 0.007). Within the COPD GOLD III stage group, there is no difference in the number of exacerbations between the patients taking verapamil and digoxin (n = 20), and the patients taking BBs alone (n = 9), as analyzed by a two-tailed t-test, p = 0.577.. Use of selective BBs in the treatment of cardiovascular comorbidity in patients with COPD represents a far better choice of pharmacological approach in the treatment of patients diagnosed with COPD GOLD II (moderate) stage.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Bisoprolol; Case-Control Studies; Digoxin; Disease Progression; Forced Expiratory Volume; Humans; Metoprolol; Nebivolol; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Verapamil; Vital Capacity

Mutlu M, Aslan Y, Kader Ş, Aktürk-Acar F, Dilber E. Clinical signs and symptoms of toxic serum digoxin levels in neonates. Turk J Pediatr 2019; 61: 244-249. Digoxin is widely used in the treatment of congestive heart failure and some arrhythmias. Digoxin toxicity may occur easily because digoxin has a narrow therapeutic index. This retrospective study was conducted to evaluate the clinical signs and symptoms of toxic serum digoxin levels in neonates. Medical reports of the neonates who had serum digoxin concentrations > 2 nanogram/milliliter (ng/ml) were reviewed in terms of patient demographics, serum digoxin concentrations, signs and symptoms of digoxin toxicity, serum digoxin and electrolyte levels, renal function tests, electrocardiograms, echocardiography, and treatments applied. Digoxin toxic levels were identified in the 13 neonates. Of the 13 neonates with digoxin toxic level, 9 (69%) were term and 8 (62%) were female. Twenty-three percent (3/13) of newborn infants were symptomatic. Symptomatic patients had statistically significantly higher serum digoxin levels, at 7.76±2.76 (5.4-10.8) ng/ml, than asymptomatic patients, at 3.31±1.09 (2.02-4.95) (p=0.036). Symptoms related to toxic digoxin levels were observed in the three neonates with plasma digoxin levels > 5 ng/ml. Gastrointestinal and central nervous system symptoms were the major clinic findings. Despite high digoxin levels, no digoxin-related arrhythmia was observed on electrocardiography, other than sinus bradycardia. Two premature neonates were treated with digoxin-specific antibody Fab fragments (DigiFab®) and hypokalemia developed in both of them. Our data suggests that symptoms related with digoxin toxic levels were observed in neonates with plasma digoxin levels > 5 ng/ml. Serum digoxin levels should be measured in case of signs and symptoms of digoxin toxicity or risk factors for such toxicity.

Topics: Arrhythmias, Cardiac; Cardiotonic Agents; Digoxin; Disease Progression; Drug-Related Side Effects and Adverse Reactions; Echocardiography; Electrocardiography; Female; Heart Failure; Humans; Immunoassay; Infant, Newborn; Male; Retrospective Studies; Risk Factors

Due to the narrow therapeutic range of digoxin, determining serum/plasma digoxin concentrations is critical for assessing patients with congestive heart failure, atrial fibrillation, and certain types of arrhythmias. However, digoxin quantification by competitive immunoassays is susceptible to interferences that may alter the accuracy of its measurement in patient plasma. This study aimed to characterize the extent of bilirubin interference in three commonly used digoxin immunoassays.. Digoxin concentrations were compared using the Beckman Coulter® Unicel DxI 800, the Vitros® 4600, and the Roche Cobas® 8000 in neat or digoxin-spiked icteric and non-icetric plasma samples. A mixing study was performed to demonstrate how digoxin quantification is affected by bilirubin. An equation was derived that predicts the response of the DxI 800, given known bilirubin and digoxin concentrations.. The DxI reported detectable concentrations of digoxin in high bilirubin samples with no added digoxin, while the Vitros® 4600 and Cobas® 8000 gave virtually undetectable results. Spiking digoxin into samples with elevated bilirubin concentrations resulted in a higher percent recovery for the DxI 800 when compared to the other two platforms. The mixing study also revealed an increase in the percent recovery in the DxI 800, while the Vitros® 4600 and Cobas® 8000 were comparable to the expected concentration of digoxin.. The DxI 800 is most prone to interference by bilirubin, while the Vitros® 4600 and Cobas® 8000 are relatively unaffected. Icteric samples should be interpreted with caution if digoxin quantification is needed, especially on the DxI 800 assay.

Topics: Arrhythmias, Cardiac; Bilirubin; Digoxin; Drug Monitoring; Heart Failure; Humans; Immunoassay

Although the mechanism of action is not well known, intravenous lipid emulsion (ILE) has been shown to be effective in the treatment of lipophilic drug intoxications. It is thought that, ILE probably separates the lipophilic drugs from target tissue by creating a lipid-rich compartment in the plasma. The second theory is that ILE provides energy to myocardium with high-dose free fatty acids activating the voltage-gated calcium channels in the myocytes. In this study, effects of ILE treatment on digoxin overdose were searched in an animal model in terms of cardiac side effects and survival. Forty Sprague-Dawley rats were divided into five groups. As the pre-treatment, the groups were administered saline, ILE, DigiFab and DigiFab and ILE. Following that, digoxin was infused to all groups until death except the control group. First arrhythmia and cardiac arrest observation times were recorded. According to the results, there was no statistically significant difference among the group in terms of first arrhythmia time and cardiac arrest times. However, when the saline group compared with ILE-treated group separately, significant difference was observed. DigiFab, ILE or ILE-DigiFab treatment make no significant difference in terms of the first arrhythmia and cardiac arrest duration in digoxin-intoxicated rats. However, it is not possible to say that at the given doses, ILE treatment might be successful at least as a known antidote. The fact that the statistical significance between the two groups is not observed in the subgroup analysis, the study should be repeated with larger groups.

Topics: Animals; Antidotes; Arrhythmias, Cardiac; Cardiotoxicity; Chemical and Drug Induced Liver Injury; Cytoprotection; Digoxin; Disease Models, Animal; Fat Emulsions, Intravenous; Fatty Liver; Heart Arrest; Immunoglobulin Fab Fragments; Kidney; Liver; Rats, Sprague-Dawley

Digoxin is the oldest drug used in the pharmacotherapy of heart failure (HF). However, digoxin remains an important therapeutic option for patients with persistent symptoms of HF occurring despite the implementation of standard pharmacotherapy. Digoxin concentration serum (SCD) should equal 1-2ng/ml. The aim of our study was to measure of SCD among the hospitalized patients as well as to determine the selected factors influencing the concentration of the digoxin in the blood.. The presented research was based on a retrospective analysis including 2149 patients treated with digoxin and hospitalized between 1980 and 2000. Was used for the determination of SCD automatic analyzer TDX ABBOTT GmbH - fluorescence polarization immunoassay (FPIA), with therapeutic range for digoxin of 0.8-2.0ng/ml.. Average SCD result in the study population was located within the therapeutic range and amounted 1.06ng/ml (55.7% of patients). Statistically significant differences in digoxin level were observed depending on the way of medicine administration (p=0.000001) and the daily amount (p=0.001). Moreover, statistically significant differences in digoxin level were observed depending on sex (p=0.00002).. An elevated level of digoxin was observed in the case of patients who received the medication both orally and intravenously, together with an increase in the daily amount of digoxin doses. It was confirmed that an elevated digoxin level occurs in the course of treatment in the case of women.

Topics: Administration, Intravenous; Administration, Oral; Aged; Arrhythmias, Cardiac; Cardiotonic Agents; Digoxin; Drug Administration Schedule; Drug Monitoring; Female; Heart Failure; Humans; Male; Middle Aged; Poland; Retrospective Studies; Risk Factors; Sex Factors; Time Factors; Treatment Outcome

Digoxin is considered contraindicated in light-chain (AL) amyloidosis, given reports of increased toxicity published 30-50 years ago. We sought to determine the frequency of digoxin toxicity in patients with AL.. We identified 107 patients with AL amyloidosis who received digoxin between 2000 and 2015.. Digoxin may be cautiously utilized in AL amyloidosis patients. We suggest its use in lower doses and frequent drug concentration monitoring along with close monitoring of electrolytes and renal function. Nonetheless, toxicity at low serum concentration cannot be excluded due to potential for toxic concentration at the tissue level and should be taken under consideration when prescribing digoxin for these patients. Studies with higher-level evidence are needed to confirm these findings.

Topics: Adult; Arrhythmias, Cardiac; Digoxin; Female; Glomerular Filtration Rate; Heart Failure; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Retrospective Studies

Multifocal atrial tachycardia (MAT) has a well-known association with Costello syndrome, but is rarely described with related RAS/MAPK pathway disorders (RASopathies). We report 11 patients with RASopathies (Costello, Noonan, and Noonan syndrome with multiple lentigines [formerly LEOPARD syndrome]) and nonreentrant atrial tachycardias (MAT and ectopic atrial tachycardia) demonstrating overlap in cardiac arrhythmia phenotype. Similar overlap is seen in RASopathies with respect to skeletal, musculoskeletal and cutaneous abnormalities, dysmorphic facial features, and neurodevelopmental deficits. Nonreentrant atrial tachycardias may cause cardiac compromise if sinus rhythm is not restored expeditiously. Typical first-line supraventricular tachycardia anti-arrhythmics (propranolol and digoxin) were generally not effective in restoring or maintaining sinus rhythm in this cohort, while flecainide or amiodarone alone or in concert with propranolol were effective anti-arrhythmic agents for acute and chronic use. Atrial tachycardia resolved in all patients. However, a 4-month-old boy from the cohort was found asystolic (with concurrent cellulitis) and a second patient underwent cardiac transplant for heart failure complicated by recalcitrant atrial arrhythmia. While propranolol alone frequently failed to convert or maintain sinus rhythm, fleccainide or amiodarone, occasionally in combination with propranolol, was effective for RASopathy patient treatment for nonreentrant atrial arrhythmia. Our analysis shows that RASopathy patients may have nonreentrant atrial tachycardia with and without associated cardiac hypertrophy. While nonreentrant arrhythmia has been traditionally associated with Costello syndrome, this work provides an expanded view of RASopathy cardiac arrhythmia phenotype as we demonstrate mutant proteins throughout this signaling pathway can also give rise to ectopic and/or MAT.

Topics: Amiodarone; Arrhythmias, Cardiac; Calcium; Cardiomyopathy, Hypertrophic; Costello Syndrome; Digoxin; Female; Humans; Infant; Infant, Newborn; LEOPARD Syndrome; Male; Noonan Syndrome; Propranolol; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Proto-Oncogene Proteins c-raf; Proto-Oncogene Proteins p21(ras); ras Proteins; SOS1 Protein; Tachycardia, Ectopic Atrial

Monitoring dramatic changes in intracellular calcium ion levels during cardiac contraction and relaxation, known as calcium transient, in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) would be an attractive strategy for assessing compounds on cardiac contractility. In addition, as arrhythmogenic compounds are known to induce characteristic waveform changes in hiPSC-CMs, it is expected that calcium transient would allow evaluation of not only compound-induced effects on cardiac contractility, but also compound arrhythmogenic potential. Using a combination of calcium transient in hiPSC-CMs and a fast kinetic fluorescence imaging detection system, we examined in this study changes in calcium transient waveforms induced by a series of 17 compounds that include positive/negative inotropic agents as well as cardiac ion channel activators/inhibitors. We found that all positive inotropic compounds induced an increase in peak frequency and/or peak amplitude. The effects of a negative inotropic compound could clearly be detected in the presence of a β-adrenergic receptor agonist. Furthermore, most arrhythmogenic compounds raised the ratio of peak decay time to peak rise time (D/R ratio) in calcium transient waveforms. Compound concentrations at which these parameters exceeded cutoff values correlated well with systemic exposure levels at which arrhythmias were reported to be evoked. In conclusion, we believe that peak analysis of calcium transient and determination of D/R ratio are reliable methods for assessing compounds' cardiac contractility and arrhythmogenic potential, respectively. Using these approaches would allow selection of compounds with low cardiotoxic potential at the early stage of drug discovery.

Topics: Arrhythmias, Cardiac; Astemizole; Calcium; Calcium Channel Blockers; Cardiotonic Agents; Cell Differentiation; Cells, Cultured; Digoxin; Dose-Response Relationship, Drug; Drug Discovery; Fluoroquinolones; Induced Pluripotent Stem Cells; Isoproterenol; Moxifloxacin; Myocardial Contraction; Myocytes, Cardiac; Propranolol; Toxicity Tests; Verapamil

To describe a case in which digoxin-specific immune Fab was used successfully in a dog with severe oleander toxicosis secondary to ingesting plant material.. A 6-year-old intact female Rhodesian Ridgeback mixed breed dog was presented for severe oleander toxicosis and was refractory to all antiarrhythmic therapies and supportive care. Digoxin-specific immune Fab was successful in treating this dog. The dog recovered but suffered ischemic injuries, the long-term effects of which are unknown.. This report describes the successful use of digoxin-specific immune Fab in the treatment of oleander toxicosis in a dog, which has not previously been published in veterinary literature. Oleander poisoning can be associated with permanent cardiac arrhythmias due to the ischemic damage.

Topics: Animals; Anti-Arrhythmia Agents; Antibodies, Blocking; Arrhythmias, Cardiac; Digoxin; Dogs; Female; Immunoglobulin Fab Fragments; Nerium; Plant Poisoning

Topics: Arrhythmias, Cardiac; Cardiotonic Agents; Child, Preschool; Digoxin; Electrocardiography; Emergency Service, Hospital; Heart Rate; Humans; Male

Digoxin is a cardiac glycoside that is frequently prescribed in atrial fibrillation and heart failure. Symptoms such as nausea, hyperkalaemia, cardiac arrhythmias and cardiac arrest are seen in digoxin toxicity. The treatment focuses on reduction of digoxin absorption, prevention of hypokalaemia and hyperkalaemia, treatment of symptoms and, in severe toxicity, administration of digoxin antibodies.. A 73-year-old man with a history of extensive cardiac disease was seen 45 minutes after ingesting 20 mg of digoxin. The patient developed ventricular fibrillation within 3 hours of ingestion, before arrival of the digoxin antibodies. The patient passed away despite resuscitation and administration of an insufficient amount of digoxin antibodies.. The national supply of digoxin antibodies in the Netherlands proved to be too limited for the treatment of a patient with severe digoxin toxicity. An increase in the supply, and central storage, of digoxin antibodies could promote faster administration of an adequate amount of the antibodies. Timely transportation to an extra corporeal membrane oxygenation centre should also be considered.

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Fatal Outcome; Heart Arrest; Humans; Male; Netherlands; Ventricular Fibrillation

Serum digoxin levels have limited utility for determining digoxin toxicity in adults. Paediatric data assessing the utility of monitoring serum digoxin concentration are scarce. We sought to determine whether serum digoxin concentrations are associated with signs and symptoms of digoxin toxicity in children.. We carried out a retrospective review of patients 2 ng/ml).. There were 87 patients who met study criteria (male 46%, mean age 8.4 years). CHD was present in 67.8% and electrocardiograms were performed in 72.4% of the patients. The most common indication for digoxin toxicity was heart failure symptoms (61.5%). Toxic serum digoxin concentrations were present in 6.9% of patients (mean 2.6 ng/ml). Symptoms associated with digoxin toxicity occurred in 48.4%, with nausea/vomiting as the most common symptom (36.4%), followed by tachycardia (29.5%). Compared with those without toxic serum digoxin concentrations, significantly more patients with toxic serum digoxin concentrations were female (p=0.02). The presence of electrocardiogram abnormalities and/or signs and symptoms of digoxin toxicity was not significantly different between patients with and without serum digoxin concentrations (p>0.05).. Serum digoxin concentrations in children are not strongly associated with signs and symptoms of digoxin toxicity.

Topics: Adolescent; Age Factors; Arrhythmias, Cardiac; Cardiovascular Agents; Child; Child, Preschool; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Infant; Male; Nausea; Retrospective Studies; Texas; Vomiting

Topics: Adenosine; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Catheter Ablation; Defibrillators, Implantable; Digoxin; Evidence-Based Medicine; Heart Conduction System; Humans; Pacemaker, Artificial; Pulmonary Veins; Randomized Controlled Trials as Topic

Topics: Aged; Antidotes; Arrhythmias, Cardiac; Digitalis; Digoxin; Electrocardiography; Female; Humans; Hyperkalemia; Male; Nausea; Vomiting

In Uganda, few children with congenital heart diseases (CHD) benefit from early corrective cardiac surgery. These children are at high risk of developing heart failure and electrolyte imbalances; factors which increase their risk of developing arrhythmias. This study aimed to determine the prevalence and factors associated with arrhythmias among children with congenital heart diseases receiving care at Mulago Hospital.. This was a cross-sectional study carried out from August 2013 to March 2014 at Mulago Hospital. Children were consecutively enrolled into the study. Standard 12-lead electrocardiograms (ECGs) were performed on 194 children with CHD (age range 10 days-15 years). Data was analysed using SPSS 16.0.. Out of 194 children studied, 53/194 (27.3 %, 95 % CI 21.0 - 33.6) children had arrhythmias. Of the CHD children, 44/194 (22.7 %, 95 % CI 16.8 - 28.6) had first degree AV block while 9/194 (4.6 %, 95 % CI 1.7 - 7.6) children had either ectopic atrial rhythm, premature atrial contractions, junctional rhythm, complete atrioventricular (AV) dissociation or premature ventricular contractions. Children using digoxin were more likely to have first degree AV block (OR 3.75, 95 % CI 1.60-8.86) while those aged 5 years and below were less likely to have first degree AV block (OR 0.16, 95 % CI 0.07-0.37).. Arrhythmias are common among children with CHD receiving care from Mulago Hospital. These are associated with digoxin use, child's age and electrolyte imbalances; factors which can easily be assessed, managed and where possible modified in these children during their care.

Topics: Adolescent; Age Factors; Arrhythmias, Cardiac; Cardiotonic Agents; Child; Child, Preschool; Cross-Sectional Studies; Digoxin; Electrocardiography; Female; Heart Defects, Congenital; Hospitals; Humans; Infant; Infant, Newborn; Male; Prevalence; Referral and Consultation; Risk Factors; Time Factors; Uganda; Water-Electrolyte Imbalance

Digitalis preparations are commonly used by children and adults with heart diseases worldwide, although excessive doses may cause cardiac effects. The aim of the study is to evaluate the antiarrhythmic effect of Crataegus oxyacantha extract on digoxin-induced arrhythmias in anesthetized Wistar rats.. Control and experimental groups were evaluated for arrhythmias induced by digoxin. Fifteen rats (7 as controls and 8 as the experimental group) were included in the study. The dry fruits of 100 mg Crataegus oxyacantha were extracted by percolation method. Digoxin, at a dose of 40 µg/kg/min, was infused to form the arrhythmias in all rats. Simultaneously, the extract was infused into the experimental group, while 0.9% NaCl was infused into control group. Electrocardiographic QRS prolongation and arterial blood pressure changes were analyzed.. The experimental group lived longer (62.13±2.20 min) than the controls (p=0.002). On the other hand, the time to beginning of QRS prolongation did not differ between the two groups (p=0.812). Bradycardia was significant in the control group (288.01±10.54 beat/min and p=0.01). The maximum QRS duration was observed in the control group during the digoxin and 0.9% NaCl infusion period (53.29±3.99 ms and p=0.001). Also, the durations of atrial and ventricular arrhythmias were shorter in the experimental group. However, arterial blood pressure dipping was significant in the experimental group (23.67±10.89 mm Hg and p<0.001).. Crataegus oxyacantha alcoholic extract produced an antiarrhythmic effect that was induced by digoxin in Wistar rats. However, in the clinical use of this extract, the hypotensive effect should be considered. Also, the alcoholic extract of Crataegus oxyacantha may be an alternative treatment medication for arrhythmias induced by digoxin toxicity in humans.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Crataegus; Digoxin; Disease Models, Animal; Heart Rate; Male; Phytotherapy; Plant Extracts; Random Allocation; Rats; Rats, Wistar

Rate and rhythm control strategies for atrial fibrillation (AF) are not always effective or well tolerated in patients with congestive heart failure (CHF). We assessed reasons for treatment failure, associated characteristics, and effects on survival.. A total of 1,376 patients enrolled in the AF-CHF trial were followed for 37  ±  19 months, 206 (15.0%) of whom failed initial therapy leading to crossover. Rhythm control was abandoned more frequently than rate control (21.0% vs. 9.1%, P < 0.0001). Crossovers from rhythm to rate control were driven by inefficacy, whereas worsening heart failure was the most common reason to crossover from rate to rhythm control. In multivariate analyses, failure of rhythm control was associated with female sex, higher serum creatinine, functional class III or IV symptoms, lack of digoxin, and oral anticoagulation. Factors independently associated with failure of rate control were paroxysmal (vs. persistent) AF, statin therapy, and presence of an implantable cardioverter-defibrillator. Crossovers were not associated with cardiovascular mortality (hazard ratio [HR] 1.11 from rhythm to rate control; 95% confidence interval [95% CI, 0.73-1.73]; P = 0.6069; HR 1.29 from rate to rhythm control; 95% CI, 0.73-2.25; P = 0.3793) or all-cause mortality (HR 1.16 from rhythm to rate control, 95% CI [0.79-1.72], P = 0.4444; HR 1.15 from rate to rhythm control, 95% [0.69, 1.91], P = 0.5873).. Rhythm control is abandoned more frequently than rate control in patients with AF and CHF. The most common reasons for treatment failure are inefficacy for rhythm control and worsening heart failure for rate control. Changing strategies does not impact survival.

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Arrhythmias, Cardiac; Atrial Fibrillation; Creatinine; Defibrillators, Implantable; Digoxin; Disease Progression; Female; Follow-Up Studies; Heart Failure; Heart Rate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Sex Factors; Treatment Failure

Topics: Adrenergic beta-Antagonists; Arrhythmias, Cardiac; Digoxin; Heart Rate; Humans

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Disease; Diagnosis, Differential; Digoxin; Electrocardiography; Female; Humans; Myocardial Ischemia; Signal Processing, Computer-Assisted

The ideal treatment for fetal arrhythmias associated with hydrops is not known. This case report describes a novel approach to fetal cardioversion using oral maternal bolus dosing of flecainide.

Topics: Administration, Oral; Arrhythmias, Cardiac; Digoxin; Dose-Response Relationship, Drug; Drug Administration Schedule; Echocardiography, Doppler; Electric Countershock; Female; Fetal Diseases; Flecainide; Follow-Up Studies; Gestational Age; Humans; Maternal-Fetal Exchange; Pregnancy; Pregnancy Outcome; Severity of Illness Index; Treatment Outcome; Ultrasonography, Prenatal; Young Adult

The importance of heart rate in the pathophysiology of heart failure with reduced LVEF has recently attracted attention. In particular, the findings of the Systolic Heart failure treatment with the I(f) inhibitor ivabradine Trial (SHIFT) have put special emphasis on heart rate reduction with ivabradine for improvement in clinical outcomes. Of course, there is a much older drug that reduces heart rate, i.e. digoxin.. In this short commentary, we retrospectively analyse the Digitalis Investigation Group (DIG) Trial looking at the primary composite endpoint used in SHIFT (i.e. cardiovascular death or hospital admission for worsening heart failure) and compare the effect of digoxin on this endpoint with that of ivabradine. A remarkably similar risk reduction in the composite outcome and in its components appears evident among patients receiving the active treatment in both studies (although ivabradine was added to a beta-blocker, whereas digoxin was not).. This raises the question of whether the Cardiological community dismissed digoxin too readily and if we should reappraise its potential role in the treatment of heart failure.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzazepines; Digoxin; Female; Heart Failure; Humans; Ivabradine; Kaplan-Meier Estimate; Male; Middle Aged; Randomized Controlled Trials as Topic; Retrospective Studies; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left

We present case a male patient who attempted suicide by ingestion of 90 tablets of digoxin in total dose of 22.5 mg. A measured peak level of digoxin was 6,75 ng/ml. Temporary invasive cardiac pacing with single chamber ventricular pacer was performed for treatment of the life-threatening rhythm and conduction disturbances that revealed within few hours after admission. According to the authors, presented method of therapy should always be taken into consideration in case development of cardiovascular disturbances in acute poisoning with digoxin.

Topics: Adult; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Digoxin; Drug Overdose; Humans; Male; Suicide, Attempted

Topics: Adrenergic beta-Agonists; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzazepines; Digoxin; Diltiazem; Heart Diseases; Heart Rate; Humans; Hypertension; Ivabradine; Verapamil

Digoxin is an inhibitor of the sodium-potassium ATPase. In overdose, hyperkalemia is common. Although hyperkalemia is often treated with intravenous calcium, it is traditionally contraindicated in digoxin toxicity.. To analyze records from patients treated with intravenous calcium while digoxin-toxic.. We reviewed the charts of all adult patients diagnosed with digoxin toxicity in a large teaching hospital over 17.5 years. The main outcome measures were frequency of life-threatening dysrhythmia within 1 h of calcium administration, and mortality rate in patients who did vs. patients who did not receive intravenous calcium. We use multivariate logistic regression to ensure that no relationship was overlooked due to negative confounders (controlling for age, creatinine, systolic blood pressure, peak serum potassium, time of development of digoxin toxicity, and digoxin concentration).. We identified 161 patients diagnosed with digoxin toxicity, and were able to retrieve 159 records. Of these, 23 patients received calcium. No life-threatening dysrhythmias occurred within 1 h of calcium administration. Mortality was similar among those who did not receive calcium (27/136, 20%) compared to those who did (5/23, 22%). In the multivariate analysis, calcium was non-significantly associated with decreased odds of death (odds ratio 0.76; 95% confidence interval [CI] 0.24-2.5). Each 1 mEq/L rise in serum potassium concentration was associated with an increased mortality odds ratio of 1.5 (95% CI 1.0-2.3).. Among digoxin-intoxicated humans, intravenous calcium does not seem to cause malignant dysrhythmias or increase mortality. We found no support for the historical belief that calcium administration is contraindicated in digoxin-toxic patients.

Topics: Aged; Arrhythmias, Cardiac; Calcium; Digoxin; Humans; Hyperkalemia; Injections, Intravenous; Treatment Outcome

Digitalis glycosides are among the oldest drugs used in cardiology. Nowadays, due to the limited indications for their use (advanced heart failure, usually concomitant with atrial fibrillation), cases of poisoning induced by this class of drugs are rarely observed. Digoxin produces a positive inotropic and bathmotropic effect on the heart, but has a negative chronotropic and dromotropic effect. Cardiac glycosides have a narrow therapeutic window, so digitalis treatment can easily lead to symptoms of overdose. In patients taking digoxin, the drug therapeutic level should be maintained at 1-2 ng/ml; the toxic effects occur at concentrations > 2.8 ng/ml and are mainly related to disturbances of cardiac function and of the circulatory system, as well as gastrointestinal symptoms and CNS disturbances. We present, a 45-years-old patient who was hospitalized following the ingestion with suicidal intent of 100 0.25 mg tablets of digoxin. In spite of rapidly applied gastric irrigation and administration of activated charcoal, the drug level in the patient's blood was estimated at 12.0 ng/ml. During her stay on the ward, typical symptoms of severe poisoning were observed: from gastric symptoms (severe nausea, vomiting) to numerous severe arrhythmias and conduction disturbances. Type I, II and III AV blocks were detected, as well as numerous ventricular and supraventricular extrasystoles. These conduction disorders required the use of temporary endocardial pacing. Due to the unavailability of specific antidotes (antidigitalis antibodies) and lack of efficient methods of extracorporeal elimination of the drug, symptomatic treatment comprising the correction of electrolyte disturbances and heart rate control remains the most effective.

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Fluid Therapy; Humans; Middle Aged; Nausea; Suicide, Attempted; Vomiting; Water-Electrolyte Imbalance

All cardiac steroids have a similar structure, bind to and inhibit the ubiquitous transmembrane protein Na(+), K(+)-ATPase and increase the force of contraction of heart muscle. However, there are diverse biological responses to different cardiac steroids both at the cellular and at the molecular level. Moreover, we have recently shown that ouabain inhibits digoxin- and bufalin-induced changes in membrane traffic. The present study was designed to test the hypothesis that ouabain also has an inhibitory effect on cardiotoxicity induced by other cardiac steroids.. The hypothesis was tested in isolated heart muscle preparations and in an in vivo model of cardiotoxicity in guinea pigs.. Ouabain at a low dose attenuated the toxicity induced by bufalin and digoxin in heart muscle preparations. In addition, ouabain at the low dose (91 ng.kg(-1).h(-1)), but not at a higher dose (182 ng.kg(-1).h(-1)), delayed the development of digoxin-induced (500 microg.kg(-1).h(-1)) cardiotoxicity in anaesthetized guinea pigs, as manifested by delayed arrhythmia and terminal ventricular fibrillation, as well as a reduced heart rate. In addition, as observed with ouabain, the phosphoinositide 3-kinase inhibitor wortmannin (100 microg.kg(-1).h(-1)) delayed the digoxin-induced arrhythmia in anaesthetized guinea pigs.. The present study demonstrates the inhibitory effect, probably through signal transduction pathways, of ouabain on digoxin- and bufalin-induced cardiotoxicity in guinea pigs. Further understanding of this phenomenon could be beneficial for increasing the therapeutic window for cardiac steroids in the treatment of chronic heart failure.

Topics: Androstadienes; Animals; Arrhythmias, Cardiac; Bufanolides; Cardiotonic Agents; Digoxin; Dose-Response Relationship, Drug; Guinea Pigs; Heart Rate; Male; Myocardium; Ouabain; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Signal Transduction; Sodium-Potassium-Exchanging ATPase; Ventricular Fibrillation; Wortmannin

Topics: Arrhythmias, Cardiac; Cardiotonic Agents; Child, Preschool; Diagnosis, Differential; Digoxin; Eating; Electrocardiography; Heart Rate; Humans; Intensive Care Units, Pediatric; Male

The protocols described in this unit are used to assess the effects of new chemical entities on arrhythmias in the guinea pig. In the anesthetized guinea pig, arrhythmias are induced by a slow intravenous infusion of digoxin, which provokes extrasystoles, ventricular tachyarrhythmias, and ultimately cardiac arrest. Imipramine precipitates the occurrence of arrhythmias, whereas propranolol shows protection against them.

Topics: Animal Husbandry; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Clinical Protocols; Digoxin; Disease Models, Animal; Dose-Response Relationship, Drug; Guinea Pigs; Imipramine; Male; Propranolol

Despite administration of Fab fragments in digitalis poisoning, high mortality rates are consistently reported. A previous study suggested that Fab fragments prescribed as first-line therapy might improve mortality rate. Our objective was to evaluate this approach.. Retrospective chart review (January 1990 to January 2004).. University hospital intensive care unit.. Consecutive patients admitted for cardiac glycoside poisoning.. First-line therapy with Fab fragments (with or without atropine) in either curative or prophylactic doses.. A total of 141 patients were admitted for digitalis poisoning of whom 66 received first-line Fab fragment therapy. Their median age was 74 years (25th to 75th percentiles: 51-83); 76% were women. Half were intoxicated by digitoxin and half by digoxin. Median serum concentration was 168 (108-205) ng/mL for digitoxin and 6.2 (4.3-13.5) ng/mL for digoxin. Conduction disturbances were reported in 45 cases (68%) and ventricular arrhythmia in six cases (9%). Fab fragments were administered as curative treatment in 21 patients (32%) and prophylactically in 45 patients (68%). The median cumulative dose was 4 (4-6) vials. No adverse effects were reported. Five patients (7.6%) died.. First-line therapy with Fab fragments in patients with digitalis poisoning was associated with a low mortality rate.

Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Atropine; Cardiotonic Agents; Critical Care; Digitalis Glycosides; Digitoxin; Digoxin; Female; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Poisoning; Retrospective Studies

Congenital diverticulum of the left ventricle is a malformation, often associated with midline thoraco-abdominal defects. Here we describe a case of isolated congenital left ventricular diverticulum that presented with an abnormal four-chamber view and fetal dysrhythmia on ultrasonography. Maternal digoxin therapy was started due to significant ventricular ectopy. Restoration of fetal sinus rhythm was achieved within 48 h. Serial fetal echocardiograms were performed every week, followed by a normal vaginal delivery at term. The child is surviving at 1 year of age.

Topics: Adult; Arrhythmias, Cardiac; Diagnosis, Differential; Digoxin; Disease Management; Diverticulum; Female; Fetal Diseases; Heart Defects, Congenital; Heart Ventricles; Humans; Infant, Newborn; Pregnancy; Ultrasonography, Prenatal

The present study aimed to evaluate the management of fetal cardiac dysrhythmias based on prior identification of the underlying electrophysiological mechanism.. We studied 36 consecutive fetuses with cardiac dysrhythmia. Rhythm diagnosis was based on M-mode, pulsed wave Doppler and tissue Doppler imaging (TDI). Only fetuses with: (i) incessant tachycardia (> 12 h) and mean ventricular rate > 200 beats/min, (ii) signs of left ventricular dysfunction, or (iii) hydrops, were treated using oral maternal drug therapy.. The mean gestational age at diagnosis was 24.3 +/- 4.5 weeks. Twenty-one fetuses had tachycardia with a 1: 1 atrial-ventricular (AV) conduction. Based on ventricular-atrial interval, prenatal diagnosis was: permanent junctional reciprocating (n = 6), atrial ectopic (n = 6) or atrial-ventricular re-entry tachycardia (n = 9). One had atrial flutter, one ventricular tachycardia and four congenital AV block. Nine showed premature atrial or ventricular beats. Fifteen fetuses with incessant tachycardia, left ventricular dysfunction or hydrops were prenatally treated with maternal administration of digoxin, sotalol or flecainide. The total success rate (sinus rhythm or rate control) was 14/15 (93%). Seven fetuses were hydropics. Three of these died (one at 28 weeks of gestation, two in the first week of life). The prenatal diagnosis of dysrhythmia was confirmed at the birth in 31 of 35 live-born. No misdiagnosis was made using TDI. At 3 +/- 1.1-year follow-up, 33/35 children were alive and well.. Fetal echocardiography could clarify the electrophysiological mechanism of fetal cardiac dysrhythmias and guide the therapy.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Fetal Diseases; Humans; Tachycardia, Atrioventricular Nodal Reentry; Ultrasonography, Prenatal

Cardiac arrhythmias and osteoporotic fractures are common in the elderly.. We studied whether tachyarrhythmia and/or the drugs used to treat arrhythmias affect risk of fracture.. In a population-based nation-wide pharmaco-epidemiological case-control design, we compared 124,655 patients that sustained a fracture during 2000 with 373,962 age- and gender-matched controls. We used computerized registers to assess individual drug use and related these data to individual fracture data and information on confounders.. Risk of any fracture was increased in patients with atrial fibrillation [Odds ratio (OR): 1.14; 95% confidence interval (95%CI): 1.08-1.21] and in patients currently treated with amiodarone (OR: 1.47; 95%CI: 1.21-1.78). Conversely, current use of digoxin decreased fracture risk (OR: 0.75; 95%CI: 0.71-0.79). Subanalysis showed similar effects in men and in women, but drug treatment only affected fracture risk in subjects older than 65 years of age. In current users of digoxin, risk of any fracture and risk of hip and forearm fracture decreased dose-dependently with increased dose. The use of other antiarrhythmics did not affect fracture risk.. Special attention should be paid to patients on treatment with amiodarone and/or a diagnosis of atrial fibrillation as they may have an increased risk of fracture. Conversely, treatment with digoxin may reduce fracture risk.

Topics: Adult; Age Factors; Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Case-Control Studies; Digoxin; Dose-Response Relationship, Drug; Female; Forearm Injuries; Fractures, Bone; Hip Fractures; Humans; Male; Osteoporosis; Risk Factors; Sex Factors; Tachycardia

Topics: Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiotonic Agents; Digoxin; Drug Utilization; Female; Heart Failure; Humans; Male

Topics: Aged, 80 and over; Arrhythmias, Cardiac; Cardiovascular Agents; Colitis, Ischemic; Colonic Neoplasms; Colonic Polyps; Colonoscopy; Digoxin; Drug Therapy, Combination; Female; Humans; Hypertension; Intestinal Mucosa; Nicardipine; Postoperative Complications; Propranolol; Risk Factors; Sigmoid Neoplasms

We recently observed a case of digoxin and insulin self-poisoning without cardiac repercussion. We raised the hypothesis that insulin may have a cardio-protective effect in case of digoxin toxicity. We have therefore evaluated the effect of glucose-insulin infusion on mortality and ECG abnormalities during acute digoxin toxicity in rats. Before and after a hyperinsulinemia-euglycemia clamp, rats in glucose-insulin-digoxin (GID) group (n=10) received an intravenous infusion of 12ml/h or 2,5ml/h digoxin (0.25mg/ml) respectively until death occured. Animals receiving digoxin or saline solution intravenously served as control (n=10). ECG recording was performed in all animals over the entire period. Serum insulin and digoxin concentrations were measured by ELISA method after digoxin administration. When digoxin was administered after the clamp, all animals in GID group were alive, whereas 80% of animals in the digoxin group were dead (p<0.001) after 30min. The administration of Digoxin provoked rapid death of rats in the digoxin group in 15+/-12min whereas in GID group the survival period was significantly increased to 38+/-3min (p<0.001). Twenty minutes after digoxin administration, P waves disappeared for 78% of animals in digoxin group while they were present in all rats of GID group (p<0.001). Animal death occurred after a digoxin infusion volume of 7.7+/-0.6ml and 3.0+/-2.4ml in GID and digoxin group respectively (p<0.001). Five minutes after digoxin administration, potassium plasmatic level increased significantly in digoxin group as compared to GID group: 7.1+/-2mmol/l versus 4.4+/-0.4mmol/l (p<0.001). When digoxin was infused before the clamp, 40% of animals in GID group were alive after 180min and the other 60% died after 137+/-40min whereas death of rats in the digoxin group occurred within 80+/-10min (p<0.001). The death of animals was preceded by the P waves disappearing. Thirty minutes after digoxin administration, the potassium plasmatic level increased significantly in the digoxin group as compared to the GID group: 6.9+/-0.5mmol/l versus 4.9+/-0.3mmol/l (p<0.001). At the time of death, both volume of digoxin infusion and serum digoxin concentration were increased in GID group as compared to digoxin group: 5.7+/-1.6ml versus 3.3+/-0.4ml (p<0.001) and 10.7+/-8.3mg/l versus 8.5+/-4.6mg/l.. Glucose-insulin infusion delayed the abnormalities in cardiac conduction and improved rat survival after acute digoxin toxicity. These results suggest a cardioprotective effect of insulin in case of acute digoxin toxicity.

Topics: Animals; Arrhythmias, Cardiac; Cardiotonic Agents; Digoxin; Electrocardiography; Enzyme-Linked Immunosorbent Assay; Female; Glucose; Hypoglycemic Agents; Infusions, Intravenous; Insulin; Potassium; Rats; Rats, Wistar; Survival Rate; Time Factors; Toxicity Tests, Acute; Treatment Outcome

We present a case of multiple arrhythmias in a 3-year-old child who was presented to the emergency department with emesis. Initial vital signs were significant for a heart rate from 40 to 60 beats per minute with stable blood pressure. An electrocardiogram showed complete atrioventricular block with a junctional escape rhythm of 40 to 55 bpm that subsequently progressed to atrial flutter/fibrillation and then to a junctional escape rhythm. She was given intravenous atropine, resulting in acceleration of the junctional rhythm. Sinus rhythm resumed with a prolonged PR interval a few hours later with normalization of the electrocardiogram the following day. Routine laboratory tests, toxicology screens, and tests for other cardiac medications in the home were negative. However, at 20 hours after presentation, her digoxin level was 2.9 ng/mL. Parents denied that the child had access to any digoxin-containing substances. This case illustrates that digoxin toxicity can manifest with multiple arrhythmias and that recognition of this can be very difficult, especially when there is no witness to ingestion. Clinicians should be suspicious for digoxin toxicity when a child presents with persistent emesis, altered level of consciousness, and bradyarrhythmias with or without hemodynamic instability.

Topics: Arrhythmias, Cardiac; Child, Preschool; Digoxin; Female; Humans

Although ventricular cardiomyocytes express inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] receptors, it is unclear how these Ca2+ channels contribute to the effects of Gq-coupled agonists. Endothelin-1 augmented the amplitude of pacing-evoked Ca2+ signals (positive inotropy), and caused an increasing frequency of spontaneous diastolic Ca2+-release transients. Both effects of endothelin-1 were blocked by an antagonist of phospholipase C, suggesting that Ins(1,4,5)P3 and/or diacylglycerol production was necessary. The endothelin-1-mediated spontaneous Ca2+ transients were abolished by application of 2-aminoethoxydiphenyl borate (2-APB), an antagonist of Ins(1,4,5)P3 receptors. Incubation of electrically-paced ventricular myocytes with a membrane-permeant Ins(1,4,5)P3 ester provoked the occurrence of spontaneous diastolic Ca2+ transients with the same characteristics and sensitivity to 2-APB as the events stimulated by endothelin-1. In addition to evoking spontaneous Ca2+ transients, stimulation of ventricular myocytes with the Ins(1,4,5)P3 ester caused a positive inotropic effect. The effects of endothelin-1 were compared with two other stimuli, isoproterenol and digoxin, which are known to induce inotropy and spontaneous Ca2+ transients by overloading intracellular Ca2+ stores. The events evoked by isoproterenol and digoxin were dissimilar from those triggered by endothelin-1 in several ways. We propose that Ins(1,4,5)P3 receptors support the development of both inotropy and spontaneous pro-arrhythmic Ca2+ signals in ventricular myocytes stimulated with a Gq-coupled agonist.

Topics: Animals; Arrhythmias, Cardiac; Boron Compounds; Calcium; Calcium Channels; Calcium Signaling; Digoxin; Endothelin-1; Heart Ventricles; Inositol 1,4,5-Trisphosphate; Inositol 1,4,5-Trisphosphate Receptors; Isoproterenol; Myocytes, Cardiac; Rats; Rats, Wistar; Receptors, Cytoplasmic and Nuclear; Type C Phospholipases

Topics: Aged, 80 and over; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Humans; Male

The aim was to delineate the significance and natural history of fetal arrhythmias and provide information about their management. A cohort of 114 infants with fetal arrhythmias detected during prenatal ultrasound (US) screening were studied. All subjects underwent echocardiography and were treated as clinically indicated. Postnatal outcome was obtained in 100% of infants until 1 year of age. The incidence of fetal arrhythmias was 0.3%. Among the 87 fetuses with atrial extrasystoles, 2.3% developed supraventricular tachycardia (SVT) in utero. Of the 10 SVT cases, only five required antiarrhythmic therapy in utero with digoxin and propafenone, which successfully restored sinus rhythm in 100% of fetuses, both nonhydropic and hydropic. Sinus bradycardia was associated with structural anomalies in 5 of 6 patients and only 2 of 4 fetuses with atrioventricular block survived. It is concluded that prognosis is good for most fetal tachyarrhythmias, whereas it is less favorable for bradyarrhythmias.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cohort Studies; Digoxin; Fetal Diseases; Fetal Therapies; Heart Defects, Congenital; Humans; Prognosis; Tachycardia, Ectopic Atrial; Ultrasonography, Prenatal

Application of implantable cardioverter defibrillator (ICD) therapy is expanding to include both primary and secondary prevention of sudden cardiac death and has been proven to be superior to conventional antiarrhythmic therapies. Concomitant antiarrhythmic drug therapy in patients with ICD is common. These drugs are potentially proarrhythmic, alter defibrillation thresholds, and may affect response to device therapy. However, the impact of concomitant antiarrhythmic drug therapy on survival in patients with ICD devices is unknown.. We investigated the effect of different antiarrhythmic drugs on survival when given concomitantly in 360 consecutive ICD patients from our university medical center. Mortality data were obtained from the national death index. Survival analysis was performed using the Kaplan-Meier method. Corrections for significant covariates and group differences were made using the Cox regression model.. Patients were followed up for 4.4 +/- 3.7 years. There were 68 deaths over this period with a 5-year survival of 80%. Patient characteristics were: age 62 +/- 13 years, left ventricular (LV) ejection fraction (EF) 33 +/- 17%, ischemic etiology of LV dysfunction 68%, diabetes mellitus 19%, hypertension 49%, atrial fibrillation 23%, digoxin 43%, beta-blocker 46%, amiodarone 28%, and sotalol 9%. The use of beta-blockers was associated with a better survival (P = 0.0005). This effect persisted after correcting for age, heart rate, EF, and ischemic etiology. The beneficial effect of beta-blocker was unrelated to its effect on heart rate. Digoxin use was associated with a lower survival only on univariate analysis (P = 0.006), but not after adjusting for other variables on a Cox regression model (P = 0.093). Amiodarone and sotalol were found to have a neutral effect on survival.. In patients with ICDs, beta-blockers had a favorable effect on survival. Sotalol and amiodarone had a neutral effect on survival. There was a trend toward a deleterious effect with digoxin use. These findings suggest a need for further investigation addressing survival effects of antiarrhythmic drugs when given concomitantly in patients with ICDs.

Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Combined Modality Therapy; Death, Sudden, Cardiac; Defibrillators, Implantable; Digoxin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Proportional Hazards Models; Sotalol; Stroke Volume; Survival Rate

To analyze action of digoxin and some non-digitalis drugs (beta-blockers, verapamil, amiodarone, d,l-sotalol) and their combinations on electrical activity of atria, frequency and structure of ventricular rhythm in patients with permanent atrial fibrillation.. One hundred patients with permanent atrial fibrillation and heart rate at rest above 80 bpm were divided into 9 treatment groups. High-resolution orthogonal Frank lead ECG was recorded before and after allocated treatment. Analysis included construction of ff-waves periodograms, histograms of RR interval, cardiointervalograms and application of autocorrelation function.. It was demonstrated that frequency and form (structure) of ventricular rhythm was determined not only by the state of AV conduction but also by value of basic period of ff-waves. The mechanisms of ventricular rate deceleration by investigated drugs were not identical. beta-blockers and verapamil directly slowed AV conduction without changing parameters of ff-waves and differed from each other only in action on parameters of concealed conduction in AV node. Action of digoxin in patients with ff-waves period equal to or exceeding 0,15 s was biphasic. During phase I shortening of ff-wave period (by 0.025+/-0.012 s) occurred. This was associated with increase of their concealed conduction through AV node. The latter phenomenon represented independent mechanism of ventricular rhythm deceleration. During phase II of digoxin action direct inhibition of AV conduction took place. Amiodarone and d,l-sotalol increased basic ff-waves period. This facilitated their conduction through AV node. Greater heart rate slowing effect of d,l-sotalol was attributed to its ability to augment concealed conduction. Due to their antiarrhythmic qualities amiodarone and d,l-sotalol slowed heart rate in patients with peak RR duration in the region of 0.28-0.46 s. These patients often had bi- and tri-modal structure of interval RR histogram. Changes of ventricular rhythm structure during use of various drugs were different. Action of digoxin was most whilst that of beta-blockers least favorable.. Choice of a drug for treatment of permanent atrial fibrillation should be conducted with consideration of ff-waves periodicity, parameters of RR interval histogram, and characteristics of ventricular rhythm structure.

Topics: Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Periodicity; Sotalol; Ventricular Premature Complexes; Verapamil

To elucidate whether endoxin is one of important factors involved in myocardial ischemia reperfusion (MIR) injury, the change of myocardial endoxin level was determined in rats with MIR injury model and the effects of anti-digoxin antiserum (ADA), an endoxin specific antagonist, on MIR injury were studied.. MIR injury model was obtained by ligating left anterior descending coronary artery 30 min followed by 45 min reperfusion. Sprague-Dawley rats were randomly divided into six groups of 10 rats, each. Sham group, MIR group, normal saline group, ADA 9, 18 and 36 mg.kg(-1). ECG was continuously recorded. After reperfusion left ventricular myocardium samples of ischemic area were processed immediately. Myocardial endoxin level, Na(+)-K(+)-ATPase, Ca(2+)-ATPase, Mg(2+)-ATPase activities, and intramitochondrial Ca(2+) content were measured.. Myocardial endoxin level was significantly increased; Na(+)-K(+)-ATPase, Ca(2+)-ATPase, and Mg(2+)-ATPase activities were remarkably decreased; intramitochondrial Ca(2+) content was remarkably raised; ST segments of ECG were significantly elevated and occurrence and scores of ventricular arrhythmias were significantly increased in early stage of reperfusion in rats with MIR. In all groups with ADA, myocardial endoxin level was remarkably decreased; Na(+)-K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase activities were drastically increased; intramitochondrial Ca(2+) content was declined; ST segments and ventricular arrhythmias were improved.. Myocardial endoxin level was increased in MIR, which implies that the elevated endoxin may be one of major factors inducing MIR injury. This postulate is supported by the observation that ADA has protective and therapeutic effects against MIR injury probably by antagonizing the action of endoxin. The underlying mechanism may be ascribed to restoration of energy metabolism, and attenuation of intracellular Ca(2+) overload.

Topics: Animals; Arrhythmias, Cardiac; Ca(2+) Mg(2+)-ATPase; Calcium; Calcium-Transporting ATPases; Cardenolides; Digoxin; Disease Models, Animal; Electrocardiography; Enzyme Inhibitors; Immune Sera; Male; Mitochondria, Heart; Myocardial Reperfusion Injury; Myocardium; Rats; Rats, Sprague-Dawley; Saponins; Sodium-Potassium-Exchanging ATPase

Topics: Acute Disease; Arrhythmias, Cardiac; Cardiotonic Agents; Causality; Colectomy; Confusion; Digoxin; Diuretics; Electrocardiography; Emergencies; Humans; Hypokalemia; Male; Middle Aged; Muscle Weakness; Nursing Assessment; Paresthesia; Patient Care Planning; Patient Education as Topic; Potassium

Topics: Alabama; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Compensation and Redress; Coronary Artery Bypass; Digoxin; Humans; Liability, Legal; Licensure, Nursing; Male; Malpractice; Medication Errors; Nursing Staff, Hospital; Risk Management

The design, synthesis, and biological properties of novel inhibitors of the Na(+),K(+)-ATPase as potential positive inotropic compounds are reported. Following our model of superposition between cassaine and digitoxigenin, digitalis-like activity has been elicited from a non-digitalis steroidal structure by suitable modifications of the 5alpha,14alpha-androstane skeleton. The strong hydrophobic interaction of the digitalis or cassaine polycyclic cores can be effectively obtained with the androstane skeleton taken in a reversed orientation. Thus, oxidation of C-6 and introduction in the C-3 position of the potent pharmacophoric group recently introduced by us, in the 17 position of the digitalis skeleton, namely, O-(omega-aminoalkyl)oxime, led to a series of substituted androstanes able to inhibit the Na(+),K(+)-ATPase, most of them with an IC(50) in the low micromolar level, and to induce a positive inotropic effect in guinea pig. Within this series, androstane-3,6,17-trione (E,Z)-3-(2-aminoethyl)oxime (22b, PST 2744) induced a strong positive inotropic effect while being less arrhythmogenic than digoxin, when the two compounds were compared at equiinotropic doses.

Topics: Androstanes; Animals; Arrhythmias, Cardiac; Dogs; Enzyme Inhibitors; Etiocholanolone; Guinea Pigs; Models, Molecular; Myocardial Contraction; Sodium-Potassium-Exchanging ATPase; Stereoisomerism; Stimulation, Chemical; Structure-Activity Relationship

(E,Z)-3-((2-Aminoethoxy)imino)androstane-6,17-dione hydrochloride (PST2744) is a novel Na(+)/K(+) pump inhibitor with positive inotropic effects. Compared with digoxin in various experimental models, PST2744 was consistently found to be less arrhythmogenic, thus resulting in a significantly higher therapeutic index. The present work compares the electrophysiological effects of PST2744 and digoxin in guinea pig ventricular myocytes, with the aim to identify a mechanism for their different toxicity. The work showed that 1) the action potential was transiently prolonged and then similarly shortened by both agents; 2) the ratio between Na(+)/K(+) pump inhibition and inotropy was somewhat larger for PST2744 than for digoxin; 3) both agents accelerated inactivation of high-threshold Ca(2+) current (I(CaL)), without affecting its peak amplitude; 4) the transient inward current (I(TI)) induced by a Ca(2+) transient in the presence of complete Na(+)/K(+) pump blockade was inhibited (-43%) by PST2744 but not by digoxin; 5) the conductance of Na(+)/Ca(2+) exchanger current (I(NaCa)), recorded under Na(+)/K(+) pump blockade, was only slightly inhibited by PST2744 (-14%) and unaffected by digoxin; and 6) both agents inhibited delayed rectifier current I(Ks) (

Topics: Animals; Arrhythmias, Cardiac; Calcium Channels; Cardiotonic Agents; Cell Separation; Digoxin; Dose-Response Relationship, Drug; Electrophysiology; Enzyme Inhibitors; Etiocholanolone; Female; Guinea Pigs; Heart Diseases; In Vitro Techniques; Membrane Potentials; Myocardium; Potassium Channels, Inwardly Rectifying; Sodium-Potassium-Exchanging ATPase

trans-1,2-Cyclohexanediol, the major metabolite of the cilexetil moiety of candesartan cilexetil (CC), has been reported to have potent pro-arrhythmic effects in dogs with congestive heart failure (CHF), especially when co-administered with digoxin. To verify this and to clarify the clinical relevance and the underlying mechanisms, a series of in vivo and in vitro experiments was conducted. When CC up to 300 mg/kg was administered orally to intact dogs, no changes in the electrocardiograms (ECG) or the required cumulative doses of ouabain to induce ventricular arrhythmias were observed. In dogs with CHF, intravenous bolus administration of trans-1,2-cyclohexanediol at 4 mg/kg followed by continuous infusion at 0.1 mg x kg(-)(1) x min(-)(1) had no effects on the ECG parameters, the type, incidence, and onset time of digoxin-induced arrhythmias or the metabolism of digoxin. In an in vitro experiment using isolated guinea pig papillary muscle, trans-1,2-cyclohexanediol (1 - 100 micromol/L) showed no effects on any parameter of the action potentials. Because no effects were observed in these experiments where the exposure levels of trans-1,2-cyclohexanediol were extremely high compared to those in humans given the maximum therapeutic dose of CC, it is unlikely that CC would induce arrhythmias in clinical use even in patients treated with cardiac glycosides.

Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Benzimidazoles; Biphenyl Compounds; Cyclohexanols; Digoxin; Dogs; Drug Interactions; Guinea Pigs; Heart Failure; In Vitro Techniques; Male; Papillary Muscles; Tetrazoles

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Humans

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Heart Failure; Humans

A 65-year-old woman with a history of alcoholic liver disease and presenting with fever and vomiting was admitted to an internal medicine unit. In view of recent atrial fibrillation with inadequate heart rate control, digoxin and propafenone were included in the therapeutic regimen. After a few days sinus rhythm was restored but suddenly ventricular arrhythmias with the characteristics of a non-responsive electrical storm arose shortly following the appearance of clinical symptoms of drug intoxication.

Topics: Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Drug Therapy, Combination; Electrocardiography; Female; Humans; Liver Diseases, Alcoholic; Propafenone

Potential risks of cyclohexanol (CH) and cyclohexanediol (CHD) isomers, which are the metabolites derived from cilexetil ester side-chain of several prodrugs such as antibiotics (e.g. cefotiam hexetil) and an antihypertensive agent (candesartan cilexetil), were examined in beagles that were made congestive heart failure (CHF) by rapid ventricular pacing. The following three experiments tested the cardiac effects of i.v. doses of: (1) the metabolites alone, (2) the metabolites under the digoxin-induced bradycardia, and (3) the metabolites given concomitantly with digoxin (0.02 mg kg(-1)). Experiment 1: t-1,2- or 1,4-CHD alone (0.1-12 mg kg(-1)) exerted transient yet reproducible supraventricular or ventricular arrhythmia dose-dependently, whereas CH and 1,3-CHD at 12 mg kg(-1) showed no cardiac effect at all. Experiment 2: t-1,2-CHD (0.1-4 mg kg(-1)), but not CH or 1,3-CHD, induced the additive arrhythmia dose-dependently; t-1,2-CHD (12 mg kg(-1)) caused frequent premature supraventricular contractions and/or irreversible paroxysmal supraventricular tachycardia. Experiment 3: t-1,2-CHD, not CH or 1,3-CHD, caused fatal arrhythmia: one dog showed torsade de pointes followed by ventricular fibrillation, while another showed 3rd degree atrioventricular block and eventually cardiac arrest. In both Experiments 2 and 3, saline vehicle added onto digoxin never caused the irreversible, fatal arrhythmia. In a separate study using healthy dogs without CHF, none of these metabolites did produce cardiac effect. Given the potential risk of generating cardiotoxic metabolites from cilexetil-bearing prodrugs, the use of such prodrugs should be avoided from the patients with CHF, particularly from those who are receiving cardiac glycosides.

Topics: Animals; Antihypertensive Agents; Arrhythmias, Cardiac; Benzimidazoles; Biphenyl Compounds; Cardiac Pacing, Artificial; Cardiotonic Agents; Digoxin; Dogs; Dose-Response Relationship, Drug; Heart Failure; Heart Ventricles; Prodrugs; Tetrazoles

To evaluate the proportion of inappropriate digoxin level determinations.. We performed a retrospective analysis of 210 randomly selected digoxin plasma level determinations in inpatients. Appropriateness criteria were defined combining existing criteria from the literature. The main outcome measure was the proportion of digoxin levels assessed as inappropriate using a priori defined criteria.. Of the 210 digoxin levels assessed, 125 (59%; 95% confidence interval [CI] 52-66%) were considered inappropriate, 81 (39%; 95% CI: 32-45%) were appropriate, and 4 (2%) determinations could not be evaluated. Of the 125 levels assessed as inappropriate, the majority (79%) was performed as routine monitoring. Extrapolating the results to all digoxin level determinations in inpatients at our institution resulted in estimated yearly costs of CHF 28,025 (approximately B 18,995) for inappropriate digoxin level determinations.. The majority of digoxin plasma levels determinations were assessed as inappropriate. This was mainly due to the lack of an adequate indication and due to incorrect timing of drawing the blood samples. With regard to indication, routine monitoring was the reason for the majority of levels assessed as inappropriate.

Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Cardiotonic Agents; Confidence Intervals; Digoxin; Female; Hospitals, University; Humans; Inpatients; Male; Middle Aged; Monitoring, Physiologic; Retrospective Studies; Sampling Studies; Sensitivity and Specificity; Switzerland

Reactive oxygen species, generated and released during digoxin-induced cardiotoxicity, can produce an activation of poly (ADP-ribose) synthase (PARS). Our objective was to examine the effects of PARS inhibitors, 3-aminobenzamide (3-AB ) and nicotinamide, on digoxin-induced arrhythmias in guinea-pig isolated hearts. 3-AB (0.1-0.3 mM) and nicotinamide (0.3 mM) were added to the perfusion solution starting 10 min before digoxin infusion (8 microg x ml (-1)min (-1)reaching the heart) and maintained throughout the experiments. Electrocardiograms and coronary perfusion pressure were recorded continuously, and digoxin-induced arrhythmias were determined. Nicotinamide markedly inhibited ventricular tachycardia (VT) incidence (from 100%, n= 7, to 29%, n= 7), and abolished ventricular fibrillation (VF) incidence. 3-AB (0.1 mM, n= 9) significantly decreased VT incidence from 100% ( n= 7) to 22% ( n= 9) and VF incidence from 86% ( n= 7) to 11% ( n= 9). Both nicotinamide and 3-AB (0.1 mM) markedly decreased number of ventricular ectopic beats (VEBs) and arrhythmia score. 3-AB at 0.3 mM ( n= 8) appeared to decrease the VT (to 63%) and VF incidence (to 38%), but these reductions did not reach statistically significance levels. Moreover, 3-AB at high concentration (0.3 mM) did not significantly modify the number of VEBs and arrhythmia score. There were no significant changes in coronary perfusion pressure, heart rate or pressure rate index measured at certain time points throughout the experiment in all groups. Our results suggest that PARS activation plays a role in the digitalis-induced cardiotoxicity in guinea-pig isolated hearts.

Topics: Animals; Arrhythmias, Cardiac; Benzamides; Blood Pressure; Digoxin; Guinea Pigs; Heart Rate; In Vitro Techniques; Male; Niacinamide; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases

Various cardio-active stimuli, including endothelin-1 (ET-1), exhibit potent arrhythmogenicity, but the underlying cellular mechanisms of their actions are largely unclear. We used isolated rat atrial myocytes and related changes in their subcellular Ca(2+) signalling to the ability of various stimuli to induce diastolic, premature extra Ca(2+) transients (ECTs). For this, we recorded global and spatially resolved Ca(2+) signals in indo-1- and fluo-4-loaded atrial myocytes during electrical pacing. ET-1 exhibited a higher arrhythmogenicity (arrhythmogenic index; ratio of number of ECTs over fold-increase in Ca(2+) response, 8.60; n = 8 cells) when compared with concentrations of cardiac glycosides (arrhythmogenic index, 4.10; n = 8 cells) or the beta-adrenergic agonist isoproterenol (arrhythmogenic index, 0.11; n = 6 cells) that gave similar increases in the global Ca(2+) responses. Seventy-five percent of the ET-1-induced arrhythmogenic Ca(2+) transients were accompanied by premature action potentials, while for digoxin this proportion was 25 %. The beta-adrenergic agonist failed to elicit a significant number of ECTs. Direct activation of inositol 1,4,5-trisphosphate (InsP(3)) receptors with a membrane-permeable InsP(3) ester (InsP(3) BM) mimicked the effect of ET-1 (arrhythmogenic index, 14.70; n = 6 cells). Inhibition of InsP(3) receptors using 2 microM 2-aminoethoxydiphenyl borate, which did not display any effects on Ca(2+) signalling under control conditions, specifically suppressed the arrhythmogenic action of ET-1 and InsP(3) BM. Immunocytochemistry indicated a co-localisation of peripheral, junctional ryanodine receptors with InsP(3)Rs. Thus, the pronounced arrhythmogenic potency of ET-1 is due to the spatially specific recruitment of Ca(2+) sparks by subsarcolemmal InsP(3)Rs. Summation of such sparks efficiently generates delayed after depolarisations that trigger premature action potentials. We conclude that the particular spatial profile of cellular Ca(2+) signals is a major, previously unrecognised, determinant for arrhythmogenic potency and that the InsP(3) signalling cassette might therefore be a promising new target for understanding and managing atrial arrhythmia.

Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Calcium; Calcium Channels; Calcium Signaling; Cardiotonic Agents; Digoxin; Electric Stimulation; Electrophysiology; Endothelin-1; Heart Atria; Immunohistochemistry; In Vitro Techniques; Inositol 1,4,5-Trisphosphate; Inositol 1,4,5-Trisphosphate Receptors; Male; Membrane Potentials; Microscopy, Fluorescence; Patch-Clamp Techniques; Rats; Receptors, Cytoplasmic and Nuclear; Subcellular Fractions

Topics: Arrhythmias, Cardiac; Depression; Digoxin; Drug Overdose; Electrocardiography; Enzyme Inhibitors; Humans; Hyperkalemia; Male; Middle Aged; Sodium-Potassium-Exchanging ATPase; Suicide, Attempted; Vomiting

Much evidence has been accumulated that human plasma contains digitalis-like factor(s) with Na/K ATPase inhibitor properties. Increased concentrations of ouabain-like factor (OLF) have been reported in patients with moderate to severe hypertension and in patients with overt congestive heart failure due to dilated cardiomyopathy.. The presence of circulating OLF has not been investigated in borderline to mild hypertension or in the early stage of dilated cardiomyopathy.. The study population consisted of 18 normal volunteers, 24 patients with borderline to mild hypertension, 47 patients with asymptomatic left ventricular dysfunction (ALVD) due to dilated cardiomyopathy and 26 patients with cardiac arrhythmias but normal left ventricular function. OLF values (pM ouabain equivalent) were assayed in extracted plasma, using a radioimmunoassay for ouabain. OLF was, respectively, 29.4+/-20.6 pM in normal controls, 39.1+/-23.8 pM in hypertensives, 35+/-18 pM in patients with cardiac arrhythmias, 52.3+/-25.8 pM in ALVD patients not treated with digoxin and 64.6+/-29.6 pM in ALVD patients treated with digoxin. Patients with ALVD, both treated and not treated with digoxin, had OLF significantly higher (P<0.05) than all the other groups. In patients with ALVD no correlation between OLF and left ventricular ejection fraction was observed. In the hypertensive group no correlation between OLF and both diastolic and systolic pressure was found.. Increased concentrations of OLF were observed in patients with left ventricular dysfunction due to dilated cardiomyopathy, before the occurrence of overt heart failure, suggesting that OLF may be an early marker of the disease.

Topics: Adult; Aged; Arrhythmias, Cardiac; Cardenolides; Cardiomyopathy, Dilated; Digoxin; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Prognosis; Reference Values; Saponins; Ventricular Dysfunction, Left

Atrioventricular (AV) dissociation is an electrocardiographic syndrome; a descriptive term for a variety of conditions of abnormal cardiac conduction which all feature independent function of the atria and ventricles. AV dissociation can be subclassified as AV dissociation by default (an independent ventricular pacemaker responds to slowing of the dominant atrial pacemaker) versus AV dissociation by usurpation (acceleration of a latent pacemaker takes control of cardiac conduction by exceeding the intrinsic atrial rate). Inclusion of third degree AV block (complete heart block) as a manifestation of AV dissociation is controversial, yet is functionally appealing in that this disorder also features independent activity of the atria and ventricles.

Topics: Aged; Arrhythmias, Cardiac; Bradycardia; Calcium Channel Blockers; Coronary Disease; Diagnosis, Differential; Digoxin; Electrocardiography; Emergencies; Female; Heart Atria; Heart Block; Heart Ventricles; Humans; Male; Middle Aged; Sinoatrial Node; Suicide; Tachycardia, Ventricular

The diagnosis and management of fetal cardiac arrhythmias requires complex skills and knowledge, and has had a great impact on the care of infants with congenital heart disease and their families. Optimal benefits will be derived from a thoughtful team approach, with skillful internal communication, and especially when parental involvement is encouraged in the decision making process.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Female; Fetal Diseases; Fetal Monitoring; Humans; Infant, Newborn; Pregnancy

Endothelial nitric oxide synthase (eNOS) mediates attenuation of the L-type calcium channel and modulates myocyte contractility. Arrhythmogenic afterdepolarizations are seen in vitro in ouabain-treated isolated myocytes from eNOS-deficient mice. The aim of these studies was to characterize the baseline electrophysiologic (EP) phenotype of eNOS-deficient mice and their potential susceptibility to cardiac conduction abnormalities and inducible arrhythmias.. Surface ECG and in vivo intracardiac EP studies were performed in 27 mice lacking the eNOS gene and 21 wild-type littermate control mice. Baseline studies were performed in 10 eNOS-deficient mice and 10 wild-type controls. Subsequently, 17 eNOS-deficient mice and 11 wild-type controls were pretreated with digoxin, and ECG and EP testing were repeated. Data analysis revealed no significant differences in ECG intervals or cardiac conduction parameters, except sinus cycle length was higher in eNOS-deficient mice than wild-type mice (P < 0.01). After digoxin pretreatment, 7 of 17 eNOS-deficient mice had inducible ventricular tachycardia and 2 others had frequent ventricular premature beats, compared with only 3 of 11 wild-type mice with inducible ventricular tachycardia. In addition, 2 digoxin-treated eNOS-deficient mice and 1 wild-type mouse had inducible nonsustained atrial fibrillation.. Mice with a homozygous targeted disruption of the eNOS gene have slower heart rates but no other distinguishable EP characteristics under basal sedated conditions. Partial inhibition of the Na+/K+ ATPase pump with digoxin administration increases ventricular ectopic activity in eNOS-/- mice, a phenotype analogous to afterdepolarizations seen in vitro in this eNOS-deficient mouse model.

Topics: Animals; Arrhythmias, Cardiac; Atropine; Digoxin; Disease Models, Animal; Disease Susceptibility; Electrocardiography; Electrophysiologic Techniques, Cardiac; Endothelium, Vascular; Enzyme Inhibitors; Female; Genotype; Heart Conduction System; Heart Rate; Male; Mice; Models, Cardiovascular; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Observer Variation; Parasympatholytics; Propranolol; Sympatholytics

Topics: Aged; Arrhythmias, Cardiac; Cardiac Output, Low; Digoxin; Diuretics; Emergencies; Furosemide; Humans; Male; Potassium

The management of arrhythmias during pregnancy is, in principle, similar to that in nonpregnant patients, however, special consideration must be given, to avoid adverse fetal effects. In pregnant women without organic heart disease, no drug therapy is usually needed for the management of supraventricular or ventricular premature beats, but potential stimulants, such as smoking, caffeine, and alcohol should be eliminated. In patients with mitral valve prolapse beta blocker may be preferred drug. In pregnant patients with organic heart disease, paroxysmal atrial or ventricular tachycardia may induce hemodynamic changes with consequences to the fetus. In paroxysmal atrial tachycardia vagal stimulation maneuvers should tried and, if this is not effective, adenosine or beta-adrenergic blocking agents should be used. Alternatively, verapamil may be given. In pregnant with atrial fibrillation, the goal of treatment is conversion to sinus rhythm or control of the ventricular rate by digoxin. Synchronized electrical cardioversion may become necessary when signs of cardiac decompensation or hypotension were developed. Ventricular arrhythmias may occur in the pregnant women with cardiomyopathy, valvular heart disease, mitral valve prolapse and congenital Q-T prolongation. Termination of ventricular arrhythmias can usually be achieved by intravenous lignocaine or procainamide or by electrical cardioversion. To prevent recurrences, quinidine can be used if the arrhythmia was not induced by QT prolongation or procainamide.

Topics: Adrenergic beta-Antagonists; Alcohol Drinking; Arrhythmias, Cardiac; Digoxin; Electric Countershock; Female; Heart Valve Diseases; Humans; Lidocaine; Mitral Valve Prolapse; Pregnancy; Pregnancy Complications, Cardiovascular; Procainamide; Quinidine; Secondary Prevention; Smoking; Smoking Prevention; Verapamil

We have investigated the effects of nitric oxide synthase inhibitor (L-NAME), nitric oxide precursor (L-arginine) and nitric oxide donor (sodium nitroprusside) on digoxin-induced arrhythmias both in guinea-pig isolated hearts and in anaesthetised animals. Sodium nitroprusside (0.1 mumol kg-1 min.-1 for 70 min.) caused a marked inhibition in mortality and arrhythmia score but L-NAME (10 mg kg-1) and L-arginine (30 mg kg-1 intravenous bolus followed by 10 mg kg-1 min.-1 for 60 min.) treatments were ineffective in anaesthetised guinea-pigs. None of the drugs markedly affected the time of onset of first arrhythmias or ventricular fibrillation incidence. In isolated heart experiments, nitric oxide generated by either L-arginine (1 mM) or sodium nitroprusside (1 mM) significantly reduced the arrhythmia score whereas L-NAME (1 mM) had no effect. Ventricular fibrillation incidence was totally abolished by sodium nitroprusside and none of the hearts treated with L-arginine had an irreversible ventricular fibrillation. L-NAME decreased ventricular tachycardia duration but increased ventricular fibrillation duration. There were no marked changes in the time of onset of first arrhythmias with these drugs in in vitro experiments. These results suggest that nitric oxide may play a modulatory role in the digoxin-induced arrhythmias in guinea-pigs.

Topics: Animals; Arginine; Arrhythmias, Cardiac; Blood Pressure; Digoxin; Guinea Pigs; In Vitro Techniques; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitroprusside; Time Factors; Ventricular Fibrillation

In the present study, the possible role of oxygen-derived free radicals (OFR) on digoxin- (0.6 mg/kg(-1) IV bolus) induced arrhythmias of anesthetized guinea-pigs has been investigated. Guinea-pigs (300400 g) of either sex were anesthetized with urethane (1.5 g/kg(-1),IP), and their trachea for respiration, left common carotid artery for blood pressure monitoring, and right jugular vein for drug administration were cannulated. ECG and haemodynamics were recorded throughout the experiments. None of the agents used [N-acetyl-L-cysteine (20 mg/kg(-1)IV bolus), or SOD (30,000 IU/kg(-1) IV bolus) + catalase (15,000 IU/kg(-1) IV bolus)] significantly inhibited the arrhythmias except desferrioxamine which reduced the incidence of ventricular fibrillation and arrhythmia score. Desferrioxamine, by acting intracellularly unlike other agents used, might prevent the reduction of Fe(+3) by ascorbate and superoxide anion thus inhibiting the formation of cytotoxic hydroxyl radical in this experimental setting.

Topics: Animals; Antioxidants; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Female; Free Radical Scavengers; Free Radicals; Guinea Pigs; Male; Reactive Oxygen Species; Tachycardia, Ventricular; Ventricular Fibrillation

Digoxin inhibits the membrane-bound ATPase enzyme, resulting in a rise in intracellular sodium and activated outward potassium current, predisposing to arrhythmias. In this study, the effect of ketanserin, thought to block outward potassium currents, was investigated on digoxin-induced arrhythmias. Twenty-four guinea-pigs were studied in four groups (control, ketanserin 0.5 mg/kg, ketanserin 1 mg kg, ketanserin 2 mg/kg). Under pentobarbital anaesthesia (40 mg/kg), 15 min after injection of saline or ketanserin, digoxin (0.6 mg/kg) was administered through the jugular vein. Carotid artery blood pressure and electrocardiogram (ECG) were recorded. The time for the onset of the first arrhythmia and incidence of ventricular tachycardia (VT), ventricular fibrillation (VF), and premature ventricular contraction (PVC) were determined. Arrhythmias were scored according to the MacLeod scale. Ketanserin produced minor haemodynamic effects and lacked, by itself, arrhythmogenic effects at the doses studied. However, it increased the time for the onset of the first digoxin-induced arrhythmia and decreased the incidence of VT, VF and PVC. We conclude that ketanserin inhibits digoxin-induced arrhythmias in guinea-pigs.

Topics: Animals; Antihypertensive Agents; Arrhythmias, Cardiac; Blood Pressure; Digoxin; Dose-Response Relationship, Drug; Electrocardiography; Enzyme Inhibitors; Female; Guinea Pigs; Heart Rate; Injections, Intravenous; Ketanserin; Male

Although it is known that amiodarone inhibits myocardial Na+-K+ pump activity, the potency and the time course of this inhibition are unknown. The aim of this study was to investigate these aspects with reference to digoxin, using guinea pigs treated with either intraperitoneal amiodarone (20mg/kg per week, up to 12 weeks, n = 26) or the same amount of vehicle as a control (n = 24). ECG recording and microelectrode experiments were conducted every 2 weeks. QT interval corrected by heart rate and action potential duration were prolonged as a function of the time of exposure to amiodarone. Hyperpolarization observed immediately after the overdrive (1.0Hz) termination or K+-replenishment following K+-depletion in the presence of 0.1mM Ba2+ was compared in the amiodarone-treated and untreated groups, as an index of the Na+-K+ pump activity. The resting membrane potential recovery from overdrive-induced depolarization was slower and the amplitude of K+-induced hyperpolarization was smaller in the amiodarone-treated group than in the untreated group. These changes were evident as the chronic amiodarone treatment progressed, although the changes in these parameters were greater in the case of acute application of 50 microM digoxin. In conclusion, this study indicates that treatment with amiodarone for longer than several weeks moderately inhibits the myocardial Na+-K+ pump.

Topics: Amiodarone; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Enzyme Inhibitors; Guinea Pigs; Heart; Heart Rate; Injections, Intraperitoneal; Membrane Potentials; Microelectrodes; Myocardial Contraction; Myocardium; Papillary Muscles; Sodium-Potassium-Exchanging ATPase

Although there is renewed enthusiasm for the use of digoxin in patients with heart failure, current dosing guidelines are based on a nomogram published in 1974. We studied the incidence of and risk factors for elevated digoxin levels in patients admitted to a community hospital, and compared their dosage regimens to published guidelines.. We reviewed the charts of all patients who had serum digoxin levels greater than 2.4 ng/mL during a 6-month period. We collected demographic and clinical data, indications for digoxin use, digoxin dosage, concurrent medications, laboratory data, and clinical and electrocardiographic features of digoxin toxicity.. Of the 1,433 patients with digoxin assays, 115 (8%) patients had elevated levels. Of the 82 patients with complete records and correctly timed digoxin levels, 59 (72%) had electrocardiographic or clinical features of digoxin toxicity. Patients with serum digoxin levels >2.4 ng/mL were slightly older (78 +/- 8 versus 73 +/- 9 years of age; P = 0.12) and had greater serum creatinine levels (3.1 +/- 7.3 versus 1.4 +/- 0.3 mg/dL; P = 0.01) than those with levels < or =2.4 ng/mL. Forty-seven patients had elevated digoxin levels on admission, including 21 patients admitted for digoxin toxicity. Impaired or worsening renal function contributed to high levels in 37 patients, and a drug interaction was a contributory factor in 10 cases. Twenty (43%) of these patients were taking the recommended maintenance dose based on the scheme employed in the Digitalis Investigation Group study. Thirty-five patients developed high digoxin levels while in hospital. In 26 patients, this followed a loading dose of digoxin for the control of rapid atrial fibrillation. Impaired renal function was implicated in all of these patients. Despite the elevated digoxin level, rate control was achieved in only 11 patients of these patients.. Elevated digoxin levels and clinical toxicity remains a common adverse drug reaction. Elderly patients, particularly those with impaired renal function and low body weights, are at the greatest risk. As published digoxin nomograms often result in toxicity, clinical variables need to be monitored. In patients with congestive heart failure and normal sinus rhythm the potential benefit of digoxin is small; thus, patients should receive a dose that minimizes the risk of toxicity. For patients with new onset atrial fibrillation, other agents may be preferable for rate control.

Topics: Age Factors; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Atrial Fibrillation; Chi-Square Distribution; Creatinine; Digoxin; Drug Interactions; Drug Monitoring; Electrocardiography; Female; Heart Failure; Hospitalization; Humans; Kidney Diseases; Male; Risk Factors

The effect of a leukotriene D4 (LTD4) receptor antagonist, L-648,051, was investigated in digoxin-induced cardiac toxicity in isolated guinea-pig hearts (Langendorff preparation). Digoxin infusion (25 microg.ml-1, 0.5 ml.min-1) increased perfusion pressure and contractile force initially, but decreased them later. The onset of first ventricular premature beats (VPBs) matched the increase phase, but the decrease phase was accompanied by ventricular tachycardia (VT) and fibrillation (VF). In the presence of L-648,051 (5 micromol. l-1), the initial phase was similar to that observed with digoxin alone, but the marked reduction was inhibited. This drug increased the concentration of digoxin required for VBSs and cardiac arrest, but it could not prevent the formation of VT and VF. The duration of VT was significantly decreased by L-648,051. It is concluded that the leukotriene receptor antagonist might have beneficial effects on digoxin-induced arrhythmias. Whether this effect depends on direct or indirect actions is uncertain.

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Guinea Pigs; Heart; Keto Acids; Leukotriene Antagonists; Male; Myocardial Contraction; Organ Culture Techniques; Sulfones

This study attempted to identify which group of cardiac patients is most at risk when dental extractions are performed under a local anesthetic with a vasopressor.. Forty cardiac patients who had dental extractions under local anesthesia were connected to a Holter monitor for 24 hours, starting an hour before the procedure. The electrocardiogram was analyzed for the number of premature beats, ST depression, and cardiac rhythm. A mean rate was calculated for the first 2 hours after injection of the local anesthetic and for the subsequent 22 hours. The preoperative electrocardiogram was compared with the electrocardiogram performed 1 week before treatment.. Electrocardiographic changes were observed in 15 patients (37.5%), and all occurred during the first 2 hours after injection of the local anesthetic. Of the 15 patients, eight were being treated with digoxin.. Cardiac patients being treated with digoxin had more electrocardiographic changes after administration of a local anesthetic than other cardiac patients. When the local anesthetic contained a vasopressor, there was a greater incidence of tachycardia but less arrhythmia or ST depression.

Topics: Adult; Aged; Aged, 80 and over; Anesthesia, Dental; Anesthetics, Local; Arrhythmias, Cardiac; Contraindications; Dental Care for Chronically Ill; Digoxin; Drug Interactions; Electrocardiography, Ambulatory; Epinephrine; Female; Heart Diseases; Humans; Lidocaine; Male; Middle Aged; Myocardial Ischemia; Tooth Extraction; Vasoconstrictor Agents

Contrary to cardiac glycoside poisoning often seen in medical practice, intentional digoxin poisoning is rather rare and its course is serious only if very high doses have been ingested. Ventricular arrhythmias and severe conduction disturbances are the most threatening sings may need the use of antiarrhythmic agents, temporally endocardial stimulation or digoxin specific antibody Fab fragments. The course and the management of digitalis poisoning is described in two young patients (female aged 37 and male aged 26). Before admission to the hospital they were healthy, without any heart problem. Only one patient (female) had short spell of nausea and vomiting as well as green vision phenomenon. This patient developed transitory non-life threatening conduction disturbances (degree and II degree a-v block). The second patient had nausea and vomiting but no serious cardiac symptoms. In both patients very high digoxin plasma levels were found (19.88 ng/ml and 9.63 ng/ml), but no one of them had serious poisoning symptoms and did not require any specific therapy. After 3 (male) and 4 (female) days both patients left the hospital.

Topics: Adult; Arrhythmias, Cardiac; Digoxin; Female; Heart Block; Humans; Male; Nausea; Poisoning; Suicide, Attempted; Vomiting

There are a lot of publications about fetal arrhythmia in singletons, but up to now there are no published data about fetal arrhythmia in multiple pregnancies. In the present study a case history of fetal and neonatal arrhythmia in one of twins from two mothers treated with betamimetic agents due to imminent preterm labor is reported and discussed. A first case with fetal bradycardia due to complete A-V block had congenital cordis abnormalities (VSD and PFO). The second case with prenatal detected extrasystoles had normal heart anatomy. Digoxin was administered to the mother, in the aim to treat fetal arrhythmia without success, because the baby had postnatal bradycardia. After hospitalisation in Cardiology Department the described cases were successfully treated. In both cases the second twins were without neonatal arrhythmia and with no structural heart abnormalities. We summarise that in situation of detection fetal arrhythmia the complexity of the problems experienced may warrant early referral to a tertiary centre where the overall management of the mother, fetus and neonate, may be undertaken.

Topics: Arrhythmias, Cardiac; Bradycardia; Cardiac Complexes, Premature; Digoxin; Diseases in Twins; Female; Fetal Diseases; Fetal Heart; Gestational Age; Heart Block; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Obstetric Labor, Premature; Pregnancy; Twins; Ultrasonography, Prenatal

A series of digitalis-like compounds, with the lactone ring shifted from the original position through a spacer or replaced by a series of guanylhydrazone substituent-bearing chains, was synthesized and evaluated for inhibition of Na+,K(+)-ATPase and for inotropic activity. The highest Na+,K(+)-ATPase inhibition (IC50) and inotropic activity (EC50) were reached with the vinylogous guanylhydrazone 5 where a cardenolide-like polarized alpha,beta-unsaturated system and a basic guanidino group were both present at the 17 beta-position; for this compound IC50 and EC50 values were comparable to or higher than those of Thomas' parent guanylhydrazone 1, digitoxigenin, and digoxin. A substantial improvement of the desired positive inotropic activity versus the toxic arrhythmogenic concentration was not reached within this series; only a slightly better therapeutic index can be envisaged for compounds 5 and 4, even though, for the latter, to the detriment of potency, presumably because of a weaker interaction with the receptor, due to the lack of a cardenolide-like polarized system.

Topics: Androstanes; Animals; Arrhythmias, Cardiac; Cardiotonic Agents; Dogs; Enzyme Inhibitors; Guinea Pigs; Hydrazones; Kidney; Molecular Structure; Myocardial Contraction; Sodium-Potassium-Exchanging ATPase; Structure-Activity Relationship

Topics: Arrhythmias, Cardiac; Cardiotonic Agents; Digoxin; Heart Failure; Hospitalization; Humans

To investigate the prevalence of and indications for digoxin use and the prevalence of beta blocker and calcium channel blocker use in older patients with previous myocardial infarction or coronary artery disease (CAD), and the prevalence of use of diuretics, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium channel blockers in older patients with hypertension in an academic hospital-based geriatrics practice.. A retrospective analysis of charts from 528 unselected older patients, seen from June 1995 through July 1996 at an academic hospital-based geriatrics practice, was performed to investigate the prevalence of digoxin use and indications for digoxin use, the prevalence of beta blocker and calcium channel blocker use in older patients with previous myocardial infarction or coronary artery disease (CAD), and the prevalence of use of diuretics, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium channel blockers in older patients with hypertension.. An academic hospital-based, primary care geriatrics practice staffed by fellows in a geriatrics training program and full-time faculty geriatricians.. A total of 416 women and 112 men, mean age 81 +/- 8 years (range 58 to 101), were included in the study.. Ninety-two of the 528 patients (17%) were taking digoxin. Recorded indications for digoxin were atrial fibrillation with or without congestive heart failure (CHF) in 39% of patients, CHF with sinus rhythm and abnormal left ventricular ejection fraction (LVEF) in 18% of patients, a clinical assessment of CHF with sinus rhythm and no recorded measurement of LVEF in 20% of patients, paroxysmal atrial fibrillation in 14% of patients, and coronary artery disease (CAD) in 9% of patients. Of 121 patients with previous myocardial infarction, 23 (19%) were prescribed beta blockers, and 54 (45%) were taking calcium channel blockers. Of 173 patients with CAD, 41 (24%) were treated with beta blockers, and 79 (46%) were taking calcium channel blockers. LVEF was not recorded in the charts of 90 of 121 patients (74%) with prior myocardial infarction and of 125 of 173 patients (72%) with CAD. Of 480 older patients with hypertension, 154 (37%) were treated with diuretics, 55 (13%) were treated with beta blockers, 160 (38%) were treated with ACE inhibitors, and 197 (47%) were treated with calcium channel blockers.. In 528 older patients seen in an academic hospital-based geriatrics practice, the prevalence of digoxin use was 19%. Appropriate indications for digoxin were documented clearly in the charts of 53 of 92 patients (57%). Calcium channel blockers were used more often than beta blockers in patients with previous myocardial infarction or CAD. Calcium channel blockers were the most frequently used antihypertensive drugs.

Topics: Academic Medical Centers; Adrenergic beta-Antagonists; Age Factors; Aged; Aged, 80 and over; Ambulatory Care Facilities; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Calcium Channel Blockers; Cardiovascular Agents; Coronary Disease; Digoxin; Diuretics; Drug Utilization; Female; Geriatrics; Heart Failure; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Retrospective Studies

Topics: Adrenergic beta-Antagonists; Arrhythmias, Cardiac; Cardiotonic Agents; Digoxin; Drug Therapy, Combination; Heart Failure; Humans

Topics: Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Female; Humans; Middle Aged

Between January 1, 1993, and April 30, 1996, authors treated 23 fetuses with severe rhythm disturbances in their Department. The correct diagnosis was made by fetal echocardiography. They had 15 tachyarrhythmic and 8 bradyarrhythmic patients. They found hydrops fetus at 7 patients because of atrial flutter (2 fetuses), supraventricular tachycardia (4 fetuses) and severe bradycardia (1 fetus). They treated successfully 13 patients with antiarrhythmic therapy given to the mother. They had 1 intrauterine death (treated because of bradycardia) and 1 neonatal death (hydropic because of supraventricular tachycardia). The causes of severe bradycardia were maternal antibody (3 fetuses), cardiac malformation (3 fetuses) and large number of blocked atrial extrasystoles. The prognosis of fetal tachycardia is good even in cases of fetal hydrops. The prognosis of bradycardia due to heart abnormalities is poor.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Echocardiography; Female; Fetal Diseases; Fetal Heart; Hemodynamics; Humans; Hydrops Fetalis; Pregnancy; Prognosis; Ultrasonography, Prenatal

1. The effects of a lipoxygenase inhibitor, BW A4C, on digoxin-induced arrhythmias and cardiac dynamics (contractile force, perfusion pressure, heart rate) were investigated in Langendorff-perfused isolated guinea-pig hearts. In the control group, arrhythmias were induced by 25 micrograms/ml digoxin at a perfusion rate of 0.5 ml/min. In the treated groups, BW A4C (1 and 0.3 microM) perfused continuously from 15 min prior to digoxin until cardiac arrest occurred. Digoxin exposure (microgram/g wet weight of heart) for the occurrence of arrhythmias and cardiac arrest were the parameters evaluated to assess cardiotoxicity. 2. Digoxin caused a marked increase in leukotriene B4 release in the coronary effluent, and was collected during tachyarrhythmias. BW A4C markedly inhibited the digoxin-induced elevation of LTB4. 3. BW A4C (1 and 0.3 microM) did not prevent the onset of ventricular fibrillation and ventricular tachycardia despite a slight delay in the occurrence of ventricular fibrillation and cardiac arrest at the 0.3 microM concentration. 4. Contractile force increased significantly after digoxin infusion which was concomitant with the time of onset of arrhythmias. In the presence of BW A4C, the contractile force increased, but not significantly. Perfusion pressure increased initially after digoxin infusion in the absence and the presence of BW A4C, but not significantly. 5. These findings show that the lipoxygenase inhibitor lacked any protective action on digoxin-induced arrhythmias despite its effective suppression of digoxin-induced elevation of LTB4 in coronary effluent.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzeneacetamides; Blood Pressure; Digoxin; Guinea Pigs; Heart; Heart Rate; Hydroxamic Acids; In Vitro Techniques; Leukotrienes; Lipoxygenase Inhibitors; Male; Myocardium; Time Factors

Topics: Adult; Antibodies, Monoclonal; Antidepressive Agents, Tricyclic; Antivenins; Arrhythmias, Cardiac; Binding Sites, Antibody; Colchicine; Digoxin; Female; Humans; Immunization, Passive; Immunoglobulin Fab Fragments; Immunotherapy; Lipopolysaccharides; Poisoning; Sepsis; Venoms

The arrhythmogenic actions of endothelin peptides were studied in isolated perfused hearts from guinea pigs and rats. Digoxin-induced ectopic ventricular complexes were partially antagonized by phosphoramidon, an endothelin-converting enzyme inhibitor. On the contrary, these rhythm disturbances were potentiated by big endothelin-1 in isolated perfused whole hearts from guinea pigs. Endothelin-1, when infused through the coronary circulation at a concentration of 10(-10) mol/l, produced an increase in coronary perfusion pressure without altering the heart rate and contractility in the isolated perfused hearts of rats. However, ventricular ectopic complexes occurred when the rise in coronary perfusion pressure reached the peak value. BQ 485, an endothelin-A receptor antagonist, at a concentration of 10(-6) mol/l, completely blocked the vasoconstrictor and arrhythmogenic effects of endothelin-1. In BQ 485-pretreated rat hearts, endothelin-1 produced a fall in coronary perfusion pressure and a slight positive inotropic response which could be blocked by NG-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor. BQ 485 at the same concentration also caused a significant reduction in the duration but not the onset of ventricular ectopic complexes in the guinea pig isolated perfused heart induced by digoxin. These results were taken as evidence of the arrhythmogenic action of endothelin peptides and their possible participation in the ventricular dysrhythmia induced by digoxin.

Topics: Animals; Arrhythmias, Cardiac; Azepines; Cardiotonic Agents; Digoxin; Electrocardiography; Endothelin Receptor Antagonists; Endothelin-1; Endothelins; Enzyme Inhibitors; Female; Guinea Pigs; Heart; Hemodynamics; In Vitro Techniques; Male; Myocardial Contraction; Myocardium; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Oligopeptides; Protein Precursors; Rats; Receptors, Endothelin

Topics: Adult; Arrhythmias, Cardiac; Digoxin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Quinidine; Verapamil

During February 1993-May 1995, the New York City Poison Control Center (NYCPCC) was informed about onset of illness in five previously healthy men after they ingested a substance marketed as a topical aphrodisiac; four of the men died. These cases were investigated by the New York City Department of Health, the New York City Department of Environmental Protection, and the Food and Drug Administration (FDA). Four cases were referred to the NYCPCC and one case to the New York City medical examiner's office. The decedents died from cardiac dysrhythmias, and all five patients had measurable levels of digoxin* detected in their serum. Digoxin had not been prescribed for therapeutic purposes for any of these patients, and none had medical conditions associated with endogenous digoxin-like immunoreactive substances. The purported aphrodisiac contains bufadienolides, naturally occurring cardioactive steroids that have digoxin-like effects. This report describes three of the five case reports, summarizes the investigations of the five cases, and underscores the health risks associated with inappropriate use of preparations containing digoxin-like substances.

Topics: Adolescent; Adult; Aphrodisiacs; Arrhythmias, Cardiac; Bufanolides; Digoxin; Fatal Outcome; Heart Arrest; Humans; Hyperkalemia; Hypotension; Male; New York City; Poisoning

Effects of platelet-activating receptor antagonists WEB 2086 (1.0-30.0 mg.kg-1 intravenously) and BN 50730 (10.0 mg.kg-1 intravenously) alone or in combination with CGS 8515 (a specific 5-lipoxygenase inhibitor, 0.3 mg.kg-1 intravenously) and Dazmegrel (a thromboxane synthase inhibitor, 1.0 mg.kg-1.hr-1 intravenous infusion) on digoxin-induced arrhythmias were investigated in anaesthetised guinea-pigs. ECG, mean arterial blood pressure, heart rate and arrhythmias were recorded, starting 30 min. before digoxin administration and continuing for 60 min. afterwards. WEB 2086 (10.0 mg.kg-1 intravenously) reduced the mortality rate and arrhythmia score significantly compared to the control values. However, in combination with CGS 8515, it did not affect the mortality rate. BN 50730 (10.0 mg.kg-1) reduced the incidence of ventricular fibrillation and also arrhythmia score. BN 50730 in combination with Dazmegrel was reduced the arrhythmia score, incidence of ventricular fibrillation and mortality rate significantly, compared to control values. Digoxin-induced acute rise in mean arterial blood pressure was not affected by any of drug treatment except WEB 2086 (10.0 mg.kg-1) in combination with CGS 8515. Heart rate values did not differ between groups. However, pressure-rate index was reduced by WEB 2086 alone or in combination with CGS 8615. Results showed that although two different platelet-activating factor antagonists have different effects on the incidence of ventricular fibrillation and mortality, they improved the digoxin-induced arrhythmias when they were used either separately or in combination with CGS 8515 or Dazmegrel by implicating that platelet-activating factor has a role on digoxin-induced arrhythmias.

Topics: Animals; Arrhythmias, Cardiac; Azepines; Digoxin; Female; Guinea Pigs; Hemodynamics; Male; Platelet Activating Factor; Platelet Aggregation Inhibitors; Thienopyridines; Triazoles

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Bufanolides; Digoxin; Fatal Outcome; Heart Arrest; Humans; Hyperkalemia; Hypotension; Male; New York City; Poisoning

Topics: Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Cardiotonic Agents; Clinical Protocols; Digoxin; Heart Failure; Humans

The mechanisms of digoxin-induced ventricular arrhythmias were studied in vivo using a novel experimental model. Anesthetized guinea pigs were instrumented with custom-made electrode catheters which enabled the monitoring and recording of right atrial, right ventricular, and His bundle electrograms, midmyocardial monophasic action potentials (MAP), and systemic arterial blood pressure. Intravenous digoxin induced ventricular arrhythmias ranging from ventricular premature contractions (VPCs) to ventricular fibrillation (VF). These were associated with delayed afterdepolarizations (DADs) observed on the MAP recordings. The severity of the arrhythmias depended on the dose of digoxin. Short bursts of ventricular pacing neither terminated nor suppressed episodes of ventricular tachycardias (VTs). A direct relationship existed between the paced ventricular cycle length and the coupling interval between the last paced beat and the first ectopic beat (r = 0.913, P < 0.001, n = 10) and between the amplitude of the DADs and the pacing rate (r = 0.972, P < 0.05, n = 7). The increased contractility (LV dp/dt) and heart rate evoked by isoproterenol (0.1 microgram/kg) did not induce DADs in the absence of digoxin. Verapamil terminated the digoxin-induced VTs in 15 of 16 animals and abolished the associated DADs in 7 of 7 animals. Adenosine terminated the VTs in 15 of 19 animals and abolished the DADs in 8 of 10 animals. Digoxin induced VT in only 1 of 6 animals treated with reserpine (5 + 5 mg/kg) 24 and 48h prior to experimentation. However, subsequent intravenous isoproterenol (0.2 micrograms/kg) induced VT and DADs, both of which were abolished by verapamil, in all 6 animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine; Analysis of Variance; Animals; Arrhythmias, Cardiac; Catecholamines; Digoxin; Disease Models, Animal; Electrocardiography; Female; Guinea Pigs; Male; Propranolol; Random Allocation; Reserpine; Ventricular Dysfunction; Verapamil

After a short introduction about the current role of digitalis in the treatment of the supraventrical arrhythmias and about the factors that make often problematic the achievement of an optimal posology of the drug, the results relative to more recent 340 digoxinaemia determinations in patients of Policlinico in Palermo or in outpatients are presented. Just the 43.8% of the patients had a digoxinaemia value in the range considered therapeutic; just 45 patients (32.1%), out of the 140 in which the digoxinaemia had been monitored for, at least, 5 days, were in the therapeutic range at the first determination; the 47.8% of the patients were underdosed and the 38.8% of them showed higher values than the therapeutic range. Determination 5 or more days later showed digoxinaemia values in the therapeutic range in 112 patients (80%). According to the reported results, it may be presumed that the posology correction effectuated by the physician on these patients might have been driven by the digoxinaemia values, whose determination must be considered an unavoidable guide to the digitalis treatment.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Dose-Response Relationship, Drug; Humans; Italy; Practice Patterns, Physicians'; Tachycardia, Supraventricular

Responses (473) were collated from a questionnaire sent to 5054 veterinarians in Australia enquiring about drug preferences for treating cardiac disease in dogs and cats. When treating a small breed dog with endocardiosis and mild left congestive heart failure, 74% of 472 respondents used a diuretic, 67% a theophylline derivative, 27% a vasodilator and 20% a positive inotrope. Frusemide was the preferred diuretic and digoxin the preferred inotrope, but vasodilator use varied. Low sodium diets were "often recommended" by 71% of respondents. Propranolol was preferred to diltiazem for treating feline hypertrophic cardiomyopathy. Digoxin was clearly preferred for treating supraventricular dysrhythmias, while lignocaine and digoxin were preferred equally for ventricular dysrhythmias. Respondents appeared more willing than US veterinarians to use theophylline derivatives and prasozin, and less inclined to employ nitrates, hydralazine, inotropes other than digoxin, and low sodium diets.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Australia; Cardiotonic Agents; Cardiovascular Agents; Cat Diseases; Cats; Digoxin; Diuretics; Dog Diseases; Dogs; Furosemide; Heart Diseases; Heart Failure; Lidocaine; Propranolol; Surveys and Questionnaires; Vasodilator Agents

Topics: Animals; Anti-Arrhythmia Agents; Anti-Bacterial Agents; Arrhythmias, Cardiac; Cardiac Output; Cardiotonic Agents; Cardiovascular Diseases; Digoxin; Drug Utilization Review; Endocarditis, Bacterial; Heart; Heart Failure; Horse Diseases; Horses

Topics: Arrhythmias, Cardiac; Digoxin; Heart Failure; Humans; Magnesium

The aim of the study was to test the hypotheses that the concentrations of endogenous digoxin-like factor (EDLF) are (i) increased in the initial period after acute myocardial infarction (AMI) and (ii) may contribute to the genesis of ventricular arrhythmias.. Consecutive sample study.. An 800-bed city teaching hospital, primary hospitalized care centre.. Fifty-four consecutive patients of both sexes with a first transmural AMI, 16 male patients with unstable angina pectoris and eight healthy subjects.. None.. Time-course of the changes of plasma concentrations of EDLF (DELFIA digoxin fluoroimmunoassay) in patients during days 1-14 after uncomplicated AMI and AMI complicated with ventricular fibrillation and congestive heart failure.. Plasma concentrations of EDLF in patients on the 1st day after AMI were increased (1.25 +/- 0.26 ng ml-1 digoxin equivalents, P < 0.025) as compared with both healthy controls (0.34 +/- 0.06 ng ml-1) and patients with unstable angina pectoris (0.40 +/- 0.08 ng ml-1). On the 1st day after AMI the plasma levels of EDLF in seven patients with primary ventricular fibrillation were higher (2.54 +/- 0.67 ng ml-1, P < 0.05) than in 47 patients without ventricular fibrillation (1.05 +/- 0.27 ng ml-1). In 14 patients with AMI and congestive heart failure (class III, Killip), plasma concentrations of EDLF were significantly lower (0.32 +/- 0.09 ng ml-1, P < 0.01) than in 40 patients with AMI without congestive heart failure (1.51 +/- 0.32 ng ml-1). Starting from the 2nd day of AMI, plasma EDLF decreased to the level of the control values (0.35 +/- 0.04 ng ml-1) and did not change during a 2-week period of observation.. The results show an increase of plasma EDLF during the 1st day after AMI, and that higher plasma EDLF may be associated with the development of ventricular arrhythmias.

Topics: Adult; Aged; Arrhythmias, Cardiac; Blood Proteins; Cardenolides; Digoxin; Female; Humans; Male; Middle Aged; Myocardial Infarction; Saponins; Sodium-Potassium-Exchanging ATPase; Time Factors

Antiarrhythmic activity of Mexicord-Poland and Mexitil-Böehringer Ingelheim (D) was compared. In three models of experimentally evoked arrhythmia in animals, in used doses, both of examined preparations in the same degree prevented the occurrence of arrhythmia.

Topics: Aconitine; Animals; Arrhythmias, Cardiac; Barium Compounds; Chlorides; Digoxin; Electrocardiography; Female; Guinea Pigs; Male; Mexiletine; Rats

Topics: Arrhythmias, Cardiac; Digoxin; Electrocardiography; Female; Humans; Middle Aged; Poisoning

The aim was to study whether a circulating sodium pump inhibitor (endogenous digoxin-like factor) contributes to the genesis of early ventricular arrhythmias in acute myocardial ischaemia in rats.. Effects of digoxin antibody (260 micrograms.kg-1) on the incidence of ventricular arrhythmias, plasma digoxin-like immunoreactivity (DELFIA immunoassay), Na+, K+, and Mg2+ ions, and activity of the ouabain sensitive Na+, K(+)-pump in different regions of myocardium have been studied in propranolol naive and propranolol pretreated rats exposed to acute coronary artery ligation. Adult male Wistar rats were divided into six experimental groups: (1) saline pretreated controls; (2) saline pretreated coronary artery ligated rats; (3) coronary artery ligated rats pretreated with 260 micrograms.kg-1 digoxin antibody; (4) propranolol pretreated controls; (5) propranolol pretreated rats with acute myocardial ischaemia; (6) rats with acute myocardial ischaemia pretreated with both propranolol and digoxin antibody.. Acute myocardial ischaemia in saline pretreated rats was associated with a twofold increase of plasma digoxin-like immunoreactivity and ventricular arrhythmias, but did not lead to changes in myocardial Na+, K(+)-pump activity. Pretreatment of coronary artery ligated rats with digoxin antibody reduced the total duration of ventricular tachycardia and ventricular fibrillation during a 15 minute postligation period from 201 (SEM 34) to 46(18) seconds (p < 0.002) but did not alter activity of the myocardial Na+, K(+)-pump. In rats pretreated with propranolol, acute myocardial ischaemia was associated with a twofold inhibition of the Na+, K(+)-pump in left atrial and left ventricular myocardium, and with a 69% increase in plasma K+ concentration. Administration of digoxin antibody to propranolol pretreated coronary artery ligated rats in parallel with the antiarrhythmic effect prevented the increase in plasma K+ concentration and inhibition of Na+, K(+)-pump in the left atrial, but not the left ventricular myocardium.. A circulating digoxin-like factor contributes to the pathogenesis of myocardial ischaemia induced ventricular arrhythmias. As propranolol pretreatment of coronary artery ligated rats inhibited the Na, K(+)-pump in myocardium, the inhibitory effect of endogenous digoxin-like factor on Na+, K(+)-ATPase was probably masked in propranolol naive animals by the stimulatory action of catecholamines on Na+, K(+)-ATPase described previously.

Topics: Acute Disease; Animals; Antibodies; Arrhythmias, Cardiac; Blood Proteins; Cardenolides; Digoxin; Male; Myocardial Ischemia; Myocardium; Rats; Rats, Wistar; Saponins; Sodium-Potassium-Exchanging ATPase

To assess the association of age and other potential risk factors with digoxin toxicity, adverse drug reactions to digoxin (ADRDIG) were studied in all patients (n = 1338) on digoxin therapy consecutively admitted to 41 clinical wards throughout Italy during 4 months in 1988. At the time of admission, 28 patients (2.1%) had evidence of ADRDIG. In multivariate logistic regression analysis, significant associations with ADRDIG were found for age > or = 80 years compared to age 65-79 years (OR = 2.75, 95% CI = 1.17-6.45), daily digoxin dosage of > or = 0.25 mg (OR = 2.51, 95% CI = 1.16-5.47), serum creatinine > or = 120 mumol/L (OR = 3.75, 95% CI = 1.69-8.32), and for treatment with amiodarone, propafenone, quinidine or verapamil (OR = 2.60, 95% CI = 1.07-6.30). Those aged < 65 years had a similar risk of digoxin toxicity as those aged 65-79 years (OR = 1.07, 95% CI = 0.28-4.12). Adverse drug reactions to digoxin were found in 1 in 50 patients hospitalized on digoxin therapy. Patients aged 65-79 years were not at increased risk for digoxin toxicity compared to younger patients, while advanced age (> or = 80 years) was an independent risk factor for this outcome.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Amiodarone; Analysis of Variance; Arrhythmias, Cardiac; Creatinine; Digoxin; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Risk Factors

The pharmacological effects of the toad venom-containing drug "kyushin" on aconitine- and thyroxine-induced arrhythmia in guinea pigs, on the conduction system in Langendorff preparations of rabbit hearts and on the autonomic nervous system in cats were studied. "kyushin" significantly inhibited the aconitine-induced arrhythmia after intraduodenal administration (i.d.) with 80 mg/kg, and the thyroxine-induced arrhythmia with 40 mg/kg i.d. Although "kyushin" itself did not affect the conduction system with 30 mg/ml of the maximal concentration being able to be prepared, bufalin and cinobufagin as constituents of toad venom produced inhibition with 0.3 mg/ml and 1 mg/ml, respectively. The decrease in heart rate induced by electrical stimulation to the parasympathetic nerve (vagus nerve) was potentiated by "kyushin" at 30 mg/kg i.d. The anti-arrhythmic effects of "kyushin" may be attributable to both possible inhibitory effect on the conduction system and potentiating effect on the parasympathetic nervous system.

Topics: Aconitine; Amphibian Venoms; Animals; Arrhythmias, Cardiac; Autonomic Nervous System; Cats; Digoxin; Electric Stimulation; Female; Guinea Pigs; Heart Conduction System; Heart Rate; In Vitro Techniques; Male; Materia Medica; Propranolol; Rabbits; Thyroxine

Topics: Algorithms; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Heart Failure; Humans

To determine whether large prescriptions (> or = 90 days' supplies) enhance the acquisition of maintenance medications by patients.. Study 1: multisite, retrospective cohort study evaluating outpatient digoxin use. Study 2: single-site, retrospective cohort study to confirm Study 1.. Study 1: Ten Veterans Affairs Medical Centers in the Rocky Mountain region. Study 2: The only facility from Study 1 (site C) that dispensed large prescriptions of maintenance medications.. Randomly selected outpatients receiving two or more digoxin prescriptions (n = 176 in Study 1, n = 114 in Study 2).. None.. The main outcome measure was the proportion of prescribed doses of maintenance medications obtained. In Study 1, patients who received at least one large digoxin prescription obtained a mean of 137.2% of their prescribed digoxin doses over a mean of nine months, compared with 91.3% for patients who received only small prescriptions of < 90 days' supplies (p = 0.02). Patients receiving large prescriptions were more likely to obtain at least 100% of their prescribed amounts of digoxin (adjusted OR = 11.4, 95% CI = 1.3-96.8, p = 0.03). At site C, patients in Study 1 obtained a mean of 129.0% of all maintenance drugs given in large supplies, compared with 95.2% of drugs prescribed only in small supplies (p = 0.006). In Study 2, acquisition of digoxin increased progressively from 89.7% among individuals who received only small digoxin prescriptions to 113.0% for those who received only large supplies (p = 0.002), over a mean of 14 months.. Large prescriptions facilitate the acquisition of maintenance medications but may lead to oversupplies, while small prescriptions impose a barrier to obtaining these drugs.

Topics: Aged; Arrhythmias, Cardiac; Cohort Studies; Digoxin; Drug Prescriptions; Female; Heart Failure; Hospitals, Veterans; Humans; Male; Middle Aged; Patient Compliance; Practice Patterns, Physicians'; Retrospective Studies; United States

Chronic co-administration of digoxin and several antiarrhythmic drugs increases digoxin plasma levels. To determine the effects of the administration of oral cibenzoline on digoxin plasma levels and its effects on clinical and electrocardiographic parameters, we conducted a prospective multicenter study in 22 cardiac patients with a mean age of 66 +/- 12 years (39-85), who were on long term digoxin therapy (0.25 mg once daily for at least 2 weeks) and who required oral cibenzoline therapy in the prevention of recurrence of symptomatic atrial tachyarrhythmias. Cibenzoline was given for 4 weeks at a dose of 130 mg twice daily in patients aged less than 70 years (group I, n = 15) and this dosage was reduced by half in patients over 70 years of age (group II, n = 7). Evaluation of the effects of this combination on clinical and electrocardiographic tolerability as well as the drawing of blood samples for assay of cibenzoline and digoxin took place before and after 4 weeks treatment with cibenzoline. The digoxin plasma levels were (mean +/- sem) 0.96 +/- 0.1 ng.ml-1 before cibenzoline administration and remained unchanged after 4 weeks of combination therapy (1.0 +/- 0.1 ng.ml-1), p > 0.05. Digoxin plasma levels in group I varied from respectively 0.8 +/- 0.1 ng.ml-1 (0.5-1.7) to 0.8 +/- 0.1 ng.ml-1 (0.4-1.5) and in group II from 1.2 +/- 0.2 ng.ml-1 (0.6-2) to 1.4 +/- 0.3 ng.ml-1 (0.7-2.5). This therapy was well tolerated in 16 patients out of 21 evaluable patients (76%) and there was no significant change in vital signs during the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Drug Therapy, Combination; Drug Tolerance; Female; Humans; Imidazoles; Male; Middle Aged

A case of toad venom-induced digitalis toxicity is presented. A pause of 13.5 s was noted in the patient taking a Chinese medication which contained toad venom. This is the first case report of clinical digitalis toxicity related to toad venom in Western society.

Topics: Aged; Aged, 80 and over; Amphibian Venoms; Arrhythmias, Cardiac; Bufanolides; Digoxin; Drugs, Chinese Herbal; Electrocardiography; Humans; Male; Sodium-Potassium-Exchanging ATPase; Syncope

The effects of the opioid receptor agonists morphine and dynorphin on digoxin-induced arrhythmias were examined in guinea pigs that had received intravenous digoxin (50 mu/kg bolus plus 500 mu/kg/hr intravenously). Animals received either morphine (50 or 100 micrograms/kg) or dynorphin A(1-13) (50 or 100 micrograms/kg) or saline (the diluent) into the lateral cerebral ventricle (intracerebroventricularly) prior to digoxin. Morphine and dynorphin produced significant (P < 0.05) dose-dependent increases in the threshold of digoxin-induced arrhythmias. The mean digoxin dose at the development of fatal arrhythmias was 775 +/- 42 micrograms/kg in the control group but was significantly higher namely 958 +/- 45 micrograms/kg after 100 micrograms/kg of morphine ICV, and 984 +/- 47 micrograms/kg after 100 micrograms/kg of dynorphin A (1-13) intracerebroventricularly. In the absence of digoxin, the highest doses of each of these opioids did not produce arrhythmias. Changes in blood pressure and heart rate were unlikely explanations for the observed actions of these opioids as morphine accentuated the increase in blood pressure that accompanied digoxin while dynorphin was associated with a lower blood pressure with digoxin, despite similar effects on arrhythmias. In the control group, fatal digoxin-induced arrhythmias were ventricular tachyarrhythmias in two-thirds of cases and complete heart block in the rest. Morphine and dynorphin reduced the development of ventricular tachyarrhythmias. The role of the cholinergic system was explored, with morphine, utilizing atropine sulfate which crosses the blood brain barrier and atropine methylnitrate which does not enter the CNS. Atropine sulfate but not atropine methylnitrate reversed the effects of morphine on digoxin-induced arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Brain; Digoxin; Dose-Response Relationship, Drug; Dynorphins; Guinea Pigs; Heart Rate; Injections, Intraventricular; Male; Morphine

Ventricular arrhythmias were analysed in 38 patients with Stages I-IIB heart failure from 24-hour Holter monitoring data obtained before and after digoxin therapy by comparing with the concentrations of catecholamines. There was a direct relationship between the plasma levels of epinephrine and norepinephrine and the severity of ventricular arrhythmias, as well as between the changes in cumulative catecholamine levels and ventricular arrhythmias during digoxin therapy. Virtually in all cases, the antiarrhythmic effect of the drug was accompanied by lower plasma catecholamine concentrations whereas the levels of norepinephrine and epinephrine remained nearly unchanged or increased with the tentatively arrhythmogenic action. The findings may suggest that hypercatecholaminemias are essential in the genesis of ventricular arrhythmias in heart failure. Cardiac glycosides can heterogeneously affect ventricular arrhythmias by modifying the activity of the sympathoadrenal system.

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Cardiomyopathy, Dilated; Coronary Disease; Digoxin; Epinephrine; Female; Heart Failure; Humans; Male; Middle Aged; Norepinephrine; Pituitary-Adrenal System; Rheumatic Heart Disease; Sympathetic Nervous System

A total of 238 patients undergoing resection of lung cancer were studied for the occurrence of postoperative arrhythmia. Transient arrhythmia was observed in 43 of them (18.1%). Ninety-one percent of 43 patients developed atrial fibrillation (Af), even though no arrhythmia was noted on ECG in any patient preoperatively. Cardiac dysrhythmia occurred 5.2 +/- 3.8 days after operation and lasted for 1.3 +/- 0.9 days (mean +/- SD). There was a significant difference (p less than 0.05) in the incidence of postoperative arrhythmia between the male group (39/188 = 21%) and the female group (4/50 = 8%), however the cause of a difference is unknown. The incidence was higher in patients undergoing pneumonectomy than in those undergoing lobectomy. Patients, who suffered from postoperative arrhythmia, has significantly low values on pulmonary function test (FEV1.0% = 68.7%) preoperatively. The increased cardiac load after the reduction of the pulmonary vascular bed was regarded as the most important factor of arrhythmia. Prophylactic administration of digoxin was performed in another 61 male patients after resection of lung cancer. And it was found to be effective in decreasing the incidence of postoperative atrial fibrillation (5/61 = 8%).

Topics: Adult; Aged; Arrhythmias, Cardiac; Carcinoma, Bronchogenic; Digoxin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Pneumonectomy

In all cases, clinical assessment of the patient is the most critical factor in determining dose and interpreting concentrations. When done accurately, laboratory assessment of drug concentrations represents only one source of information. Serum concentrations must be taken into account along with all other relevant clinical data before one can arrive at appropriate management decisions. They must not be considered in isolation and out of context. If the laboratory report is at variance with your clinical judgment, "it will often be the better part of wisdom to question (or reject) the report."

Topics: Arrhythmias, Cardiac; Digoxin; Heart Rate; Humans

Digoxin toxicity occurs most commonly among the elderly. While the clinical syndrome of digoxin toxicity is well understood, how toxic manifestations change with age is not known.. We performed secondary analysis of data from a postmarketing surveillance study of patients with life-threatening digoxin toxicity treated with digoxin antibody therapy. Patients receiving long-term maintenance digoxin therapy and aged 55 years or older were divided into four age groups: 55 to 64, 65 to 74, 75 to 84, and 85 years and older (n = 45, 167, 183, and 83, respectively) and compared with regard to presenting manifestations, digoxin dosing, serum potassium and digoxin levels, and renal function.. The prevalence of high-degree atrioventricular block showed an increasing but nonsignificant trend with age (40%, 40%, 42%, and 47%, respectively). Age-related trends in high-degree atrioventricular block were stronger among men than women and even stronger among men with underlying cardiac ischemia. The proportion of subjects with nausea/vomiting as a toxic manifestation did not consistently change with age (42%, 48%, 48%, and 46%, respectively). There were no age-related differences in degree of renal impairment or maintenance dose, but maintenance dose decreased with increasing renal impairment.. Among patients with life-threatening digoxin toxicity, there is no age-related difference in clinical presentation.

Topics: Age Factors; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Digoxin; Female; Heart Block; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Nausea; Poisoning; Prevalence; Product Surveillance, Postmarketing; Vomiting

The aim was to compare the binding characteristics of a highly purified digoxin specific antigen binding fragment (digoxin immune Fab: DIGIBIND) with digoxin and with two commonly used derivatives of digoxin, beta methyl digoxin and beta acetyl digoxin, and to assess its ability to abolish the arrhythmogenic effects of these digitalis glycosides.. The binding characteristics of DIGIBIND with digoxin, beta methyl digoxin, and beta acetyl digoxin were assessed in vitro by measuring their ability to inhibit the binding of DIGIBIND to 3H-digoxin. From these studies the affinities of the interactions between DIGIBIND and these glycosides, and the binding capacity of DIGIBIND for each of these glycosides, could be measured. The ability of DIGIBIND to abolish the arrhythmogenic effects of digoxin, beta methyl digoxin, and beta acetyl digoxin was assessed using an in vivo anaesthetised guinea pig model (n = 36, weight 300-400 g), in which these glycosides were infused intravenously (50 micrograms.kg-1 x min-1) until the onset of ventricular arrhythmias, at which point the total amount of glycoside given was calculated. A single bolus dose of either vehicle or DIGIBIND was then given intravenously, and the time to restoration of normal cardiac rhythm noted. After the administration of DIGIBIND, a second infusion of the same glycoside was given to reinitiate the ventricular arrhythmias. The time to onset of the arrhythmias was noted, and the additional amount of glycoside given calculated.. In vitro studies showed the binding of DIGIBIND to 3H-digoxin to be inhibited by digoxin and by the two derivatives. The affinities of these interactions with DIGIBIND were significantly different, that for digoxin being some twofold greater than that for beta methyl digoxin and beta acetyl digoxin. The ED50 concentrations were 14.1 (95% CI 12.2, 15.2), 29.2(26.1, 32.7), and 36.2(33.0, 39.8) nM, respectively. However, there were no significant differences between these glycosides in their binding capacities. The in vivo studies showed that intravenous infusion of digoxin, beta methyl digoxin, or beta acetyl digoxin induced similar ventricular arrhythmias. The onset of the arrhythmias was clearly discernible, and required a significantly lower dose of digoxin compared with that of beta methyl digoxin and beta acetyl digoxin. These doses were 667(SEM 55), 868(33), and 854(40) nmol.kg-1, respectively. Termination of the infusion had no effect on the arrhythmias, and in those animals which received a bolus intravenous injection of saline there was no return to normal cardiac rhythm. By contrast, in animals which received a bolus intravenous injection of DIGIBIND, there was complete abolition of the arrhythmias within 4-6 min. Although the dose of DIGIBIND given to abolish digoxin induced arrhythmias was approximately 25% less than that given to abolish beta methyl digoxin and beta acetyl digoxin induced arrhythmias (p < 0.05), the time to restoration of normal cardiac rhythm after DIGIBIND was not significantly different for digoxin compared with beta methyl digoxin and beta acetyl digoxin, at 4.6(0.9), 4.9(0.8), and 5.7(0.8) min, respectively. To reinitiate the arrhythmias in those animals which had received DIGIBIND, a dose of glycoside was required which was not significantly different from that given prior to the DIGIBIND. This observation therefore confirmed the stoichiometric relationship between DIGIBIND and each of the glycosides in respect of the neutralising action of DIGIBIND in abolishing the arrhythmogenic effects of these agents.. Although there is some small difference in the affinities of the binding interactions, there is no difference in the binding capacities of DIGIBIND for digoxin, beta methyl digoxin, or beta acetyl digoxin in vitro. These binding interactions are manifest as the ability of DIGIBIND to abolish the arrhythmogenic effects of digoxin and the two derivatives in vivo.

Topics: Acetyldigoxins; Animals; Antigen-Antibody Reactions; Arrhythmias, Cardiac; Digoxin; Guinea Pigs; Immunoglobulin Fab Fragments; Male; Medigoxin

The cardiotonic and arrhythmogenic effects, and the excitatory effect on respiration of "Kyushin," a drug containing toad venom, were studied in comparison with those of digoxin. In anesthetized rabbits, the maximum rate of rise of left ventricular systolic pressure (max dP/dt) was measured as an index of cardiotonic effect, and the respiratory flow was measured as an index of respiratory function. Intraduodenal (i.d.) administration of 80 mg/kg "Kyushin" produced a cardiotonic effect and an excitatory effect on respiration, but i.d. administration of 16 mg/kg digoxin produced only a cardiotonic effect, and conversely inhibited respiration. In anesthetized open-chest guinea pigs, myocardial contractile force was measured as an index of cardiotonic effect and the arrhythmogenic effect was evaluated from the appearance of arrhythmic myocardial contraction. By i.d. administration of a 20% ethanol suspension or solution, "Kyushin" and digoxin showed a cardiotonic activity with doses higher than 40 mg/kg and 0.25 mg/kg, respectively. The arrhythmogenic doses of "Kyushin" and digoxin by i.d. administration were 2560 mg/kg and 2 mg/kg, respectively, suggesting that the safety margin of "Kyushin" is broader than that of digoxin.

Topics: Amphibian Venoms; Animals; Arrhythmias, Cardiac; Bufanolides; Digoxin; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Electrocardiography; Guinea Pigs; Heart; Hemodynamics; Infusions, Intravenous; Panax; Plants, Medicinal; Rabbits; Respiration

The study was undertaken to examine 84 patients mainly with coronary heart disease and various cardiac arrhythmias. Quinidine monotherapy was found to normalize heart rate depending on its baseline values: it reduced heart rate in tachycardias and increased it in bradycardia. In patients with severe myocardial damage, especially in hypertension, quinidine decreased cardiac index, whereas total peripheral resistance increased. With quinidine, systolic pressure, stroke and cardiac indices showed a more decrease, whereas diastolic pressure and total peripheral resistance displayed a more increase in the standing position. Supplement of digoxin corrected negative quinidine-induced hemodynamic changes and orthostatic failures.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Drug Evaluation; Drug Therapy, Combination; Female; Hemodynamics; Humans; Male; Middle Aged; Quinidine; Time Factors

Digoxin is frequently prescribed for patients. With a narrow therapeutic window, toxicity can quickly occur. Nurses must quickly recognize dysrhythmias associated with digoxin toxicity to prevent life-threatening situations.

Topics: Arrhythmias, Cardiac; Digoxin; Electrocardiography; Humans

Suggesting endogenous digoxin-like factor (EDLF) to display arrhythmogenic activities in myocardial ischemia (MI), we studied the effect of anti-digoxin antiserum (ADS) on the ventricular fibrillation threshold (VFT) after the coronary ligation in cats and ventricular arrhythmias caused by MI in rats and chloroform-induced hypoxia in mice. Intravenous administration of ADS (5 mg/kg) enhanced VFT in cats with MI from 11.3 +/- 1.6 to 53.3 +/- 8.1 V (M +/- m; p less than 0.01) and significantly reduced ventricular arrhythmias in rats and mice. Our experiments on the isolated electro-stimulated rat atria demonstrated that EDLF is likely not to be an adrenergic cotransmitter in the heart. Possible mechanisms of the arrhythmogenic action of EDLF are discussed.

Topics: Animals; Antibodies; Arrhythmias, Cardiac; Blood Proteins; Cardenolides; Cats; Digoxin; Heart Ventricles; Immune Sera; Male; Mice; Myocardial Infarction; Rabbits; Rats; Rats, Inbred Strains; Saponins; Sodium-Potassium-Exchanging ATPase; Ventricular Fibrillation

The relationship between levels of potassium in the serum and the development of malignant arrhythmias was examined in a retrospective study involving 1011 patients presenting with acute myocardial infarction. Thirteen percent of the overall patients studied had significant hypokalemia (k less than 3.5 mmol/liter). The average initial level of potassium in patients who developed malignant arrhythmias was (4.10 mmol/liter) significantly lower (P less than 0.01) than those patients who did not develop such arrhythmias (4.19 mmol/liter). To determine whether the level of potassium was, in itself, the primary cause of malignant arrhythmias following myocardial infarction, a subgroup analysis of factors influencing these levels was performed. It was determined that diabetics have a higher level of potassium than nondiabetics (4.2 mmol/liter versus 4.11 mmol/liter - P = 0.01) and a lower incidence of malignant arrhythmias (50.5% versus 63.5% - P = 0.002). No correlation was found between treatment with either digitalis or diuretics and malignant arrhythmias. Size and location of infarcted areas was found to have a direct relationship with development of arrhythmias. Size and location of infarctions, however, were not found to be related to levels of potassium in the serum. Our findings support and clarify earlier suggestions establishing the levels of potassium in the serum as an important causative factor, together with size and location of infarctions, in the development of malignant arrhythmias.

Topics: Adrenergic beta-Antagonists; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Diabetes Mellitus; Digoxin; Diuretics; Female; Heart Block; Homeostasis; Humans; Hyperkalemia; Hypokalemia; Male; Middle Aged; Myocardial Infarction; Potassium; Retrospective Studies; Tachycardia; Ventricular Fibrillation

Each year many people have digitalis toxicity severe enough to require extensive hospital treatment. Digoxin immune Fab[ovine]-Fab fragments (Digibind) have been shown to reverse digitalis toxicity and substantially reduce the risk of death. Data were used from uncontrolled studies of patients treated with Fab fragments as well as clinical, medical care and pharmacokinetic data from symptomatically treated patients to derive estimates of the difference in clinical outcomes and medical care costs when treating with this new drug. Estimates are derived separately for treatment of patients with toxicity that is immediately life-threatening and patients whose manifestations are not immediately life-threatening. Treatment with Fab fragments reduces the probability of dying more for the seriously toxic than for the less seriously toxic patient. Such treatment is generally associated with an increase in total medical care costs for the seriously toxic patients because more of them survive the toxic episode and require additional medical care before discharge from the hospital. For these patients, the estimated cost per life-year saved is between $1,900 and $5,400. When Fab fragments are used to treat less seriously toxic patients, total medical care costs decrease because of an estimated decreased number of days in the coronary care unit and decreased use of pacemakers and other aggressive treatments.

Topics: Accidents; Adult; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Cause of Death; Child, Preschool; Cost-Benefit Analysis; Costs and Cost Analysis; Digoxin; Electric Countershock; Heart Massage; Humans; Immunoglobulin Fab Fragments; Length of Stay; Life Expectancy; Poisoning; Probability; Suicide, Attempted; Survival Rate; Treatment Outcome

Disturbances in colour vision are a well-reported adverse ocular effect to toxic levels of digoxin. We present a case history of a patient with both colour vision changes and transient visual field defects to therapeutic serum levels of digoxin.

Topics: Adult; Arrhythmias, Cardiac; Color Vision Defects; Digoxin; Female; Humans; Visual Fields

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Female; Humans; Immunoglobulin Fab Fragments

Topics: Animals; Arrhythmias, Cardiac; Bone and Bones; Child; Digoxin; Dogs; Humans; Immunoglobulin Fab Fragments; Swine

Digoxin excess can produce characteristic bradyarrhythmias, tachyarrhythmias, and hyperkalemia. The bradyarrhythmias, which consist of disturbances in conduction and block at the level of the atrioventricular and sinus nodes, are mediated by a direct and vagotonic effect. The vagotonic effect of excess digoxin may also result in a marked slowing of the sinus rate in the setting of severe toxicity. Digoxin increases automatic and triggered electrical activity in atrial muscle, His-Purkinje system, and ventricular muscle, which predisposes to tachycardias. Many of the tachyarrhythmias are relatively specific for the toxic effects of digoxin. Atrial tachycardias with variable atrioventricular block, accelerated junctional rhythms (especially in the setting of atrial fibrillation), and fascicular tachycardias are characteristic digoxin toxic rhythms. Digoxin-specific antibody fragments should be considered the treatment of choice for any digoxin toxic arrhythmia associated with hemodynamic compromise or the threat of hemodynamic compromise. Hyperkalemia, when due to acute severe digoxin toxicity, is also an appropriate indication for digoxin-specific Fab fragment therapy. When assessing the risk:benefit ratio for using digoxin-specific Fab fragment therapy, one needs to determine, in addition to the electrocardiographic manifestations and patient's hemodynamic status (1) the severity of toxicity, as indexed by the amount ingested and/or the serum digoxin concentration; (2) the expected time course for reversal of toxicity, which is usually determined by the status of renal function; (3) the need for digoxin to provide ventricular rate control or improved ventricular contractility and therapeutic alternatives to digoxin; (4) the presence of a strong allergy history; (5) the presence of such factors as increased age and severity of heart disease that may predispose to digoxin toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arrhythmias, Cardiac; Causality; Clinical Protocols; Digoxin; Electrocardiography; Hemodynamics; Humans; Hyperkalemia; Immunoglobulin Fab Fragments; Poisoning

It is clear that Digibind needs to be administered on an emergent basis for acute digoxin ingestion and digoxin-induced lethal arrhythmias with or without hyperkalemia. This medication should be available in adequate amounts in all acute care Rhode Island hospitals.

Topics: Adult; Arrhythmias, Cardiac; Child; Digoxin; Dose-Response Relationship, Drug; Humans; Immunoglobulin Fab Fragments

1. The antiarrhythmic effect of L-propionylcarnitine (L-PC) was evaluated in the guinea-pig isolated heart; arrhythmias were induced with hypoxia followed by reoxygenation and by digitalis intoxication. 2. L-PC 1 microM, was found to be the minimal but effective antiarrhythmic concentration against reoxygenation-induced ventricular fibrillation. No antiarrhythmic effect was observed against digitalis-induced arrhythmias. D-Propionylcarnitine, L-carnitine and propionic acid did not exert antiarrhythmic effects. 3. During hypoxia and reoxygenation L-PC consistently prevented the rise of the diastolic left ventricular pressure, and significantly reduced the release of the cardiac enzymes creatine kinase (CK) and lactic dehydrogenase (LDH). 4. The electrophysiological effects of L-PC were then studied on either normal sheep cardiac Purkinje fibres or those manifesting oscillatory after potentials induced by barium or strophanthidin. 5. L-PC (1 and 10 microM) did not significantly modify action potential characteristics and contractility of normal Purkinje fibres, or the amplitude of OAP induced by strophanthidin or barium. 6. It is concluded that the antiarrhythmic action of L-PC on reoxygenation-induced arrhythmias is not correlated with its direct electrophysiological effects studied on normoxic preparations.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Barium; Carnitine; Coronary Circulation; Creatine Kinase; Digoxin; Electrocardiography; Electrophysiology; Guinea Pigs; In Vitro Techniques; L-Lactate Dehydrogenase; Membrane Potentials; Perfusion; Purkinje Fibers; Sheep; Strophanthidin

Four immunochemical methods for digoxin assay were used to analyse control samples, 33 amniotic fluid samples, 57 samples from digitalis-treated, non-pregnant women, 90 pregnancy serum samples, and 72 samples of fetal or neonatal serum with or without digoxin therapy. One hundred and five samples were also submitted to ultrafiltration before analysis. Three methods (RIA, TDX, AMERLITE) showed practically the same precision, while the precision of the DELFIA was markedly inferior. In the analysis of serum samples from digoxin-treated, non-pregnant women, RIA and TDX gave practically the same values, whereas AMERLITE and DELFIA gave significantly higher values. Pregnancy serum and fetal serum contain "digoxin-like immunoreactive factors", and the qualitative and quantitative effects of these interfering factors are different for each of the four methods. The greatest sensitivity to "digoxin-like immunoreactive factors" is shown by TDX and DELFIA, while the lowest interference by "digoxin-like immunoreactive factors" is found in the analysis of ultrafiltered samples, using the TDX method. The composition of the "digoxin-like immunoreactive factors" in pregnancy serum and in fetal serum is altered by digoxin therapy, and these changes have different effects on the various analytical methods. The concentration of "digoxin-like immunoreactive factors" in the serum of fetuses receiving digoxin is markedly lower than that of healthy fetuses. For the reliable monitoring of digoxin therapy in the maternal and fetal circulation, the blood samples must be submitted to ultrafiltration before analysis.

Topics: Amniotic Fluid; Arrhythmias, Cardiac; Blood Proteins; Cardenolides; Digoxin; Evaluation Studies as Topic; Female; Fetal Blood; Fetal Diseases; Humans; Immunoassay; Infant, Newborn; Pregnancy; Pregnancy Complications, Cardiovascular; Saponins

Anti-arrhytmic activity of cordarone was studied in 68 patients with circulatory failure (CF) and heart rhythm disorders with the aid of the 48-hour monitoring of the ECG. Cordarone was administered after the maintenance therapy with digoxin (the mean concentration of digoxin in the plasma 1.38 +/- 0.09 ng/ml) at an average dose of 300 mg/day. Cordarone suppressed supraventricular premature heart beat by 80.2%, ventricular premature heart beat (VPHB) by 76.4%, group VPHB by 82.9% and runnings of ventricular tachycardia by 86.6%. Antiarrhythmic activity of cordarone was more remarkable at the early stages of CF. The concentration of digoxin in the plasma did not exceed the mean therapeutic one. Therefore, cordarone possesses a high antiarrhythmic activity, with its efficacy being significantly higher in patients with moderately pronounced CF. At the same time cordarone influences to a less measure the quality of ventricular rhythm disorders in patients with severe CF and apparently does not avert the cases of sudden death in such patients.

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Digoxin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Shock

Topics: Adrenergic beta-Antagonists; Arrhythmias, Cardiac; Digoxin; Female; Follow-Up Studies; Heart Rate; Humans; Hungary; Incidence; Infant, Newborn; Infant, Premature, Diseases; Male; Prognosis; Risk Factors

A study was made of the effect of ethacizine administered in a single dose and continuously on myocardial contractility and hemodynamics in 78 patients with coronary heart disease, neurocirculatory dystonia and myocardiodystrophy suffering from impaired cardiac rhythm. In 28 patients, ethacizine was administered in combination with glutamic acid and in 23 with digoxin. In patients with coronary heart disease, particularly in those with heart failure, ethacizine produced a negative inotropic effect. Introduction into the treatment of digoxin or glutamic acid smoothed over the cardiodepressive action of the drug. When administered continuously in a dose of 150-300 mg/day, ethacizine is an effective antiarrhythmic drug.

Topics: Adult; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Drug Evaluation; Drug Therapy, Combination; Female; Glutamates; Glutamic Acid; Hemodynamics; Humans; Male; Middle Aged; Myocardial Contraction; Phenothiazines

Topics: Arrhythmias, Cardiac; Atrioventricular Node; Digoxin; Electrocardiography; Humans; Male; Middle Aged; Verapamil

Topics: Animals; Arrhythmias, Cardiac; Calcium Channels; Cardiotonic Agents; Digoxin; Guinea Pigs; Heart; Myocardium; Potassium Channels

Digoxin intoxication has been reported to be a common adverse drug reaction with an in-hospital incidence of 6% to 23% and an associated mortality rate as high as 41%. A retrospective review was conducted to assess the accuracy of diagnosis, the morbidity and mortality of digoxin intoxication, and its incidence in hospitalized patients with heart failure. We reviewed the medical records of 219 patients discharged with the diagnosis of digoxin intoxication between 1980 and 1988. Patients were classified as follows: (1) Definite intoxication--patients with symptoms and/or arrhythmias suggestive of digoxin intoxication that resolved after discontinuation of digoxin; (2) possible intoxication--patients with symptoms and/or arrhythmias suggestive of digoxin intoxication in the absence of documented resolution after discontinuation of digoxin, or the presence of other clinical illnesses that could possibly account for those findings; (3) no intoxication--patients whose symptoms or ECG abnormalities were clearly explained by other associated clinical illnesses and persisted after withdrawal of digoxin. We identified only 43 patients (20%) with definite intoxication. The majority of patients discharged with the diagnosis of digoxin intoxication (133 or 60%) were classified as possibly digoxin intoxicated, and 43 patients (20%) had no clinical evidence to support this diagnosis. To estimate the incidence of digoxin intoxication, we also reviewed the medical records of 994 patients admitted in 1987 with heart failure. Of these, 563 were receiving digoxin and in 27 the diagnosis of digoxin intoxication was made by their clinicians. Our review showed that only four were definitely intoxicated (0.8%), and the diagnosis could not be excluded in another 16 (4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Digoxin; Female; Hospitals, Urban; Humans; Male; Michigan; Poisoning; Retrospective Studies

A study was undertaken to examine 55 (27 females and 28 males) patients aged 25 to 74 years who had ventricular arrhythmias. Twenty five patients were diagnosed as having mitral valvular disease concurrent with predominant stenosis, 30 presented with prevalent mitral dysfunction. Twenty eight patients showed Stages I to IIA circulatory failure, and 27 had Stages IIB to III heart failure. All the patients displayed perpetual ciliary arrhythmia of various duration. More frequent and severe ventricular arrhythmias were recorded in mitral valvular disease patients with predominant mitral dysfunction than in those with stenoses. When the plasma digoxin concentration was less than 1.1 ng/ml in patients with a low end-diastolic volume and initial signs of circulatory failure, the agent produced an antiarrhythmic effects on ventricular arrhythmias in many cases, in mitral valvular disease patients with predominant stenosis in particular. The arrhythmogenic effect of digoxin was found in 47.6% patients with prevalent mitral dysfunction concurrent with Stages IIB-III circulatory failure. The agent may show arrhythmogenic action in mitral valvular disease patients with prevalent mitral dysfunction who had larger cardiac volumes and plasma digoxin concentrations of no more than 1.6 ng/ml in the absence of clinical signs of digitalis intoxication.

Topics: Adult; Aged; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Female; Heart Ventricles; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Mitral Valve Stenosis

Topics: Adolescent; Arrhythmias, Cardiac; Child; Child, Preschool; Creatinine; Digoxin; Drug Interactions; Drug Therapy, Combination; Heart Defects, Congenital; Humans; Infant; Propafenone

The authors submit a report on the effect of quinidine on plasma digoxin. The investigation was made in 20 patients wit supraventricular dysrhythmia. After initial digoxin treatment they proceeded with quinidine six hours after the last digoxin dose. Although they did not administer digoxin, the digoxin level increased during quinidine treatment in the course of 12 hours from 2.4 +/- 1.6 ng/ml to 3.8 +/- 12.4 ng/ml. The authors draw attention to the importance of following up digoxin levels in the mentioned drug combination which is supposed to prevent serious complication caused by possible digoxin intoxication.

Topics: Arrhythmias, Cardiac; Digoxin; Drug Interactions; Female; Humans; Male; Middle Aged; Quinidine

To investigate the mechanism of pressure related ventricular arrhythmias by examining them during atrioventricular (AV) block.. Complete AV block, where all ventricular beats are ectopic, was induced by AV node ablation and/or by toxic digitalisation, and rhythm changes were studied while arterial blood pressure was repeatedly raised and lowered.. 15 anaesthetised mongrel dogs, weight 15-28 kg, were used. AV block was induced in eight by chemical or mechanical ablation of the AV node. In five of these and in seven other dogs, 5.0-7.5 mg digoxin was also given.. Following AV block due to ablation, a heart rate increase (or no change) was found in 87.5% of 56 arterial pressure increases produced by elevation of an open arterial blood reservoir or by metaraminol infusion, but in only 21.8% of 55 pressure decreases caused by arterial bleeding (p much less than 0.001). Following AV block due to digitalisation, the equivalent figures were 96% of 50 pressure increases and 27.3% of 55 pressure decreases (p much less than 0.001). While arterial pressure was increased there was moderate acceleration of the escape rhythm, then appearance of premature ventricular beats, then non-sustained and finally sustained ventricular tachycardia. The reverse occurred, with some hysteresis, on decreasing the arterial pressure. In five of the digitalised animals, arterial pressure reduction to nearly zero caused reproducible sudden arrest, with resumption of the ordinary escape rhythm on increasing the pressure again.. The findings suggest the possibility of two kinds of ectopic rhythm in AV block: the "normal" escape rhythm which is only moderately affected by arterial pressure changes; and an "abnormal" faster pressure dependent rhythm which is generated by high arterial pressure and abolished by pressure near zero, as if there were a mechano-electrical association. This abnormal rhythm may prevail completely in digitalis toxicity so that if cardiac arrest occurs, no automaticity can be expected to appear unless arterial pressure is raised.

Topics: Animals; Arrhythmias, Cardiac; Atrioventricular Node; Blood Pressure; Digoxin; Dogs; Electrocardiography; Formaldehyde; Heart Block; Heart Rate; Heart Ventricles; Mechanoreceptors; Tachycardia; Ventricular Fibrillation

Topics: Arrhythmias, Cardiac; Digoxin; Heart Conduction System; Heart Failure; Humans; Injections, Intravenous

The efficacy of magnesium therapy in patients with ventricular tachycardia has previously been reported. Recently completed and ongoing studies validate earlier observations that potassium and magnesium supplementation may control other cardiac arrhythmias, particularly in hypomagnesemic patients. Magnesium treatment is a viable therapeutic option when other antiarrhythmic agents fail to suppress ventricular tachycardia, ventricular fibrillation, multifocal atrial tachycardia, atrial fibrillation and supraventricular tachycardia.

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Female; Humans; Magnesium; Magnesium Deficiency; Male; Middle Aged; Tachycardia

Topics: Adult; Age Factors; Arrhythmias, Cardiac; Biological Availability; Digoxin; Dosage Forms; Drug Interactions; Eating; Female; Humans; Infant, Newborn; Kidney Diseases; Male; Obesity; Pregnancy; Radioimmunoassay; Specimen Handling

Two-stage coronary ligation-, digitalis-, and epinephrine (EPI)-induced ventricular arrhythmias were used to establish minimum effective plasma concentrations of ME3202 in dogs. 2-(2-Diisopropylaminoethyl)-4-methyl-2-(2-pyridyl) pentanamide (ME3202) showed antiarrhythmic effects against arrhythmias in all models. The minimum effective plasma concentrations for arrhythmias induced by 24-h coronary ligation, 48-h coronary ligation, digitalis, and EPI were 4.8 +/- 1.0 [after 5 mg/kg intravenously (i.v.)], 5.3 +/- 1.3 (after 5 mg/kg i.v.), 4.1 +/- 1.1 (after 4 mg/kg i.v.), and 2.5 +/- 0.8 (after 5 mg/kg i.v.) micrograms/ml, respectively (mean +/- SD, n = 6 or 7). The minimum effective concentration for EPI-induced arrhythmias was significantly lower than those for the other types of arrhythmias. This profile is similar to those of propafenone and nicainoprol, and since ME3202 had no deleterious effects on blood pressure (BP) or sinus node rate, it is expected to be clinically useful.

Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Vessels; Digoxin; Dogs; Epinephrine; Female; Male; Propylamines; Pyridines; Sodium Channels; Time Factors

Drug efficacy and pharmacokinetics were assessed in 63 patients, aged 5 days to 30 years (mean 8 years), who received flecainide acetate for control of resistant arrhythmias. Doses of flecainide ranged from 59 to 225 mg/m2 body surface area per day (mean 141) in divided doses every 8 to 12 h and serum trough levels ranged from 0.10 to 0.99 micrograms/ml (mean 0.36). Flecainide controlled or partially controlled arrhythmia in 53 (84%) of the 63 patients: 7 of 7 patients who had the permanent form of junctional reciprocating tachycardia, 12 of 13 who had an atrial ectopic tachycardia, 10 of 10 who had ventricular tachycardia and 18 of 25 patients who had reentrant supraventricular tachycardia. Five of seven patients who had the latter arrhythmia were unsuccessfully treated with flecainide. They had Wolff-Parkinson-White syndrome and developed asymptomatic, incessant, slower orthodromic reciprocating tachycardia while receiving the drug. Transient blurred vision was reported in three patients and two patients had transient hyperactivity. No significant hemodynamic side effects were seen in any patient. Twenty-five patients underwent oral pharmacokinetic investigation. Young infants (less than 1 year of age) had a mean plasma elimination half-life (t 1/2) approximating that (11 to 12 h) found in older children and healthy adults; children aged 1 to 12 years had a shorter mean t 1/2 of 8 h. Dosing schedules based on milligrams per square meter body surface area correlated better with plasma flecainide levels than did dosing based on milligrams per kilogram body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adolescent; Adult; Arrhythmias, Cardiac; Child; Child, Preschool; Digoxin; Echocardiography; Electrocardiography; Flecainide; Follow-Up Studies; Half-Life; Humans; Infant; Tachycardia; Wolff-Parkinson-White Syndrome

A prospective study to correlate clinical digoxin toxicity with serum digoxin levels was carried out in 67 patients of whom 24 were clinically toxic and 43 were asymptomatic. The patients were clinically diagnosed to be toxic based on typical cardiac arrhythmias (n = 11) or non-cardiac symptoms (n = 13). Blood samples were collected at least six hours after the last digoxin dose and the sera assayed for digoxin using a radioimmunoassay method. The mean serum digoxin level in the toxic group (x1 = 2.09 +/- 1.28 ng/ml) was significantly higher than in the non-toxic group (x2 = 1.20 +/- 0.75 ng/ml), p less than 0.01. All the non-toxic patients had serum digoxin levels below 3 ng/ml. However, there was a considerable overlap of serum digoxin levels between the two groups of patients. Serum level cannot be the sole criterion in diagnosing digoxin toxicity. Nevertheless, raised serum digoxin levels especially above 3 ng/ml, in the presence of suggestive clinical features is strongly suggestive of toxicity.

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Cardiovascular Diseases; Digestive System; Digoxin; Female; Humans; Male; Middle Aged

This study examined effects of extracellular magnesium (Mg++0) on the positive inotropic and toxic actions of cardiotonic steroids in cardiac muscle isolated from guinea pig heart. Increasing concentrations of Mg++0 produced a negative inotropic effect in electrically paced, left atrial muscle and decreased the sensitivity to arrhythmogenic actions of digoxin without affecting the maximum developed tension observed before dysrhythmic activity. Other signs of toxicity such as contracture were less sensitive to the antagonistic effects of Mg++0. Estimates of fractional occupancy suggested that the increased tolerance to digoxin-induced arrhythmias was mediated by an altered responsiveness to given levels of receptor binding. Experiments in partially purified membrane preparations demonstrated that elevations in Mg++ increased affinity for [3H]ouabain without affecting binding site density. Na+,K+-adenosine triphosphatase activity in these membrane preparations was also enhanced by Mg++; however, increases in buffer Mg++ concentration had no effect on the Na+-pump in intact tissue. In summary, these results indicate that elevations in Mg++0 act directly on myocardium to diminish the sensitivity to cardiotonic steroid-induced arrhythmias. Furthermore, data suggest that this antagonistic action of Mg++0 is not mediated by alterations in receptor binding or Na+-pump reserve capacity.

Topics: Animals; Arrhythmias, Cardiac; Ca(2+) Mg(2+)-ATPase; Cardiac Glycosides; Digoxin; Guinea Pigs; Heart; In Vitro Techniques; Magnesium; Male; Myocardial Contraction; Ouabain; Rubidium; Sodium

Delayed afterdepolarizations occur under conditions in which there are large increase in the intracellular Ca and may be considered as one of the important mechanisms for digitalis-induced arrhythmias. Intraplatelet free calcium (Ca2i+) was measured in 25 patients, using the fluorescent indicator Quin-2. The patients included 15 with glycosides treatment (Group A) and 10 with arrhythmias indicating the presence of digitalis intoxication (Group B). The average Ca2i+ level in Group A was higher than the normal value but did not reach a statistical significance (170.8 +/- 9.09 vs 161.6 +/- 30.2, NS). The Ca2i+ level during digitalis toxicity in Group B was significantly higher than that in Group A (201.7 +/- 17.65 vs 170.18 +/- 91.09, P less than 0.01) as well as the normal value (P less than 0.01). With the disappearance of digitalis toxicity the Ca2i+ level was significantly decreased from 201.7 +/- 17.65 to 171.4 +/- 14.08 (P less than 0.001). Following the elimination of digitalis toxicity the increased digoxin concentration also declined. However, the decline of digoxin concentration did not correlate well with the decline of Ca2i+ (r = -0.57, P greater than 0.05). There is a close association between digitalis-induced arrhythmias and the change of Ca2i+ level, compatible with the tentative mechanism of delayed after depolarization (triggered activity). The poor correlation between the Ca2i+ level and digoxin concentration during the process of digitalis toxicity may suggest the presence of factors other than glycosides concentration to cause increased Cai2+ and arrhythmias.

Topics: Adult; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Blood Platelets; Calcium; Calcium Channels; Digoxin; Female; Humans; Male; Middle Aged; Myocardium

The purpose of this study was to investigate the effect of inhibition of endogenous opioid degradation on digitalis-induced arrhythmias, utilizing the inhibitors bacitracin, bestatin, captopril, and D-phenylalanine. Guinea pigs, anesthetized with pentobarbital, 50 mg/kg i.p., and breathing spontaneously received intracerebroventricular (i.c.v.) injection of bacitracin (6.8 mg/kg), bestatin (1 mg/kg), captopril (2 mg/kg), D-phenylalanine (1.2 mg/kg) or the diluent, saline. Digitalis arrhythmias were induced by a 50 micrograms/kg i.v. bolus of digoxin followed by 500 micrograms.kg-1.h-1 i.v. Bacitracin and bestatin, but not captopril or D-phenylalanine, significantly (p less than 0.05) altered the relationship between the digoxin dose and the first occurrence of arrhythmias, i.e., digoxin-induced ventricular arrhythmias became manifest at lower digoxin doses. The mean digoxin dose and ED50s, at which arrhythmias first occurred, were significantly (p less than 0.05) reduced by bacitracin and bestatin. The findings were similar for fatal arrhythmias, although D-phenylalanine appeared to decrease the digoxin dose at the development of fatal arrhythmias. The opioid antagonist naloxone, in a 50 micrograms/kg bolus and 50 micrograms.kg-1.h-1 i.c.v., completely prevented these effects of bacitracin and reduced the effect of bestatin. The relationship to arrhythmias could not be ascribed to an effect on blood pressure, as the blood pressure response to digoxin was the same in bestatin, D-phenylalanine, and control groups. To examine whether systemic administration of an inhibitor of opioid degradation had similar effects, a second protocol was selected with systemic administration of bacitracin because it altered the dose effect relationship after i.c.v. administration and systemic concentrations could be readily attained. Bacitracin, in a 13.5 mg/kg i.v. bolus and 135 mg.kg-1.h-1 i.v., was followed by 100 micrograms/kg digoxin i.v. every 15 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aminopeptidases; Animals; Arrhythmias, Cardiac; Bacitracin; Blood Pressure; Captopril; Digoxin; Dose-Response Relationship, Drug; Guinea Pigs; Injections, Intravenous; Leucine; Male

Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Atrial Fibrillation; Diagnosis, Differential; Digoxin; Female; Humans

Atrial fibrillation due to hyperthyroidism is characterized by a rapid ventricular response which is typically resistant to digoxin therapy. We report a patient with atrial flutter-fibrillation who developed cyclic sinus node dysfunction with profound ventricular pauses in response to small doses of digoxin, verapamil, and propranolol, which resolved with discontinuation of the medications. Caution is necessary to avoid paradoxical ventricular slowing when treating hyperthyroid-induced atrial fibrillation.

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digoxin; Female; Humans; Hyperthyroidism; Middle Aged; Propranolol; Verapamil

Recently, this laboratory has demonstrated an enhanced susceptibility toward the development of lethal ventricular arrhythmias occurring in response to acute posterolateral ischemia in dogs with previous anterior myocardial infarction in the presence of therapeutic serum concentrations of digoxin. In the present study, acute posterolateral myocardial ischemia was produced in the absence of previous myocardial infarction in 15 digoxin-pretreated (1.19 +/- 0.21 ng/ml serum digoxin, 5-7 days pretreatment) and 11 vehicle-pretreated dogs. The incidences of sudden ventricular fibrillation and of 24 h arrhythmic mortality in response to posterolateral ischemia were 4/15 (27%) vs. 1/11 (9%) (p = 0.23) and 7/15 (47%) vs. 4/11 (36%) (p = 0.27) for digoxin- vs. vehicle-pretreated dogs, respectively. Ventricular ectopic activity at 24 and 48 h after the onset of posterolateral ischemia was reduced significantly by both intravenous lidocaine (1.0-5.0 mg/kg) and verapamil (50.0-500.0 micrograms/kg) in the vehicle-pretreated dogs, whereas neither antiarrhythmic agent significantly suppressed ventricular ectopy in the digoxin-pretreated dogs. The mean sizes for developing posterolateral myocardial infarctions (percentage of left ventricle) were greater for the digoxin-pretreatment group (31.9 +/- 2.8%) vs. vehicle-pretreatment group (14.8 +/- 2.0%, p less than 0.001). These findings suggest that uncomplicated acute myocardial ischemia in the presence of serum concentrations of digoxin that are considered clinically therapeutic may result in the development of larger areas of developing myocardial infarction and in the occurrence of ventricular arrhythmias that are less sensitive to suppression with conventional antiarrhythmic agents.

Topics: Animals; Arrhythmias, Cardiac; Coronary Disease; Digoxin; Dogs; Electrocardiography; Heart Rate; Heart Ventricles; Infusions, Intravenous; Lidocaine; Male; Myocardial Infarction; Verapamil

Recently, this laboratory has demonstrated an enhanced susceptibility toward the development of ischemia-related lethal ventricular arrhythmias in the presence of therapeutic serum concentrations of digoxin in conscious dogs after myocardial infarction. The present study was performed to assess the effect of the interruption of cardiac sympathetic influences, via subacute left stellate ganglionectomy (LSGX), on digitalis-mediated ischemic ventricular arrhythmias. Commencing 4-5 days after anterior myocardial infarction, 11 dogs with LSGX and 14 sham controls were administered digoxin (0.0125 mg/kg/day i.v.) for 5-7 consecutive days. At baseline testing, programmed ventricular stimulation failed to initiate ventricular tachycardia in any postinfarction dog entered into this evaluation. After treatment, 11/11 digoxin + LSGX (1.33 +/- 0.10 ng/ml serum digoxin) and 14/14 digoxin-treated sham (1.23 +/- 0.14 ng/ml serum digoxin) dogs remained nonresponsive to programmed stimulation testing. The incidence of arrhythmic mortality in response to subsequent ischemia at a site remote from the infarcted anterior region was greater in the digoxin-treated sham group (1.22 +/- 0.21 ng/ml serum digoxin) than in the digoxin + LSGX group (1.33 +/- 0.10 ng/ml serum digoxin); mortality was 6/10 (60%) digoxin sham vs. 1/10 (10%) digoxin + LSGX, p less than 0.005. The underlying anterior myocardial infarct sizes (% of left ventricle: 6.8 +/- 2.3 vs. 6.6 +/- 1.1) did not differ between the digoxin sham and digoxin + LSGX groups. However, the digoxin sham controls developed larger posterolateral myocardial infarctions than did the digoxin + LSGX animals (% of left ventricle: 27.4 +/- 3.0 vs. 16.7 +/- 2.7, p less than 0.05). Norepinephrine concentrations in posterolateral through posteroseptal ventricular sections were not altered by LSGX in a separate group of digoxin-treated postinfarct dogs. The results suggest that left stellate ganglionectomy may reduce the incidence of digitalis-mediated malignant ventricular arrhythmias during ischemia, possibly due to a reduction in the severity of ischemic injury.

Topics: Animals; Arrhythmias, Cardiac; Coronary Circulation; Denervation; Digoxin; Dogs; Ganglia, Sympathetic; Male; Myocardial Infarction; Myocardium; Norepinephrine; Stellate Ganglion; Sympathectomy

This study was designed to examine effects of theophylline, a methylxanthine, on both the positive inotropic and toxic actions of cardiotonic steroids in cardiac muscle isolated from guinea pig heart. In electrically paced left atrial muscle, 0.3 mM theophylline reduced both the maximum developed tension observed in the presence of increasing concentrations of strophanthidin and the dose of this steroid that first elicited extrasystoles. Similarly, 0.3 mM theophylline decreased the time to onset of arrhythmias produced by 5 microM digoxin and the fractional occupancy of specific binding sites on Na,K-adenosine triphosphatase by digoxin at the onset of these dysrhythmic events. A higher level of theophylline (6.5 mM) severely diminished or prevented the positive inotropic and arrhythmogenic actions of cardiotonic steroids while promoting the contracture elicited by these digitalis-like compounds. In spite of the severe contracture observed in the presence of 6.5 mM theophylline plus 5 microM digoxin, the digoxin fractional occupancy was significantly less than that observed at the onset of digoxin-induced extrasystoles and contracture in the absence of theophylline. In radiolabeled ligand binding experiments, 6.5 mM theophylline reduced the affinity of specific binding sites for ouabain while having no effect on receptor density. These results, when considered in light of previous reports by other investigators, suggest that moderate concentrations of methylxanthines promote cardiotonic steroid-induced arrhythmias by increasing Ca++ influx and its uptake into sarcoplasmic reticulum. Higher levels seem to antagonize the arrhythmogenic actions by inhibition of sarcoplasmic reticular Ca++ uptake and by antagonism of receptor binding.

Topics: Animals; Arrhythmias, Cardiac; Calcium; Digoxin; Dose-Response Relationship, Drug; Guinea Pigs; In Vitro Techniques; Myocardial Contraction; Ouabain; Sodium-Potassium-Exchanging ATPase; Strophanthidin; Theophylline

The effects of AN-132, 3-(diisopropylaminoethyl-amino)-2',6'-dimethylpropionanilide.2H 3PO4, on chloroform-induced arrhythmias and plasma digoxin concentrations have been compared with those of quinidine in rats. AN-132 (0.01-3 mg kg-1) administered orally significantly inhibited the incidence of cardiac arrhythmias in a dose-related fashion. A single dose of digoxin (1 mg kg-1) given orally for 7 consecutive days was followed, on day 8, orally by digoxin alone, or together with AN-132 (50, 100 and 200 mg kg-1) or quinidine (25 and 50 mg kg-1). The AUC0-24 and Cmax of plasma digoxin were enhanced significantly by co-administration of quinidine, but not by AN-132.

Topics: Anilides; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Chloroform; Digoxin; Drug Interactions; Ethylenediamines; Male; Quinidine; Rats; Rats, Inbred Strains

The relation between serum digoxin concentration and the electrocardiogram was assessed by correlating computerized measurements of electrocardiographic parameters (PR, QRS, QT and QTc intervals, ST segment, and T-wave amplitude) with the serum digoxin concentration in 97 patients on digoxin maintenance therapy and in 40 nondigitalized control subjects. None of the patients had unstable ischemic heart disease, electrolyte disorders, medication known to influence the ST segment, and/or the presence of a bundle-branch block or ventricular hypertrophy. We found a trend toward lengthened PR interval and shortened QT and QTc intervals in digitalized versus nondigitalized patients. Increasing serum digoxin concentrations were associated with progressive depression of the ST segment and decreased T-wave amplitude (p less than 0.001). A normal ST segment in four leads (I, aVF, V5, V6) excluded the presence of a serum digoxin concentration greater than 1.3 ng/ml in our patients, whereas severe ST-segment depression with a J point of greater than or equal to 100 microV was a strong indicator for the presence of a serum digoxin concentration greater than 2.0 ng/ml in our selected patient population (specificity 99%, sensitivity 30%, predictive accuracy 85%). We conclude that computerized electrocardiographic analysis of the ST segment may provide clinically useful information for the management of selected patients on digitalis therapy and may therefore increase the diagnostic yield of the electrocardiogram in predicting the presence of higher serum digoxin concentrations in a small but significant percentage of patients.

Topics: Adult; Aged; Arrhythmias, Cardiac; Computer Systems; Digoxin; Electrocardiography; Female; Humans; Male; Middle Aged; Time Factors

1. Increased local thromboxane (Tx) formation has been considered to be a contributing factor in digitalis-induced arrhythmias. 2. A potent Tx synthetase inhibitor (TxSI), UK 38,485 (0.1, 1.0 or 10.0 mg/kg per h, administered intravenously) and a Tx receptor antagonist (TxRA), ICI 185,282 (1, 2 or 10 mg/kg bolus and 1, 2 or 10 mg/kg per h, administered intravenously) were tested for their ability to reduce digoxin-induced arrhythmias in anaesthetized guinea-pigs. 3. Electrocardiograms, mean blood pressure, heart rate and arrhythmias were recorded, starting 30 min before digoxin administration and continued for 60 min afterwards. 4. ICI 185,282, at the doses used, significantly delayed the time of onset of arrhythmias, and reduced the incidence of ventricular fibrillation, mortality and arrhythmia score. In contrast, UK 38,485 was found to be effective on all measured variables only at the dose rate of 1.0 mg/kg per h, except for time required for the development of arrhythmias. These protective effects of both TxSI and TxRA were not found to be dose-dependent. 5. Arterial blood pressure and heart rate changes caused by either UK 38,485 or ICI 185,282 infusions did not have any marked effects on digoxin-induced arrhythmias. 6. These data suggest that endogenously released TxA2 and prostaglandin endoperoxides may play an important role in digoxin-induced arrhythmias in guinea-pigs.

Topics: Anesthesia; Animals; Arrhythmias, Cardiac; Blood Pressure; Digoxin; Dioxanes; Dioxins; Dose-Response Relationship, Drug; Electrocardiography; Female; Guinea Pigs; Imidazoles; Male; Thromboxane A2; Ventricular Fibrillation

Male Wistar rats were injected intraperitoneally for 3 consecutive days with hydrochlorothiazide (HCTZ; 15 mg/kg), chlorothiazide (CTZ; 100 mg/kg), bendroflumethiazide (BFTZ; 1.5 mg/kg), chlorthalidone (CHLOR; 15 mg/kg), methyclothiazide (METH; 1.0 mg/kg) or metolazone (MET; 1.5 mg/kg). Magnesium content was measured in the hypothalamus, medulla oblongata, cerebral cortex, heart, skeletal muscle and serum. Although there was no consistent alteration of Mg in the serum, skeletal muscle and heart, there was a significant effect on hypothalamic and medullary Mg. Compared to a control value of 17.20 +/- 1.24 mEg/kg in the hypothamus there was a decrease by HCTZ (26%; p less than 0.01), CTZ (24%; p less than 0.01) and BFTZ (30%; p less than 0.01). Similarly, there was a decrease by HCTZ (22%; p less than 0.01), CTZ (30%; p less than 0.01) and BFTZ (25%; p less than 0.01) on Mg in medulla. In contrast MET increases Mg in hypothalamus (31%; p less than 0.01) and medulla (26%; p less than 0.01). Furthermore, digoxin infusion (0.051 ml/min) in animals pretreated with HCTZ induced arrhythmias earlier than in animals receiving digoxin alone (30 vs. 60 min; p less than 0.01). The effects of digoxin toxicity in HCTZ-pretreated animals were partially reversed by CNS administration of 50 micrograms of Mg. These findings strongly suggest that thiazide-induced depletion of Mg in the CNS predisposes to digoxin intoxication.

Topics: Animals; Arrhythmias, Cardiac; Bendroflumethiazide; Brain Chemistry; Digoxin; Diuretics; Electrocardiography; Hydrochlorothiazide; Magnesium; Magnesium Deficiency; Male; Muscles; Myocardium; Rats; Rats, Inbred Strains; Sodium Chloride Symporter Inhibitors

Topics: Adolescent; Arrhythmias, Cardiac; Digoxin; Humans; Long QT Syndrome; Male; Sinoatrial Block

1. The role of the parasympathetic nervous system and the effect of morphine on cardiac arrhythmias induced by digitalis was assessed in guinea-pigs that had digitalis arrhythmias produced by digoxin 50 micrograms/kg intravenously plus 500 micrograms/kg per h. 2. Morphine produced a dose-dependent rightward shift in the relationship between digoxin dose and arrhythmias. Morphine 5 mg/kg subcutaneously (s.q.) was associated with significantly (P less than 0.05) higher digoxin doses both at the onset of ventricular arrhythmias and at development of fatal arrhythmias compared with the control group that received saline s.q. 3. Vagotomy and atropine prevented the effect of morphine so that the dose-response relationships and the mean digoxin dose at onset of ventricular arrhythmias and the development of fatal arrhythmias were not significantly different from the control group receiving saline. 4. These data indicate that morphine limits the development of digitalis arrhythmias and this effect is, at least in part, mediated through the parasympathetic nervous system.

Topics: Animals; Arrhythmias, Cardiac; Atropine; Blood Pressure; Digoxin; Dose-Response Relationship, Drug; Guinea Pigs; Male; Morphine; Parasympathetic Nervous System; Vagotomy

Topics: Amiodarone; Arrhythmias, Cardiac; Coronary Disease; Digoxin; Disopyramide; Drug Synergism; Drug Therapy, Combination; Humans; Middle Aged; Moricizine; Phenothiazines

Previously, we have demonstrated an increased incidence of lethal ischemic arrhythmias in postinfarction dogs with clinically observable serum digoxin concentrations, and a significant reduction in digitalis-related lethal ischemic arrhythmias after subacute left stellectomy. In the present study, the protective actions of acute beta-adrenoceptor blockade with nadolol, 1.0 mg/kg administered intravenously immediately preceding the induction of posterolateral myocardial ischemia, were assessed in conscious dogs with recent, small anterior myocardial infarctions pretreated with digoxin, 0.0125 mg/kg/day intravenously, for 5 to 7 consecutive days (total n = 11). A cohort of postinfarction dogs pretreated with digoxin alone served as a control group (total n = 26). Pre vs postdigoxin electrophysiologic testing indicated reductions in myocardial refractoriness in ventricular noninfarct and infarct zones in both treatment groups, whereas the administration of nadolol tended to reverse the reductions in ventricular refractoriness. Arrhythmia-related deaths in response to posterolateral myocardial ischemia were reduced from 12 of 20 (60%) in the digoxin control group to 2 of 10 (20%) in the digoxin + nadolol group (p = 0.039). Serum digoxin concentrations (1.29 +/- 0.14 ng/ml vs 1.39 +/- 0.24 ng/ml), underlying anterior myocardial infarct size (6.9 +/- 1.5% vs 4.6 +/- 0.9% of left ventricle), and developing posterolateral myocardial infarct size (22.8 +/- 2.5% vs 17.5 +/- 3.6% of left ventricle) did not differ significantly between the digoxin and digoxin + nadolol groups. Acute beta-adrenoceptor blockade with nadolol appears to reduce digitalis-mediated ischemic postinfarction mortality, possibly because of a salutary increase in ventricular refractoriness.

Topics: Animals; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Digitalis; Digoxin; Dogs; Drug Administration Schedule; Electric Stimulation; Electrocardiography; Electrophysiology; Myocardial Infarction; Nadolol; Plants, Medicinal; Plants, Toxic

To examine the relation between preoperative hypokalemia and frequency of intraoperative arrhythmias, Holter monitoring was employed in 447 patients undergoing major cardiac or vascular operations, the group at greatest risk for life-threatening arrhythmias. Based on serum potassium levels measured immediately before surgery, 57% of patients were normokalemic (greater than or equal to 3.6 mEq/L), 34% hypokalemic (3.1-3.5 mEq/L), and 9% severely hypokalemic (less than or equal to 3.0 mEq/L). No arrhythmia occurred at any time in 63% of patients and minor arrhythmias (premature atrial and occasional premature ventricular contractions) occurred in 16%. Frequent or complex ventricular ectopy appeared before and during operation in 92 patients (21%) but was not related to preoperative potassium level or history of long-term diuretic therapy. Frequent and complex ventricular arrhythmias were more common in patients with a history of long-term digoxin therapy or congestive heart failure. Even among these patients, hypokalemia or diuretic therapy did not increase the incidence or severity of ectopy. These data fail to support the common practice of delaying operation for acute potassium replacement in patients whose preoperative serum potassium is less than normal, even in the presence of cardiovascular disease.

Topics: Adult; Anesthesia, General; Arrhythmias, Cardiac; Cardiovascular Diseases; Chronic Disease; Digoxin; Diuretics; Female; Humans; Hypokalemia; Intraoperative Complications; Male; Potassium; Prospective Studies; Time Factors

Topics: Arrhythmias, Cardiac; Digoxin; Heart Failure; Humans; Intestinal Absorption; Monitoring, Physiologic; Tissue Distribution

Digoxin is the third most commonly prescribed drug, yet limited information exists about its use in outpatients. Therefore, 242 medical outpatients receiving digoxin at our hospital were studied to evaluate the appropriateness of its use, defined by: (1) current or past supraventricular arrhythmias and/or (2) left ventricular systolic dysfunction (ejection fraction less than 45 percent).. Charts of 242 patients receiving digoxin were obtained. The patients were divided into groups based upon their physician's stated indication for digoxin therapy. Patients with only a clinical diagnosis of congestive heart failure (CHF) underwent echocardiography or radionuclide angiography to quantify left ventricular systolic function. Those with documented supraventricular arrhythmias and/or those with confirmed left ventricular systolic dysfunction were classified as appropriate candidates for digoxin.. Ninety-five percent of patients received digoxin for appropriate indications; 75 percent had confirmed supraventricular arrhythmias (27 percent also had CHF) and 20 percent with normal sinus rhythm had documented systolic dysfunction. However, physicians had difficulty in the clinical assessment of left ventricular function; 18 percent of patients with sinus rhythm and CHF by the Framingham scoring system and 20 percent of those with supraventricular arrhythmias and CHF had preserved systolic function. An S3 was present in 15 percent of patients with preserved ejection fraction and CHF and in 69 percent with low ejection fraction; hypertension was significantly more common in the former group. Noninvasive assessment of systolic function was obtained in 97 percent of patients independent of this study, yet some patients without supraventricular arrhythmias and with documented preservation of systolic function continued to receive the drug.. Noninvasive assessment of left ventricular function, which appears to have become routine, is of value in the appropriate utilization of digoxin, since clinicians' assessment of left ventricular function may be inaccurate. Physicians also do not always discontinue digoxin therapy when indicated.

Topics: Aged; Ambulatory Care; Arrhythmias, Cardiac; Digoxin; Female; Heart Failure; Heart Ventricles; Humans; Male; Middle Aged; Stroke Volume; Systole; Tachycardia, Supraventricular

An acute ingestion of 6 to 7 mg digoxin as a suicidal gesture in a 76-year-old man with chronic heart disease is presented. The patient arrived in the emergency department approximately 5 hours after ingestion with a normal serum potassium and increasing numbers of multifocal premature ventricular contractions. Digoxin-specific antibody fragments were administered. The patient developed ventricular tachycardia and ventricular fibrillation and was eventually stabilized 35 minutes after the Fab fragments were infused. A review of the pharmacology and indications for use of digoxin-immune Fab fragments is also presented.

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Humans; Immunoglobulin Fab Fragments; Male; Suicide, Attempted

Based on our experience with the prospective follow-up study in a group of patients (n = 21) with congestive heart failure (CHF) (NYHA III n = 10, NYHA IV n = 11) and left ventricular ejection fraction below 30%, who were referred to our ordinary care unit by their family physicians after an initial work-up, we investigated the impact of a special treatment program in 25 patients with similar CHF despite therapy (60 +/- 4 years, NYHA III n = 11, NYHA IV n = 14, LVEF less than 30%, 17 +/- 3%). The program focused on three issues: (1) individualized medical therapy of CHF, (2) antiarrhythmic treatment and close follow-up visits, and (3) continuous education of patients and physicians in order to improve treatment compliance and the early management of complications. Medical treatment was based on diuretic and vasodilator therapy in all the patients, while positive inotropic substances including digoxin were given selectively. Vasodilator treatment was started with prazosin in 22 patients and with ACE inhibitors in three patients with low serum sodium. Fifty-five percent of the patients on prazosin had to be changed over to ACE inhibitors. Amiodarone was used as first line drug to treat symptomatic ventricular tachycardia in two patients and two survivors of ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anticoagulants; Arrhythmias, Cardiac; Chronic Disease; Digoxin; Heart Failure; Humans; Patient Care Planning; Peptidyl-Dipeptidase A

The application of a new signal processing methodology to the analysis of epicardial array ECG signals is presented as an alternative to isopotential or isochrones mapping by the use of a zero-delay wavenumber spectrum (ZDWS) estimation technique. The methodology "explains" the array data as the sum of modulated wideband (non-sinusoidal) propagating waves projected onto the array plane and provides an accurate estimate of their number and bearing. The slowness distribution of each of the waves is then obtained by estimating their temporal spectrum. In this experimental study the effects of localized noninfarcting reversible low flow ischemia, digoxin toxicity and verapamil reversal of digoxin toxicity are quantified via the ZDWS methodology and are compared with the information that can be extracted from isopotential mapping. It is demonstrated that the ZDWS methodology permits the epicardial electric activation to be decomposed into a number of quantification parameters which possess a hierarchical "tree" structure and therefore provide a means for an objective and robust characterization of the effects of agents which alter myocardial conduction and arrhythmia generation.

Topics: Animals; Arrhythmias, Cardiac; Calcium; Coronary Disease; Coronary Vessels; Digoxin; Dogs; Electrocardiography; Heart; Ion Channels; Membrane Potentials; Signal Processing, Computer-Assisted; Time Factors; Verapamil

Topics: Arrhythmias, Cardiac; Digoxin; Electrocardiography; Female; Humans; Immunoglobulin Fab Fragments; Infant, Newborn; Infant, Premature, Diseases; Medication Errors; Sodium-Potassium-Exchanging ATPase

The role of the dopaminergic system in digoxin-induced cardiotoxicity has been examined. Specific dopaminergic agonists and antagonists were administered into the ventriculocisternal system of pentobarbitone-anaesthetized dogs before systemic administration of digoxin. Pretreatment with apomorphine, a specific dopamine agonist, did not significantly alter the arrhythmogenic or lethal doses of digoxin. However, the digoxin-induce increase in CSF noradrenaline was decreased significantly in apomorphine-pretreated animals. Pretreatment with pimozide, a specific dopamine antagonist, significantly decreased the arrhythmogenic dose of digoxin but did not alter the lethal dose. As with apomorphine, pimozide-pretreated animals accumulated significantly less noradrenaline in CSF compared with control dogs. These results suggest that dopamine receptors are not directly related to the cardiotoxic actions of digoxin. However, dopaminergic receptors may influence the balance of central catecholaminergic systems that influence the peripheral cardiovascular system.

Topics: Animals; Apomorphine; Arrhythmias, Cardiac; Digoxin; Dogs; Drug Interactions; Female; Injections, Intravenous; Injections, Intraventricular; Male; Norepinephrine; Pimozide; Receptors, Dopamine

Three-day ECG monitoring before and after digitalization of 55 patients with heart failure (HF) was performed. Digoxin did not make a considerable effect on the frequency of detection of high gradations of ventricular arrhythmias. Nevertheless it significantly reduced the mean number of ventricular extrasystoles (VES) per hour and the mean number of complex VES per hour in 8 (33.3%) patients out of 24 with frequent extrasystoles. A significant increase in the VES mean number per hour and in the complex VES mean number per hour was observed in 6 (25%) patients out of 24 with basal frequent extrasystoles. In patients with the antiarrhythmic effect of digoxin indices of the central hemodynamics (diastolic pressure in the pulmonary artery and ejection fraction) were significantly better and in patients with the arrhythmogenic effect of digoxin significantly worse in the absence of a significant difference between digoxin and K+ concentration in the plasma. Digoxin possessed a moderately pronounced antiarrhythmic effect mainly in the patients with HF early stages and in moderately pronounced disturbances of the central hemodynamics. In patients with severe manifestations of HF and with considerable deterioration of indices of the central hemodynamics digoxin in therapeutic concentrations can make an arrhythmogenic effect.

Topics: Adolescent; Adult; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Circadian Rhythm; Digoxin; Electrocardiography; Female; Heart Failure; Heart Rate; Hemodynamics; Humans; Male; Middle Aged; Monitoring, Physiologic; Potassium

A retrospective study of the clinical course and outcome of patients with serum digoxin concentrations (SDCs) greater than 3 ng/mL was conducted to determine the probability of a patient without initial signs or symptoms of digoxin toxicity subsequently developing signs or symptoms. Of 123 patients with SDCs greater than 3 ng/mL, 54 had no apparent signs or symptoms of toxicity at the time the index SDC was determined (group 1). Of these 54, two patients developed definite digoxin toxicity, although neither suffered significant morbidity. Digoxin administration was reduced or discontinued in all patients but one in group 1. There were no significant differences between the patients who had no signs or symptoms of digoxin toxicity (group 1) and those who did have signs or symptoms (group 2) in the mean SDC (3.9 +/- 0.1 vs 4.2 +/- 0.2 ng/mL, respectively), the serum creatinine (2.9 +/- 0.2 vs 3.4 +/- 0.4 mg/dL), or the incidence of atrial fibrillation (29/54 vs. 35/69) and coronary artery disease (21/54 vs. 18/69). The authors conclude that clinically stable patients receiving digoxin who have elevated SDCs but are without signs or symptoms of digoxin toxicity are at low risk of developing serious digoxin toxicity and do not generally require treatment beyond the discontinuation of digoxin therapy.

Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Digoxin; Female; Humans; Male; Middle Aged; Retrospective Studies

We have examined the effects of heparin infusion on the arrhythmias induced by digoxin. Digoxin treatment consisted of 0.6 mg kg-1 given i.v. 15 min after the beginning of heparin infusion. Heparin infusions (1.7 IU, 3.4 IU and 6.8 IU kg-1 min-1) were begun 15 min before digoxin injection and continued for another 30 min. ECG, blood pressure, heart rate and arrhythmias were recorded starting 15 min before and continuing for 60 min after the digoxin injection. Heparin at the infusion rates of 3.4 IU and 6.8 IU kg-1.min-1 reduced significantly the arrhythmia scores. On the other hand, heparin did not significantly alter the arterial blood pressure and heart rate values affected by digoxin.

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Digoxin; Electrocardiography; Female; Guinea Pigs; Heart Rate; Heparin; Infusions, Intravenous; Male

Topics: Aged; Antidotes; Arrhythmias, Cardiac; Digoxin; Female; Humans; Male; Middle Aged; Potassium

Topics: Amiodarone; Arrhythmias, Cardiac; Digoxin; Drug Interactions; Electrocardiography; Heart Arrest; Humans; Male; Middle Aged

Quinidine syncope and factors associated with it are well known among adult patients treated for cardiac arrhythmias. To define factors that may influence the occurrence of syncope in children taking quinidine, the clinical, anatomic, electrocardiographic, roentgenographic and pharmacologic data were compared in six patients with syncope (Group A) and 22 patients without syncope (Group B). There was a significant (chi-square = 10.2, p = 0.001) relation between heart disease and quinidine syncope: all six Group A (syncopal) patients had heart disease whereas 15 of the 22 Group B (non-syncopal) patients had no structural heart disease. In contrast, no significant difference was noted between Group A and Group B patients in mean age (11.4 versus 11.4 years), mean quinidine serum concentration (2.9 versus 2.3 micrograms/ml), mean corrected QT interval before quinidine (0.43 versus 0.40 second) or mean corrected QT interval during quinidine therapy (0.46 versus 0.46 second) or between those taking digitalis and those not. Two of the six Group A (syncopal) patients died during therapy, one 6 days after initiating therapy and one suddenly at home 6 months after beginning quinidine. Another two of the six Group A patients exhibited hypokalemia (both 2.9 mEq/liter) at the time of syncope, 2 weeks and 6 months, respectively, after initiation of quinidine therapy; both survived. Syncope occurred within 8 days of initiation of quinidine therapy in three of the six patients. Sustained ventricular tachycardia was observed during quinidine associated arrhythmia in three of six patients with syncope; nonsustained ventricular tachycardia or complex ventricular ectopic activity while on this therapy was observed before syncope in the other three patients in Group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Child; Child, Preschool; Digitoxin; Digoxin; Drug Administration Schedule; Electrocardiography; Heart Diseases; Hemodynamics; Humans; Quinidine; Syncope

The present study utilized a time course of CSF catecholamine concentrations during peripheral digoxin administration in vivo to provide a clarification of central catecholaminergic mechanisms involved in digitalis cardiotoxicity. A continuous peripheral digoxin infusion produced significant increases in CSF norepinephrine just prior to arrhythmogenesis in anesthetized dogs. Phentolamine pretreatment significantly increased the arrhythmogenic and lethal doses of digoxin. These results suggest that activation of central noradrenergic neurons may be the initiating factor in digoxin-induced arrhythmogenesis.

Topics: Animals; Arrhythmias, Cardiac; Catecholamines; Digoxin; Dogs; Norepinephrine; Phentolamine

The cardiovascular effects of D-Ala-2-Me-Phe-4-Met-(0)-Ol enkephalin were investigated after its administration into the fourth cerebroventricle of the guinea pig. This enkephalin is a synthetic Met-enkephalin analog that is more resistant to degradation and has a high affinity for opioid receptors. It produced a significant increase in blood pressure and decline in heart rate. At high concentrations, 100 micrograms/kg plus 100 micrograms/kg/hr in the fourth ventricle, it produced bradyarrhythmias that were sometimes fatal. At doses that did not alter survival or produce arrhythmia, namely 30 micrograms/kg plus 25 micrograms/kg/hr in the fourth ventricle, the response to digitalis was assessed. Significant leftward shifts in the relationships between digoxin and arrhythmia occurrence and development of fatal arrhythmias were observed. Thus, D-Ala-2-Me-Phe-4-Met-(0)-Ol enkephalin has definite cardiovascular effects that include potentiation of digoxin arrhythmias.

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Digoxin; Guinea Pigs; Heart Rate; Injections, Intraventricular; Male

A comparative study of the efficiency of digoxin and "pure" antiarrhythmic agents was carried out in 56 patients with ventricular arrhythmias and signs of circulatory insufficiency (CI). Digoxin had arrhythmogenic effect in 20% of the patients, which was twice as frequent in the marked CI group. "Pure" anti-arrhythmic agents were effective in 47% (ritmilen) to 71% (cordaron), and etmozin, in 63% of the patients, while adverse myocardial inotropic effect was only produced by ritmilen. Combined use of etmozin, ritmilen or cordaron with digoxin increases their antiarrhythmic efficiency.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Chronic Disease; Digoxin; Diuretics; Drug Evaluation; Drug Therapy, Combination; Electrocardiography; Exercise Test; Heart Failure; Hemodynamics; Humans; Monitoring, Physiologic; Time Factors

Chronic treatment of dogs with digoxin alone, quinidine alone and digoxin in combination with quinidine was initiated in dogs to assess changes in arrhythmogenic potential associated with the quinidine-induced increase in serum digoxin concentration observed during combined digoxin and quinidine treatment. The arrhythmogenic potential of digoxin was evaluated through the use of the acetylstrophanthidin (AcS) tolerance test. AcS was infused at a rate of 5 micrograms/kg/min until ventricular arrhythmias occurred during a drug-free period and during chronic treatment with digoxin, quinidine and digoxin plus quinidine. The dose of AcS required to initiate ventricular arrhythmias is inversely related to the arrhythmogenic potential of digoxin present at the time of AcS infusion. Administration of quinidine alone in two different dosage regimens produced serum quinidine concentrations of 5.99 +/- 1.18 and 2.99 +/- 0.43 micrograms/ml and significantly increased AcS tolerance, whereas digoxin alone, over a wide range of serum digoxin concentrations, significantly decreased AcS tolerance. This decrease in AcS tolerance was linearly related to the serum digoxin concentration. The addition of quinidine treatment to animals receiving digoxin resulted in a significant elevation in the steady-state serum digoxin concentration. However, the AcS tolerance determined during the elevated serum digoxin concentration induced by quinidine was greater than that determined during treatment with the same dose of digoxin alone. Thus, quinidine administration to animals receiving digoxin resulted in a significant increase in the steady-state serum digoxin concentration but did not increase the arrhythmogenic potential of digoxin over that observed during treatment with the same dose of digoxin alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Drug Interactions; Quinidine; Strophanthidin

A digitalized 75-year-old patient with postoperative renal failure demonstrated a progressive rise in serum digoxin concentration, peaking at 3.4 nmol X L-1 three days following discontinuance of the drug. This was accompanied by cardiac bradyarrhythmias. Although the serum digoxin concentration had already started to climb from a therapeutic level prior to the discontinuance of the drug, the unabated and substantial rise was consistent with a dramatic decrease in the apparent volume of distribution of digoxin accompanying acute renal failure. Serum digoxin levels were determined with fluorescence polarization immunoassay, which has an improved specificity when compared to the commonly used radioimmunoassays for digoxin.

Topics: Acute Kidney Injury; Aged; Arrhythmias, Cardiac; Digoxin; Female; Humans; Kinetics; Postoperative Complications

The effect of encainide administration on steady-state plasma digoxin levels was evaluated in 17 patients receiving stable doses of digoxin. A paired t test, comparing plasma digoxin levels (mean +/- standard error) before encainide therapy (1.05 +/- 0.14 ng/ml) and after 2 weeks of encainide, 100 mg/day (1.03 +/- 0.11 ng/ml) or 200 mg/day (1.2 +/- 0.2 ng/ml), indicates no significant (p greater than 0.05) change in digoxin levels. These results were confirmed in a second study of 10 patients with severe congestive heart failure. Also, no difference in efficacy of either drug was observed and changes in dosing of digoxin were not required. Plasma concentrations of encainide and its 2 major metabolites, O-demethyl encainide (ODE) and 3-methoxy-O-demethyl encainide, significantly increased by 31.6%, 43.1% and 35.6% after concomitant cimetidine administration in 13 healthy adult men receiving 75 mg/day of encainide. However, a retrospective evaluation of 33 patients receiving both drugs did not reveal any clinically significant interactions. Retrospective evaluation of patients enrolled in clinical studies who received concomitant digoxin (268), antiarrhythmics (118), anticoagulants (78), antidiabetics (40), antipsychotics (23), beta blockers (88), calcium-channel blockers (24) or diuretics (229) did not reveal any clinically significant interactions with encainide. Similarly, in vitro protein binding studies did not reveal any clinically significant interactions with encainide or its major metabolites. Six patients with moderate to severe renal impairment (creatinine clearance 10 to 38 ml/min) received 25 mg of encainide, 3 times/day, for 7 doses. Plasma encainide, ODE and 3-methoxy-O-demethyl concentrations were similar to those observed in normal subjects who had received twice the dose of encainide, and steady-state apparent oral clearance of encainide was reduced by 66% with renal impairment. Based on these data it is recommended that in patients with moderate to severe renal impairment encainide be initiated at one-third the normal dose, or 25 mg once a day. Doses may be elevated in small increments at 1-week intervals if needed for efficacy. The effect of hepatic impairment on the pharmacokinetics of encainide was studied in 7 patients with clinically documented cirrhosis. Compared with normal subjects studied using a similar protocol, the plasma concentrations of encainide were elevated significantly due to a 6-fold decrease in oral clearance. Howeve

Topics: Adrenergic beta-Antagonists; Adult; Amiodarone; Anilides; Anti-Arrhythmia Agents; Anticoagulants; Antipsychotic Agents; Arrhythmias, Cardiac; Calcium Channel Blockers; Cimetidine; Digoxin; Diuretics; Drug Interactions; Encainide; Humans; Hypoglycemic Agents; Kidney Diseases; Liver Diseases; Middle Aged; Prospective Studies; Protein Binding; Retrospective Studies

Amperozide is a novel psychotropic compound with specific effect in limbic brain areas. Preliminary findings have also indicated an antiarrhythmic effect in-vitro. Injections of saline, amperozide, melperone, thioridazine, bretylium or lignocaine, were given i.p. to anaesthetized guinea-pigs, which 10 min later were given digoxin s.c. to induce arrhythmia. In a series of control experiments none of these compounds caused arrhythmia in combination with the vehicle of digoxin. The time to arrhythmia was significantly prolonged after treatment with amperozide, melperone and bretylium compared with saline, but there were no differences between the treatments. The digoxin concentrations in plasma at death varied considerably within the groups and no statistical significance was found.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Guinea Pigs; Iodine Radioisotopes; Male; Piperazines

By means of abdominal fetal ECG and non-invasive ultrasound blood flow studies 113 cases of fetal cardiac arrhythmia were classified according to the origin of arrhythmia. Pregnancy outcome was characterized by an increased frequency of fetal distress and heart malformation, and increased fetal and neonatal mortality. The following types of arrhythmia were identified: supraventricular extrasystoles (n = 84), paroxysmal tachycardia (n = 6), sinus bradycardia (n = 3), atrial flutter (n = 1), ventricular extrasystoles (n = 14), and atrioventricular block (n = 5). In 37 cases the combined Doppler and real-time ultrasound technique was used to measure fetal aortic blood flow as a means of studying the circulatory effects of the arrhythmia. Increased peak velocity, rising slope and acceleration were found in the first post-pausal beat after a supraventricular extrasystole or a missed beat; this supports the validity of Frank-Starling law for the fetal heart and suggests that a strong relationship exists between these variables and myocardial contractility. In two cases of intra-uterine heart failure, the effect of digoxin treatment in utero on the fetal aortic flow variables was studied, results indicating a positive inotropic effect of the drug on the fetal myocardium. The estimation of fetal aortic volume blood flow in cases of fetal cardiac arrhythmia is useful for early detection of fetal cardiac failure, and for monitoring the effects of intra-uterine treatment.

Topics: Adult; Aorta; Arrhythmias, Cardiac; Digoxin; Echocardiography; Female; Fetal Diseases; Fetal Heart; Gestational Age; Heart Failure; Humans; Maternal Age; Pregnancy

Topics: Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Dose-Response Relationship, Drug; Heart Failure; Homes for the Aged; Humans; Nursing Homes

A retrospective study of two groups of patients with a different plasma digoxin level (Group A: digoxin greater than or equal to 2 ng/ml, n = 32, Group B: digoxin less than 2 ng/ml, n = 34; total n = 66) showed a significantly lower creatinine clearance (p less than 0.05) in group A. This group also showed a weak correlation between the digoxin level and the length of observation (R = + 0.31, p less than 0.05, n = 29). Furthermore, a weak correlation between digoxin level and the ratio of average daily dosage to creatinine clearance was found for the total sample (R = + 0.30, p less than 0.05, n = 66). Patients treated for less than 7 days and with a higher digoxin level also had a higher dosage and worse renal function (p = 0.05, p = 0.01, respectively). A weak correlation also existed between the digoxin level and creatinine clearance and body weight for the whole sample (R = -0.29, p less than 0.05; R = -0.29, p less than 0.01, respectively; n = 66). The latter correlation was also found within each group. Apart from renal function, the medication taken and body weight seem to be useful variables in predicting impending elevation of the digoxin level. In this study these variables were found to be better suited for the said purpose than the ECG. These conclusions remain to be confirmed by means of a prospective study.

Topics: Acetyldigoxins; Age Factors; Arrhythmias, Cardiac; Body Weight; Creatinine; Digoxin; Dosage Forms; Dose-Response Relationship, Drug; Drug Administration Schedule; Electrocardiography; Female; Humans; Kidney Function Tests; Male; Medigoxin; Risk

Quinidine therapy is one of the most common causes of the acquired long QT syndrome and torsade de pointes. In reviewing clinical data in 24 patients with the quinidine-associated long QT syndrome, 20 of whom had torsade de pointes, we have delineated several heretofore unreported or underemphasized features. (1) This adverse drug reaction occurred either in patients who were being treated for frequent nonsustained ventricular arrhythmias or for atrial fibrillation or flutter. (2) In patients being treated for atrial fibrillation, torsade de pointes occurred only after conversion to sinus rhythm. (3) Although most patients developed the syndrome within days of starting quinidine, four had torsade de pointes during long-term quinidine therapy, usually in association with hypokalemia. (4) Because of the large experience with this entity at our institution, we have been able to estimate the risk as at least 1.5% per year. (5) Twenty of the 24 patients had at least one major, easily identifiable, associated risk factor including serum potassium below 3.5 mEq/L (four); serum potassium between 3.5 and 3.9 mEq/L (nine); high-grade atrioventricular block (four); and marked underlying, (unrecognized) QT prolongation (two). Plasma quinidine concentrations were low, being at or below the lower limit of the therapeutic range in half of patients. The ECG features typically included absence of marked QRS widening, marked QT prolongation (by definition), and a stereotypic series of cycle length changes just prior to the onset of torsade de pointes. Torsade de pointes started after the T wave of a markedly prolonged QT interval that followed a cycle that had been markedly prolonged (usually by a post ectopic pause).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Female; Heart Ventricles; Humans; Long QT Syndrome; Male; Middle Aged; Potassium; Quinidine; Tachycardia

A total of 36 plasma quinidine concentrations from nine hospitalized pediatric patients with cardiac arrhythmias were examined retrospectively to determine factors significantly affecting quinidine dosing. Each plasma quinidine concentration was obtained after at least 24 h of inpatient therapy. Doses of quinidine base varied from 7.7 to 45.6 mg/kg/day and from 179 to 921 mg/m2/day. Six of the eight children who responded to quinidine achieved normal sinus rhythm with plasma concentrations less than 2.0 micrograms/ml. Stepwise multilinear regression analysis demonstrated that the plasma concentration was significantly affected by the quinidine dose and by the time after the dose that the plasma was obtained, but not by the age of the patient. Patient population estimates were then derived to predict the quinidine dosage necessary to achieve given plasma concentrations. The group of patients receiving digoxin concurrently were predicted to obtain higher plasma quinidine levels on smaller doses and a shorter quinidine elimination half-life compared with those patients not on digoxin. While currently recommended quinidine doses by body weight are frequently insufficient, recommended quinidine doses by body surface area are excessive. Children require larger quinidine doses on a body weight basis and respond to a wide range of plasma quinidine concentration. Patient population estimates provide useful information on dosing of infrequently prescribed drugs in children.

Topics: Adolescent; Arrhythmias, Cardiac; Body Surface Area; Body Weight; Child; Child, Preschool; Digoxin; Humans; Infant; Infant, Newborn; Quinidine; Regression Analysis; Retrospective Studies

Topics: Adult; Animals; Arrhythmias, Cardiac; Blood Proteins; Cardenolides; Child; Digitoxin; Digoxin; Humans; Immunoglobulin Fab Fragments; Saponins; Sheep

To test the hypothesis that the endogenous opioid system is operative in digitalis arrhythmias, guinea pigs anesthetized with pentothal and breathing spontaneously were allocated to a control group or four naloxone groups: 0.1 mg/kg i.v., 1.0 mg/kg i.v., 2 mg/kg i.v. or 4 mg/kg i.v. after the induction of arrhythmias by digoxin 100 micrograms/kg i.v. every 15 min. Naloxone at higher doses resulted in a rapid development of fatal arrhythmias with high degree AV block being more frequent than ventricular tachycardiac or fibrillation. Survival was significantly and inversely related to naloxone dose. The role of the autonomic nervous system was studied using cervical cord transection at the C7 level or bilateral cervical vagotomy, or atropine 1.2 mg/kg pretreatment. Cord transection, but not vagotomy, was associated with a significantly higher digoxin dose to produce arrhythmias. Naloxone 4 mg/kg i.v. shortened survival in cord transected animals, but less than in intact animals. Naloxone did not alter survival in vagotomized animals or animals that were pretreated with atropine. Thus, naloxone accelerates the development of fatal cardiac arrhythmias suggesting that endogenous opioids are involved in digitalis toxic arrhythmias an effect interrelated to the autonomic, mainly parasympathetic, nervous system.

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Digitalis Glycosides; Digoxin; Electrocardiography; Guinea Pigs; Male; Naloxone; Sympathetic Nervous System

Magnesium (Mg2+) plays a significant role in the electrical stability of the heart and hypomagnesemia may predispose patients to arrhythmias and digitalis toxicity. We measured the serum and skeletal muscle Mg2+ content of patients with chronic Chagasic cardiomyopathy (CCC) during treatment for congestive heart failure and compared it to 15 normal patients who were used to establish the normal values of our population. There is a high frequency of muscle Mg2+ deficiency (66%) in patients with CCC during treatment for heart failure. However, serum Mg2+ is not a sensitive index of deficiency, since hypomagnesemia occurred in only 50% of the patients whose muscle Mg2+ was low. Digitalis toxicity was observed in all muscle Mg2+-deficient patients (100%) and in 25% of patients with normal Mg2+ levels (P less than or equal to 0.05). Ventricular tachycardia (VT) occurred in 75% of muscle Mg2+-deficient patients and in none of the patients with normal magnesium levels (P less than or equal to 0.05). The frequency and severity of premature ventricular contractions (PVC) were higher in muscle Mg2+-deficient patients. We conclude that muscle Mg2+ deficiency is very common in patients with CCC being treated for congestive heart failure and that muscle Mg2+ deficiency defines a higher risk CCC group in terms of digitalis toxicity and severe ventricular arrhythmias such as ventricular tachycardia.

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Chagas Cardiomyopathy; Digoxin; Female; Heart Failure; Humans; Magnesium; Magnesium Deficiency; Magnesium Sulfate; Male; Middle Aged; Muscles

In addition to its role in myocardial excitation-contraction coupling, the sarcoplasmic reticulum may be involved in arrhythmogenic actions of cardiotonic steroids. This study in isolated cardiac muscle demonstrates that ryanodine can prevent the arrhythmias and reduce the positive inotropic effect produced by cardiotonic steroids without affecting their specific binding to sites on Na,K-ATPase. These data suggest that the antagonism is mediated by ryanodine-induced alterations in Ca2+ release from the sarcoplasmic reticulum.

Topics: Alkaloids; Animals; Arrhythmias, Cardiac; Cardiac Glycosides; Digoxin; Guinea Pigs; In Vitro Techniques; Kinetics; Myocardial Contraction; Receptors, Drug; Ryanodine; Sodium-Potassium-Exchanging ATPase; Strophanthidin

Propafenon's influence on the pharmacokinetic and actions of digitalis and viceversa have been evaluated in 27 patients (25 with ventricular hyperkinetic arrhythmias and 2 with paroxismal atrial fibrillation). Patients were divided in two groups according to whether the drug firstly administered were digoxin or propafenon. Plasmatic digoxin and/or propafenon's concentrations, these last performed only in 12 patients, were determined before and during the association and after propafenon's interruption at 7.55-9-11 and at 3-8 p.m. During drug's association area under the plasmatic digoxin concentration curve (AUC 12h) increased on the average by 13.8% (from 19.27 +/- 6.002 ng hours/ml to 21.94 +/- 6.198 ng hours/ml: P less than 0.05) and by 19% at the first hour. Neverthless individual behaviour was not homogeneous since the plasmatic digoxin concentration (PDC) increased in 22 cases (81.4%) and decreased in 5 (18.6%). In 6 patients mean increase was 38.8% (from 16.72 +/- 3.0 ng hours/ml to 23.21 +/- 5.44 ng hours/ml) without signs of digoxin intoxication. Another patient with congestive heart failure and basal PDC 1.87 ng/ml experienced digoxin poisoning with fatal ventricular fibrillation after propafenon. Digoxin administration in the second group's patients produced a not significant increase of plasmatic propafenon concentration (PPC). There was a good correlation among propafenon's absolute amount and plasmatic concentration and antiarrhythmic effect and no correlation among PPC and body-weight related dose. Propafenon's to digitalis association induced, in propafenon's steady state, significant P-R longation from 170 to 190 ms (P less than 0.01) but HR, QRS and QTc didn't show any important change (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Drug Interactions; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Propafenone

Arrhythmias are common in patients with congestive heart failure (CHF), especially those with concomitant ischemic heart disease. The degree of left ventricular dysfunction is the most important indicator of prognosis in patients with severe heart failure. In general, the better the patient's ventricular function, the greater his chance of survival. In addition, the severity of arrhythmias is also related to survival; patients with simple arrhythmias have higher survival rates than those with complex arrhythmias. All drugs used in the treatment of CHF have a potential proarrhythmic effect. In a study involving the new class of positive inotropic agents, a trend toward higher mortality was evident in CHF patients with ischemic heart disease compared with those with congestive dilated cardiomyopathy. A subgroup of patients also treated with antiarrhythmic agents had lower sudden death rates than those not receiving antiarrhythmics. A double-blind clinical trial of antiarrhythmic agents for patients with CHF is warranted.

Topics: Arrhythmias, Cardiac; Digoxin; Diuretics; Female; Heart Failure; Heart Ventricles; Humans; Male; Prognosis; Sex Factors; Vasodilator Agents

A study of digoxin antiarrhythmic effect in 44 patients with recurrent ventricular extrasystole showed the drug to be effective in an average 34% of patients, the effect being more marked in patients with originally impaired ventricular function.

Topics: Adult; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Digoxin; Electrocardiography; Exercise Test; Heart Ventricles; Hemodynamics; Humans; Male; Middle Aged

Prompt control of heart rate is important for successful treatment of supraventricular tachyarrhythmias early after open heart surgery when sympathetic tone is high and ventricular response rates may be rapid. Esmolol, a new ultrashort-acting (9 minute half-life) beta-receptor blocking agent, was given by continuous intravenous infusion for up to 24 hours in 24 patients (21 with isolated coronary bypass surgery and 3 with valve replacement) 1 to 7 days after surgery. Atrial fibrillation was present in 9 patients, atrial flutter in 2 and sinus tachycardia in 13. Eleven patients had received intravenous digoxin (average dose 0.6 mg, average serum level 1.19 mg/100 ml) before esmolol infusion without adequate control of the supraventricular tachyarrhythmia. After a 1 minute loading infusion of esmolol (500 micrograms/kg per min), maintenance dose, titrated to heart rate and blood pressure response, varied from 25 to 300 micrograms/kg per min. After esmolol administration, at an average dose of 139 +/- 83 micrograms/kg per min, mean heart rate decreased from 130 +/- 15 to 99 +/- 15 beats/min. Within 5 to 18 minutes after initiation of therapy, all patients had achieved a 15% reduction in heart rate at a maintenance dose of 150 micrograms/kg per min or less. A 20% reduction in heart rate was attained in 19 of the 24 patients, and conversion to sinus rhythm occurred during esmolol infusion in 5 of the 11 patients with atrial flutter or fibrillation. Transient asymptomatic hypotension (less than 90/50 mm Hg) was seen in 13 patients, requiring cessation of esmolol therapy in 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenergic beta-Antagonists; Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Blood Pressure; Cardiac Surgical Procedures; Digoxin; Dose-Response Relationship, Drug; Heart Rate; Humans; Hypotension; Infusions, Parenteral; Middle Aged; Postoperative Complications; Premedication; Propanolamines; Tachycardia

The importance of cardiovascular system involvement in hyperthyroidism has been recognized for many years. In the middle-aged and elderly patient, often with mild but prolonged elevation of plasma thyroid hormones, symptoms and signs of heart failure and complicating atrial fibrillation may dominate the clinical picture and mask the more classical endocrine manifestations of the disease. Pitfalls in diagnosis and the importance of early recognition and treatment are discussed. Despite experimental evidence for a short-term inotropic action of thyroid hormone excess, clinical data support the existence of a reversible cardiomyopathy in hyperthyroidism with impaired contractile reserve. Enhanced myocardial performance at rest primarily reflects the peripheral actions of thyroid hormone excess. Most, if not all, of the cardiac abnormalities return to normal once a euthyroid state has been achieved, although atrial fibrillation may persist in a minority. Optimum treatment requires rapid and definitive antithyroid therapy, usually using a large dose of radio-iodine, and rapid control of heart failure. Systemic anticoagulation is indicated in the presence of atrial fibrillation and should be continued until sinus rhythm has been present for at least three months, either spontaneously or after cardioversion.

Topics: Adrenergic beta-Antagonists; Angina Pectoris; Arrhythmias, Cardiac; Atrial Fibrillation; Cardiomyopathies; Digoxin; Drug Therapy, Combination; Heart Diseases; Heart Rate; Hemodynamics; Humans; Hyperthyroidism; Myocardial Contraction; Myocardial Infarction; Sympathetic Nervous System; Thyroid Function Tests; Thyroid Hormones

Effects of amiloride on the inotropic and toxic actions of cardiac glycosides were examined using left atrial muscle isolated from guinea pig heart. Preincubation of atrial muscle with amiloride significantly decreased the maximum positive inotropic effect of dihydrodigoxin but failed to reduce that of isoproterenol. Amiloride prevented the contracture and significantly reduced the incidence of arrhythmias induced by 2 microM digoxin. Similar experiments examining 5 microM digoxin-induced arrhythmias showed that amiloride increased both the time required to produce arrhythmias and the fractional occupancy of sarcolemmal Na,K-ATPase by digoxin at the onset of arrhythmias. The antagonism of cardiac glycoside actions was best observed during the decline in developed tension elicited by amiloride subsequent to its initial positive inotropic effect. Amiloride had no effect on binding site concentration for ATP-dependent [3H]ouabain binding but decreased affinity of the binding sites for ouabain in membrane preparations obtained from guinea pig heart. Furthermore, amiloride inhibited Na,K-ATPase activity and increased the IC50 value for ouabain inhibition of the enzyme. These results indicate that amiloride antagonizes the positive inotropic and toxic effects of cardiac glycosides. Possible mechanisms for the antagonism include inhibition of sarcolemmal Na+/Ca2+ or Na+/H+ exchange.

Topics: Amiloride; Animals; Arrhythmias, Cardiac; Binding, Competitive; Cardiac Glycosides; Digoxin; Guinea Pigs; In Vitro Techniques; Male; Myocardial Contraction; Myocardium; Ouabain; Receptors, Drug; Sodium-Potassium-Exchanging ATPase; Time Factors

Topics: Arrhythmias, Cardiac; Digoxin; Heart Failure; Humans; Patient Education as Topic; Self Administration

The incidence, risk factors and long-term prognosis of complex ventricular arrhythmias after coronary artery bypass graft surgery are not known. Complex ventricular arrhythmias are defined as Lown grades 4a (couplets), 4b (ventricular tachycardia) and 5 (R on T phenomenon). Ninety-two patients with normal left ventricular function who underwent elective coronary artery bypass graft surgery were prospectively evaluated. Ventricular arrhythmias were documented by predischarge 24 hour ambulatory electrocardiographic monitoring; 43% of patients had no or simple ventricular arrhythmias (Lown grades 1 to 3) and 57% had complex ventricular arrhythmias. Risk factors analyzed included age, sex, diabetes, hypertension, smoking, preoperative digoxin or propranolol therapy, cardiopulmonary bypass time, aortic cross-clamp time, number of vessels bypassed, peak creatine kinase (CK) elevation and pericarditis. No risk factor identified patients at higher risk for complex ventricular arrhythmias. Patients were followed up for 6 to 24 months (mean 16). Patients with complex ventricular arrhythmias did not have a higher incidence of sudden death, cardiac death, syncope, angina, myocardial infarction or cerebrovascular accident. It was concluded that: Complex ventricular arrhythmias are common after coronary artery bypass graft surgery. None of the risk factors considered identify high risk patients. Complex ventricular arrhythmias after coronary artery bypass graft surgery do not indicate a poor prognosis in patients with normal left ventricular function.

Topics: Ambulatory Care; Angina Pectoris; Arrhythmias, Cardiac; Coronary Artery Bypass; Digoxin; Electrocardiography; Electrophysiology; Female; Follow-Up Studies; Heart Ventricles; Humans; Male; Middle Aged; Monitoring, Physiologic; Premedication; Prognosis; Propranolol; Prospective Studies; Random Allocation; Risk; Time Factors

The rational therapy of cardiovascular disease in horses requires a thorough knowledge of the pharmacology and pharmacokinetics of several specific drugs (digitalis, digoxin). Calcium solutions, dopamine, and dobutamine are frequently used to treat congestive heart failure in horses. Quinidine, procainamide, lidocaine, and propranolol are used to treat a variety of supraventricular and ventricular arrhythmias. Furosemide, a highly potent loop diuretic, is used to eliminate edema and promote diuresis. A thorough understanding of the applied pharmacology, dosage recommendations, toxicity, and practical considerations must be attained before these drugs can be used effectively.

Topics: Administration, Oral; Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Digoxin; Diuretics; Dobutamine; Dopamine; Drug Administration Schedule; Edema; Heart Diseases; Heart Failure; Heart Rate; Hemodynamics; Horse Diseases; Horses; Injections, Intravenous; Lidocaine; Procainamide; Propranolol; Quinidine

Cardiac arrhythmias are probably more common in horses than in any other domestic animal species. The most frequent clinical complaint associated with cardiac arrhythmias is exercise intolerance. Physical examination is characterized by auscultation abnormalities such as fast or slow heart rate, irregular rhythm, extra sounds, long pauses, or abnormal heart sounds. The electrocardiogram is used to make a definitive diagnosis of the dysrhythmia. Other laboratory and cardiac function tests are employed to determine the etiology and to assess the significance of the arrhythmia. Antiarrhythmic therapy is given when clinical signs specifically related to the arrhythmia are present, when hemodynamic parameters are compromised by the arrhythmia, or when the ECG reveals abnormalities that put the patient at risk for development of more severe arrhythmias. The cardiovascular drugs most frequently used are digoxin and quinidine. Digoxin is most commonly used for supraventricular arrhythmias, especially arrhythmias characterized by fast heart rates. Quinidine is very effective for short-term treatment of ventricular and supraventricular arrhythmias but must be used with caution because of the potential for toxic side effects. The cardiac arrhythmias due to vagal tone (sinus arrhythmia, sinus block, sinus arrest, sinus bradycardia, wandering pacemaker, first-degree AV block, and second-degree AV block) that are found in resting horses are generally considered to be normal and generally do not require therapy.

Topics: Animals; Arrhythmias, Cardiac; Autonomic Agents; Clinical Laboratory Techniques; Diagnosis, Differential; Digoxin; Electrocardiography; Heart Auscultation; Heart Rate; Heart Sounds; Horse Diseases; Horses; Physical Examination; Quinidine

During treatment with amiodarone, digoxin and nadolol, asystole occurred repeatedly in a patient with chronic persistent automatic atrial tachycardia. Asystole did not occur after discontinuation of drug therapy, and rechallenge with amiodarone alone produced marked overdrive suppression of all pacemakers resulting in asystole. Amiodarone serum level was within therapeutic range. The possible electrophysiologic mechanisms by which amiodarone might suppress both normal and abnormal pacemakers are discussed. The occurrence of asystole at therapeutic serum concentration of amiodarone suggests that this drug should be used with caution.

Topics: Adult; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Digoxin; Drug Therapy, Combination; Electrocardiography; Female; Heart Arrest; Heart Atria; Heart Rate; Humans; Nadolol; Propanolamines; Tachycardia

Fetal cardiac arrhythmias are usually first suspected on the basis of auscultatory findings during routine examination in pregnancy. With improved ultrasonic equipment a more accurate diagnosis of the type of arrhythmia can be made, associated problems such as structural cardiac defects and cardiac compromise can be recognized, and the effects of intrauterine treatment schedules can be closely monitored. The success of intrauterine therapy depends first and foremost on accurate intrauterine diagnosis. Until now intrauterine therapy for fetal cardiac arrhythmias has remained almost entirely restricted to pharmacological interventions.

Topics: Amiodarone; Arrhythmia, Sinus; Arrhythmias, Cardiac; Chromosome Aberrations; Chromosome Disorders; Diagnosis, Differential; Digoxin; Drug Therapy, Combination; Echocardiography; Edema, Cardiac; Female; Fetal Diseases; Fetal Growth Retardation; Fetal Heart; Gestational Age; Heart Rate; Humans; Karyotyping; Lung; Maternal-Fetal Exchange; Pregnancy; Procainamide; Prognosis; Propranolol; Quinidine; Ultrasonography; Vena Cava, Superior; Verapamil

Cardiac anatomy and rhythm were evaluated in the fetuses of 18 pregnant women (between 20 and 42 weeks of gestation) referred because of abnormal fetal heart rate or rhythm. Utilizing a 3 MHz two-dimensional scan head with M-mode capability, M-mode recordings were obtained at paper speeds of 50 and 100 mm/s from 16 fetuses. The arrhythmia of two fetuses was diagnosed using two-dimensional echo alone. Semilunar and atrioventricular valve opening and closing points, A waves, plus ventricular wall motion were used for timing purposes; and heart rate and rhythm were determined. Diagnoses made were atrial premature beats n = 3, ventricular premature beats n = 3, congenital heart block n = 4, supraventricular tachycardia n = 3, sinus bradycardia n = 1, and blocked atrial beats n = 1. In three fetuses no arrhythmia was identified. Cardiac anatomy was normal in 16 fetuses, with two (congenital heart block) felt to have univentricular hearts. Fourteen pregnancies went to term, two were delivered prematurely, and two fetuses with congenital heart block were stillborn. In three fetuses arrhythmia was confirmed during labor by fetal scalp electrode. Arrhythmia was absent after birth in 11 of 16 infants, with congenital heart block persistent in two infants, and supraventricular tachycardia, atrial premature beats, and blocked atrial premature beats remaining in one each. Intervention with medical management was attempted in four pregnancies, with successful termination of arrhythmia supraventricular tachycardia) in two fetuses. We conclude that combined two-dimensional M-mode capability is useful in the diagnosis of fetal rhythm disturbances, and perhaps in the selection of timing, and mode of intervention.

Topics: Adult; Arrhythmias, Cardiac; Digoxin; Echocardiography; Female; Fetal Diseases; Follow-Up Studies; Humans; Pregnancy; Verapamil

Topics: Arrhythmias, Cardiac; Digoxin; Humans; Magnesium Deficiency; Magnesium Sulfate

To determine the incidence of cardioversion-induced ventricular arrhythmias in patients with therapeutic serum levels of digoxin, 19 patients (average age [+/- standard deviation] 61 +/- 12 years) undergoing elective direct current cardioversion for atrial fibrillation were studied. Only patients with therapeutic serum digoxin levels (range 0.5 to 1.9 ng/ml; mean 1.1 +/- 0.5) at the time of cardioversion were included. Patients with acute myocardial ischemia or unstable angina, serious electrolyte disturbance or those requiring class I antiarrhythmic agents for control of ventricular or supraventricular arrhythmias were excluded. Ambulatory electrocardiograms were recorded for 24 hours before and 6 hours after cardioversion. No patient developed malignant ventricular arrhythmias (ventricular triplets or tachycardia) in the immediate 3 hour period after cardioversion. Furthermore, there were no significant (p less than 0.05) differences in the frequency of ventricular premature beats or couplets before and after cardioversion. To determine whether the level of serum digoxin or the strength of the applied shock had a significant effect on the development of postcardioversion arrhythmias, the change in frequency of single premature ventricular beats after cardioversion was compared with the serum digoxin level (ng/ml) and the applied energy level (joules) by means of linear regression analysis. There was no significant (p less than 0.05) relation between these variables. These findings suggest that patients with therapeutic serum levels of digoxin may safely undergo cardioversion without the concomitant use of class I antiarrhythmic agents.

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Electric Countershock; Heart Ventricles; Humans; Middle Aged; Time Factors

This study investigated the effects of therapeutic and subtoxic doses of digoxin on the risk of ventricular tachycardia (VT) after graded, transthoracic shocks in anesthetized dogs. A series of direct current shocks (5, 10, 25, 50, 75, 100, 150 and 200 J) was delivered to 33 normal dogs and 6 dogs with a healed (32 +/- 7 days) myocardial infarct (MI). In 10 untreated dogs, the duration of post-shock VT was highly reproducible when 3 separate series of shocks were delivered at 2-hour intervals. In 6 normal dogs treated with oral digoxin (0.5 mg/day for 5 to 7 days), a series of shocks delivered before and during treatment (serum levels 1.5 +/- 0.5 ng/ml) resulted in the same duration of post-shock VT. In 18 normal and 6 dogs with MI, a series of shocks was given before and 90 minutes after a therapeutic dose of digoxin (0.05 mg/kg intravenously). At this dose of digitalis (serum level 2.5 +/- 1.0 ng/ml), there was no difference in the duration of post-shock VT in either normal dogs or dogs with MI. A third series of shocks was given after achieving subtoxic digitalization with additional intravenous digoxin (0.01 mg/kg) every 30 minutes until a premature ventricular stimulus evoked a repetitive ventricular response. The subtoxic doses of digitalis (serum levels 13.9 +/- 4.7 ng/ml) increased the duration of post-shock VT in both normal dogs (100%) and dogs with MI (700%) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Dose-Response Relationship, Drug; Electric Countershock; Electrocardiography; Heart Ventricles; Myocardial Infarction; Risk; Tachycardia

In a prospective and a retrospective study, the effects of hyperkalemia on the electrocardiogram (ECG) of patients treated with customary maintenance doses of digoxin were examined and the results were compared with the effects of hyperkalemia in patients not receiving digitalis. The prospective study included 11 patients treated and 11 not treated with digitalis, and the retrospective study 27 patients treated and 61 not treated with digitalis. In all patients serum potassium concentrations (Ks) were determined within 1 hour of the recorded electrocardiogram. Serum digoxin concentrations, measured in 11 patients in the prospective and in 4 in the retrospective study, ranged from 0.7 to 5.0 ng/ml, and exceeded 2.0 ng/ml in 10 of 15 patients. Since the results of the prospective and of the retrospective study were similar, they were combined. In patients treated with digitalis, Ks ranged from 5.5 to 6.6 mEq/liter in 21 patients, from 6.7 to 7.5 mEq/liter in 17 and from 7.6 to 8.5 mEq/liter in 6; the Ks was 9.1 mEq/liter in 1 patient. The ventricular rate in patients treated with digitalis ranged from 48 to 140 beats/min, and was not significantly different from that in untreated patients within each range of Ks. Atrioventricular (AV) junctional rhythm occurred more frequently in the electrocardiograms of digitalis-treated patients (15 of 45 vs 2 of 76, p less than 0.001). The average PR intervals were longer in patients treated with digitalis who had Ks greater than 6.6 mEq/liter, but no patient in the study had greater than first-degree AV block, and no patient required a pacemaker.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Arrhythmias, Cardiac; Digitalis; Digoxin; Electrocardiography; Female; Heart Rate; Humans; Hyperkalemia; Male; Middle Aged; Plants, Medicinal; Plants, Toxic; Prospective Studies; Retrospective Studies

In a review of the records of 81 patients with the discharge diagnosis of digitalis toxicity, I found a preponderance of very old patients, many of whom had anorexia, nausea, and prerenal azotemia. Arrhythmias were common (93%) and reflected enhanced automaticity, enhanced AV block, or both. Atrial fibrillation with complete heart block and a regular junctional rhythm should particularly elicit suspicion of digitalis toxicity. Atrial tachycardia with block is less specific and less frequent.

Topics: Adult; Age Factors; Aged; Anorexia; Arrhythmias, Cardiac; Atrial Fibrillation; Digitalis; Digoxin; Heart Atria; Heart Block; Humans; Middle Aged; Nausea; Plants, Medicinal; Plants, Toxic; Radioimmunoassay; Tachycardia; Uremia

The effect of diltiazem on digoxin serum concentration was evaluated in 9 patients who had been treated chronically for heart disease with digoxin, 0.25 mg/day. The indications for digoxin therapy were arrhythmias in 5 patients and mild heart failure in the other 4. Renal digoxin clearance was also evaluated in 8 of these patients. Serum digoxin concentration was measured at control, 7 +/- 2 days after initiation of 120 mg/day of diltiazem and 11 +/- 5 days after increasing the dose of diltiazem to 240 mg/day. Serum digoxin concentration was 0.9 +/- 0.4 ng/ml at control, 0.8 +/- 0.4 ng/ml with 120 mg/day of diltiazem, and 0.8 +/- 0.3 ng/ml during therapy with 240 mg/day. The differences between these values were not significant. Renal digoxin clearance also did not show a significant change after diltiazem therapy (44 +/- 15 ml/min before diltiazem and 46 +/- 13 ml/min with 240 mg/day of diltiazem). This study shows no effect of diltiazem in doses of 120 to 240 mg/day on serum digoxin concentration or renal digoxin clearance in patients who are treated chronically for heart disease with digoxin. In this dose range, diltiazem has advantages over verapamil, which markedly elevates digoxin levels.

Topics: Adult; Aged; Arrhythmias, Cardiac; Benzazepines; Cross Reactions; Digoxin; Diltiazem; Female; Heart Failure; Humans; Kidney; Male; Middle Aged; Radioimmunoassay

Topics: Animals; Arrhythmias, Cardiac; Chick Embryo; Digoxin; Fetal Heart; Heart; Heart Arrest; Medigoxin; Myocardial Contraction

We report two patients who developed symptomatic life-threatening ventricular tachyarrhythmias with changing QRS axes (resembling torsades de pointes), during treatment of their supraventricular tachycardias with oral amiodarone. Like other effects of amiodarone on the body, the arrhythmias became evident several days after initiating therapy, at which time electrocardiographic QT prolongation was present. The arrhythmias subsided after amiodarone treatment was withdrawn. No other drugs or electrolyte disturbances could be incriminated as a cause.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Digoxin; Electrocardiography; Female; Humans; Tachycardia

We examined by medical-record review why long-term digitalis therapy was prescribed in 150 outpatients, the reasons were: supraventricular tachyarrhythmias (35): supraventricular tachyarrhythmias and heart failure (33); and heart failure with sinus rhythm (82). In the patients without supraventricular tachyarrhythmias we scrutinized the diagnosis of heart failure using a clinicoradiographic scoring system and found the diagnosis unlikely in 32 patients. When these 32 patients are combined with the 31 patients who had only one occurrence of supraventricular tachyarrhythmias or heart failure, 42% of the patients were on long-term digitalis therapy for a questionable reason. We conclude that a substantial fraction of general medical outpatients might benefit from digitalis withdrawal, if evidence for heart failure is lacking or if the reason prompting digitalis therapy is isolated to the distant past.

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Female; Heart Failure; Humans; Male; Outpatient Clinics, Hospital; Time Factors

The frequency of therapy with digitalis glycosides was determined in 4.143 patients on their first visit at a medical outpatient clinic. 508 (12.3%) patients said to take digitalis. Of 480 (94.5%) patients, a digoxin serum concentration was obtained. It was in 229 (47.7%) patients below, in 31 (6.5%) above, and in 220 (45.8%) within the therapeutic range (0.8-2.0 ng/ml). From the 251 patients with a serum digoxin concentration greater than or equal to 0.8 ng/ml, 220 (87.7%) were not included in a withdrawal trial on the basis of predetermined criteria, mainly because of cardiac diseases (52%). Digitalis therapy was withdrawn in 31 patients. 5 patients started to take the drug again on their own; they were considered drop-outs. In the remaining 26 patients, no symptoms of heart failure appeared during a 3-month observation period; in 2 patients, however, atrial fibrillation requiring intervention occurred. Our results confirm the frequent use of digitalis therapy in Germany, but also the frequent presence of subtherapeutic serum digoxin concentrations. Withdrawal should be considered in patients with a questionable indication for this therapy; the occasional occurrence of supraventricular arrhythmias, and not so much of heart failure, should be anticipated.

Topics: Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Female; Heart Diseases; Heart Failure; Humans; Male; Middle Aged; Substance Withdrawal Syndrome

34 patients aged between 2 and 80 years were treated with digoxin specific antibody (Fab) fragments for severe digitalis poisoning. In 27 cases, the glycoside was taken with suicidal intent; in 3 cases accidentally and 4 were iatrogenic. The following criteria were considered to be indications for use of Fab fragments: the appearance of life-threatening arrhythmias such as high-grade atrioventricular conduction disorders (grade 2 and 3 A-V block), multifocal ectopic beats, ventricular tachycardia, and relapsing ventricular fibrillation. Serum digoxin concentrations were between 3.4 and 29ng/ml before the start of treatment. Between 240 and 800mg of Fab were administered; the majority of patients received 480mg. Regression of arrhythmias was seen between 0.5 and 8 hours after Fab infusion. There was a rapid fall in the free digoxin in the serum to concentrations that were no longer measurable and a marked rise in bound digoxin with a simultaneous increase of excretion of bound digoxin in the urine. Fab therapy is considered to be a major advance in the treatment of severe, previously fatal, glycoside poisoning. No notable side effects or allergic reactions were observed.

Topics: Adolescent; Adult; Aged; Antibody Specificity; Arrhythmias, Cardiac; Child; Child, Preschool; Digitalis Glycosides; Digoxin; Female; Humans; Immunoglobulin Fab Fragments; Kinetics; Male; Middle Aged

The first use of Fab fragments to treat digoxin toxicity in a premature infant with renal failure, 18 h after the onset of severe arrhythmias, is reported with dramatic results. The development of digoxin toxicity in the context of accepted therapeutic dosing to treat heart failure due to a cerebral arteriovenous malformation is discussed.

Topics: Arrhythmias, Cardiac; Digoxin; Disorders of Sex Development; Humans; Immunoglobulin Fab Fragments; Infant, Newborn; Infant, Premature, Diseases

Topics: Adult; Arrhythmias, Cardiac; Biological Availability; Digoxin; Drug Interactions; Drug Therapy, Combination; Humans; Male; Middle Aged; Phenytoin; Procainamide; Propranolol

Nursing home patients were studied to determine the usefulness of a maintenance dose of digoxin in elderly patients with normal sinus rhythm. Of 64 patients, 26 were identified to be on digoxin. Thorough history and physical examination were done on all the patients. Baseline electrocardiogram showed normal sinus rhythm in 19 patients, who were observed very closely for the period of four months after withdrawal of digoxin. Eighteen of 19 patients did well without digoxin, which suggests that most of the elderly nursing home patients with normal sinus rhythm do not need a maintenance dose of digoxin.

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Male; Nursing Homes; Substance Withdrawal Syndrome

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Drug Interactions; Heart Failure; Hemodynamics; Humans; Kinetics; Male; Potassium

Topics: Adolescent; Amiodarone; Arrhythmias, Cardiac; Child; Child, Preschool; Digoxin; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Male; Prognosis; Propranolol

The effects of hypoxia on the tolerance of myocardium to the toxic actions of digitalis were studied in isolated heart muscle preparations. Perfusion of Langendorff preparations of guinea-pig heart with a hypoxic solution failed to alter Na, K-ATPase with respect to its activity, its sensitivity to inhibition by dihydrodigoxin, or the number of [3H]ouabain binding sites and their affinity for ouabain, when these activities were estimated in ventricular muscle homogenates obtained after the hypoxic perfusion. Hypoxia potentiated the development of digoxin-induced contracture, as well as digoxin-induced changes in maximal upstroke velocity and the amplitude of action potentials, and the resting transmembrane potential in atrial and ventricular muscle preparations of guinea-pig heart. Under hypoxic conditions, however, digoxin failed to induce arrhythmias. In Purkinje fibers of cat heart, the time to onset of digoxin-induced arrhythmias, or the development of afterdepolarizations, was not affected by hypoxia. These results indicate that hypoxia alters the nature of toxic effects of digitalis in isolated heart muscle preparations, the development of contracture instead of arrhythmias being the primary toxicity in hypoxic muscle.

Topics: Animals; Arrhythmias, Cardiac; Cats; Coronary Disease; Digitalis Glycosides; Digoxin; Female; Guinea Pigs; Heart; In Vitro Techniques; Male; Membrane Potentials; Myocardial Contraction; Ouabain; Oxygen; Sodium-Potassium-Exchanging ATPase; Tritium

We estimated the effect of digoxin on the myocardial potassium content and the action potentials of the left ventricular papillary muscles in dystrophic mice (C57BL/6JCL dy X dy). All of 10 dystrophic mice died following ip injection of digoxin at a dose of one quarter of the iv LD50 for normal mice. The myocardial digoxin concentration and the myocardial potassium content in dystrophic mice were similar to those in normal mice before and 60 min after the ip injection of digoxin. The action potential durations (APD) in dystrophic mice were significantly longer than those in normal mice. Perfusion of digoxin (2 micrograms/ml) for 30 min reduced the APD significantly and induced arrhythmias in dystrophic mice, but it did not bring about any significant change in normal mice. These data suggest that dystrophic mice have increased sensitivity to digitalis. This hypersensitivity to digitalis is not due to increased myocardial digoxin uptake or decreased myocardial potassium content.

Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Digoxin; Female; Male; Mice; Mice, Inbred C57BL; Muscular Dystrophy, Animal; Myocardium; Papillary Muscles; Potassium; Sodium-Potassium-Exchanging ATPase

Topics: Adrenergic beta-Antagonists; Angina Pectoris; Arrhythmias, Cardiac; Calcium Channel Blockers; Digoxin; Drug Interactions; Humans; Hypertension; Hypoglycemic Agents; Kinetics; Liver; Myocardial Infarction

An elderly woman developed a high serum digoxin concentration resulting in toxicity when alprazolam was added to her digoxin therapy. The reduced renal clearance of digoxin is postulated as the mechanism for this interaction.

Topics: Aged; Alprazolam; Anti-Anxiety Agents; Arrhythmias, Cardiac; Benzodiazepines; Digoxin; Drug Interactions; Female; Half-Life; Humans; Kinetics

Calcium antagonists, of which the best known are verapamil, nifedipine and diltiazem, are a powerful group of cardioactive agents with a clinical spectrum of indications rather similar to those of beta-adrenoceptor blockade, including angina of effort, angina at rest, hypertension and supraventricular tachycardias (nifedipine is ineffective for the latter). In angina caused by coronary spasm, calcium antagonists are preferred to beta-blockade. Calcium antagonists have a basically different mode of action from beta-adrenoceptor blockade, although both ultimately act on the free cytoplasmic calcium ion concentration. Critical differences between the calcium antagonists are dependent on the individual properties of the calcium antagonists concerned. Different binding sites on the sarcolemma have been identified for nifedipine-like agents and verapamil, but with a different interaction with the nifedipine site. None of these sites might be relevant to the binding of calcium antagonists to the tissue of their therapeutic site of action (arterial smooth muscle for all; atrioventricular node for verapamil and diltiazem). As a group, calcium antagonists cause vascular dilation and do not cause bronchial constriction, in contrast to the beta-adrenoceptor blocking agents. In many patients, these diverse properties allow safe combination of calcium antagonists and beta-adrenoceptor blockers if due care is observed, especially in the case of nifedipine. The clinical differences between the effects of various calcium antagonists reflect: (i) the greater vasodilator capacity of nifedipine, so that at a given concentration the afterload effect dominates over possible effects on the nodal or myocardial tissue; (ii) the greater inhibition of vagal tone by nifedipine than by verapamil or diltiazem; and (iii) the greater inhibition of the atrioventricular node by verapamil and diltiazem. In angina of effort, calcium antagonists are now becoming the agents of first choice in some centers. Experimental use of calcium antagonists include the possible prevention of ventricular fibrillation, the inhibition of ischemic injury, the prevention of catecholamine mediated injury to the myocardium and decreased arterial calcinosis.

Topics: Adrenergic beta-Antagonists; Angina Pectoris; Animals; Arrhythmias, Cardiac; Calcium; Calcium Channel Blockers; Catecholamines; Coronary Disease; Coronary Vasospasm; Coronary Vessels; Digoxin; Drug Interactions; Heart; Heart Failure; Humans; Hypertension; Myocardial Contraction; Myocardial Infarction; Myocardium; Prazosin; Sinoatrial Node; Structure-Activity Relationship; Ventricular Fibrillation

The ligation of a main branch of coronary vein elevates the sensitivity of isolated, perfused (Langendorff) preparations of guinea-pig heart to arrhythmogenic actions of digoxin. Retrograde perfusion studies indicate that the presence of an area with a high extracellular K+ concentration, adjacent to an area with normal K+ concentration and exposed to the glycoside, predisposes the heart to digitalis-induced toxicity. This model may be useful in studying the mechanism by which acute myocardial infarction decreases the therapeutic index of cardiac glycosides.

Topics: Animals; Arrhythmias, Cardiac; Coronary Circulation; Digoxin; Female; Guinea Pigs; Heart; Male; Myocardium; Potassium; Sodium-Potassium-Exchanging ATPase

Topics: Aged; Antibodies; Antibody Specificity; Arrhythmias, Cardiac; Digitoxin; Digoxin; Electrocardiography; Humans; Immunoglobulin Fab Fragments; Male; Suicide, Attempted

3 cases of fetal complete heart block, 1 case of fetal bradycardia and 2 cases of fetal supraventricular tachycardia were studied. Using an ultrasonic technique combining real-time ultrasound with a pulsed Doppler system, blood flow measurements at the lower thoracic level of the fetal descending aorta were taken. Despite alterations in rhythm, the blood flow in the aorta descendens was maintained within normal range. With a reduced heart rate, there was an increase in stroke volume, blood flow velocity, acceleration of blood flow velocity and maximum diameter change; conversely, with an increased heart rate the same four parameters were lowered. These alterations reflect changes in cardiac contraction force, and illustrate the ability of the fetal myocardium in maintaining blood flow in the growing fetus.

Topics: Aorta; Arrhythmias, Cardiac; Blood Circulation; Digoxin; Female; Fetal Diseases; Heart Rate; Humans; Pregnancy; Stroke Volume; Ultrasonography

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Digoxin; Drug Therapy, Combination; Electrocardiography; Furosemide; Humans; Hydrochlorothiazide; Male; Methyldopa; Middle Aged; Nitroglycerin; Potassium Chloride; Quinidine

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Digitoxin; Digoxin; Humans; Plants, Medicinal; Plants, Toxic

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Female; Humans; Patient Education as Topic

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Cardiac Surgical Procedures; Digoxin; Extracorporeal Circulation; Female; Hematocrit; Humans; Male; Middle Aged; Postoperative Period; Premedication

Lidoflazine is a calcium channel blocking agent that is effective and safe in the treatment of angina pectoris, but has been reported to be associated with sudden death when administered for the treatment of supraventricular arrhythmias. Studies were performed in dogs to determine if lidoflazine caused a rise in serum digoxin concentration that could cause arrhythmias or if it was directly arrhythmogenic. Dogs received chronic injections of digoxin and then digoxin in combination with lidoflazine. No increase in digoxin concentration was found. Dogs also underwent programmed electrical stimulation while not receiving medications and then after incremental doses of lidoflazine administered intravenously. Lidoflazine did not cause spontaneous ventricular tachycardia and did not lower the threshold of ventricular tachycardia induction. Combined administration of lidoflazine and digoxin did not facilitate arrhythmia induction. These studies do not support a digoxin-lidoflazine interaction or a direct arrhythmogenic action of lidoflazine.

Topics: Animals; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Digoxin; Dogs; Drug Interactions; Female; Lidoflazine; Male; Piperazines

Owing to its positive inotropic action, digitalis is indicated in congestive heart failure; because of its effect on AV conduction it can also be used in arrhythmias. However the nature of the dysrhythmia and the underlying causes of congestive heart failure and arrhythmia need to be further differentiated. Any underlying disease (e.g. renal failure) must be treated primarily. Also, the value of inotropic agents in obstructive lesions needs to be considered. In cardiac arrhythmias digitalis can elicit potentially dangerous arrhythmias owing to AV block. Shortening of the refractory period of "bypass tracts" and by changing automaticity in autonomic focus atrial tachycardia. The possibility of interactions with such commonly used antiarrhythmic drugs as quinidine and amiodarone must be considered. All patients receiving digitalis should be carefully followed and monitored using physical examination, ECG, echocardiographic assessments and digitalis blood level determinations.

Topics: Arrhythmias, Cardiac; Child, Preschool; Digitalis Glycosides; Digoxin; Dose-Response Relationship, Drug; Drug Interactions; Electrocardiography; Heart Defects, Congenital; Heart Failure; Hemodynamics; Humans; Infant; Infant, Newborn

Bretylium has been well-recognized as an effective antiarrhythmic agent for acute ventricular arrhythmias, but its use is believed to be contraindicated in digitalis intoxication. We report of two patients in whom digitalis-induced malignant ventricular arrhythmias were refractory to lidocaine. One patient had had repeated episodes of ventricular fibrillation associated with digitoxin and quinidine intoxication, and one patient had had malignant premature ventricular beats associated with digoxin intoxication. Cardiac electrical activity was paced in both instances. In the two patients, ventricular arrhythmias rapidly resolved, and no side effect was encountered. These observations support the administration of bretylium for severe digitalis-induced ventricular arrhythmias.

Topics: Aged; Arrhythmias, Cardiac; Blood Pressure; Bretylium Compounds; Bretylium Tosylate; Digoxin; Electric Countershock; Electrocardiography; Female; Heart Ventricles; Humans; Lidocaine; Male; Middle Aged; Suicide, Attempted

The increasing use of amiodarone as antiarrhythmic drug has raised the possibilities of dangerous effects from amiodarone-digitalis interaction. We have studied twelve patients who were taking digitalis and to whom amiodarone was administered because of arrhythmias. We found a 75,42% increase of digitalis plasma levels (p less than 0,001) in the early days of amiodarone therapy, and a 52,1% increase (p less than 0,001) in the medium term. An inverse correlation was found (r = -0,65; p less than 0,05) between the plasma levels of digitalis during the steady-state control period and during the following 2-to-6 months evaluation. Acute episodes of cardiac failure caused in our patients an abrupt increase of digitalis plasma levels: in three patients digitalis toxicity occurred. Based on our experience, we recommend that the dose of digitalis be halved when the two drugs are given together in patients with various degree of cardiac failure; moreover digitalis plasma levels should be frequently monitored in these patients. On the other hand digitalis administered according to age, sex, weight, kidney function, together with amiodarone, can be given at full dosage in patients without cardiac failure.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Digitalis Glycosides; Digoxin; Drug Interactions; Female; Heart Diseases; Humans; Male; Medigoxin; Middle Aged

Topics: Arrhythmias, Cardiac; Digoxin; Humans; Male; Middle Aged; Myocardial Infarction; Nursing Assessment

To extend the potential application of digoxin-specific immunoglobulin (Ig) (Fab) fragments for the reversal of advanced digitalis intoxication, monoclonal digoxin-specific antibodies were obtained by fusion of myeloma cell lines with spleen cells from mice immunized with a digoxin-serum albumin conjugate. The monoclonal antibody from the cell line designated Dig 26-10 had high affinity (KA = 5 X 10(9) M-1) and specificity for digoxin and was tested for its efficacy in the reversal of advanced, otherwise lethal digoxin toxicity in guinea pigs given a loading dose of 500 micrograms of digoxin per kg b.wt. i.v. followed by continuous infusion of digoxin at 10 (IgG-treated group) or 50 (Fab-treated group) microgram/kg/min. Control animals given nonspecific rabbit or mouse Igs after the onset of digoxin-toxic ventricular arrhythmias all died. Administration of monoclonal digoxin-specific antibody as intact IgG in doses stoichiometrically equivalent to the digoxin dose fully reversed digoxin toxicity in six of eight animals and prolonged survival somewhat in the remaining two animals. Fab fragments from the Dig 26-10 monoclonal antibody were even more effective, with rapid reversal (mean time 7 min) of all arrhythmias and survival of all animals so treated. We conclude that murine monoclonal antibodies and their Fab fragments are capable of reversing advanced and otherwise lethal digoxin-induced arrhythmias in a guinea-pig experimental model and offer potential advantages over polyclonal antibodies in the management of this clinically important problem.

Topics: Animals; Antibodies, Monoclonal; Arrhythmias, Cardiac; Digoxin; Female; Guinea Pigs; Heart Ventricles; Immunoglobulin Fab Fragments; Immunotherapy; Male

Serum drug concentration data from the first of the two patients described herein suggest that rifampin may directly increase the metabolism of quinidine and thereby negate the influence of quinidine on the serum digoxin concentration (SDC). Data on the second patient suggest that rifampin may directly increase the metabolism of digoxin producing lower SDC values. In both cases, the discontinuation of rifampin therapy appears to have allowed reversion toward prerifampin metabolism of both quinidine and digoxin.

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Drug Interactions; Drug Therapy, Combination; Female; Humans; Kinetics; Middle Aged; Quinidine; Rifampin; Tuberculosis, Pulmonary

In pentobarbital-anaesthetized (60 mg/kg i.p.) guinea-pigs injections of Na salicylate (50 and 100 mg/kg i.v.) had a protective effect against arrhythmias induced by digoxin or BaCl2. A lower (25 mg/kg) and a higher (200 mg/kg) dose exerted no clearcut antiarrhythmic effect. Plasma concentrations of Na salicylate up to 1 mg/ml influenced neither the heart rate nor the ECG parameters. The antiarrhythmic effect of the drug may be explained by an inhibition of cardiac cyclooxygenase.

Topics: Animals; Arrhythmias, Cardiac; Barium; Barium Compounds; Blood Pressure; Chlorides; Digoxin; Electrocardiography; Guinea Pigs; Heart Rate; Male; Sodium Salicylate

To date, 16 patients with severe glycoside poisoning have been treated with Fab as part of the clinical trial for efficacy and tolerance. The ages of the patients ranged from 4 to 77 years. In 13 cases, the substance was taken with suicidal intent. The following were considered to be indications for the use of Fab: the appearance of life-threatening arrhythmias as high-grade atrioventricular conduction disorders, multifocal ectopic beats, ventricular tachycardia, and relapsing ventricular fibrillation in 5 cases. Serum digoxin concentrations were between 3.8 and 78 ng/ml before the start of treatment. The amount of Fab administered was 240-800 mg, in the majority of cases 480 mg. Regression of the arrhythmias was seen in all patients during or shortly after the Fab infusion. There was a rapid fall in the free digoxin in the serum to levels that were no longer measurable and a marked rise in bound digoxin with a simultaneous intensive excretion of bound digoxin in the urine. Fab therapy is considered to be a major advance in the treatment of severe, previously fatal, glycoside poisoning. No notable side effects were observed, nor were there any allergic reactions to foreign protein.

Topics: Acetyldigoxins; Adolescent; Adult; Aged; Antibodies; Arrhythmias, Cardiac; Child, Preschool; Digoxin; Dose-Response Relationship, Drug; Female; Humans; Immunoglobulin Fab Fragments; Male; Medigoxin; Metabolic Clearance Rate; Middle Aged; Suicide, Attempted

Amiodarone, a potent antiarrhythmic agent, has been shown to depress sinus node function. Therefore, this study was undertaken to assess the effect of chronic amiodarone therapy on heart rate during graded exercise testing. 13 patients treated with amiodarone for ventricular arrhythmias were administered symptom-limited graded exercise testing before and 12 weeks after drug therapy. None of the patients had prior evidence of sinus node dysfunction. The mean resting heart rate (beats per minute; bpm) before and after amiodarone therapy was 75 +/- (SD) 13 versus 60 +/- 7 bpm, respectively (p less than 0.005), and the maximal heart rate was 135 +/- 30 versus 109 +/- 24 bpm (p less than 0.005). However, the change in heart rate from rest to maximum exercise (heart rate reserve) was not affected by the drug. Heart rate measured at comparable exercise levels before and during amiodarone therapy was 124 +/- 25 versus 104 +/- 31 (p less than 0.025). There was no change in the systolic blood pressure readings at these respective measured heart rates. Estimated maximal functional capacity before and after drug therapy was 4.9 +/- 1.8 versus 4.7 +/- 2.2 METs (p = NS). In conclusion, chronic amiodarone therapy significantly decreases heart rate at rest and during exercise without altering systolic blood pressure and functional capacity.

Topics: Adult; Aged; Amiodarone; Animals; Arrhythmias, Cardiac; Benzofurans; Blood Pressure; Depression, Chemical; Digoxin; Exercise Test; Female; Heart Rate; Heart Ventricles; Humans; Male; Middle Aged; Physical Exertion; Rabbits; Sinoatrial Node; Thyroxine

Topics: Antibodies; Antibody Specificity; Antidotes; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Humans; Immunoglobulin Fab Fragments

Twenty-two patients were given amiodarone for refractory cardiac arrhythmias, and pre- and post-amiodarone serum digoxin levels were studied. The interval between pre- and post-amiodarone serum digoxin levels ranged from five days to nine months (mean interval, seven weeks). The mean (+/- SD) pre-amiodarone serum digoxin level was 1.0 +/- 0.4 ng/ml, and the post-amiodarone serum digoxin level was 1.9 +/- 0.8 ng/ml (p less than .001). To develop an animal model for study of the digoxin-amiodarone interaction, 18 pigs were given digoxin for a four-week period. Half of the animals were given amiodarone as well as digoxin for the last two weeks of the study. At the end of the initial two-week period, there was no difference in serum digoxin levels between the two groups. At the end of the second two-week period, the serum digoxin level in the group receiving digoxin alone was 0.6 +/- 0.2 ng/ml, and the serum digoxin level in the group receiving the digoxin and amiodarone was 1.2 +/- 0.6 ng/ml (p less than .01). These data confirm the presence of an amiodarone-digoxin interaction in man and show that the pig is an appropriate model for study of this clinical phenomenon in the animal laboratory.

Topics: Adolescent; Adult; Aged; Amiodarone; Animals; Arrhythmias, Cardiac; Benzofurans; Digoxin; Drug Interactions; Female; Humans; Male; Middle Aged; Models, Biological; Retrospective Studies; Swine

Topics: Arrhythmias, Cardiac; Cardiac Surgical Procedures; Digoxin; Female; Heart Valve Diseases; Humans; Middle Aged; Monitoring, Physiologic; Postoperative Period

Topics: Aminopyridines; Animals; Arrhythmias, Cardiac; Brain; Cats; Cimetidine; Digoxin; Female; Pyrilamine; Time Factors

We have examined the species-specific arrhythmogenic effects of digoxin in the rat (resistant species) and in the guinea-pig (sensitive species). 26 adult rats and 23 adult guinea-pigs were anaesthetized with pentobarbitone and injected subcutaneously with varying doses of digoxin. Electrocardiograms were monitored continuously for 4 1/2 h following digoxin administration. The arrhythmogenic dose (AD50) and lethal dose 50 under anaesthesia (LD50) were determined using the method of Litchfield & Wilcoxin. AD50 in rats was 13.0 +/- 1.0 mg kg-1 (mean +/- s.d.) compared with 0.60 +/- 0.04 (P less than 0.01) in the guinea-pig and LD50 was 30.0 +/- 1.9 mg kg-1 in the rat compared with 0.60 +/- 0.04 (P less than 0.01) in the guinea-pig. The onset of arrhythmias was not dose-dependent in the rat but was clearly so in the guinea-pig; for example 102 +/- 15 min (mean +/- s.e.m.) following 0.5 mg kg-1, and 43 +/- 2 min following 1 mg kg-1. In the rat the onset of arrhythmias was 54.0 +/- 11.5 min. Supraventricular arrhythmias (paroxysmal atrial tachycardia) appeared in 73% of rats compared with only 18% of guinea-pigs whereas ventricular arrhythmias (ventricular tachycardia), multiple premature ventricular contractions and or multifocal PVC's occurred in 100% of guinea-pigs compared with only 32% of rats. All guinea-pigs that developed arrhythmias died whereas several rats recovered from supraventricular tachycardias. In conclusion, the guinea-pig is much more sensitive to digoxin toxicity than the rat, develops arrhythmias at much lower doses and these arrhythmias are much more likely to be ventricular in origin and cause fatality.

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dose-Response Relationship, Drug; Electrocardiography; Female; Guinea Pigs; Lethal Dose 50; Rats; Species Specificity

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Humans; Intraoperative Complications; Middle Aged; Neuromuscular Nondepolarizing Agents; Pancuronium; Potassium; Succinylcholine

The hypothesis that digitalis-induced arrhythmias occur when Na,K-ATPase inhibition exhausts the sodium pump reserve capacity, producing an accumulation of intracellular Na+, was tested by reducing the reserve capacity in isolated left atrial muscle of guinea pig heart and estimating specific digoxin binding and Na,K-ATPase activity in atrial muscle homogenized at the onset of digoxin-induced arrhythmias. Reductions in reserve capacity were produced by either increasing the stimulation frequency of the atrial muscle or adding a sodium ionophore, monensin, to the media bathing the tissue. As stimulation frequency was increased, both the time required to produce arrhythmias with a given concentration of digoxin and the amount of digoxin bound to sarcolemmal Na,K-ATPase at the onset of arrhythmias were reduced. Similarly, monensin treatment produced reductions in the time to arrhythmia and in digoxin binding and Na,K-ATPase inhibition observed at the onset of arrhythmias. These results support the above proposal suggesting that a decrease in reserve capacity of the sodium pump enhances cardiac sensitivity to digitalis-induced arrhythmias.

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Drug Interactions; Electric Stimulation; Furans; Guinea Pigs; Male; Monensin; Myocardial Contraction; Ouabain; Reserpine; Sodium; Sodium-Potassium-Exchanging ATPase; Time Factors

The digitalis glycosides are potent cardiovascular drugs with a low therapeutic index and a high incidence of iatrogenic complications. Digoxin is the most commonly used preparation. Common indications include rate control in atrial fibrillation, as well as the treatment of other atrial tachyarrhythmias, and low-output congestive heart failure. Digitalis is contraindicated in idiopathic hypertrophic subaortic stenosis (unless atrial fibrillation is present) and in some patients with Wolff-Parkinson-White syndrome.

Topics: Arrhythmias, Cardiac; Biological Availability; Digitalis Glycosides; Digitoxin; Digoxin; Drug Administration Schedule; Drug Interactions; Heart; Humans; Ion Channels; Stimulation, Chemical

Topics: Animals; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Dogs; Drug Interactions; Heart Diseases; Humans; Immunoglobulin Fab Fragments; Macaca mulatta

In 18 patients with gastrointestinal manifestations of digoxin toxicity the mean serum digoxin concentration (+/- SEM) was 3.16 micrograms/l (+/- 0.25), the calcium to potassium ratio 0.31 (+/- 0.01), and the mean arterial pH 7.406 (+/- 0.017). In contrast 19 patients with digoxin induced automaticity had a mean serum digoxin concentration of 1.24 micrograms/l (+/- 0.15; p less than 0.001), a calcium to potassium ratio of 0.38 (+/- 0.01; p less than 0.01), and an arterial pH of 7.498 (+/- 0.008; p less than 0.001). Eight out of 13 patients with digoxin induced cardiotoxicity had serum concentrations of the drug within the therapeutic range (0.8-2.0 micrograms/l). The calcium to potassium ratio, however, was lower than in the patients with automaticity (0.31 +/- 0.02; p less than 0.01) and the arterial pH was 7.370 (+/- 0.033; p less than 0.05). Serum magnesium concentrations were similar in all groups. In this study patients with digoxin induced gastrointestinal symptoms had high serum concentrations of the drug, whereas those with drug induced automaticity had therapeutic concentrations. This second group, however, was identified by their higher calcium to potassium ratios and higher pH values.

Topics: Arrhythmias, Cardiac; Arteries; Calcium; Digoxin; Gastrointestinal Diseases; Humans; Hydrogen-Ion Concentration; Magnesium; Potassium

Topics: Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Gastrointestinal Diseases; Humans; Immunoglobulin Fab Fragments

Amiodarone was administered to 80 patients with recurrent cardiac tachyarrhythmias previously resistant to drug treatment. Forty nine patients were treated for ventricular tachycardia or fibrillation and 31 for supra-ventricular arrhythmias. The mean (range six days to 51 months), permitting a total of 100 patient years of observation. Adverse reactions were observed in 69 patients. Severe side effects were encountered in 13: four patients developed interstitial pneumonitis, four patients developed incessant ventricular tachycardia, three patients taking amiodarone and digoxin sustained sinus node arrest with depression of escape foci, one patient developed hepatitis, and one patient developed hypercalcaemia with renal failure. Furthermore, a rise in the serum concentration of digoxin and potentiation of warfarin anticoagulation occurred in cases in which these agents were combined with amiodarone. Amiodarone was stopped in 14 patients because of side effects. Although amiodarone is effective in suppressing arrhythmias in most patients in whom extensive use of antiarrhythmic drugs has been unsuccessful, it is associated with diverse and serious toxicity. These observations suggest that at present the use of amiodarone should be reserved for patients with life threatening or seriously disabling arrhythmias in whom longer established drugs have been ineffective or are contraindicated.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Digoxin; Drug Interactions; Female; Humans; Male; Middle Aged; Pulmonary Fibrosis; Recurrence; Respiratory Function Tests; Tachycardia

Gated cardiac scanning was used to evaluate the hemodynamic effects of encainide in 19 patients (1 woman) with complex ventricular arrhythmia and depressed left ventricular (LV) function (ejection fraction less than 45%). Patients were 36 to 80 years old (average 61). All were candidates for long-term encainide therapy after having failed with currently available antiarrhythmics. Sixty-three percent had congestive heart failure before they received encainide. All were evaluated in the hospital before encainide therapy by a gated cardiac scan performed at least 3 days after discontinuing all antiarrhythmic drugs. Patients received oral encainide in doses of 75 to 200 mg. Gated cardiac scans were repeated 1 to 2 weeks later when an 80% reduction in frequency of premature ventricular complexes was observed on a 24-hour Holter recording. No patient had worsening of congestive heart failure during encainide therapy. Encainide did not significantly affect ejection fraction, which averaged 22 +/- 10% before and 25 +/- 14% (SD) after encainide (difference not significant [NS]). Other hemodynamic variables, including heart rate, blood pressure, stroke volume and end-diastolic volume, remained unchanged during encainide therapy. Digoxin blood levels in 10 patients averaged 1.04 +/- 0.43 before and 1.22 +/- 0.47 mg/ml (NS) during encainide therapy. Thus, encainide given orally in clinically effective doses does not appear to have significant hemodynamic effects in patients with ventricular arrhythmia and depressed LV function.

Topics: Adult; Aged; Anilides; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Blood Pressure; Digoxin; Electrocardiography; Encainide; Erythrocytes; Heart; Heart Rate; Hemodynamics; Humans; Middle Aged; Radionuclide Imaging; Stroke Volume; Technetium

The clinical efficacy of amiodarone in the management of complex cardiac arrhythmias refractory to therapy with two or more conventional or other investigational antiarrhythmic agents was determined by long-term follow-up in patients who had received the drug for at least 3 months. A total of 181 patients, classified into four groups (group 1, supraventricular arrhythmias, n = 42; group 2, frequent ventricular premature complexes, n = 46; group 3, nonsustained ventricular tachycardia, n = 16; and group 4, sustained ventricular tachycardia, n = 77) received a daily maintenance dose of 200 to 800 mg amiodarone for up to 30 months. There was a total of 26 deaths (14%). Ten of these were probably attributable to arrhythmia, although all patients had either good or excellent response to therapy over a mean follow-up of 14.9 months prior to death. The drug had to be permanently discontinued because of side effects in only three patients, and in the majority of patients with side effects, symptoms could be alleviated with adjustment of dosage, thyroid replacement therapy, or temporary cessation of therapy. We conclude that amiodarone is highly effective in high-risk patients with complex refractory cardiac arrhythmias, and that close monitoring and prompt recognition of side effects and appropriate adjustment of dosage or institution of supplemental or replacement therapy (in less than 5% of patients) will allow continuation of amiodarone. The benefit of suppression of symptomatic arrhythmias and the potential of prevention of sudden death clearly outweigh the modest incidence of severe side effects.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Digoxin; Dose-Response Relationship, Drug; Drug Interactions; Drug Resistance; Female; Follow-Up Studies; Humans; Male; Middle Aged; Warfarin

Preexisting anomalies of impulse formation and conduction, cardiac failure, myocardial ischemia and abnormal peripheral vasoregulation predispose the elderly patient to frequent and often severe side-effects of antiarrhythmic drugs. Paroxysmal supraventricular tachycardia in patients with sick sinus syndrome can be especially difficult to treat, as most antiarrhythmics further prolong the sinus node recovery time. Thus, implantation of a pacemaker is often necessary to prevent symptomatic bradycardia. Concomitant treatment with diuretics or digitalis also increases the risk of drug induced ventricular dysrhythmias. Interaction between quinidine, verapamil, amiodarone and digoxin may be the reason for drug toxicity. To compensate for decreased renal or metabolic drug clearances antiarrhythmic treatment in elderly patients should be initiated with lower doses than usual.

Topics: Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Bradycardia; Digoxin; Heart Ventricles; Hemodynamics; Humans; Kidney Function Tests; Liver Function Tests; Metabolic Clearance Rate; Risk; Tachycardia

Verapamil and digoxin are often used in combination and clinical experience suggests that verapamil may increase digoxin toxicity. We have explored the effects of verapamil upon digoxin induced tachyarrhythmias and have undertaken a preliminary study of the influence of verapamil on digoxin pharmacokinetics in the rat. Anesthetized rats received 20 mg/kg of digoxin intraperitoneally followed by verapamil i.v., 0.3 mg/kg, in repeated doses either immediately after digoxin or only after the onset of digoxin induced arrhythmias. Digoxin alone produced prolonged paroxysmal atrial tachycardia in 88-100% of rats and verapamil converted 75% of rats to sinus rhythm and significantly reduced digoxin induced mortality. In a later study, rats were injected with 10 mg/kg verapamil i.p. twice a day for 7 days or only with saline. On the seventh day all the rats received 0.5 mg/kg of digoxin i.p. Eight hours later the animals were sacrificed and plasma, heart, brain, liver, kidney and muscle (diaphragm) digoxin concentration was measured by radioimmunoassay. Digoxin levels were twice as high in plasma, heart, liver and muscle of verapamil pretreated rats (p less than 0.01). Two types of verapamil - digoxin interactions are demonstrated in the above studies; one in which verapamil modifies digoxin induced arrhythmias and a second pharmacokinetic effect in which pretreatment with verapamil increases digoxin concentration in the plasma and in several tissues.

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dose-Response Relationship, Drug; Drug Interactions; Kinetics; Male; Rats; Rats, Inbred Strains; Time Factors; Tissue Distribution; Verapamil

Topics: Acid-Base Imbalance; Action Potentials; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Electrocardiography; Heart; Humans; Water-Electrolyte Imbalance

This review of practical and theoretical advances in antiarrhythmic drug therapy consists of four parts. Part 1, on clinical applications, compares the approaches to treatment 25 years ago with those of today, examines the current status of antiarrhythmic drugs used 25 years ago, reports on drugs approved for clinical use during the past 25 years, reviews new experimental drugs and suggests an approach to classification of antiarrhythmic drugs. Part 2 summarizes the contributions of cellular electrophysiology to the understanding of drug action, with emphasis on the drug-induced block of the voltage- and time-dependent properties of the rapid sodium channel. The subsequent section contains a brief discussion of the impact made by the new knowledge and the new diagnostic technology on the contemporary practices. The main conclusions are 1) that the more rational approach to treatment has benefited proportionately more patients with supraventricular than with ventricular arrhythmias, and 2) that new advances have made it possible to design successful treatments for certain patients with problems that could not be resolved in the past.

Topics: Action Potentials; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Electrocardiography; Heart; Humans; Lidocaine; Phenytoin; Procainamide; Quinidine

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Humans; Immunoglobulin Fab Fragments; Male

Topics: Arrhythmias, Cardiac; Digoxin; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male

This review is an attempt to demonstrate the safety and usefulness of the simple maneuver of carotid sinus stimulation with selected subjects undergoing exercise tests. In a variety of circumstances the addition of CSP before or after treadmill walking can yield clinically relevant information relating to arrhythmias, conduction disturbances, symptoms, and pacemakers. Further applications and benefits of these combined procedures remain to be clarified and expanded for judicious application with attention to safeguards.

Topics: Angina Pectoris; Arrhythmias, Cardiac; Bundle-Branch Block; Cardiac Pacing, Artificial; Carotid Sinus; Digoxin; Electrocardiography; Exercise Test; Heart Rate; Humans; Physical Stimulation; Pressure; Propranolol

Topics: Acute Kidney Injury; Adult; Aged; Arrhythmias, Cardiac; Diabetes Mellitus; Digoxin; Female; Half-Life; Hemoperfusion; Humans; Hypotension; Kidney Failure, Chronic; Male; Middle Aged; Polystyrenes; Polyvinyls; Renal Dialysis

17 patients on maintenance hemodialysis were monitored for cardiac arrhythmias using ambulatory electrocardiographic recording. Atrioventricular dissociation was found in a patient with an elevated serum digoxin concentration, intradialytic supraventricular tachycardia had been present in a second patient during acute uremic pericarditis prior to the study. Ventricular premature beats (VPB) were absent or of low grade (occasional/uniform) in 14 patients and did not increase on dialysis. 3 patients had potentially dangerous VPB of higher grades (multiform, salvos or R on T) which occurred on or after dialysis in 2. 2 of these 3 patients were overdigitalized, and 2 had severe cardiac disease (amyloid, old myocardial infarction). Several other risk factors (age, hypertension, cardiac hypertrophy, smoking, hyperlipidemia, electrolyte changes) did not seem to be of importance for VPB. In these patients on maintenance hemodialysis, potentially dangerous VPB were rare and occurred mainly during or after dialysis in patients with preexisting heart disease and/or digitalization.

Topics: Arrhythmias, Cardiac; Chronic Disease; Digoxin; Electrocardiography; Female; Glomerulonephritis; Humans; Hyperlipidemias; Hypertension; Kidney Diseases; Male; Middle Aged; Phenacetin; Polycystic Kidney Diseases; Renal Dialysis; Risk

Internal defibrillating leads were implanted in 6 dogs through a left thoracotomy and in 6 pigs through a subxiphoid approach. The effects of digoxin (0.04 mg per kilogram of body weight), procainamide (15 mg per kilogram), and propranolol (0.2 mg per kilogram) on the defibrillation threshold was determined 30 to 60 minutes following intravenous administration. Resultant blood levels were equal to or greater than therapeutic levels. Individually these drugs resulted in no appreciable change in the defibrillation threshold from baseline. Pathological study of the myocardium obtained from 6 dogs that underwent more than two hundred shocks each did not demonstrate any abnormality. The 6 pigs were reliably defibrillated, this indicating that thoracotomy is not required for successful implantation. The automatic implantable defibrillator is not the definitive treatment for recurrent ventricular arrhythmias, but is a practical regimen of therapy for a select group of high-risk, out-of-hospital patients. These observations advance our knowledge of the use of this device and give more assurance for future implantation in this select group of patients.

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Electric Countershock; Heart; Heart Rate; Myocardium; Procainamide; Propranolol; Swine

Atropine alone in the two lower doses (20mg/kg and 40mg/kg) did not produce any arrhythmias while 80mg/kg of atropine produced arrhythmias in 33% of animals after 31.0 +/- 7.5 min. Only 11% of these rats developed paroxysmal atrial tachycardia. Atropine in lower doses (20,40mg/kg) with digoxin (40mg/kg) decreased the total percent of digoxin induced arrhythmias, delayed their onset, and changed the type of arrhythmias as compared with the digoxin group alone. Atropine given in higher dosage (80mg/kg) with digoxin (40mg/kg) produced arrhythmias in 100% of rats as did digoxin alone, but significantly shortened their onset and modified the types of arrhythmias seen. In conclusion, atropine in varying doses significantly modified digoxin toxicity.

Topics: Animals; Arrhythmias, Cardiac; Atropine; Digoxin; Drug Interactions; Electrocardiography; Female; Rats

Topics: Adult; Aged; Arrhythmias, Cardiac; Digoxin; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Quinidine

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Humans; Hyperkalemia; Immunoglobulin Fab Fragments

Oscillatory fluctuations in diastolic potential [4, 10] and triggered rhythmical activity [4] are well known manifestations of digitalis intoxication and are attributed to intracellular Ca2+ overload consecutive to an elevated intracellular Na+ [7]. In the present paper we report the electrophysiological effects of elevated extracellular Na+ on the spontaneous rhythmical activity and oscillatory fluctuations in digoxin-intoxicated ventricular cells. Our results show that by increasing extracellular Na+ from 135 mM to 175 mM, we were able to abolish spontaneous rhythmical activity but were not able to suppress the damped sinusoidal oscillations in the resting membrane potential. We suggest that Na+-Ca2+ exchange would be stimulated by a greater Na+ gradient, resulting in an enhanced Ca2+ extrusion.

Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Calcium; Digoxin; Guinea Pigs; Myocardium; Osmolar Concentration; Sodium

The prognostic importance of ventricular arrhythmias detected during 24 hour ambulatory monitoring was evaluated in 395 patients with and 260 patients without significant coronary artery disease. Ventricular arrhythmias were found to be strongly related to abnormal left ventricular function. A modification of the Lown grading system (ventricular arrhythmia score) was the most useful scheme for classifying ventricular arrhythmias according to prognostic importance. When only noninvasive characteristics were considered, the score contributed independent prognostic information, and the complexity of ventricular arrhythmias as measured by this score was inversely related to survival. However, when invasive measurements were included, the ventricular arrhythmia score did not contribute independent prognostic information. Furthermore, ejection fraction was more useful than the ventricular arrhythmia score in identifying patients at high risk of sudden death.

Topics: Adrenergic beta-Antagonists; Ambulatory Care; Angina Pectoris; Arrhythmias, Cardiac; Cardiac Catheterization; Cardiac Output; Coronary Disease; Death, Sudden; Digoxin; Electrocardiography; Female; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Contraction; Myocardial Infarction; Prognosis

Toxicity from cardiac drugs is a particular management challenge since the manifestations of an acute overdose and the initial indications for the drug are often similar. Plasma drug levels are essential but must be interpreted in light of the clinical picture. Hypotension, due to either vasodilatation or decreased myocardial contractility, and arrhythmias are the principal cardiac manifestations, but noncardiac effects are sometimes more troublesome. An antiarrhythmic agent of the same class should not be used in treating an arrhythmia resulting from an overdose.

Topics: Arrhythmias, Cardiac; Bretylium Compounds; Cardiovascular Agents; Cardiovascular Diseases; Digoxin; Disopyramide; Humans; Hypotension; Lidocaine; Liver; Phenytoin; Procainamide; Propranolol; Quinidine; Vasodilator Agents

Topics: Adult; Anti-Arrhythmia Agents; Aprindine; Arrhythmias, Cardiac; Digoxin; Drug Therapy, Combination; Electrocardiography; Female; Humans; Indenes; Syndrome

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Digoxin; Drug Interactions; Heart Ventricles; Humans

Eighteen infants, each weighing less than 1,500 gm, were treated with low dose digoxin therapy for patent ductus arteriosus and signs of circulatory congestion. Nine of the 18 developed one or more signs of clinical deterioration felt to be related to digoxin therapy: eight infants experienced frequent episodes of bradycardia, six had cardiac arrhythmias, and six experienced feeding difficulties. All signs disappeared when digoxin therapy was discontinued. Digoxin, even in relatively low dosages, can have deleterious complications in seriously ill low-birth-weight infants. Alternatives to digoxin in this patient population should be considered before institution of digoxin therapy.

Topics: Arrhythmias, Cardiac; Bradycardia; Digoxin; Ductus Arteriosus, Patent; Feeding Behavior; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases

Topics: Adult; Arrhythmias, Cardiac; Digoxin; Humans; Male; Phenytoin

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Drug Interactions; Gastrointestinal Diseases; Humans; Quinidine; Tissue Distribution

Digoxin remains a very useful agent for chronic atrial fibrillation or for the ectopic beats associated with heart failure. But when rapid control of the ventricular rate is required to arrhythmias such as atrial fibrillation, atrial flutter, or paroxysmal atrial tachycardia, a slow infusion of verapamil is the agent of choice. In general, verapamil may be added to digoxin or given intravenously while a digoxin effect is awaited, unless there is digitalis toxicity. In digitalis toxicity, lignocaine remains the agent of choice for ventricular arrhythmias, and is given in the same doses as for acute myocardial infarction; phenytoin is used for digitalis-arrhythmias with A-V block. Verapamil may be infused very cautiously for digitalis-induced supraventricular tachyarrhythmias. The use of oral agents such as quinidine, disopyramide and mexilitene for chronic prophylaxis of ventricular ectopic beats is of doubtful effectiveness, unless the ectopic activity is symptomatic. Serious ventricular arrhythmias may be induced by quinidine and disopyramide. Beta-blockade is especially useful for ectopic beats associated with anxiety, or when arrhythmias are associated with angina of effort or hypertension. As always, major contraindications to the use of beta-blockade include cardiomegaly, heart failure or asthma.

Topics: Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Disease; Digitalis; Digoxin; Heart Ventricles; Humans; Plants, Medicinal; Plants, Toxic; Potassium; Quinidine; Verapamil

A 66-year-old mand suffering from severe coronary heart disease took digoxin with suicidal intent an was treated for the ensuing complete atrioventricular block with digoxin-specific antibody fragments. Two and a half hours after intravenous infusion of the antibody fragments, the signs of intoxication passed off, and atrial fibrillation with a normal ventricular rate was reinstated. Antibody therapy is capable of permanently abolishing the signs of symptoms of digitalis poisoning after a matter of hours. Such a rapid or complete response cannot be achieved by any conventional form of treatment. This advantage must be weighed against the risks (immunologic reactions, loss of the therapeutic effect of the cardiac glycoside if an overdose of antibody is given). Moreover, antibody therapy does not take effect immediately, as is understandable in view of the mechanism of action. It should therefore be instituted in good time in potentially life-threatening cases of intoxication.

Topics: Aged; Antibodies; Arrhythmias, Cardiac; Digoxin; Heart Failure; Humans; Immunoglobulin Fab Fragments; Male; Suicide, Attempted; Water-Electrolyte Balance

Topics: Adolescent; Adult; Age Factors; Aged; Arrhythmias, Cardiac; Child; Child, Preschool; Digitalis Glycosides; Digoxin; Heart Block; Humans; Infant; Infant, Newborn; Lanatosides; Medigoxin; Middle Aged

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digoxin; Electric Countershock; Female; Heart Diseases; Humans; Male; Middle Aged; Tachycardia

A prospective study of 182 patients undergoing cardiac surgery was performed. The patients were divided into three groups. Group I consisted of 83 patients who had never been treated with digitalis. Group II comprised 59 patients who were taking digoxin before operation and had medication discontinued 24 to 48 hours prior to surgery; they did not receive maintenance digoxin in the postoperative periods. Group III was made up of 40 patients who were given prophylactic digoxin in the perioperative period; none had taken digoxin before. Sixty of 83 group I patients (72%) and two of the group III patients (5%) developed postoperative supraventricular tachyarrhythmia. Digoxin was reinstituted in 56 of group II patients (95%) for supraventricular arrhythmia and/or heart failure. Of the various factors evaluated, only valvular surgery and ECG evidence of myocardial infarction were associated with postoperative supraventricular tachyarrhythmias.

Topics: Adult; Aged; Arrhythmias, Cardiac; Cardiac Surgical Procedures; Digoxin; Female; Humans; Male; Middle Aged; Myocardial Infarction; Postoperative Complications; Premedication; Preoperative Care; Prospective Studies

The aim of Mobile Coronary Care Units (M.C.C.U.) is to reduce the delay in delivering intensive care to patients with a heart attack. In the city of Florence a M.C.C.U. has been available since November 1979. During the first year the staff of the M.C.C.U. has treated 158 cases of serious cardiac arrhythmias which occurred among 486 interventions. In 94 patients cardiac arrhythmias followed an acute coronary attack. In 64 patients coronary heart disease could not be demonstrated. This study concerns the latter group of patients. The mean age was 65.2 years and 39 patients (61%) were women. The mean time from the onset of the symptoms to the arrival of the M.C.C.U. team was 3h and 2 min, whereas the mean time from the call to the arrival was 14 min. Sixty patients had atrial arrhythmias (29 atrial fibrillation, 2 atrial flutter, 22 atrial tachycardia, 7 premature atrial contractions) and 4 patients had ventricular arrhythmias (1 ventricular tachycardia, 1 ventricular flutter, 2 premature ventricular contractions). In thirty-nine patients (61%) the cardiac arrhythmia was abolished by the staff of the M.C.C.U.. Of the remaining 28 patients, 10 were brought to the hospital and 18 were left at home. None of these needed later admission to the hospital. So the treatment at home of cardiac arrhythmias has been successful in the majority of patients. Bunaftine was the antiarrhythmic drug more frequently used (23 cases, 34%) with a high percentage of success (87%). In planning medical emergency services to the community, one can envisage the use of the M.C.C.U. facilities to treat at home those arrhythmias that are not associated with an acute coronary attack.

Topics: Adult; Aged; Ajmaline; Ambulances; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Bunaftine; Coronary Care Units; Digoxin; Female; Humans; Italy; Male; Middle Aged; Verapamil

The probability of experiencing adverse drug reactions increases with age. Polypharmacy, pharmacokinetic changes (altered drug distribution, reduced renal and hepatic drug clearances), unusual pharmacological effects and impaired compensatory mechanisms are the principal reasons for the diminished tolerance of elderly patients to several drugs. Especially neuroleptics, antidepressants, tranquilizers, digoxin, potent diuretics, betablockers, and antiarrhythmics have to be employed with special care. To prevent adverse reactions in geriatric patients, prescriptions should be limited to a few essential drugs, dosage reduced, and dosing regimens simplified. However, therapeutic nihilism can never be justified by old age alone.

Topics: Acute Kidney Injury; Adrenergic beta-Antagonists; Aged; Antidepressive Agents; Antipsychotic Agents; Arrhythmias, Cardiac; Benzodiazepines; Creatine; Digoxin; Diuretics; Drug-Related Side Effects and Adverse Reactions; Female; Geriatrics; Humans; Hypotension; Male

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Carotid Sinus; Digoxin; Electric Countershock; Heart Rate; Humans; Massage; Tachycardia; Verapamil

Systolic time interval (STI) measurements were made in 44 patients with coronary artery disease: 38 had regional left ventricular (LV) asynergy, and the remaining 6 had normal ventricular contraction patterns on left ventricular angiography. There was a significant correlation between both the preejection period (PEP) (r = 0.70) and the PEP/LVET (LV ejection time) ratio (r = 0.66), with the extent of regional ventricular dysfunction measured quantitatively on the left ventricular angiogram (P less than 0.001). A PEP/LVET ratio greater than 0.50 was associated with ventricular asynergy involving more than 40% of the LV circumference at end diastole. STI measurements also correlated with ejection fraction but not with ventricular end diastolic pressure nor with the number of obstructed coronary arteries.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Arrhythmias, Cardiac; Coronary Disease; Digoxin; Heart Ventricles; Hemodynamics; Humans; Middle Aged; Mitral Valve Insufficiency; Myocardial Contraction; Systole; Time Factors

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atropine; Bradycardia; Cardiac Complexes, Premature; Digoxin; Heart Block; Heart Failure; Humans; Lidocaine; Myocardial Infarction; Propranolol; Tachycardia

The arrhythmogenic and inotropic effects of digoxin were studied in normokalemic controls, chronically hypokalaemic, and potassium-repleted dogs instrumented to maintain heart rate, mean aortic pressure, mean left atrial pressure and autonomic tone constant. The duration of digoxin infusion needed to produce ventricular tachycardia (VT) was 56.7 +/- 3.6 min in depleted dogs, 69.0 +/- 2.7 min in controls (P less than 0.005 compared with depleted dogs), and 60.5 +/- 3.0 min in repleted dogs. Baseline left ventricular dP/dt (LV dP/dt) was similar in all groups. After digoxin, LV dP/dt increased more in controls and repleted dogs than in chronically hypokalaemic dogs; eg, after 45 min of digoxin infusion LV dP/dt increased 12.7 +/- 4.4% in hypokalaemic dogs; eg, after 45 min of digoxin infusion LV dP/dt increased 12.7 +/- 4.4% in hypokalaemic dogs, 43.8 +/- 3.3% in controls (P less than 0.025) and 39.3 +/- 8.5% in repleted dogs (P less than 0.025). The inotropic response to isoprenaline was also attenuated in the chronically hypokalaemic dogs. Plasma digoxin was similar in all groups. LV digoxin was also similar in control and depleted dogs. Although inhibition of Na+, K+-ATPase and the initial velocity of 3[H]-ouabain specific binding was less in depleted dogs at VT than in controls (P less than 0.05), the magnitude of this difference was not sufficient to explain the attenuated inotropic response. No histological abnormalities were seen on light or electron microscopy in any of the groups. Therefore chronic hypokalaemia has two deleterous effects. It increases sensitivity to the arrhythmogenic effects of digoxin and impairs the inotropic response to digoxin, and isoprenaline.

Topics: Animals; Arrhythmias, Cardiac; Binding Sites; Digoxin; Dogs; Female; Heart Conduction System; Heart Rate; Hypokalemia; Isoproterenol; Male; Myocardial Contraction; Myocardium; Ouabain; Potassium; Sodium-Potassium-Exchanging ATPase; Stimulation, Chemical

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Digoxin; Drug Interactions; Humans

To assess the effectiveness of halothane as an antiarrhythmic agent against atrial arrhythmias brought about by hyperventilation of digitalized subjects, the effects of halothane end-tidal (ET) = 1.0% and hypocapnia (PCO2ET = 25 vs 40 torr) on stimulated atrial arrhythmias (atrial echoes [echoes]; repetitive atrial firing [RAF]) and supraventricular conduction and refractoriness were assessed digitalized dogs. Ten dogs received low dose (LD, 22 microgram/kg/day X 7 days) and nine dogs received high dose (HD, 44 microgram/kg/day X 7 days) digoxin. Serum digoxin levels following LD were 0.5 to 1.8 ng/ml (mean +/- 1 SD = 1.16 +/- 0.31) and following HD were 2.0 to 4.0 ng/ml (3.06 +/- 0.71 ng/ml). High right atrial pacing and extrastimulation and catheter His bundle electrocardiography were used. Spontaneous arrhythmias or conduction disturbances were not observed. Halothane enhanced RAF but not echoes in dogs given LD and HD. It also increased supraventricular conduction time and refractoriness. Hypocapnia had no effect on echoes or RAF and minimal effects on conduction and refractoriness. By analysis of variance, digoxin had no effects on echoes, RAF, refractory periods, or conduction. It is concluded that halothane affords no protection against stimulated arrhythmias in hypocapneic or eucapneic, nontoxic digitalized dogs.

Topics: Animals; Arrhythmias, Cardiac; Carbon Dioxide; Cardiac Pacing, Artificial; Digitalis Glycosides; Digoxin; Dogs; Electric Stimulation; Halothane; Heart Atria

Arrhythmias induced by digitalis are believed to be secondary to changes in ion concentrations in the myocardial cells or changes in the transcellular ion gradient. Both diuretic induced hypokalemia and digitalis inhibit the membrane-Na+K+ ATPase activity which cause a decrease of the intracellular potassium concentration. This may explain the risk of cardiac arrhythmias during digitalis treatment and during severe hypokalemia, and may further explain the increase for myocardial sensitivity for digitalis when hypokalemia is present. The myocardial uptake of digitalis however is markedly increased at low extracellular potassium concentration and this may be the explanation of the interaction between digitalis and hypokalemia. Not only the myocardial digoxin kinetic is changed during hypokalemia but the renal excretion rate of digoxin is markedly reduced during hypokalemia leading to increased serum digoxin concentration and thereby the risk of digitalis intoxication.

Topics: Animals; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Diuretics; Drug Interactions; Humans; Hypokalemia; Kinetics

Reviews of large series of patients with digitalis-induced arrhythmias create a seeming paradox: Hypokalemia is infrequently associated with digitalis-induced arrhythmias but the clinical benefit of supplementation of potassium for most digitalis-induced arrhythmias is obvious. Examination of the electrophysiologic abnormalities induced by digitalis coupled with the electrophysiologic effects dependent on the ratio of intracellular to extracellular concentrations of potassium clarifies the issue. We present evidence that supports additive effects of the toxicity of digitalis and abnormal ratios of concentrations of potassium inside and outside the cardiac cell using metabolic alkalosis as a marker of intracellular potassium depletion. Patients with metabolic alkalosis and normokalemia with "therapeutic" concentrations of digoxin had significantly greater prevalence of arrhythmias than did patients without alkalosis. We presume this effect of alkalosis to be mediated by effects on extra- to intracellular ratios of potassium.

Topics: Adult; Aged; Alkalosis; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Female; Humans; Intracellular Fluid; Male; Middle Aged; Potassium

Regimens of acute preoperative digitalization have been evaluated previously in the prophylaxis of supraventricular tachycardias (SVT) following coronary artery bypass operations, with equivocal results. This study assesses the effectiveness of immediate postoperative digitalization on the incidence of arrhythmias in 407 consecutive patients recovering from myocardial revascularization. In 137 patients treated by our regimen, which begins digitalization within 4 hours postoperatively, the incidence of supraventricular tachyarrhythmias was 2%, while the corresponding figure for 270 untreated patients was 15%. Digitalization reduced the incidence of supraventricular arrhythmias significantly (p less than 0.01), whereas death, ventricular ectopy, and infarction rates were similar in the two groups. The few patients who did have supraventricular arrhythmias while receiving prophylactic digoxin were no more easily treated than patients in the undigitalized group. The timing of administration of digoxin for SVT prophylaxis may be more important than previously recognized. Immediately postoperative digitalization, theoretically preferable to preoperative regimens, is a safe, effective way to reduce the incidence of supraventricular arrhythmias following myocardial revascularization.

Topics: Arrhythmias, Cardiac; Coronary Artery Bypass; Digoxin; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Postoperative Complications; Postoperative Period; Time Factors

Topics: Arrhythmias, Cardiac; Digoxin; Drug Interactions; Humans; Quinidine

Certain arrhythmias detected on the electrocardiogram are considered to be reliable indicators of digitalis intoxication. We have evaluated the incidence of these arrhythmias on 24-hour electrocardiographic monitoring (Holter monitoring) in 69 consecutive patients who had serum levels of digoxin determined within 24 hours of the onset of continuous electrocardiographic monitoring. According to teh serum level of digoxin, the patients were divided into the following three groups: (1) group 1 had 0 to 1.0 ng/ml (31 patients); (2) group 2 had 1.1 to 2.0 ng/ml (27 patients); and group 3 had greater than or equal to 2.1 ng/ml (11 patients). The following arrhythmias were considered to reflect digitalis-provoked arrhythmias: (1) persistent sinus bradycardia or sinus pauses (or both); (2) atrioventricular block; (3) paroxysmal atrial tachycardia with block; (4) accelerated junction rhythm; (5) complex ventricular arrhythmias (multifocal ventricular premature beats, bigeminy and trigeminy, and pairs); and (6) ventricular tachycardia. There was no significant difference in the incidence of these six categories of arrhythmias among the three groups. In addition, there was no significant difference in the mean serum level of digoxin for patients with and without the arrhythmias within each category. Ten of the 69 patients had combinations of three of the so-called digitalis-provoked arrhythmias, with incidences among the three groups showing no significant differences. In conclusion, rhythms considered to be potentially due to digitalis intoxication are frequently observed in hospitalized patients undergoing 24-hour electrocardiographic monitoring, are frequently unrelated to the serum level of digoxin, and appear unlikely to reflect true digitalis intoxication in many of these patients.

Topics: Aged; Arrhythmias, Cardiac; Bradycardia; Digoxin; Electrocardiography; Heart Block; Humans; Monitoring, Physiologic; Retrospective Studies; Tachycardia

To determine whether nontoxic doses of digoxin increase the risk of serious ventricular arrhythmias after d.c. cardioversion, studies were made of the effects of different doses of digoxin on the incidence and severity of ventricular arrhythmias after graded, external d.c. shocks in 14 closed-chest dogs. Electrocardiograms were recorded continuously for 20 min before and 10 min immediately after sequential QRS-synchronized shocks of 10, 100 and 150 joules. Ventricular premature beats were counted and their severity was graded. Digoxin (0.01--0.05 mg/kg) was then given i.v. to 12 dogs. Despite a wide range of serum digoxin concentrations (1.3--12.5 ng/ml), electrocardiographic signs of digitalis toxicity did not develop in any of these animals. The same sequence of d.c. shocks was repeated after 2 hr in nine dogs and after more than 24 hr in three dogs. Neither the total number of ventricular ectopic beats nor the arrhythmia grade postshock differed significantly before and after digoxin. Furthermore, more dogs developed ventricular ectopy at each energy level after control shocks than following shocks after digoxin administration. Two additional dogs were given repeated digoxin doses until electrocardiographic evidence of digitalis toxicity was apparent. Both developed sustained ventricular tachycardia after electrical shocks at all energy levels. Whereas overt digitalis toxicity predisposes to serious ventricular arrhythmias after d.c. shocks, we conclude that the risk of postshock ventricular ectopy is not increased by pretreatment with apparently nontoxic digoxin doses.

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Electric Countershock; Electrolytes; Time Factors

Studies on the efficacy of phenytoin administered directly into the cerebrospinal fluid in protecting against digoxin-induced arrhythmias were carried out in 20 anesthetized dogs. Phenytoin was administered in an average dose of 10 mg directly into the cisterna magna of 10 dogs. The other control dogs received only the vehicle for phenytoin intrathecally. Both groups of dogs subsequently received a toxic dose of digoxin (0.2 mg/kg) intravenously. The time after intravenous digoxin to the onset of ventricular premature beats, ventricular tachycardia and ventricular fibrillation (VF) was significantly shorter in control animals compared to the phenytoin-treated dogs. In the control group, one dog survived the 3-h observation period without developing ventricular fibrillation, whereas 5 of the 10 phenytoin-treated dogs survived this period without VF (P less than 0.05). Phenytoin had a similar protective effect against digoxin-induced arrhythmias in 10 other dogs that received phenytoin intravenously. In the animals that received phenytoin intrathecally, plasma concentrations of phenytoin were undetectable. Thus, in this experimental model, phenytoin exerts a protective effect against digoxin-induced ventricular arrhythmias which is mediated via the central nervous system.

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Heart; Heart Rate; Heart Ventricles; Phenytoin

The clinician may often be uncertain about the presence of digoxin toxicity. This uncertainty is particularly important when the clinician must make initial therapeutic decisions about continuing or discontinuing digoxin. We describe a method that helps to clarify the role of the serum digoxin test in decreasing the uncertainty surrounding the diagnosis and treatment of toxicity. The relation between the test and toxicity was first determined in our patient population. An approach to the interpretation of the test based on the likelihood ratio was then developed by combining our data with selected data from the literature. The relation between the pretest risk of toxicity (the estimated risk of toxicity in the population under investigation before the test result is known) and the predictive value of the test was established. This relation was also used to analyze the importance of the degree of elevation of the test. The appropriate threshold probability for institution of treatment of toxicity was then determined by an interview technique. The test was able to make the patient's probability of toxicity cross the threshold probability for treatment of toxicity for an intermediate range of pretest risk. Our analysis suggests that the serum digoxin test may have a critical effect on therapeutic decisions and can be best considered as contributing to the spectrum of risk.

Topics: Arrhythmias, Cardiac; Digoxin; Female; Humans; Male; Mathematics; Probability; Risk

Topics: Age Factors; Aged; Arrhythmias, Cardiac; Cardiomyopathies; Creatinine; Digitalis Glycosides; Digoxin; Electrocardiography; Female; Humans; Kidney; Male; Middle Aged

Toxicity to digoxin was monitored in 437 consecutive recipients in a comprehensive drug surveillance programme, Adverse reactions developed in 19.5% and, in contrast to previous reports, were generally of a relatively benign nature. There were no drug-related deaths, but patients with adverse reactions spent longer in hospital. Low body weight, impaired renal function, old age and concurrent use of diuretics individually did not increase the risk of toxicity. This was attributed to improvements in the prescribing of digoxin. There was a highly significant excess of gastrointestinal reactions in women, which tended to occur early in the course of therapy. This susceptibility is not widely recognized. The use of loading doses may have caused many early reactions and it is suggested that this practice cold be abandoned in all but the most urgent cases.

Topics: Age Factors; Aged; Arrhythmias, Cardiac; Digoxin; Diuretics; Drug Administration Schedule; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Potassium; Sex Factors; Time Factors; Uremia

The time course of the rise in serum digoxin concentration was followed in 18 patients treated with digoxin as quinidine treatment was started with a loading dose. The mean serum digoxin levels rose significantly during the first 24 hours after administration of quinidine was begun, and reached a new steady state concentration after about 48 hours. Digoxin kinetics were studied in two groups of normal volunteers: Group 1 (n = 7) received a small dose of quinidine, 800 mg/day, and group II (n = 8) received 1,600 mg/day. There was no significant mean change in the apparent volume of distribution of digoxin in either group. In group I (small dose), quinidine reduced the digoxin clearance values: total clearance by 30 percent, renal clearance by 32 percent and nonrenal clearance by 29 percent. In group II (large dose), quinidine reduced digoxin total clearance by 36 percent, renal clearance by 54 percent and nonrenal clearance by 22 percent. The reduction in digoxin volume of distribution and renal clearance during quinidine treatment were a function of the serum quinidine concentration. The change in nonrenal clearance of digoxin was independent of serum quinidine concentration.

Topics: Adult; Aged; Arrhythmias, Cardiac; Creatinine; Digoxin; Drug Interactions; Female; Humans; Kinetics; Male; Middle Aged; Quinidine; Time Factors

To ascertain whether electrical cardioversion increases ventricular ectopy in patients receiving nontoxic doses of digitalis, we recorded continuous electrocardiograms in 21 patients for at least 1 hour before and immediately after direct-current countershock. Seventeen patients also received specific antiarrhythmic therapy. There were no consistent differences in the frequency of severity of ventricular ectopy before and after cardioversion despite a wide range of serum digoxin levels (0.1 to 3.0 ng/mL; mean, 1.6 ng/mL). No patient had ventricular tachycardia after cardioversion, and all eight patients with serum digoxin levels greater than 2.0 ng/mL had the same or fewer ventricular ectopic beats per hour and the same or lower ectopy grades after cardioversion when pre- and postshock recordings were compared. These findings suggest that patients receiving digoxin without clinical evidence of digitalis toxicity are at low risk for serious postcardioversion ventricular arrhythmias, even when serum digoxin levels are modestly elevated. The extent to which this low risk is due to concomitant antiarrhythmic therapy is unknown

Topics: Adult; Aged; Arrhythmias, Cardiac; Digoxin; Electric Countershock; Electrocardiography; Female; Heart Ventricles; Humans; Male; Middle Aged

To evaluate the effect of maturation on the renal disposition of digoxin, the ratio of digoxin clearance to creatinine clearance was determined in 35 patients who were 3 days to 79 yr old. All were at steady-state levels for digoxin treatment. A mean ratio of 1.49 +/- 0.67 (SD) was obtained in the group of prepubertal children and infants greater than or equal to 2 mo of age. The mean ratio decreased to 0.82 +/- 0.25 (SD) in the adult group; adults were defined as sexually mature adolescents or older (P less than 0.005). The decrease in net renal tubular secretion of digoxin appears to occur at puberty. This observation can provide one explanation for the apparently larger doses of digoxin required by infants and children than by adults. It may also represent a developmental change in renal tubular physiology with broader significance than for digoxin disposition alone.

Topics: Adolescent; Adult; Age Factors; Aged; Arrhythmias, Cardiac; Child; Child, Preschool; Creatinine; Digoxin; Heart Failure; Humans; Infant; Infant, Newborn; Kidney; Middle Aged; Sexual Maturation

Digoxin therapy was withdrawn over a four-year period in the geriatric wards of Skellefteå Hospital, if the indications for it were not clear, the medication was of doubtful value and there were no contraindications to withdrawal. Contraindications comprised symptoms of cardiac failure at rest or during light physical activity, X-ray signs of pulmonary congestion, a proven need for digoxin therapy following earlier withdrawal, or atrial fibrillation with a ventricular rate higher than 95 beats/min. A patient, who within two months presented signs of cardiac failure or an arrhythmia requiring digoxin, was considered to be in need of digoxin. Digoxin was withdrawn from a total of 141 patients, of whom 134 were examined after two months. According to our criteria, 108 (81%) of these 134 patients did not require digoxin treatment.

Topics: Age Factors; Aged; Arrhythmias, Cardiac; Digoxin; Drug Utilization; Female; Heart Arrest; Humans; Male; Middle Aged

In clinical Arrhythmology it is often necessary to associate digitalis and antiarrhythmic agents. This calls for study of possible interaction between the employed drugs. We found a statistically significant correlation between digitalis and amiodarone plasma level in patients on long term treatment with both drugs. A statistically significant linear correlation between plasma amiodarone level and digoxin (0.25 mg/day) or beta-methyldigoxin (0.20 mg/day) was documented in 33 patients. 23 patients had been treated with these drugs for paraxysmal reciprocating supraventricular tachycardia since an average of 52 months (computerized follow-up). (Amiodarone average weekly dose was 1078 +/- 168 mg after a loading dose of 12 gm given over one month). 10 patients were on chronic treatment with higher weekly doses of amiodarone (average dose 2380 +/- 731 mg per week). Thyroid function tests (T4; T3; T3UP; TSH; rT3) were checked in every patients. Further studies are warranted to understand the mechanism of the interaction between amiodarone and digitalis. As a clinical implication we point out that amiodarone-digoxin (or betamethyldigoxin) interaction in our patients has neither resulted in over-therapeutic plasma level nor in signs of digitalis toxicity.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Digoxin; Drug Interactions; Female; Humans; Male; Medigoxin; Middle Aged; Tachycardia, Paroxysmal

Topics: Arrhythmias, Cardiac; Digoxin; Drug Therapy, Combination; Electrocardiography; Female; Heart Rate; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Propranolol

Topics: Adult; Aged; Arrhythmias, Cardiac; Digoxin; Female; Humans; Isosorbide Dinitrate; Male; Middle Aged

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Drug Interactions; Heart Failure; Humans; Quinidine

Ten cases of chaotic atrial tachycardia (CAT) in childhood are reported. Patients' ages ranged from 1 day to 18 years (average, 3.5 years) at the time of diagnosis. The patients were divided into groups according to the following criteria: (1) no cardiac disease (n = 5), (2) congenital heart disease (n = 4), and (3) acquired heart disease (n = 1). Nine of the children were treated with digoxin; however, it appears there was no beneficial effect. In fact, the single death in our study group may have been attributable to digitalis intoxication. No children have had recurrence of the arrhythmia after discontinuation of the drug. The duration of the tachyarrhythmia was extremely variable; however, CAT was well tolerated and was self-limiting in our patients.

Topics: Adolescent; Arrhythmias, Cardiac; Child; Child, Preschool; Chronic Disease; Digoxin; Electrocardiography; Female; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Male; Propranolol; Quinidine; Rheumatic Heart Disease; Tachycardia

Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Aprindine; Arrhythmias, Cardiac; Bretylium Compounds; Digoxin; Disopyramide; Heart Conduction System; Hemodynamics; Humans; Lidocaine; Mexiletine; Procainamide; Quinidine; Verapamil

The serum digoxin concentration (SDC) was measured in 100 consecutive patients with suspected digitalis-induced arrhythmias. In 24 (toxic group) of these subjects arrhythmias disappeared after glycoside withdrawal. The mean (+/- SD) SDC was 2.88 +/- 1.89 ng/ml in the toxic group and 1.00 +/- 0.61 in the nontoxic group (p less than 0.0001). With respect to digitoxicity, the SDC showed a predictive accuracy rate of 88%, a specificity rate of 89%, and a sensitivity rate of 62%. Since our results were obtained from symptomatic patients, we observed a better predictive accuracy rate than other authors, who studied symptomatic and asymptomatic subjects. The high percentage of false-negatives makes it impossible to consider the SDC by itself a diagnostic test for digitoxicity. However, the SDC is a useful test since all other parameters are less sensitive and/or less rapid indicators of probable digitalis intoxication.

Topics: Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Female; Humans; Male; Middle Aged

17 patients on maintenance hemodialysis were monitored for cardiac arrhythmias by ambulatory electrocardiographic recording. Only 3 patients had ventricular premature beats of potentially dangerous grades. Two of these cases were overdigitalized and two had severe cardiac disease (amyloid, old myocardial infarction).

Topics: Adult; Aged; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Digoxin; Electrocardiography; Electrolytes; Hemoglobins; Humans; Hydrogen-Ion Concentration; Middle Aged; Osmotic Pressure; Renal Dialysis

We monitored, by the Holter method, 23 clinically stable maintenance hemodialysis patients for 5 +/- (SEM) 2 hours before hemodialysis, 5.0 +/- 0.5 hours during hemodialysis, and 13 +/- 3 hours after hemodialysis. Of 23 patients, 9 (39%) had unexpected frequent or complex ventricular arrhythmias recorded and after hemodialysis with a potassium dialysate bath concentration of 2.0 mEq/liter. Patients with ventricular arrhythmias were more likely to be using digoxin (8/9 vs. 1/4) and to have evidence of left ventricular hypertrophy (9/9 vs. 7/4 than were those patients without arrhythmias. Of these 9 patients with arrhythmias, 6 underwent repeat Holter monitoring during multiple dialysate protocols. Of the 6 patients, 4 had a significant reduction in the frequency of ventricular ectopy when a dialysate of 3.5 mEq/liter potassium was used (P < 0.05), but of these 6, 3 still had complex arrhythmias. The use, however, of a 3.5 mEq/liter potassium dialysate plus the administration of a 400-mg dose of quinidine sulfate orally 45 min prior to hemodialysis was successful in reducing ventricular ectopic frequency and complexity in all the patients studied. Conclusion. Maintenance hemodialysis patient using digoxin and with left ventricular hypertrophy have an unexpectdly high indicence of occult, potentoial serious, ventricular arrhythmias during and after hemodialysis, revealed by Holter monitoring. There is preliminary evidence that a low-potassium bath concentration may play a role in predisoposing patients to these arrhythmias. Further prospective studies with largaer number of patients will be needed, however, to evaluate the significance of these findings.

Topics: Adult; Aged; Arrhythmias, Cardiac; Cardiomegaly; Digoxin; Electrolytes; Female; Humans; Male; Middle Aged; Monitoring, Physiologic; Potassium; Prospective Studies; Renal Dialysis

Topics: Aged; Aging; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digitoxin; Digoxin; Heart; Heart Failure; Humans; Patient Compliance

Topics: Adult; Arrhythmias, Cardiac; Cross Reactions; Digitoxin; Digoxin; Female; Heart Block; Humans; Immunoglobulin Fab Fragments; Potassium; Suicide, Attempted; Ventricular Fibrillation

Topics: Arrhythmia, Sinus; Arrhythmias, Cardiac; Digoxin; Drug Synergism; Female; Heart Arrest; Humans; Middle Aged; Verapamil

Topics: Animals; Arrhythmias, Cardiac; Coronary Vessels; Digoxin; Dogs; Female; Magnesium Sulfate; Male; Potassium; Sodium; Veins

Results of studies of 15 adults placed on quinidine therapy after their serum digoxin concentrations were stabilized showed significantly increased digoxin concentrations. The average digoxin concentration before quinidine therapy was 0.75 +/- 0.28 ng/mL and after 4 days of quinidine therapy was 1.41 +/- 0.43 ng/mL. During this period, the renal clearance of digoxin decreased from 53.4 +/- 21 mL/min . 1.73 m to 35.3 +/- 12.6 mL/ min . 1.73 m. No significant correlation was found between the individual rise in serum digoxin concentrations and the rise in serum quinidine concentrations. These results suggest that serum digoxin concentration should be monitored closely for at least the first 4 days of quinidine therapy.

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Heart Failure; Heart Ventricles; Humans; Middle Aged; Prospective Studies; Quinidine; Tachycardia, Paroxysmal

Topics: Aconitine; Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Female; Glycogen; Male; Myocardium; Phosphorylases

The potency of 17 derivatives of 16 alpha-gitoxin was tested in the isolated atrium and heart of the guinea pig and the contractility-increasing activity of the 16 alpha-gitoxin 16 alpha-acetate was compared with that of 16 alpha-gitoxin in the anesthetized dog. The potency of 16 alpha-gitoxin was increased by the substitution of 16 alpha-OH for 16 alpha-methyl ether, 16 alpha-acetate and 16 alpha-nitrate. Substitution of the 16 alpha-acetyl group for substituents with a higher molar volume diminished this enhanced potency. Variation in the digitoxose moiety caused an increase or decrease in potency depending on the position and number of the substituted OH groups. In spite of changes in 16 alpha-OH, the low influence on rhythmicity persisted, as was found in experiments in the dog.

Topics: Acetyldigoxins; Animals; Arrhythmias, Cardiac; Cardiac Glycosides; Digoxin; Dogs; Dose-Response Relationship, Drug; Female; Guinea Pigs; Heart; Heart Rate; Isomerism; Male; Myocardial Contraction; Stimulation, Chemical; Structure-Activity Relationship

Topics: Adult; Aged; Animals; Arrhythmias, Cardiac; Digitoxin; Digoxin; Electrocardiography; Female; Heart Failure; Heart Rate; Humans; In Vitro Techniques; Male; Middle Aged; Monitoring, Physiologic; Rabbits

Topics: Adult; Aged; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Female; Humans; Male; Middle Aged

We investigated the age-specific arrhythmogenic effects of digoxin in the rat. Adult female rats (n = 26) and one-day-old newborns (n = 20) were anesthetized with pentobarbital and injected subcutaneously with varying doses of digoxin. Electrocardiograms (ECG) were monitored continuously for four and one-half hours following digoxin administration. The arrhythmogenic dose 50 (AD50) and lethal dose 50 under anesthesia (LD50) were determined using the method of Litchfield and Wilcoxon. AD50 in adults was 13.0 +/- 1.0 mg/kg (X +/- SD) compared with 2.9 +/- 0.3 mg/kg in the newborns (P less than 0.01), and LD50 in adults was 30.0 +/- 1.9 mg/kg compared with 5.0 +/- 0.2 mg/kg in the newborns (P less than 0.01). Arrhythmias appeared earlier in adults (54 +/- 11.5 minutes after digoxin, X +/- SEM) than in newborns (132.2 +/- 11.0 minutes, P less than 0.01). Paroxysmal atrial tachycardia was the predominant arrhythmia in adults (73%), while transient sinus bradycardia appeared in only 9%. In contrast, all newborns with arrhythmias had severe sinus bradycardia and 69% had profound first degree heart block as well. In conclusion, the newborn rat is more sensitive to digoxin toxicity and develops lethal arrhythmias much more readily than the adult.

Topics: Aging; Animals; Animals, Newborn; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Female; Heart Diseases; Rats

Topics: Adult; Arrhythmias, Cardiac; Cardiac Surgical Procedures; Digoxin; Female; Heart Valve Diseases; Heart Ventricles; Humans; Male; Middle Aged; Postoperative Complications

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Female; Glaucoma; Humans; Propanolamines; Timolol

The effect of NiCl2 on digoxin induced cardiac arrhythmias were studied in anesthetized dogs and in isolated perfused hearts of rabbits, guinea pigs and rats. The results indicate that NiCl2 can effectively antagonize the digoxin induced cardiac arrhythmias in both intact as well as in isolated hearts. Sinus rhythm was restored and the cardiovascular status of the animal (which was digitoxic) eventually restored to normal. When not treated with NiCl2 the cardiovascular status of the dogs was progressively worsened leading to death. NiCl2 alone did not have any marked effect in normal hearts. It is likely that Ni2+ might be competing with Ca2+ at the cell membrane sites thereby antagonizing the toxic effects of digoxin. It is also possible that an increase in malic acid and oxaloacetic acid activity induced by NiCl2 may play a role in reversing the toxicity of digoxin.

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Female; Heart; In Vitro Techniques; Male; Nickel; Species Specificity; Time Factors

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Quinidine

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Digitalis Glycosides; Digoxin; Humans

The contribution of atrial systole in the left ventricular (LV) function and the effects of oral digoxin maintenance therapy on the LV function were evaluated noninvasively in patients who had artificial pacemakers but no clinical manifestation of congestive heart failure (NYHA Class I). Diastolic dimension (Dd), ejection time (ET), and stroke volume were constant in 8 patients without P waves on their electrocardiograms, but in 20 patients with P waves they were variable from beat to beat because of the variation of the PR intervals which caused them to reach their maximum values when the PR intervals were 160 to 200 msec. Ten out of the 28 patients were given 0.25 mg of digoxin daily for 10 days. Dd did not change significantly, but the ET and the systolic dimension were significantly shortened (P < 0.001). Posterior wall excursion, ejection fraction, and mean posterior wall velocity were significantly increased (P < 0.001). It is concluded that (1) atrial contraction is important to the LV function in patients with artificial pacemakers, and (2) that favorable effects on the LV function can be obtained by a small dose of digoxin administered to the patients who had artificial pacemakers but no congestive heart failure.

Topics: Adult; Aged; Arrhythmias, Cardiac; Cardiac Output; Digoxin; Electrocardiography; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Contraction; Pacemaker, Artificial; Phonocardiography

A variety of atrial dysrhythmias including paroxysmal atrial tachycardia, atrial tachycardia with 2nd-grade atrioventricular block, atrial fibrillation, and atrial flutter developed in a 5-year-old Quarter Horse gelding. Quinidine and propranolol were not successful in restoring normal sinus rhythm. Sinus rhythm was re-established during digoxin therapy, but later reverted to atrial dysrhythmia. At necropsy, multiple, discrete pale areas were found on both atria and the interatrial myocardium. Histologic examination of these lesions demonstrated myocytolysis and replacement by fibrous connective tissue.

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Heart Atria; Horse Diseases; Horses; Male; Tachycardia

This report describes a clinical syndrome of arrhythmias that may have neural origin. Two patients presented with episodes of loss of consciousness, disorientation, and paroxysmal supraventricular tachycardia (PSVT). One patient reported experiencing neurologic symptoms without tachycardia. When electrophysiologic testing with intracardiac recordings and programmed stimulation yielded no abnormalities that could account for the arrhythmias, a primary neurologic abnormality was sought. The electroencephalograms of both patients showed epileptiform discharges that supported this hypothesis. Arrhythmias and neurologic symptoms were controlled by treatment with the antiepileptic drug carbamazepine in one patient. Findings in these two patients suggest that in some patients arrhythmias may be a manifestation of seizures.

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Carbamazepine; Digoxin; Electroencephalography; Electrophysiology; Epilepsy; Humans; Male; Phenytoin; Tachycardia, Paroxysmal

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged

The purpose of this study was to establish the incidence of pre-operative digitalization by intravenous digoxin on cardiac arrhythmias in 24 patients with ischemic heart disease who underwent abdominal surgery. Ambulatory electrocardiographic monitoring was performed for 12 hours before digitalization, for 12 hours during digitalization (before surgery), for the whole period of anesthesia. General anesthesia used thiopentone, phenoperidine, pancuronium and suxamethonium for endotracheal intubation. No more premature ventricular (PVC) and auricular contractions were detected after digitalization and during anesthesia and surgery. But PVC with begeminism or severe bradycardia were recorded in two patients and episodes of "torsades de pointes" occurred in two other patients during endotracheal intubation. "Torsades de pointes" have never been reported after suxamethonium and endotracheal intubation in digitalized patients. Digitalization, ischemic heart disease, cardiac effects of suxamethonium might be factors of the onset of these first reported "torsades de pointes". In conclusion, after a pre-operative digitalization in the coronary patients the frequency of arrhythmias is not exaggerated during the pre- or per-operative period except during induction and intubation. As the role of suxamethonium seems to be important as a trigger for severe arrhythmias endotracheal intubation in digitalized coronary patients should be performed without suxamethonium.

Topics: Acid-Base Equilibrium; Aged; Arrhythmias, Cardiac; Coronary Disease; Digoxin; Electrocardiography; Female; Humans; Intraoperative Complications; Male; Middle Aged; Oxygen; Potassium; Preoperative Care

Topics: Adrenergic beta-Antagonists; Ajmaline; Amiodarone; Anti-Arrhythmia Agents; Arrhythmia, Sinus; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Cardiac Pacing, Artificial; Digoxin; Disopyramide; Electric Countershock; Humans; Phenytoin; Procainamide; Quinidine; Tachycardia; Tachycardia, Paroxysmal; Verapamil

In a prospective survey of treatment on a coronary care unit 23.6% of patients who received medication had one or more side effects. In several cases these were severe enough to cause marked deterioration of the patient's clinical status. Whilst antiarrhythmic therapy is an integral part of modern coronary care its potential hazards should be recognized, particularly in the elderly patient.

Topics: Adrenergic beta-Antagonists; Adult; Age Factors; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atropine; Coronary Care Units; Digoxin; Humans; Lidocaine; Middle Aged; Myocardial Infarction; Prospective Studies

On the patients with moderate and severe heart insufficiency haemodynamic, clinical and electrocardiographic examinations were carried out. After the application of digitoxin at the beginning in the majority of cases no favourable effects on clinical and haemodynamic findings could be proved. In 2 patients with cor pulmonale even a drastic deterioration with increase of the pulmonary pressure and formation of a pulmonary oedema developed. The temporary analysis of the systole and the estimation of the glycoside level did not give any reliable references. The recompensation began only after 2-3 days. In 5 out of 10 patients in whom the cardiac rhythm was continuously controlled by means of a tape storage device, after the application of digoxin ventricular extrasystoles appeared. Also in these cases increased as well as subtherapeutic digoxin-plasma levels were present. In 2 patients with hypertrophic obstructive cardiomyopathy the infundibular gradients were considerably increased by strophantin. The causes of the different reaction patters are to be sought in disease-specific peculiarities, in the degree of severity of the heart insufficiency, in the speed of the flooding of glycoside and several extracardiac factors.

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Blood Pressure; Cardiac Complexes, Premature; Cardiomyopathy, Hypertrophic; Digitalis Glycosides; Digoxin; Female; Heart; Heart Diseases; Heart Failure; Heart Valve Diseases; Humans; Male; Middle Aged; Pulmonary Edema; Pulmonary Heart Disease

Topics: Arrhythmias, Cardiac; Digoxin; Humans; Kidney Diseases; Radioimmunoassay

Topics: Animals; Antibodies; Arrhythmias, Cardiac; Digoxin; Humans; Immunoglobulin Fab Fragments; Sheep

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Digoxin; Female; Humans; Male; Middle Aged

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Child; Digoxin; Female; Heart Diseases; Humans; Male; Middle Aged; Taiwan

Topics: Adult; Age Factors; Aged; Arrhythmias, Cardiac; Creatinine; Digitalis Glycosides; Digoxin; Female; Hospitalization; Humans; Kidney Diseases; Male; Middle Aged; Potassium; Prospective Studies

Glycoside toxicity, a common and potentially fatal complication among patients taking digoxin, is treated basically by managing cardiac arrythmias until the patient can excrete enough drug to decrease the intoxication. Patients with renal failure, however, are particularly difficult to manage. We describe a case of advanced digoxin toxicity in an elderly man with severe renal failure, treated with a charcoal hemoperfusion device.

Topics: Aged; Arrhythmias, Cardiac; Charcoal; Digoxin; Half-Life; Heart Failure; Hemoperfusion; Humans; Kidney Failure, Chronic; Male

In a prospective study 73 patients on maintenance digitalis treatment at the Paracelsus Institute, Bad Hall, were clinically examined and the dosage of the drug was adjusted according to cardiac symptoms. The clinical effects were correlated to digoxin concentrations measured on the day following admission to hospital and on the 21st day of treatment. The following practical conclusions were reached: 1. More than 50% of the patients were underdigitalized. 2. There is often no indication for digitalis therapy in patients with a low daily maintenance digoxin dosage and normal renal funciton. 3. The usual recommended maintenance dosage of digoxin provides serum digoxin levels in the lower region of the therapeutic range. 4. Patients with symptoms of decompensation taking an average dosage of digoxin need more digitalis. There is generally no danger of toxicity when the dosage is increased. 5. The serum digoxin concentration in patients with slightly reduced renal function lies in the upper region of the therapeutic range with usual doses of digoxin.

Topics: Arrhythmias, Cardiac; Austria; Digitalis Glycosides; Digoxin; Humans; Kidney; Prospective Studies

Topics: Arrhythmias, Cardiac; Cardiomyopathies; Digoxin; Diuretics; Humans

In 1976, 130 patients aged 70 or older were admitted to the Coronary Care Unit (CCU) at Toronto Western Hospital. Arrhythmias were noted in all but 24 percent. Digoxin was given to 53 patients, lidocaine to 24, propranolol to 28, and quinidine to 11. In 2 patients, cardioversion by direct current was required for supraventricular arrhythmias. In 26 patients, temporary pacemakers were used. Of 13 patients who experienced at least one cardiac arrest in the CCU, 10 survived to be discharged to the ward. In total, only 12 of the 130 elderly patients died in the hospital, and in only 3 of these was arrhythmia the primary cause of death. The treatment of arrhythmias in the elderly is as successful and rewarding as in younger patients. Indications for the various antiarrhythmic drugs are similar. Except for digoxin, the dosages of such drugs for the elderly are the same as those for younger patients. Adverse effects apparently are not more common in the elderly.

Topics: Aged; Arrhythmias, Cardiac; Atropine; Cardiac Pacing, Artificial; Coronary Care Units; Digoxin; Electric Countershock; Electrocardiography; Female; Humans; Lidocaine; Male; Myocardial Infarction; Ontario; Procainamide; Propranolol; Quinidine

Topics: Adult; Aged; Animals; Antibody Specificity; Arrhythmias, Cardiac; Cats; Digitalis Glycosides; Digoxin; Dogs; Female; Humans; Immunization, Passive; Male

Topics: Arrhythmias, Cardiac; Chronic Disease; Coronary Circulation; Coronary Disease; Digitalis Glycosides; Digoxin; Heart Failure; Hemodynamics; Humans; Myocardial Contraction; Myocardium; Ouabain; Oxygen Consumption

To increase the limited knowledge of the effects of digitalis on sinus nodal function in patients with sinus nodal dysfunction and to initiate an investigation into the mechanisms underlying its effects, 34 patients with sinus nodal dysfunction were studied. Twenty patients underwent determination of sinus cycle length, estimated sinoatrial conduction time and maximal corrected sinus recovery time before and after the administration of 0.75 mg of intravenous digoxin. For the group, sinus cycle length did not change, sinoatrial conduction time increased insignificantly and maximal corrected sinus recovery time shortened; however, individual variation occurred. The effects of acute digitalization appeared to predict the effects of chronic digitalis administration on sinus nodal function in the eight patients who subsequently continued to take digoxin. Fourteen patients received digoxin after vagal blockade with atropine. After vagal blockade, digoxin lengthened sinus cycle length, sinoatrial conduction time and maximal corrected sinus recovery time. The effects of digoxin administered after atropine could be antiadrenergic, direct, or both, and are opposite to those induced by atropine alone. Because these effects are similar to those of vagotonia yet are not apparent when the vagi are unblocked, digoxin may have direct excitatory, adrenergic or previously unrecognized vagolytic effects on sinus nodal function in man and their manifestation may be dependent on heart rate or autonomic tone.

Topics: Adult; Aged; Arrhythmias, Cardiac; Atropine; Bradycardia; Cardiac Pacing, Artificial; Digoxin; Electrocardiography; Female; Humans; Injections, Intravenous; Male; Middle Aged; Sinoatrial Block; Sinoatrial Node; Tachycardia; Vagus Nerve

Quinidine causes an increase in the serum digoxin concentration. Three patients were studied to determine if the increase in serum concentration is paralleled by an increase in the cardiac effect of digoxin. Each patient's clinical condition and serum digoxin concentration were stable when quinidine administration was begun. In all three patients, serum digoxin concentrations increased significantly after beginning quinidine, and decreased when quinidine was discontinued. While taking quinidine, all three patients had ECG findings that suggested enhanced digitalis effect and one patient had clinical evidence of an increased hemodynamic effect. These effects paralleled the increases in serum digoxin concentration. Our findings suggest that the increase in serum digoxin concentration, which occurs after beginning quinidine, is associated with an increase in the effect of digoxin on the heart.

Topics: Aged; Aortic Valve Stenosis; Arrhythmias, Cardiac; Digoxin; Drug Synergism; Female; Heart; Hemodynamics; Humans; Male; Middle Aged; Quinidine

Topics: Arrhythmias, Cardiac; Barbiturates; Digitalis Glycosides; Digitoxin; Digoxin; Diuretics; Drug Interactions; Humans; Hypokalemia; Phenylbutazone; Potassium; Quinidine

We used charcoal hemoperfusion coupled with hemodialysis to treat a woman with massive digoxin ingestion complicated by hyperkalemia. Although dialysis controlled the serum potassium levels, hemoperfusion removed less than 1% of the total ingested dose. Hemoperfusion has a relatively minor impact on digoxin elimination and remains of unproved value in the therapy for digoxin overdose.

Topics: Adult; Arrhythmias, Cardiac; Charcoal; Digoxin; Female; Hemoperfusion; Humans; Hyperkalemia; Myocardium; Potassium; Renal Dialysis

Topics: Aged; Arrhythmias, Cardiac; Bethanidine; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Furosemide; Humans; Hyperkalemia; Hypotension, Orthostatic; Male; Middle Aged; Spironolactone; Uremia

Topics: Adult; Arrhythmias, Cardiac; Digoxin; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Postoperative Complications

Arrhythmias often complicate the course of patients with severe respiratory disease; the frequency of arrhythmias in patients with this condition approaches that seen with acute myocardial infarction. No one rhythm disturbance predominates, but rapid atrial and ventricular rhythms are characteristic. In the setting of acute respiratory failure, several conditions may predispose to arrhythmias. Hypoxemia, a serum pH that is too high or too low, and a low serum potassium may produce arrhythmias by disturbing the myocardial cellular milieu. Drugs such as digitalis, epinephrine, and theophylline may also act as myocardial irritants. The first step in therapy is to careful examination, it is helpful to note the specific effect of the arrhythmia on the patient. Some rhythm disturbances are well tolerated, while others are associated with serious problems in ventilation and perfusion. In many cases the control of respiration, correction of pH and electrolyte imbalance, and provision of bronchial hygiene will restore a normal sinus rhythm. Such measures are essential even when antiarrhythmic drugs or cardioversion are needed.

Topics: Arrhythmias, Cardiac; Chronic Disease; Digoxin; Humans; Hypokalemia; Hypoxia; Lidocaine; Lung Diseases; Oxygen Inhalation Therapy; Procainamide; Propranolol; Pulmonary Atelectasis; Quinidine

In previous studies we have come to doubt that ventricular rhythms of an automatic nature will arise spontaneously from the peripheral Purkinje system. In 20 anesthetized dogs, digoxin was administered i.v. (0.1-1.0 mg/kg) and in 12 dogs by selectively perfusing the atrioventricular (AV) node artery (2 ml; 40 microgram/ml). We obtained the following results. First, selective pharmacological production of complete AV block (acetylcholine or physostigmine) interrupts the "ventricular" arrhythmias considered characteristic of digitalis intoxication.Second, digitalis arrhythmias are difficult to produce when this type of complete heart block had been previously established. Third, abolition of ventricular arrhythmias by selective pharmacological production of heart block can be reversed (i.e., the arrhythmia restored) with atropine. Fourth, rapid pacing of the ventricles during complete heart block in dogs poisoned with digitalis can eventually induce ventricular arrhythmias, but not quickly. We interpret that these digitalis arrhythmias originated within the acetylcholine-sensitive portion of the AV node-His bundle region.

Topics: Acetylcholine; Animals; Arrhythmias, Cardiac; Atrioventricular Node; Digoxin; Dogs; Electrophysiology; Female; Heart Block; Heart Conduction System; Male; Physostigmine

Topics: Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Heart Failure; Humans

Carotid sinus hyperaesthesia (CSH) was found in 605 of the clinical cases observed by the authors in a 6-year period. In the patients with CSH, disorders of impulse formation and conduction, both at rest and in response to the carotid compression test, were prevalent. No relationship was demonstrable between the duration of carotid compression and the consequent rhythm disorders. Nor did the vascular state of the CSH patients affect the type, duration or severity of arrhythmia elicited by carotid compression. In 8 cases of CSH unilateral carotid sinus infiltration with lidocain was performed with the objective of pharmacological denervation. Predominance of sympathicotonia induced in this manner was not found to be provocative of arrhythmia. Sensitization of the carotid sinus reflex in response to i.v. administration of 0.5 mg digoxin was confirmed on the evidence of clinical investigations.The results thus obtained are primarily attributed to a decreased sympathetic efferentation.

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Carotid Sinus; Digoxin; Electrocardiography; Female; Humans; Hyperesthesia; Hypertension; Lidocaine; Male; Middle Aged; Reflex, Abnormal

Between 1968 and 1977, 87 patients underwent pneumonectomy at Rhode Island Hospital. Postoperatively, 25 patients developed arrhythmia (29 percent), giving rise to hemodynamic deterioration necessitating aggressive treatment. There were nine hospital deaths (10 percent). The effect of preoperative digitalis was analyzed in 68 patients over age 50 years.In Group 1, digoxin was not used until the onset of arrhythmia. There were 40 patients in this group; 18 developed arrhythmia (45 percent) with four deaths (22 percent).In Group 2, patients were given digitalis preoperatively. There were 28 patients; six developed arrhythmia (21 percent) with no deaths.Thus, the high incidence (45 percent in Group 1 and 21 percent in Group 2), as well as risk of mortality (4/18 patients) from arrhythmia following pneumonectomy, in patients over 50 years of age without digitalization, is a strong indication for preoperative digitalis.

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Humans; Middle Aged; Pneumonectomy; Postoperative Complications

Topics: Arrhythmias, Cardiac; Digoxin; Drug Utilization; Heart Failure; Humans

Digoxin serum levels in 41 children with clinical and/or ECG symptoms of digitoxicity were determined by radioimmunoassay and compared to the normal values. 54% of the cases showed a good relationship between clinical and/or ECG signs of toxicity and digoxin levels; on the contrary, 29% of patients exhibited only clinical and/or ECG signs of toxicity with normal digoxin levels and 17% of patients had high digoxin levels without signs of toxicity. The significance and possible causes of this relative discrepancy are discussed.

Topics: Adult; Arrhythmias, Cardiac; Cardiomyopathies; Child; Child, Preschool; Digitalis Glycosides; Digoxin; Heart Defects, Congenital; Heart Failure; Humans; Infant; Radioimmunoassay

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Female; Humans; Magnesium Deficiency; Magnesium Sulfate; Male

The effects of digoxin on monovalent cation active transport were determined in cardiac tissue obtained from dogs given inotropic, toxic, or lethal doses of digoxin. In hemodynamically monitored dogs, active uptake of the K+ analogue Rb+ was determined in vitro in a control myocardial biopsy, and then in serial biopsies from the same dog after the infusion of [3H]digoxin in doses sufficient to cause a sustained positive inotropic effect in the absence of toxicity, and finally after additional doses to induce overt toxicity. Nontoxic digoxin doses producing a mean increase of 20% in left ventricular (LV) dP/dt significantly reduced Rb+ active transport by 25% below control values. At the onset of digoxin-induced arrhythmias, maximal LV dP/dt was 53% above control whereas active Rb+ transport was reduced by 60% below baseline values (P less than 0.001). Control dogs given vehicle alone showed no significant change in contractility or in monovalent cation active transport. In another group of dogs given a lethal dose of digoxin, Rb+ active transport was reduced 59% below control levels at the onset of overt toxicity and was further reduced 80% below control at the time of onset of a fatal rhythm disturbance. When dogs were given high affinity digoxin-specific IgG or Fab fragments at the onset of overt toxicity, toxicity was rapidly reversed, and monovalent cation active transport increased to 51% of control at the time of restoration of sinus rhythm. Twenty-four hours after antibody reversal of arrhythmias, monovalent cation transport values approximated normal control levels. These data provide quantitative estimates of the extent of inhibition of monovalent cation transport by digoxin at inotropic, toxic, and lethal endpoints. Similar degrees of transport inhibition were present at the time of onset of digoxin-induced arrhythmias and at the time or arrhythmia reversal by digoxin-specific antibodies.

Topics: Animals; Arrhythmias, Cardiac; Biological Transport, Active; Biopsy; Digoxin; Dogs; Female; Immunoglobulin Fab Fragments; Immunoglobulin G; Male; Myocardial Contraction; Myocardium; Pharmaceutical Vehicles; Rubidium

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Drug Therapy, Combination; Female; Heart Block; Heart Conduction System; Humans; Male; Middle Aged; Propranolol

The formation of digoxin-specific antibodies was induced in sheep by immunization with a digoxin-albumin conjugate. The efficacy of the antibodies was investigated in anesthetized cats. When the digoxin-specific antibodies were administered prophylactically as a gammaglobulin, IgG or F (ab')2 preparation, the dose of digoxin needed to induce ventricular dysrhythmia was significantly greater (p less than 0.001) for the pretreated animals than for the controls. To investigate therapeutic efficacy, the animals were digitalized with digoxin over a period of three days and were given digoxin injections on the fourth day to provoke ventricular tachycardia. Of the control animals, three died before two hours had elapsed and the arrhythmia persisted in the two remaining animals. By contrast, a stable sinus rhythm was restored in all animals which were treated with F (ab')2 fragment of the digoxin-specific antibodies after onset of ventricular tachycardia. The doses of digoxin required to trigger renewed ventricular dysrhythmia in these animals were greater than those required at the start of the experiment. The potential clinical use of digoxin-specific antibodies is discussed in the light of these results and reports in the literature.

Topics: Animals; Arrhythmias, Cardiac; Calcium; Cats; Digoxin; Female; gamma-Globulins; Immunoglobulin Fab Fragments; Immunoglobulin G; Infusions, Parenteral; Injections, Intramuscular; Male; Phosphates; Potassium; Sodium

Topics: Aged; Arrhythmias, Cardiac; Berlin; Cardiac Complexes, Premature; Digitalis Glycosides; Digoxin; Diuretics; Drug Therapy, Combination; Drug Tolerance; Female; Heart Block; Humans; Hypokalemia; Male; Myocardium; Pacemaker, Artificial; Potassium; Prospective Studies; Retrospective Studies; Ventricular Fibrillation

Topics: Arrhythmias, Cardiac; Biological Availability; Digoxin; Humans; Patient Dropouts

The EKG response to exercise and the working capacity in a group of 70 patients with positive serology for Chagas' disease has been determined by stress testing on a bicycle-ergometer, in order to establish the usefulness of such a test in the early diagnosis of Chagas' cardiomyopathy. The exercise EKG provides information which cannot be obtained by other diagnostic procedures, since the stress test can induce or increase ventricular arrhythmia, and is particularly indicated in patients with Chagas' infection and the incipient forms of Chagas' cardiomyopathy. Measuring the working capacity is useful in order to establish the degree of functional impairment of each individual patient. After the application of oral digoxin, no significant increase of ventricular extrasystoles following exercise has been observed and the working capacity has improved in the majority of the studied cases with Chagas' cardiomyopathy.

Topics: Administration, Oral; Adult; Aged; Arrhythmias, Cardiac; Cardiomyopathies; Chagas Disease; Digoxin; Exercise Test; Female; Humans; Male; Middle Aged

A prospective study of consecutive patients admitted to a medical service was undertaken to evaluate the prevalence of cardiac digitalis toxicity and the relative diagnostic values of serum digoxin versus an empiric method, based on calculations of digoxin dose in relation to kidney function and body weight. Of 711 patients admitted, 109 were treated with digitalis on admission. Sixteen of the patients developed cardiac arrhythmias consistent with digitalis intoxication. Five of these, none with serum digoxin above 1.6 ng/ml, were not toxic. The remaining eleven patients, all with serum digoxin levels above 1.6 ng/ml, were either definitely or possibly toxic. A similar borderline between intoxicated and nonintoxicated patients could not be established on the basis of calculations based on body weight and renal function. In all cases in which suspicion of digitalis intoxication was raised, serum digoxin measurements could discriminate between the toxic and the nontoxic patients.

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Humans; Middle Aged; Models, Biological

Serum and myocardial digoxin levels were studied in 18 patients who came to autopsy. An independent analysis of electrocardiograms prior to death was made to ascertain the relationship between serum and tissue levels of digoxin and clinical estimation of drug toxicity. Patients with arrhythmias of digoxin toxicity had higher mean serum and tissue digoxin levels than patients without arrhythmia. There was overlap in the patient groups, however, and the differences were not statistically significant. The tissue to serum ratio was lower in the toxic patients. The latter phenomenon is unexplained but may be related to decreased tissue binding.

Topics: Aged; Arrhythmias, Cardiac; Autopsy; Child; Digoxin; Electrocardiography; Humans; Middle Aged; Myocardium

Topics: Aged; Anorexia; Arrhythmias, Cardiac; Deglutition Disorders; Digitalis Glycosides; Digitoxin; Digoxin; Female; Heart Failure; Humans; Male

Correlative studies of serum digoxin levels, cardiac rhythm and related clinical laboratory data were carried out in 114 patients. Seventy-three patients who presented with 79 episodes of arrhythmias typical of digitalis intoxication could be separated into a normokalemic group of 55 patients whose serum digoxin level was 6.68 +/- 0.17 ng/ml (mean +/- standard error of the mean), and a hypokalemic group of 24 with a mean serum digoxin level of 1.13 +/- 0.04 ng/ml (P less than 0.001). Of 45 consectutive normokalemic patients with a high serum digoxin level (more than 2 mg/ml) who underwent serial studies, 17 had arrhythmias. Serial studies in 10 hypokalemic patients revealed an inconsistent relation between presence of arrhythmia and serum digoxin level. During repletion of serum potassium in seven of these patients with an arrhythmia, the arrhythmia disappeared without a significant change in serum digoxin level in four patients. A group of seven patients had 16 episodes of serum digoxin level greater than 2.2 ng/ml, but an arrhythmia occurred during only 3 of these episodes. A sharp border between toxic and therapeutic serum digoxin values was not found in these groups of study patients. The serum digoxin level at which arrhythmias occurred appeared to be variable for both groups and individual patients. However, correlative studies utilizing serum digoxin levels can define existing thresholds for therapeutic and toxic effects and may often be more useful than isolated observations.

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Humans; Hypokalemia; Male; Middle Aged; Myocardial Contraction; Potassium; Radioimmunoassay

1 Twenty-nine dogs were given digoxin (0.25 mg) by mouth twice daily for eight days. Some of them (group 1) also received diuretics and others (group 2) a mineralocorticoid. The dogs were then given an intravenous bolus injection of digoxin and plasma and cardiac muscle were analysed for digoxin and potassium. 2 In the digitalized dogs, myocardial potassium concentration decreased following the intravenous injection of either 0.05 or 0.15 mg/kg digoxin; in contrast, in those dogs given diuretics or mineralocorticoid the potassium concentration increased. 3 Ventricular arrhythmias occurred after digoxin injection (0.05 mg/kg) in the hypokalemic dogs, in those given a mineralocortocoid and in those dogs which received a toxic digoxin dose (0.15 mg/kg). No arrhythmias where seen in the control (digitalized) group. 4 Myocardial digoxin concentrations were similar in the control digitalized group and in the mineralocorticoid-treated dogs after the intravenous administration of the lower digoxin dose (0.05 mg/kg). The myocardial digoxin concentration was significantly higher in the hypokalemic group and in the group receiving the higher digoxin dose (0.15 mg/kg). 5 There was no obvious relationship between the occurrence of arrhythmias and the myocardial concentration of digoxin or potassium.

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Hemodynamics; Myocardium; Potassium; Sodium; Time Factors

The serum digoxin concentration increased in 25 of 27 study patients (93%), and the mean serum digoxin concentration rose from 1.4 ng/ml to 3.2 ng/ml during quinidine therapy. Anorexia, nausea, or vomiting developed in 16 patients (59%) but disappeared in all ten patients for whom the digoxin dose alone was reduced, suggesting that digoxin excess caused these symptoms. Ventricular premature depolarizations developed in three patients after starting quinidine therapy; ventricular tachycardia developed in one patient, and another died suddenly. When starting quinidine therapy in patients who are taking digoxin, the clinical course, ECG, and serum digoxin level should be followed closely.

Topics: Aged; Anorexia; Arrhythmias, Cardiac; Digoxin; Drug Interactions; Female; Humans; Male; Middle Aged; Nausea; Quinidine; Vomiting

Topics: Adult; Arrhythmias, Cardiac; Child; Digitalis Glycosides; Digoxin; Erythrocytes; Humans; Infant; Ions; Myocardial Contraction; Potassium; Sodium

The usefulness of measuring plasma digoxin concentrations in the diagnosis of digoxin toxicity has been assessed in 83 in-patients. The mean plasma digoxin concentration in clinically toxic patients was significantly higher than the mean concentration in non-toxic patients. The overlap between the groups, however, was extensive and could partly be accounted for by hypokalaemia in those toxic patients whose plasma digoxin concentration was less than 3 ng/ml. There was, in addition, a higher incidence of hyperkalaemia, without obvious cause, in toxic patients than in non-toxic patients. Consideration of the incidence of various non-cardiac factors, specifically plasma potassium concentration greater than 5.0 mmol/l, plasma creatinine concentration greater than 150 mumol/l, daily maintenance dose greater than 6 microgram/kg, and age greater than 60 years, led to the development of guidelines to aid in the diagnosis of digoxin toxicity. Patients with plasma digoxin concentration greater than 3 ng/ml or with hypokalaemia should be considered probably toxic and those with plasma digoxin concentration greater than or equal to 3 ng/ml in the absence of hypokalaemia should only be considered toxic if they have at least two of the non-cardiac factors outlined above. Plasma digoxin concentrations could not be predicted with more than 31 per cent certainty by considering the magnitude of those non-cardiac factors.

Topics: Aged; Arrhythmias, Cardiac; Creatinine; Digoxin; Female; Humans; Male; Middle Aged; Potassium

The prolonged QT interval syndrome without hearing loss (Romano-Ward syndrome) is described in three families with 48 affected members. Syncope or dizziness caused by different ventricular tachyarrhythmias were the presenting symptoms in the symptomatic patients. Four of the subjects died suddenly. Right stellate ganglionectomy was performed in one patient in order to abolish the ventricular dysrhythmia. beta-blockers are considered the drug of choice in patients with hereditary prolonged QT interval; if the beta-blockers fail to abolish the syncopal attacks of severe bradycardia complicates the clinical course, a pharmacological blockade of the stellate ganglia should be performed and its results carefully evaluated in order to establish whether a stellate ganglionectomy is justified.

Topics: Adult; Arrhythmias, Cardiac; Child; Digoxin; Female; Humans; Isoproterenol; Male; Pedigree; Propranolol; Syndrome; Tachycardia

Topics: Administration, Oral; Adult; Arrhythmias, Cardiac; Biological Availability; Digoxin; Humans

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Family Practice; Heart Diseases; Humans

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digoxin; Female; Humans; Male; Middle Aged

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Humans; Lidocaine; Phenytoin; Procainamide

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Electrocardiography; Humans

The diagnostically relevant data of 1164 patients under digitalis were stored in a computer and compared statistically for toxic and nontoxic patients. Resulting from this a questionnaire was developed in which each item was weighted according to its own diagnostic value. In a prospective study 77 suspected cases of digitalis intoxication were classified according to their scoring in the questionnaire. In 92% of the patients this classification was confirmed by the final diagnosis (after withdrawal of the glycoside). Mean score and mean serum digoxin concentration (SDC) of the toxic patients were significantly higher. There was a high consensus between the final diagnosis, the classification by the questionnaire and the SDC. The questionnaire proved to be a useful aid in the bedside diagnosis of digitalis intoxication.

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Humans; Poisoning; Risk; Surveys and Questionnaires

Topics: Adult; Aged; Arrhythmias, Cardiac; Digoxin; Female; Humans; Male; Middle Aged; Sinoatrial Node

Topics: Arrhythmias, Cardiac; Digoxin; Humans

The inotropic and arrhythmogenic effects of 16-acetyl-gitoxin and digoxin were studied in isolated cardiac preparations and in anaesthetized dogs. ECG alteration-producing and lethal doses of both glycosides were determined in anaesthetized cats. In the isolated guinea-pig atrium, the properties of 16-acetyl-gitoxin are identical with those of ouabain, and in the isolated guinea-pig heart they are equal to those of digoxin, while gitoxin and penta-acetyl-gitoxin produce equieffective reactions at higher glycoside concentrations. In the cat, 75% of lethal doses of 16-acetyl-gitoxin and digoxin provoke ECG changes (qrs complex prolongation). The ratio of the lethal doses amounts to 1:2.8 and 1:3.5 (digoxin:16-acetyl-gitoxin). In case of equal contractile increment, the ratio of glycoside doses in dogs amounts to 1:1.3, while the percentages of rhythm disturbances following both glycosides are identical. Apart from slight deviations of the doses used, the cardiac properties of 16-acetyl-gitoxin are equal to those of digoxin.

Topics: Acetyldigoxins; Animals; Arrhythmias, Cardiac; Atrial Function; Cats; Digoxin; Dogs; Female; Guinea Pigs; Heart; Heart Rate; Isomerism; Male; Myocardial Contraction; Ouabain; Species Specificity; Structure-Activity Relationship

The serum-digoxin level was measured by radio-immunoassay (Immutope) on 245 patients in a coronary care unit. Cardiac arrhythmias were assumed to be digoxin-induced if they disappeared after the drug had been stopped. Patients who had received digitoxin or spironolactone were excluded. The results indicated a normal digoxin range of 1.52 +/- 0.2 ng/ml and a toxic one of 2.78 +/- 0.38 ng/ml. First degree A-V block, atrial ectopic beats and ventricular ectopics with variable coupling intervals were frequently associated with serum-digoxin levels of 1.5-2.5 ng/ml, while higher grade A-V block, atrial tachycardia, bigeminy and atrial tachycardia with block were more frequent with higher serum-digoxin levels (greater than 3.0 ng/ml). Atrial arrhythmias were especially frequent with serum levels above 3.0 ng/ml. This suggests different sensitivities of atrial and ventricular myocardium. Atrial arrhythmias thus in general indicate a higher degree of toxicity at high serum levels, while ventricular ectopic beats occur both with high serum levels and also with increased digoxin sensitivity of the ventricles.

Topics: Arrhythmias, Cardiac; Cardiac Complexes, Premature; Coronary Disease; Digoxin; Heart Block; Humans; Radioimmunoassay; Reference Values; Tachycardia

Topics: Arrhythmias, Cardiac; Digoxin; Humans

Topics: Adenosine Triphosphatases; Animals; Arrhythmias, Cardiac; Biological Availability; Blood Pressure; Digoxin; Dogs; Drug Interactions; Female; In Vitro Techniques; Male; Membranes; Myocardial Contraction; Myocardium; Potassium; Sodium; Spironolactone

Recently direct myocardial effects of antikaliuretic diuretics with respect to contractility parameters and prevention of digitalis-induced arrhythmias were published. In order to test the value of these reports we measured the effect of potassium-canrenoate and triamterene on cardiac output and on digitalis-induced arrhythmias in patients during diagnostic and the therapeutic flow directed right heart catheterization (Swan-Ganz) in our intensive care unit. In addition the influence of these drugs on (Na+ + K+)-ATPase and on (3H)g-strophanthin binding to human cardiac cell membranes was investigated to gain information on the mechanism of their action. Triamterene (100-200 mg p.o.) was without any effect on cardiac output, the same was found true for potassium-canrenoate given in a single dose (200-1000 mg intravenously). However, when applied in two doses (200 mg i.v. and 60 min later 400 mg i.v.), potassium-canrenoate increased cardiac output by 11 percent (p less than 0.05). Only in 2 out of 14 patients potassium-canrenoate (200-400 mg i.v.) suppressed digitalis-induced ventricular ectopic beats. Canrenone, the active metabolite of potassium-canrenoate displaces [(3H)]g-strophanthin from its binding sites in human cardiac cell membranes and inhibits (Na+ + K+)-ATPase activity. These in vitro effects were measured at the same concentrations as found in vivo after "therapeutical" doses. The effects of triamterene in this respect were found only in extremely high concentrations. Our results imply that canrenone has cardiac glycoside-like effects in human cardiac cell membranes.

Topics: Adenosine Triphosphatases; Adult; Aged; Arrhythmias, Cardiac; Canrenoic Acid; Cardiac Output; Cell Membrane; Coronary Disease; Digoxin; Diuretics; Dose-Response Relationship, Drug; Drug Interactions; Female; Heart; Humans; In Vitro Techniques; Male; Middle Aged; Myocardium; Ouabain; Potassium; Receptors, Drug; Sodium; Triamterene

A novel benzanilide derivative, MJ 9067, has been shown to abolish experimental atrial and ventricular arrhythmiase effectively and promote the return of normal sinus rhythm in a variety of animal models. At intravenous dose levels ranging from 0.5 to 3.2 mg/kg, MJ 9067 successfully converted atrial fibrillation induced by either local application of aconitine or electrical stimulation, and ventricular tachycardia elicited by intravenous injection of ouabain or digoxin. The compound was equally effective in vagotomized or nonvagotomized dogs, and in intact cats and monkeys. The ventricular ectopic rate in conscious dogs 18 to 20 hours after two-stage ligation of a coronary artery was also markedly reduced by the drug at 2 mg/kg i.v. At antiarrhythmic dose levels, there were no undesirable effects noted on peripheral blood pressure, heart rate or the configuration of the electrocardiogram.

Topics: Aconitine; Anilides; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Blood Pressure; Cats; Digoxin; Dogs; Electric Stimulation; Electrocardiography; Female; Haplorhini; Heart Rate; Male; Ouabain; Piperidines; Saimiri; Tachycardia

Topics: Arrhythmias, Cardiac; Cardiomyopathies; Chagas Disease; Digoxin; Exercise Test; Heart Rate; Humans

Topics: Acute Disease; Adult; Aged; Arrhythmias, Cardiac; Digoxin; Female; Humans; Male; Middle Aged

In 5 adult dogs experimental chronic digitalis intoxication was produced by oral administration of different digitalis-types (digoxin, beta-methyl-, beta-acetyl-digoxin, digitoxin). 18 to 24 hours after the last application of digitalis, charcoal hemoperfusion was performed in Dipidolor-N2O-anesthesia and serum digitalis-concentrations in the arterial and venous lines of the hemoperfusion system were determined by RIA J125. The Ecg was registered continuously as a simple clinical parameter of cardiac digitalis intoxication. Initial multiple cardiac arrhythmias (AVII degree, SAII degree, tachycardia of the atrium) subsided in the dogs with digoxin, beta-methyl- and beta-acetyl-digoxin during hemocolperfusion within 130 to 160 min. The disturbances of rhythm persisted up to 200 min after onset of hemoperfusion in the dog intoxicated by digitoxin. The clearances of digoxin and derivatives (35.8--43.1 ml/min) are higher than the digitoxin clearance (17--23.2 ml/min) which is supposed to be the reason for cardiac detoxication in the digoxin-intoxicated dogs. Hemoperfusion using polymer coated charcoal appears to be effective for the elimination of digoxin leading to a marked improvement of cardiac arrhythmias. By contrast digitoxin induced cardiac arrhythmias are not influenced during hemoperfusion.

Topics: Animals; Arrhythmias, Cardiac; Charcoal; Digitoxin; Digoxin; Disease Models, Animal; Dogs; Electrocardiography; Hemoperfusion

Topics: Acute Disease; Adolescent; Arrhythmias, Cardiac; Digoxin; Female; Glucose; Humans; Insulin; Water-Electrolyte Balance

Topics: Arrhythmias, Cardiac; Digoxin; Heart; Heart Failure; Humans; Injections, Intravenous; Medigoxin; Pacemaker, Artificial

6 patients with severe digitalis intoxication were studied while hospitalised in a coronary care unit. 2 and 4 patients had ingested high doses of lanatosid C and digoxin, respectively. In three cases ventricular arrhythmias, in one of these and two further cases SA blocking and an additional A-V-block in one case were observed. Maximum blood levels of digoxin between 3.4 and 20 ng/ml were determined several hours after the ingestion. The maximal blood levels were achieved in one patient only 52 h after ingesting lanatosid C and in one patient taking digoxin after 12.5 h. Potassium concentrations in plasma were elevated in 4 patients. Antiarrhythmic and electrolyte therapy is discussed and the usefulness of a stomach lavage for diminishing the quantity of absorbed lanatosid C is shown in one patient who had a maximal blood level of 3.4 ng/ml after taking 23.7 mg of lanatosid C. Cumulative urinary excretion of this patient was 0.68 mg within 5.5 days. This result confirms the minimal enteral absorption under the therapy chosen.

Topics: Adult; Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Female; Heart Block; Humans; Intestinal Absorption; Kinetics; Lanatosides; Male; Middle Aged; Poisoning

A family had an unusual and perhaps unique familial dysrhythmia. The proband had a short PR interval with normal QRS and chronic recurrent paroxysmal atrial tachycardia (Lown-Ganong-Levine syndrome). The arrhythmia produced left ventricular dysfunction. Both paroxysmal atrial tachycardia (PAT) and left ventricular dysfunction were reversed with administration of digoxin and propranolol hydrochloride. Three family members had paroxysmal or chronic atrial fibrillation, first diagnosed at a relatively young age (23 years, 38 years, and early 40s, respectively). Five additional family members had short PR intervals with normal QRS, and eight other family members had borderline short PR intervals. The mode of inheritance appeared to be autosomal dominant with varying expressivity. We have described a familial syndrome characterized by PAT or atrial fibrillation in its advanced form with short PR interval as a possible identifying trait. The future course of members with isolated short PR is unknown.

Topics: Adult; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Female; Heart Atria; Humans; Male; Pedigree; Propranolol; Syndrome; Tachycardia, Paroxysmal

Topics: Arrhythmias, Cardiac; Digoxin; Humans; Hypokalemia

In 1164 cases clinical and electrocardiographical findings were correlated with serum digoxin concentrations (SDC). The diagnosis of digitalis intoxication was based on rhythm disturbances which disappeared on withdrawel of the drug. The mean SDC for patients with digitalis-induced arrhythmias was 3.07 ng/ml compared to 1.02 ng/ml for patients with normal Ecg's and 1.01 ng/ml for patients with rhythm disturbances of other origin. Taking 2.0 ng/ml as the lower limit of digitalis intoxication a more than 85% coincidence was found between the diagnosis based on serial Ecg's and on SDC levels. No signs of cardiac toxicity were found in patients with SDC's less than 1.6 ng/ml, some patients, however, showed normal Ecg's despite SDC's up to 4.5 ng/ml. Patients with SDC's greater than 1.9 ng/ml and normal Ecg's were significantly younger than patients with digitalis-induced arrhythmias at comparable SDC's. Although no definite diagnosis of cardiac toxicity could be established in 327 cases, the clinical data of patients with SDC's of 2.0 ng/ml and greater resemble closely those with digitalis-induced arrhythmias while patients with SDC's less than 2.0 ng/ml showed close resemblance to patients with no cardiac evidence of toxicity with regard to: mean age, kidney function, mean digoxin dosage and mean body weight. Patients with elevated SDC's showed a 45% incidence of severely impaired kidney function in contrast to 28% of the patients with SDC's less than 2.0 ng/ml. Even in patients with normal kidney function the correlation between the orally administered digoxin dosage and SDC levels was poor. The correlation was significantly better when dogoxin was administered intravenously. Therefore knowing the amount of digoxin taken (according to the patient's statement) seems of little benefit in the evaluation of digitalis toxicity. In patients with digitalis-induced arrhythmias mean age and mean body weight were significantly lower, mean creatinine concentration and the incidence of severe cardiac insufficency and of typical ST-T-changes were significantly higher. There was no significant difference in mean potassium concentration and incidence of coronary artery disease compared to nontoxic patients. Compared to patients with cardiac arrhythmias of other origin there were no significant differences in mean age, mean potassium and creatinine concentrations and cardiac insufficiency while the incidence of coronary artery disease was significantly higher among patien

Topics: Arrhythmias, Cardiac; Creatinine; Digoxin; Electrocardiography; Heart Failure; Humans; Kidney Failure, Chronic; Potassium

1 An in vitro technique is described for measuring the uptake of 86Rb by human erythrocytes. 2 Fifteen patients were treated with digoxin for atrial fibrillation and other fast arrhythmias. 3 86Rb uptake by the patients' own red cells fell from pre-treatment values during digitalization. 4 The therapeutic response of patients with atrial fibrillation correlated better with the changes in 86Rb uptake than with plasma digoxin concentrations.

Topics: Adult; Aged; Arrhythmias, Cardiac; Digoxin; Erythrocytes; Female; Humans; In Vitro Techniques; Male; Middle Aged; Radioisotopes; Rubidium; Time Factors

Topics: Arrhythmias, Cardiac; Digoxin; Drug Administration Schedule; Humans

Reviews of large series of patients with digitalis-induced arrhythmias create a seeming paradox: Hypokalemia is infrequently associated with digitalis-induced arrhythmias but the clinical benefit of supplementation of potassium for most digitalis-induced arrhythmias is obvious. Examination of the electrophysiologic abnormalities induced by digitalis coupled with the electrophysiologic effects dependent on the ratio intracellular to extracellular concentrations of potassium clarifies the issue. We present evidence that supports additive effects of the toxicity of digitalis and abnormal ratios of concentrations of potassium inside and outside the cardiac cell. We provide guidelines for assessing this crucial ratio of intracellular to extracellular concentrations of potassium to aid the clinician in the diagnosis and effective treatment of digitalis-induced arrhythmias.

Topics: Adult; Aged; Alkalosis; Arrhythmias, Cardiac; Digoxin; Female; Humans; Male; Middle Aged; Potassium; Potassium Deficiency; Prospective Studies

Topics: Adult; Aged; Arrhythmias, Cardiac; Coronary Disease; Digoxin; Female; Heart Diseases; Heart Failure; Humans; Male; Middle Aged

The usefulness of serum digoxin measurements in the diagnosis of digitalis toxicity was studied prospectively in hospitalized patients. Serum levels were increased above 2 ng/ml in 28 of 32 cases with digoxin-induced arrhythmias and/or gastrointestinal symptoms, whereas only 1 of 35 non-toxic patients had an abnormal serum concentration. There was, however, no direct relationship between the type of toxic manifestation and absolute values of serum digoxin.

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Drug Interactions; Humans; Spironolactone

Serum digitalis concentration was measured radioimmunologically on 1006 patients in the period from 1974-1976. The serum levels were correlated with the clinical signs of digitalis toxicity and the indications for determination of the serum digoxin concentration were established. Clinical signs of toxicity appear at a serum level of digoxin above 2.5 ng/ml. Therapeutic limits (range) are most influenced by individual factors. Serum digoxin determination is especially necessary in patients with renal failure and in undisciplined patients with erratic digitalis intake. It is a useful aid in controlling the course of digitalis intoxication, in "low dosage" digitalization and in the case of possible drug interactions.

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Eye Manifestations; Gastrointestinal Diseases; Heart Failure; Humans; Patient Compliance

In 59 digitalized and 3 non digitalized patients the effect of digitalis during the 1st to 4th days after transmural myocardial infarction was controlled. Rhythm disturbances in acute myocardial infarction may arise secondary to a complicating cardiac failure and may be influenced by digitalis. In 9 of 17 cases (53 p.c.) with ventricular or supraventricular extrasystoles daily doses of 0,4 mg beta-Methyldigoxin or 0,4 mg Digoxin i.v. resulted in undisturbed sinus rhythm. In two cases supraventricular tachycardia and extrasystoles with rapid ventricular rate were abolished by 1,2 mg beta-Methyldigoxin within 12 hours, in three other cases an improvement was recorded. Dysrhythmias or other complications did not occur in previously non digitalized patients. When the antiarrhythmic effect of digitalis cannot be obtained cardiodepressive complications by treatment with typical antiarrhythmic agents are diminished. In patients on digitalis and in cardiogenic shock, digitalization should be performed carefully. Intoxication leads to a diminution of cardiac output and to cardiac dysrhythmias.

Topics: Acute Disease; Adult; Aged; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Digitalis Glycosides; Digoxin; Drug Interactions; Female; Heart Block; Humans; Male; Middle Aged; Myocardial Infarction; Premedication; Shock, Cardiogenic; Tachycardia

Serum digoxin levels, estimated by radioimmuno assay, technique, and the pattern of cardiac arrhythmias due to digoxin intoxication seem to be correlated in cases with high serum digoxin levels. The prognostic value of those correlations is demonstrated and discussed. Serial observations of the course of cardiac arrhythmias under the suspicion of digoxin intoxication together with blood level measurements allow to introduce more objective criteria in clinical management of poor risk patients receiving digoxin.

Topics: Arrhythmias, Cardiac; Bradycardia; Cardiac Complexes, Premature; Cardiac Glycosides; Digoxin; Heart Block; Humans; Tachycardia

Serum magnesium estimation was done in 19 children who had heart failure of varied etiology. Five of nine toxic patients and three of 10 nontoxic ones had magnesium deficiency (serum magnesium less than 1.5 mEq. per liter). Mean serum magnesium level was significantly lowered (P less than 0.01) in 19 children and it was further lowered in nine toxic patients (P less than 0.001) as well as in eight hypomagnesemic patients (P less than 0.001) than in healthy control subjects. Mean serum digoxin level in toxic patients was significantly higher than in nontoxic ones (P less than 0.05). In three cases magnesium sulfate was successfully used for the management of cardiac arrhythmias.

Topics: Adolescent; Arrhythmias, Cardiac; Child; Child, Preschool; Digoxin; Heart Defects, Congenital; Heart Failure; Humans; Magnesium; Magnesium Deficiency; Magnesium Sulfate; Rheumatic Heart Disease

The efficacy of potassium canrenoate in suppressing frequent ventricular premature depolarizations and ventricular bigeminal and trigeminal rhythms thought to be due to digitalis overdose was studied in seven men and five women (average age, 54.5 years). A mean dose of 525 mg. (1.31 mEq.) of potassium canrenoate administered intravenously effectively suppressed the ventricular rhythm disturbances in eight of the 12 patients for from several minutes to 4 hours. The mean serum digoxin level determined in seven patients was greater than 2.3 ng. per milliliter. The ability of potassium canrenoate to counteract digitalis intoxication suggests that the molecule of canrenoate is unique in the clinical setting since it shows both diuretic and antiarrhythmic properties.

Topics: Adult; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Canrenoic Acid; Digitalis Glycosides; Digoxin; Diuretics; Humans; Middle Aged; Pregnadienes; Ventricular Fibrillation

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Diuretics; Drug Therapy, Combination; Heart Diseases; Heart Failure; Humans; Myocardial Infarction; Potassium

Ten digitalized patients were monitored for detection of cardiac arrhythmias 0 to 8 hr after daily maintenance dose of digoxin in the fasting state. Transient cardiac arrhythmias attributable to digoxin were seen at 2 to 5 hr in 5 subjects. Initial serum concentrations of digoxin were within standard clinical limits in all subjects, but, higher steady-state levels were present in patients with arrhythmias (1.2 to 1.7 ng/ml) than in the others (0.7 to 1.2 ng/ml). The postadministrative serum peak concentrations were also higher in the patients with arrhythmias.

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Female; Humans; Male; Middle Aged

Experiments an anaesthetized dogs, rabbits and guinea pigs show that with clinically relevant doses of 3-(2-diethyl-aminoethyl)-4-methyl-7-(carbethoxy-methoxy)-2-oxo-1,2-chromene-hydrochloride (carbocromen, Intensain¿) the LD100 of digoxin (+50%) and ouabain (+60%) considerably increase. The positive inotropic effect of digoxin is not influenced by carbocromen. The appearance of arrhythmias is significantly delayed, the coupling between atrial and ventricular activity continues for a longer time. Besides effects on myocardial metabolism a membrane effect of carbocromen could be responsible for the improvement of the therapeutic range of digoxin and ouabain.

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Chromonar; Coumarins; Digoxin; Dogs; Drug Interactions; Female; Guinea Pigs; Heart; Heart Rate; Male; Myocardial Contraction; Rabbits

In small and medium doses 3 beta, 14 beta-dihydroxy-16 beta-formyloxy-5 beta-card-20-[22]-enolide-3-tetraformyltridigitoxoside (pentaformylgitoxin; gitoformate) shows a greater positive inotropic and blood pressure increasing potency than do digitoxin and beta-acetyldigoxin. In high doses this influence on contractility is exceeded by digitoxin, that on blood pressure is equalled. None of the substances tested changes heart rate. Arrhythmias with gitoformate are only seen in lethal doses, with digitoxin and beta-acetyldigoxin two dose levels earlier.

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Cardiovascular System; Cats; Digitalis Glycosides; Digitoxin; Digoxin; Heart Rate; Myocardial Contraction

The effect of intravenous injections of digoxin (20 mug/kg every 15 minutes) on spontaneously occurring activity in autonomic efferent nerves, motor nerves, afferent nerves, electrocardiogram and on arterial blood pressure was evaluated in chloralose-anesthetized cats. Administration of digoxin enhanced neural activity in pre- and postganglionic cardiac synpathetic nerves and this enhancement occurred near the time the disturbances in ventricular rhym were noted. Neural activity continued to increase during ventricular tachycardia and maximum enhancement was observed just proir to ventricular fibrillation. Similar results were observed when digoxin was administered to animals in which neural activity was recorded from preganglionic splanchnic and superior cervical nerves. Digoxin administration also increased discharge frequency from vagus (efferent fibers), phrenic and carotid sinus nerves. Denervation of cardiovascular reflexogenic areas prevented the increased discharge in vagus nerves, reduced it in phrenic nerves, but did not affect nerve discharge in sympathetic nerves. These results suggest that digoxin-induced hyperactivity in synpathetic nerves was related to a central nervous system effect of the drug, whereas the mechanism for the digoxin-induced hyperactivity in vagus nerves involved a peripheral reflex effect of the drug. Both sites were involved in the digoxin-induced hyperactivity in phrenic nerves. Enhancement of cardiac sympathetic nerve activity appeared to be responsible for the ventricular arrhythmias provoked by digoxin as 1) a temporal relationship was observed between augmented nerve activity and arrhythmia development, 2) a centrally acting sympathetic nervous system depressant drug, clonidine, converted the ventricular arrhythmia to normal rhythm, and 3) removal of sympathetic influence to the heart by spinal cord transection decreased the sensitivity of the heart to the arrhythmogenic effect of digoxin. These results suggest that digoxin partially responsible for its cardiotoxic effects.

Topics: Adrenal Glands; Animals; Arrhythmias, Cardiac; Autonomic Fibers, Postganglionic; Autonomic Fibers, Preganglionic; Blood Pressure; Cats; Digoxin; Electrocardiography; Female; Heart; In Vitro Techniques; Male; Neurons; Neurons, Afferent; Phrenic Nerve; Vagus Nerve

Topics: Administration, Oral; Adult; Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Female; Humans; Male; Middle Aged

Topics: Aged; Aging; Anesthesia; Arrhythmias, Cardiac; Blood Circulation; Cardiovascular Physiological Phenomena; Digoxin; Heart Failure; Humans; Hypertension; Myocardial Infarction; Pacemaker, Artificial; Propranolol; Risk

It is the bicentennial anniversary of the introduction of digitalis into medicine. Digitalis is one of the most important drugs ever discovered, and after two centuries, it is still the most widely used drug in cardiology. However, it was at one time so badly abused that for nearly a century it was almost abandoned. Early in this century, the valuable effects of digitalis were once again recognized and extended. The molecular basis of action has been defined and now methods are available to detect early toxicity. Recent advances in combating toxic effects show considerable promise. Skillful administration of the drug, using purified standard tablets, careful monitoring by clinical electrocargiography, and analytical methods can secure the maximun benefits with the minimum degree of toxicity.

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digitoxin; Digoxin; England; Heart; Heart Failure; History, 18th Century; Humans; Intestinal Absorption; Intestines; Ischemia; Pacemaker, Artificial; Suicide; Tablets; Time Factors

A case is reported in which a Digoxin intoxication led to irregularities in atrial rhythm. This case, which was diagnosed by an intraatrial cardiogram, shows the usefulness of this method which is easy to practise and leads to special therapeutic aid.

Topics: Arrhythmia, Sinus; Arrhythmias, Cardiac; Diagnosis, Differential; Digoxin; Electrocardiography; Heart Atria; Heart Block; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Poisoning; Postoperative Complications; Tachycardia

Twelve patients with congestive heart failure receiving maintenance therapy with digoxin and potent diuretics were followed closely during development of hypokalemia and potassium loss. Cardiac arrhythmias compatible with digoxtin toxicity developed in 6 patients in the presence of stable, normal serum digoxin concentrations. The mechanisms involved in the development of the rhythm disturbances are discussed with regard to hypokalaemia, intracellular potassium loss, intra-/extracellular potassium gradients and digoxin, and the significance of maintaining a normal potassium balance in this setting is stressed.

Topics: Arrhythmias, Cardiac; Creatinine; Digoxin; Diuretics; Electrocardiography; Heart Failure; Humans; Hypokalemia; Middle Aged; Potassium; Potassium Deficiency

1 The tendency of a given oral dose of digoxin to induce cardiac dysrhythmia was determined indirectly at various times after its administration to eight conscious dogs by measurement of the intravenous dose of acetylstrophanthidin necessary to induce toxic changes in the ECG. Acetyl-strophanthidin was used because its rapid elimination from the body permitted estimates to be made 45, 180 and 360 min after digoxin administration. 2 Each dog underwent four studies in which doses of 0.05, 0.1, 0.2 and 0.4 mg/kg digoxin were used in a randomized sequence allowing at least ten days between each dose. 3 Digoxin reduced the amount of acetylstrophanthidin required to cause toxic changes in the ECG; this increase in cardiac sensitivity was dose-dependent. 4 There was no correlation between plasma levels of digoxin and the tendency to dysrhythmia, since peak plasma concentrations of digoxin were reached at about 60 min after dosing whereas maximal sensitivity to acetylstrophanthidin was found 3 to 6 h after administration of digoxin. 5 These results suggest that there is little or no increased risk of cardiotoxicity during periods of transient increase in plasma levels of digoxin.

Topics: Animals; Arrhythmias, Cardiac; Calcium; Digoxin; Dogs; Electrocardiography; Female; Heart Block; Heart Rate; Male; Potassium; Strophanthidin; Time Factors; Urea

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Humans; Hypokalemia; Myocardium; Potassium; Potassium Deficiency

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Drug Hypersensitivity; Humans; Hypokalemia; Myocardium; Potassium

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Humans; Hypokalemia; Male

Arrhythmias were analyzed in 50 patients undergoing cardiac surgery: 27 with valve surgery, 15 with coronary artery bypass (CAB), 5 with CAB and valve surgery, and 3 with miscellaneous procedures. The role of electrolyte abnormalities, pericarditis, serum osmolarity, digoxin level, and the type of surgery performed was evaluated. Thirty-seven out of 50 patients (74 per cent) had a postoperative arrhythmia, and a total of 78 different arrhythmias were noted. Twenty-six out of 27 patients with valve surgery had an arrhythmia vs. six out of 15 patients with CAB (p less than 0.001). Atrial fibrillation was the most common arrhythmia in all groups. Although postoperative hypocalcemia, hypomagnesemia, pericarditis, and wide shifts in osmolarity were common, they did not correlate with arrhythmias. Seventeen patients developed postoperative arrhythmias compatible with digitalis toxicity, including junctional rhythm, atrioventricular dissociation, or atrial tachycardia with block. However, the range of serum digoxin levels in these patients was zero to 2.80 ng. per milliliter. This suggests increased sensitivity to digitalis glycosides or the effects of surgical trauma as the etiology of arrhythmia in many patients. The distinction between digitalis-induced arrhythmia and spontaneously occurring arrhythmia cannot be made with certainty in most postoperative patients. Therapy should reflect an awareness of the potential for postoperative digitoxicity.

Topics: Aortic Valve; Arrhythmias, Cardiac; Blood; Bradycardia; Bundle-Branch Block; Calcium; Carbon Dioxide; Cardiac Surgical Procedures; Coronary Artery Bypass; Creatinine; Digoxin; Heart Auscultation; Heart Block; Heart Valve Prosthesis; Humans; Hydrogen-Ion Concentration; Magnesium; Mitral Valve; Osmolar Concentration; Postoperative Complications; Potassium; Serum Albumin; Sodium; Tachycardia, Paroxysmal; Time Factors

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Bradycardia; Cardiovascular Diseases; Digoxin; Emergencies; Epinephrine; Female; Fetal Diseases; Fetal Heart; Haplorhini; Heart Failure; Heart Rate; Humans; Hypoxia; Infant; Infant, Newborn; Infant, Newborn, Diseases; Isoproterenol; Lidocaine; Pregnancy; Radiography; Resuscitation; Transposition of Great Vessels

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digitoxin; Digoxin; Gastrointestinal Diseases; Humans; Neurologic Manifestations

Clinical, electrocardiographic and laboratory data were found out in 52 patients with cardiac arrhythmias and conduction defects due to digoxin intoxication. Forty six nontoxic patients were also studied for comparison. Blood urea concentration was significantly higher in toxic patients as compared to nontoxic ones (P less than 0-01). Ventricular bigeminy and trigeminy (38.6%), multifocal ventricular premature beats (25%) and second or third degree A-V blocks (25%) were very much prevalent. Fairly good correlations have been observed between different cardiac arrhythmias and serum digoxin levels. Significantly higher mean serum digoxin levels were observed in patients with A-V block and multifocal ventricular premature beats as compared to patients with supraventricular arrhythmias.

Topics: Adult; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Female; Heart Block; Heart Failure; Humans; Male; Middle Aged; Pulmonary Heart Disease; Rheumatic Heart Disease; Tachycardia; Ventricular Fibrillation

The clinical course is described of a patient who took an overdose of 15 mg of digoxin in a suicidal attempt. He developed several cardiac arrhythmias like atrial fibrillation, atrial flutter, sino-atrial block. atrio-ventricular block 3 degree and ventricular extrasystoles. His plasma digoxin level rose to 38.7 ng/ml as determined by radioimmunoassay. He was treated with Aprindine and recovered without sequelae. A survey of the complications of acute massive digoxin intoxication is offered as well as a summary of treatment.

Topics: Arrhythmias, Cardiac; Delirium; Digoxin; Humans; Male; Middle Aged; Suicide

The effects of potassium canrenoate on arrhythmias induced by long-term progressive digoxin toxicity were studied in eight conscious beagle dogs. Sinus bradycardia and sinoatrial block, as well as atrioventricular (A-V) conduction disturbances, were consistently alleviated by administration of potassium canrenoate. Premature supraventricular (including junctional) and ventricular depolarizations as well as ventricular tachycardias were also suppressed. Although potassium canrenoate always terminated the digitalis-induced arrhythmias, it usually converted the rhythm to sinus arrhythmia rather than to normal sinus rhythm. Equimolar sodium canrenoate, but not potassium chloride, had similar reversal effects on arrhythmias induced by long-term digoxin intoxication. These data indicate that canrenoate, a diuretic agent with reported positive inotropic effects, may be useful in the treatment of digitalis-induced arrhythmias in man.

Topics: Animals; Arrhythmia, Sinus; Arrhythmias, Cardiac; Atrioventricular Node; Bradycardia; Bundle of His; Digoxin; Diuretics; Dogs; Electrocardiography; Female; Heart Block; Heart Ventricles; Ketosteroids; Male; Mineralocorticoid Receptor Antagonists; Potassium; Potassium Chloride; Pregnadienes; Sodium; Tachycardia

Seventy-six patients with clinical and ECG evidence of digitalis toxicity and serum-digoxin concentrations over 2.5 ng/ml were investigated for possible correlation between certain ECG changes and the level of serum digoxin, but no correlation was found. However, radioimmunological determination of digoxin level proved to be a reliable means of deciding whether abnormalities of impulse formation or conduction were due to digitalis. In only one case (during haemodialysis) was there a fall in potassium level below normal, with signs of digitalis toxicity electrocardiographically. In five other patients with serum digoxin levels above 6 ng/ml high potassium values were found. Caution in the administration of potassium is advised: it should be given only if it is demonstrated to be below normal. Fifty-one of the patients had impaired renal function.

Topics: Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Electrocardiography; Female; Humans; Hypokalemia; Kidney Failure, Chronic; Male; Middle Aged; Potassium; Radioimmunoassay; Renal Dialysis

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digitalis Glycosides; Digoxin; Female; Humans; Male; Middle Aged; Tachycardia

Forty-nine patients admitted to a Coronary Care Unit with myocardial infarction complicated by left ventricular failure, were treated with 1.75 mg Lanoxin over 36 hours. Serum digoxin levels were measured by radioimmunoassay at 8, 24, and 48 hours. No difference in serum levels was observed between those patients who received 'old' (reduced bioavailability) and those who received 'new' Lanoxin. Serum levels were significantly higher at 8 and 24 hours in those patients who received their first dose intramuscularly compared with those who received their first dose orally, irrespective of the bioavailability of the oral preparation used. No correlation was observed between serum digoxin levels and serum urea or creatinine during the 48-hour period of study. The incidence of arrhythmias is reported, but no conclusion can be drawn as to whether or not the glycoside contributed to this in any way. The use of digoxin in patients with acute myocardial infarction complicated by left ventricular failure is justifiable in the light of available evidence. However, in view of the possible predisposition of such patients to toxicity, lower serum levels than were achieved in many of our patients seem desirable and a modified dosage schedule is suggested.

Topics: Administration, Oral; Arrhythmias, Cardiac; Creatinine; Digoxin; Heart Arrest; Humans; Injections, Intramuscular; Middle Aged; Myocardial Infarction; Radioimmunoassay; Urea

To determine the prognostic significance of ventricular arrhythmias persisting during the hospital ambulatory phase of acute myocardial infarction, 64 patients with acute myocardial infarction underwent continuous 10-hour Holter monitoring an average of 11 days after discharge from the coronary care unit (CCU). Patients were categorized according to the results of ambulatory monitoring: 27 patients had ventricular extrasystoles, which were complicated (multifocal, R on T, paired, more than 5/min), or ventricular tachycardia; 22 had uncomplicated premature ventricular contractions; and 15 exhibited no ventricular arrhythmias. The 64 patients were followed prospectively for an average course of 25.8 months; 12 died suddenly; 8 died of other causes, and 44 survived. In all patients who died suddenly, ventricular ectopy was recorded on Holter monitoring before their discharge from the hospital (complicated premature ventricular contractions, eight patients; uncomplicated premature ventricular contractions, four patients); there were no sudden deaths in the patients without ventricular arrhythmias. Patients who died suddenly and those survived were similar in respect to age (60, 62 years), sex, location of infarction, presence of coronary risk factors, severity of acute myocardial infarction (Q waves, cardiac enzymes), serum cholesterol levels, evidence of cardiomegaly on roentgenograms, presence of ventricular gallop and drug therapy received. The occurrence of acute arrhythmias in the CCU did not separate patients who died suddenly from those who survived; there were no differences in ventricular tachycardia or ventricular fibrillation (3 or 12 patients who died suddenly, 6 of 44 patients who survived) or complicated premature ventricular contractions (4 or 12 patients who died suddenly, 18 of 44 patients who survived). Electrocardiograms obtained late in the hospital course revealed no differences in the extent of Q or T wave changes between these two groups. However, the extent of S-T segment abnormality was greater in patients who died suddenly than in patients who survived (5.6 compared to 1.8 leads/standard tracing, p smaller than 0.02) suggesting that the arrhythmias in the former were related to persistent ischemia or segmental ventricular dyssynergy. Thus, in this relatively small number of patients, ventricular arrhythmias persisting late in the hospital course of patients admitted for acute myocardial infarction are shown to predispose to subsequen

Topics: Acute Disease; Adult; Aged; Arrhythmias, Cardiac; Aspartate Aminotransferases; Creatine Kinase; Death, Sudden; Digoxin; Diuretics; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; L-Lactate Dehydrogenase; Male; Middle Aged; Myocardial Infarction; Potassium; Procainamide; Quinidine; Sodium; Time Factors

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Black People; Child; Child, Preschool; Digoxin; Electrocardiography; Female; Heart Auscultation; Heart Sounds; Humans; Infant; Infant, Newborn; Male; Middle Aged; Nigeria

4 patients tried to commit suicide by ingestion of 45 to 100 tablets of digoxin (Lanicor 0,25 mg) and acteyldigoxin (Novodigal 0,2 mg) respectively. In all patients cardiac arrhythmias occurred including 3 rd degree av-block, tachyarrhythmias and ventricular fibrillation which was lethal in two patients. After a short period hyperkaliaemia a rapid decrease of potassium in the serum was observed 3-12 hours after administration of digoxin. This loss of potassium was due to an increased excretion of potassium and sodium in the urine. It is thought that a reversible tubular leakage is responsible for the loss of electrolytes by the kidney rather than an inhibition of the ATPase in kidney tissue. From our observations the following therapy scheme for digitalis-intoxication is recommended: 1. Gastric lavage and administration of absorbents (charcoal, cholestyramin) in order to decrease the absorption of the glycosides and to interrupt the enterohepatic circulation. 2. Substitution of electrolytes by infusions and by oral route to balance sodium and potassium levels in the serum. 3. Administration of diphenylhydantoin for treatment of cardiac arrhythmias. 4. Implantation of a temporary pacemaker for treatment of cardiac arrhythmias especially for the management of bradycardias. 5. Plasmapheresis to lower the glycosid concentration in the heart muscle and in other tissues.

Topics: Adult; Arrhythmias, Cardiac; Charcoal; Digoxin; Female; Gastric Lavage; Humans; Hyperkalemia; Hypokalemia; Kidney; Male; Middle Aged; Pacemaker, Artificial; Phenytoin; Plasmapheresis; Poisoning; Potassium; Sodium; Suicide; Water-Electrolyte Balance

Cardiac arrhythmias, digoxin concentration in plasma and urine, digoxin and creatine clearances, electrolytes in plasma and in erythrocytes, and subjective symptoms have been carefully studied for 5 consecutive days in 19 patients with definite or suspected digitalis intoxication. The digoxin treatment was discontinued during the observation period. Eleven controls without any signs of toxicity were similarly followed on unchanged maintenance dosage. All patients were independently classified as toxic or non-toxic from the follow-up of extended ECG recordings and subjective symptoms. In 9 definitely toxic patients a plasma digoxin concentration 3.1 plus or minus 0.7 ng/ml was found, as compared to 1.4 plus or minus 0.5 ng/ml for the 11 controls. In the suspect toxic group 1.5-3.9 ng/ml was found. The high digoxin level in the toxic group corresponds to a low digoxin clearance. In the toxic patients cardiac arrhythmias were related in most cases to a plasma digoxin level above 2.5 ng/ml and usually disappeared when the concentration had decreased below this. Suspect toxic patients, classified as probably non-toxic, and controls had with two exceptions plasma digoxin levels below 2 ng/ml. It is suggested that digitalis toxicity should be considered at a plasma digoxin concentration above 2 ng/ml. It must be stressed that this limit is not absolute and is affected by, among other things, a disturbance of intra- and extracellular electrolytes.

Topics: Arrhythmias, Cardiac; Digoxin; Electrocardiography; Electrolytes; Humans

Serum digoxin estimations were done in 98 patients receiving digoxin for heart failure of varied aetiology. Digoxin toxicity or the lack of it was determined on the basin of established electrocardiographic criteria. Fifty-two patients were classified as 'toxic' and 46 as 'non-toxic'. The difference is the mean digoxin levels between the two groups was highly significant (P less than 0.001). The mean serum digoxin level in 'non-toxic' patients was slightly higher than that found by other investigators. Fairly good correlations have been noted between different dosage schedules and various rhythm disturbances. Death was attributed to digoxin toxicity in only 2 patients who showed electrocardiographic evidence of intoxication at the time of death.

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Radioimmunoassay

The authors used radioimmunity to study blood digoxin behaviour in patients with normal renal function and with variable BUN. The computerized and mathematically considered data showed that digitalic intoxication occurs with higher digoxin blood levels in patients with renal failure than in normal renal function cases. In the first case, moreover, it occurs sooner than in the second one, and the total digoxin dose is smaller than in normal patients. We have found that the large range of digosin blood levels is vital in deciding the therapeutic and toxic dose; that may be done, for most cases, following the estimate of the theoretical saturation dose using our method.

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Female; Heart Block; Heart Failure; Humans; Kidney Failure, Chronic; Male; Middle Aged; Radioimmunoassay

Alpha,alpha-Dimethyl-4-(alpha,alpha,beta,beta-tetrafluorophenethyl)benzylamine (MK-251) has been found to prevent certain types of experimentally induced ventricular arrhythmias and at maximally effective doses possesses substantial hemodynamic safety in contrast to standard antiarrhythmic agents. MK-251 prevented or modified ventricular arrhythmias produced by injection of tetrafluorohexachlorobutane into the coronary artery of dogs and baboons. In dogs, the dose estimated to prevent 80% of the arrhythmic impulses (ED80) was 0.5 mg/kg i.v. and 5.0 mg/kg p.o. The duration of action after oral administration of 5.0 mg/kg to the dog or baboon exceeded 5 to 6 hours. MK-251 delayed the onset of arrhythmias resulting from coronary artery ligation, reduced their severity and permitted a conversion back to normal sinus rhythm earlier than in control dogs. In cats, the doses of digoxin required to induce ventricular ectopic activity, ventricular tachycardia and ventricular fibrillation were elevated by MK-251. In anesthetized dogs, 4 times the i.v. ED80 produced no change in blood pressure, cardiac contractility or output, or in ventricular conduction. The only effect after 8 times the ED80 was a slight decrease in contractility. In contrast. lidocaine at its ED80 (0.21 mg/kg/min), decreased blood pressure and contractility; there was no change in ventricular conduction. Quinidine at the ED80 (8.8 mg/kg i.v.) and above produced hypotension, decreased contractility and prolonged conduction in a dose-related manner.

Topics: Amines; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzyl Compounds; Benzylamines; Blood Pressure; Cardiac Output; Coronary Vessels; Digoxin; Dogs; Female; Heart Conduction System; Heart Rate; Hemodynamics; Hydrocarbons, Fluorinated; Male; Myocardial Contraction; Myocardial Infarction; Papio

Serum glycoside concentration was 2.3 ng/ml or more in 299 patients digitalised with digoxin or digoxin derivatives. Mean serum glycoside concentration was 3.4 +/- 1.3 ng/ml (range 2.3-11.00 ng per ml). Usually, high serum concentrations were associated with advanced den or digoxin-derivative overdosage occurred in only 10% of patients. Almost three quarters of those with intoxication had impaired renal function. There was some evidence that low body-weight increased the potential risk of intoxication.

Topics: Arrhythmias, Cardiac; Body Weight; Digoxin; Heart Block; Humans; Kidney Failure, Chronic; Tachycardia

Topics: Arrhythmias, Cardiac; Binding Sites, Antibody; Digoxin; Humans; Radioimmunoassay; Serum Albumin; Serum Globulins

Topics: Animals; Antibody Specificity; Arrhythmias, Cardiac; Depression, Chemical; Desipramine; Digoxin; Drug Interactions; Epinephrine; Guinea Pigs; Kidney; Myocardium; Norepinephrine; Phenytoin; Reserpine

The mechanism by which magnesium affects digitalis-induced arrhythmias was studied in dogs with and without beta-receptor blockade. Digoxin was infused at a rate of 2.5mug/kg/min until ventricular tachycardia developed, then half the animals were given MgSO4, the other half saline. In animals given MgSO4, sinus rhythm was immediately re-established; in animals given saline, ventricular tachycardia persisted. In animals with beta-receptor blockade, MgSO4 was as effective in abolishing ventricular tachycardia as in those without beta-receptor blockade. We found no evidence that magnesium re-activated digoxin-inhibited (Na+, K+)-ATPase, altered myocardial or microsomal digoxin binding, or acted via the autonomic nervous system. Magnesium's direct effect on calcium and potassium fluxes across the myocardial cell membrane may be the mechanism of its antiarrhythmic action in digitalis-toxic arrhythmias.

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Electrocardiography; Heart Conduction System; Hemodynamics; Magnesium

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Child; Child, Preschool; Digoxin; Female; Humans; Magnesium; Magnesium Sulfate; Male; Middle Aged

In the present paper, the naturally occurring glycosides digitoxin, gitoxin, 16-acetyl-gitoxin, digoxin, cymarol, ouabain, and proscillaridin, and the semi-synthetic 16-epi-gitoxin and 16-acetyl-16-epi-gitoxin are investigated as to their inotropic action and their effects on rhythmicity at isolated spontaneously beating atria of the guinea-pig heart in dependence on the variation of the potassium concentration of the nutritive fluid ([K+]0: 1.34, 2.68, and 5.36 mM resp.). The major results are as follows. 1. Effects of raising [K+]0 from 1.34 to 2.68 mM: The range of the inotropically effective concentrations as well as the size of the maximum inotropic action are more or less strongly improved with all glycosides. The glycoside concentrations required to get inotropic maximum had to be increased to a high degree with proscillaridin and digoxin. The mean arrhythmia percentage occurring at the inotropic maximum is either decreased (gitoxin, 16-epi-gitoxin, digoxin, proscillaridin), unchanged (digitoxin, 16-acetyl-16-epi-gitoxin) or even increased (16-acetyl-gitoxin, cymarol, ouabain). The inotropic value is improved to a high extent with gitoxin only. 2. Effect of raising [K+]0 from 2.68 to 5.36 mM: The range of the inotropically effective concentrations is extended (digitoxin and cymarol) or diminished (proscillaridin), but remains essentially unchanged with most glycosides. The size of the maximum inotropic effect is increased with digoxin, ouabain and 16-epi-gitoxin, but decreased significantly with digitoxin and proscillaridin. The glycoside concentrations required to produce the inotropic maximum are essentially unchanged with the exception of 16-epi-gitoxin, 16-acetyl-gitoxin and ouabain. The mean arrhythmia percentage at the maximum inotropic effect is dramatically reduced with digoxin, cymarol and proscillaridin. The inotropic value is improved with all glycosides except digitoxin. 3. Evaluation of the various glycosides: When judged on the basis of the range of inotropically effective concentrations, the maximum inotropic effect, the mean arrhythmia percentage at the inotropic maximum and the inotropic value, the best first three glycosides include 16-epi-gitoxin and digoxin. 16-Epi-gitoxin and its 16-acetate show that most favourable relationship between the effect on contractility and rhythmicity. The cause of the differential actions of the structurally-different glycosides on contractility and rhythmicity is hypothesized to be due to divergen

Topics: Animals; Arrhythmias, Cardiac; Cardiac Glycosides; Cymarine; Digitoxin; Digoxin; Dimethylformamide; Female; Guinea Pigs; Heart Conduction System; Male; Myocardial Contraction; Ouabain; Potassium; Proscillaridin; Stimulation, Chemical

Topics: Adult; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Chronic Disease; Coronary Disease; Digoxin; Female; Humans; Male; Middle Aged; Strophanthins

In 20 children needing treatment for symptomatic sick sinus syndrome, the average age at presentation was 7.1 years and ranged from 9 months to 18 years. Symptoms were never precise but, in retrospect, 5 children had syncope, 7 had a rapid heart action, 6 had dyspnoea or tachypnoea, 2 had nonspecific chest pains, 2 had pale spells, and 1 had a sudden hemiplegia. Symptoms followed cardiac surgery in 15 cases and were related to unoperated congenital heart disease in 2 and to myocarditis in 2. The aetiology was unknown in 1 case. The type of cardiac surgery resulting in the development of the sick sinus syndrome was predominantly related to atrial suturing. Both tachy- and bradydysrhythmias were found, including wandering atrial pacemaker (9 cases), junctional rhythm (19 cases), supraventricular tachycardia (9 cases), atrial flutter (11 cases), and atrial fibrillation (2 cases). Both atrial (8 cases) and ventricular (7 cases) premature beats were seen. All patients were given trials of drug therapy but difficulties were encountered. Cardioversion was used for tachyarrhythmias in 11 cases without serious problems. Six children had permanent cardiac pacemakers inserted with good results. Recognition of the sick sinus syndrome in childhood is important and treatment must be regulated by the severity of symptoms.

Topics: Adolescent; Arrhythmia, Sinus; Arrhythmias, Cardiac; Bradycardia; Cardiac Catheterization; Child; Child, Preschool; Digoxin; Dyspnea; Female; Heart Block; Heart Defects, Congenital; Heart Rate; Hemiplegia; Humans; Infant; Male; Myocarditis; Pacemaker, Artificial; Pallor; Syncope

According to own experiences and after a review of the literature a survey of therapy of cardiac arrhythmias in infancy and childhood is given. In this age group most of the occurring cardiac arrhythmias are harmless and pass without serious circulatory disturbances. Therefore in these cases no specific treatment is necessary, except of course the treatment and management of the disease which is causing the arrythmia. This report is concerned more detailed with the therapy of rhythm disturbances which are life threatening or will become fatal if they continue untreated for a longer period. In spite of the therapeutic recommendations given we are aware of the fact that it is impossible to predict the success of therapy. This turned out to be so especially in the case of tachycardias. The difficulties in long-term management of postoperative heart block are mentioned. Antiarrhythmic drugs, their indications, efficacy, side-effects and contraindications are listed in separate tables ("FdM-Tabellen für die Praxis" Nr. 30/1975, Fortschr. Med. 93, 30: 1447, 1975).

Topics: Age Factors; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Child; Child, Preschool; Digoxin; Electric Countershock; Heart Block; Humans; Infant; Metaproterenol; Pacemaker, Artificial; Tachycardia; Verapamil

Topics: Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Electrocardiography; Female; Humans; Male; Middle Aged; Poisoning

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Heart Failure; Humans; Kidney; Kidney Failure, Chronic; Potassium; Renal Dialysis; Time Factors

1. In anesthetized cats 2,4,7-triamino-6-phenyl-pteridine (triamterene) (5 mg/kg i.v.) causes a short-lasting increase in blood pressure, a decrease in heart rate, whereas the contractility (see article) remains unchanged. N-Amidino-3,5-diamino-6-chloropyrazinecarboxamide (amiloride) (5 mg/kg i.v.) causes a fall of blood pressure, an increase in heart rate, and an increase in contractility. 2. In cats the i.v. toxicity of digoxin is diminished by pretreatment with triamterene or amiloride; the arrhythmias and the cardiac arrest are significantly delayed in the course of an infusion of digoxin. In guinea-pigs a pretreatment with triamterene only delays the arrhythmias but not the lethal effect of digoxin or g-strophanthin. 3. In the isolated atria of the guinea-pig triamterene and amiloride (5 mug or 50 mug/ml) lowers the rate of contraction and prolongs the functional refractory period. The force of contraction is increased by triamterene and diminished by amiloride.

Topics: Amiloride; Animals; Arrhythmias, Cardiac; Blood Pressure; Cats; Digoxin; Drug Evaluation, Preclinical; Female; Guinea Pigs; Heart Rate; Hemodynamics; Male; Myocardial Contraction; Ouabain; Pyrazines; Triamterene

Topics: Adrenergic beta-Antagonists; Animals; Arrhythmias, Cardiac; Cats; Depression, Chemical; Digoxin; Female; Heart Rate; Male; Ouabain; Practolol; Sotalol

Topics: Administration, Oral; Adrenergic beta-Antagonists; Animals; Antibody Formation; Antigens; Arrhythmias, Cardiac; Biopharmaceutics; Digitalis Glycosides; Digitoxin; Digoxin; Drug Interactions; Humans; Rabbits; Radioimmunoassay

Topics: Animals; Arrhythmias, Cardiac; Barbiturates; Bemegride; Biopharmaceutics; Blood Pressure; Cardiac Output; Digoxin; Dose-Response Relationship, Drug; Electrocardiography; Heart; Heart Arrest; Heart Rate; Specific Gravity; Vascular Resistance; Ventricular Fibrillation

Topics: Administration, Oral; Adult; Age Factors; Animals; Arrhythmias, Cardiac; Digitalis; Digitoxin; Digoxin; Heart; Humans; Infant; Methods; Myocardium; Plants, Medicinal; Plants, Toxic; Radioimmunoassay

Topics: Aged; Ajmaline; Aniline Compounds; Arrhythmias, Cardiac; Benzyl Compounds; Bone Marrow Examination; Cell Survival; Chromium Radioisotopes; Clot Retraction; Digoxin; Drug Combinations; Drug Hypersensitivity; Ethylenediamines; Histocytochemistry; Humans; Imidazoles; Male; Megakaryocytes; Phenobarbital; Sparteine; Thrombocytopenia

Topics: Administration, Oral; Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digitoxin; Digoxin; Heart Block; Heart Diseases; Heart Failure; Humans; Hyperthyroidism; Injections, Intravenous; Kidney Failure, Chronic; Middle Aged; Obesity; Ventricular Fibrillation

Topics: Adult; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Female; Heart Block; Humans; Hyperkalemia; Injections, Intravenous; Magnesium Sulfate; Medical Laboratory Science; Pacemaker, Artificial; Potassium; Renal Dialysis; Self Medication; Time Factors

Topics: Adult; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Electric Countershock; Female; Humans; Male; Middle Aged; Prospective Studies

Topics: Ajmaline; Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Electrocardiography; Female; Male

Topics: Age Factors; Arrhythmias, Cardiac; Creatinine; Digitoxin; Digoxin; Dose-Response Relationship, Drug; Drug Interactions; Half-Life; Humans; Hypoxia; Intestinal Absorption; Ion Exchange Resins; Kidney Function Tests; Kinetics; Metabolic Clearance Rate; Methods; Models, Biological; Myocardium; Phenytoin; Procainamide; Radioimmunoassay; Thyroid Gland; Water-Electrolyte Balance

Topics: Administration, Oral; Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Electrocardiography; Electrophysiology; Guinea Pigs; Heart; Heart Conduction System; Injections, Intravenous; Male; Perfusion; Strophanthins; Taurine

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digitalis; Digoxin; Electric Countershock; Heart Block; Heart Ventricles; Humans; Lidocaine; Myocardial Infarction; Pacemaker, Artificial; Phenytoin; Phytotherapy; Plants, Medicinal; Plants, Toxic; Procainamide; Propranolol; Quinidine; Tachycardia; Tachycardia, Paroxysmal; Ventricular Fibrillation

Topics: Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digitoxin; Digoxin; Heart Block; Heart Failure; Heart Valve Diseases; Humans; Middle Aged; Myocardial Infarction; Potassium Deficiency; Strophanthins

Topics: Absorption; Arrhythmias, Cardiac; Digoxin; Female; Humans; Male

Topics: Arrhythmias, Cardiac; Atropine; Cardiac Glycosides; Digoxin; Home Nursing; Humans; Lidocaine; Myocardial Infarction; Ouabain; Practolol; Procainamide; Quinidine; Valsalva Maneuver

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Blood Pressure; Bradycardia; Digoxin; Electrocardiography; Female; Heart Ventricles; Humans; Injections, Intravenous; Male; Methyldopa; Middle Aged; Syndrome; Tachycardia; Tachycardia, Paroxysmal; Verapamil; Wolff-Parkinson-White Syndrome

Topics: Arrhythmias, Cardiac; Blood Pressure; Digoxin; Heart Failure; Heart Rate; Hemodynamics; Humans; Venous Pressure

Topics: Adult; Arrhythmias, Cardiac; Carotid Sinus; Citrates; Digoxin; Female; Humans; Male; Potassium Chloride; Pressure

Topics: Arrhythmia, Sinus; Arrhythmias, Cardiac; Coronary Disease; Digoxin; Diuretics; Electroconvulsive Therapy; Endocarditis, Bacterial; Heart Aneurysm; Heart Failure; Heart Valve Diseases; Heart Ventricles; Humans; Lidocaine; Myocardial Infarction; Pacemaker, Artificial; Pericarditis, Constrictive; Potassium Deficiency; Rupture; Spironolactone; Tachycardia; Ventricular Fibrillation; Wolff-Parkinson-White Syndrome

Topics: Administration, Oral; Adolescent; Arrhythmias, Cardiac; Child; Child, Preschool; Digoxin; Drug Evaluation; Female; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Injections, Intramuscular; Myocarditis; Pregnancy

Topics: Adult; Aged; Arrhythmias, Cardiac; Digitoxin; Digoxin; Electrocardiography; Female; Humans; Male; Middle Aged; New Jersey

Topics: Aged; Arrhythmias, Cardiac; Bronchial Diseases; Bronchography; Digoxin; Female; Hot Temperature; Humans; Humidity; Lung; Mucus; Positive-Pressure Respiration; Postoperative Complications; Pulmonary Atelectasis; Quinidine; Tomography, X-Ray

Topics: Arrhythmias, Cardiac; Digoxin; Female; Furosemide; Heart Arrest; Heart Failure; Humans; Lidocaine; Middle Aged

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Diagnosis, Differential; Digoxin; Electrocardiography; Heart Conduction System; Humans; Male; Pacemaker, Artificial; Tachycardia

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digitalis Glycosides; Digoxin; Drug Synergism; Drug Therapy, Combination; Electrocardiography; Heart Conduction System; Heart Rate; Humans; Lanatosides; Propranolol; Quinidine; Refractory Period, Electrophysiological; Tachycardia

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Diuretics; Electrocardiography; Exercise Test; Humans; Tachycardia

Topics: Age Factors; Aged; Arrhythmias, Cardiac; Creatinine; Digoxin; Hospitalization; Humans; Middle Aged; Outpatient Clinics, Hospital; Potassium; Radioimmunoassay

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Glucose; Heart; Heart Rate; Hypokalemia; Insulin; Liver; Muscles; Myocardium; Potassium; Time Factors; Tritium

Topics: Administration, Oral; Arrhythmias, Cardiac; Child; Child, Preschool; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Hydrogen-Ion Concentration; Infant; Injections, Intramuscular; Injections, Intravenous; Kinetics; Male; Radioimmunoassay; Time Factors; Water-Electrolyte Balance

Topics: Aged; Arrhythmias, Cardiac; Bradycardia; Digoxin; Female; Heart Block; Heart Diseases; Humans; Hypertension; Middle Aged; Pacemaker, Artificial; Sinoatrial Node; Syncope

Topics: Adult; Arrhythmias, Cardiac; Depression, Chemical; Digoxin; Electrocardiography; Female; Heart Block; Humans; Injections, Intravenous; Male; Phenytoin; Time Factors

Topics: Adipose Tissue; Arrhythmias, Cardiac; Child; Child, Preschool; Creatinine; Digoxin; Extracorporeal Circulation; Heart Defects, Congenital; Humans; Hypokalemia; Muscles; Myocardium; Postoperative Complications; Radioimmunoassay

Topics: Age Factors; Aged; Aortic Diseases; Arrhythmias, Cardiac; Cardanolides; Coronary Disease; Digoxin; Female; Gastrointestinal Diseases; Heart Block; Heart Failure; Heart Valve Diseases; Humans; Lung Diseases; Male; Middle Aged; Mitral Valve Insufficiency; Rheumatic Heart Disease; Tachycardia

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Digoxin; Female; Heart Failure; Humans; Iodine Radioisotopes; Male; Radioimmunoassay; Retrospective Studies; Urea

Topics: Administration, Oral; Adult; Aged; Arrhythmias, Cardiac; Digoxin; Drug Evaluation; Female; Heart Failure; Humans; Injections, Intravenous; Male; Middle Aged

Topics: Arrhythmias, Cardiac; Carbon Dioxide; Cardiac Complexes, Premature; Cardiomegaly; Coronary Disease; Digoxin; Heart Failure; Heart Rate; Humans; Hypertension, Pulmonary; Male; Oxygen; Potassium; Pulmonary Heart Disease

Topics: Aortic Valve Stenosis; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Cardiomyopathies; Coronary Disease; Digoxin; Electrocardiography; Heart; Heart Ventricles; Humans; Hypertension; Middle Aged; Mitral Valve Stenosis; Myocardial Infarction; Pulmonary Heart Disease; Time Factors

Topics: Adenosine Triphosphatases; Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Heart; In Vitro Techniques; Myocardium; Perfusion; Phenytoin; Potassium; Sodium; Time Factors

Topics: Adult; Aged; Arrhythmias, Cardiac; Creatinine; Digoxin; Electrocardiography; Female; Hospitalization; Humans; Male; Middle Aged; Prospective Studies; Pulse; Radioimmunoassay; Tritium; Urea

Topics: Adult; Aged; Animals; Arrhythmias, Cardiac; Digoxin; Extracorporeal Circulation; Female; Humans; Male; Methanol; Middle Aged; Myocardium; Postoperative Complications; Rabbits; Radioimmunoassay

Topics: Aortic Valve; Arrhythmias, Cardiac; Carbon Dioxide; Coronary Artery Bypass; Digitoxin; Digoxin; Extracorporeal Circulation; Female; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Mitral Valve; Monitoring, Physiologic; Oxygen; Radioimmunoassay; Time Factors

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Female; Heart Failure; Humans; Male; Myocardial Infarction; Pulse; Venous Pressure

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Electrocardiography; Heart Failure; Heart Rate; Humans; Injections, Intravenous; Lanatosides; Time Factors

Topics: Arrhythmias, Cardiac; Atropine; Diet Therapy; Digoxin; Electrocardiography; Female; Furosemide; Heart Block; Heart Failure; Heparin; Hospitalization; Humans; Hypotension; Male; Middle Aged; Monitoring, Physiologic; Myocardial Infarction; Oxygen Inhalation Therapy; Progressive Patient Care; Shock, Cardiogenic

Topics: Administration, Oral; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digoxin; Electrocardiography; Heart Failure; Humans; Injections, Intravenous; Monitoring, Physiologic; Myocardial Infarction; Ouabain; Tachycardia, Paroxysmal

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Electrocardiography; Female; Male

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Female; Indoles; Male; Sympatholytics

Topics: Arrhythmias, Cardiac; Atropine; Bradycardia; Digoxin; Electrocardiography; Heart Arrest; Heart Atria; Heart Block; Heart Conduction System; Humans; Hyperkalemia; Male; Middle Aged; Pacemaker, Artificial; Time Factors

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Cats; Digitoxin; Digoxin; Ethanolamines; Female; Heart; Heart Rate; Male; Nitrobenzenes; Oxygen; Partial Pressure; Phenethylamines; Tachycardia

Topics: Adult; Arrhythmias, Cardiac; Digoxin; Humans; Male; Middle Aged; Propranolol

Topics: Adolescent; Aged; Arrhythmias, Cardiac; Child; Digitalis Glycosides; Digitoxin; Digoxin; Humans; Radioimmunoassay; Radioisotopes; Rubidium; Tritium

Topics: Adult; Aminohippuric Acids; Arrhythmias, Cardiac; Creatinine; Digitalis Glycosides; Digoxin; Electrocardiography; Glomerular Filtration Rate; Humans; Inulin; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Metabolic Clearance Rate; Middle Aged; Radioimmunoassay; Tritium

Topics: Amino Alcohols; Animals; Arrhythmias, Cardiac; Blood Pressure; Cardiac Glycosides; Cardiac Output; Cats; Digitoxin; Digoxin; Drug Interactions; Drug Synergism; Female; Guinea Pigs; Heart; Heart Rate; Isoproterenol; Male; Ouabain; Phenethylamines; Propiophenones; Reserpine; Sympathomimetics

Topics: Arrhythmias, Cardiac; Child, Preschool; Digoxin; Female; Follow-Up Studies; Heart Arrest; Heart Block; Hemorrhage; Humans; Hypotension; Infant; Male; Methods; Postoperative Complications; Propranolol; Transposition of Great Vessels

Topics: Adolescent; Adult; Aged; Animals; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Bradycardia; Cardiac Catheterization; Digoxin; Dogs; Electrocardiography; Electrodes, Implanted; Female; Functional Laterality; Heart Atria; Heart Conduction System; Humans; Male; Middle Aged; Ouabain; Pacemaker, Artificial; Tachycardia; Vagotomy

Topics: Aged; Aminosalicylic Acids; Arrhythmias, Cardiac; Arteriosclerosis; Cerebrovascular Disorders; Coronary Disease; Digoxin; Electrocardiography; Furosemide; Heart Conduction System; Humans; Hypertension; Isoniazid; Kidney Failure, Chronic; Lung Diseases, Obstructive; Middle Aged; Myocardial Infarction; Phenytoin

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Digoxin; Drug Interactions; Female; Heart Rate; Phenelzine; Rabbits; Time Factors

Topics: Adult; Arrhythmias, Cardiac; Coumarins; Digoxin; Electrocardiography; Female; Follow-Up Studies; Glycolates; Heart Block; Humans; Poisoning; Prognosis; Suicide; Time Factors

Topics: Arrhythmias, Cardiac; Birth Injuries; Clavicle; Digoxin; Electrocardiography; Fractures, Bone; Humans; Infant, Newborn; Obstetrical Forceps; Tachycardia, Paroxysmal

Topics: Administration, Oral; Aged; Arrhythmias, Cardiac; Digoxin; Humans; Middle Aged; Time Factors

Topics: Administration, Oral; Age Factors; Arrhythmias, Cardiac; Digoxin; Humans; Kidney Diseases; Middle Aged; Time Factors

Topics: Acute Disease; Arrhythmias, Cardiac; Bradycardia; Digoxin; Electrocardiography; Humans; Hypercalcemia; Male; Middle Aged; Nausea; Suicide; Vomiting

Topics: Analgesics; Anxiety; Arrhythmias, Cardiac; Coronary Care Units; Digoxin; Diuretics; Heparin; Home Care Services; Humans; Lidocaine; Myocardial Infarction

Topics: Ajmaline; Apgar Score; Arrhythmias, Cardiac; Cesarean Section; Digoxin; Electrocardiography; Extraction, Obstetrical; Female; Fetus; Heart Block; Humans; Infant; Infant, Newborn; Lanatosides; Pregnancy; Prenatal Diagnosis; Tachycardia; Tachycardia, Paroxysmal; Ventricular Fibrillation; Verapamil; Wolff-Parkinson-White Syndrome

Topics: Arrhythmias, Cardiac; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Child; Digoxin; Heart Failure; Humans; Postoperative Care; Postoperative Complications; Premedication; Preoperative Care

Topics: Ajmaline; Amiodarone; Arrhythmias, Cardiac; Digoxin; Disopyramide; Humans; Procainamide; Propranolol

Topics: Arrhythmias, Cardiac; Digoxin; Humans; Poisoning

Topics: Adrenergic beta-Antagonists; Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Female; Male; Pindolol

Topics: Aged; Alcoholism; Allopurinol; Arrhythmias, Cardiac; Chloral Hydrate; Colchicine; Digoxin; Drug Synergism; Gastrointestinal Hemorrhage; Gout; Hospitals, Teaching; Humans; Liver Diseases; Male; Middle Aged; Nitroglycerin; Patient Care Team; Pharmacists; Pharmacy Service, Hospital; Quinidine; Warfarin; Washington

Topics: Arrhythmias, Cardiac; Digoxin; Humans; Hyperkalemia; Hypokalemia; Suicide

Topics: Administration, Oral; Arrhythmias, Cardiac; Body Weight; Computers; Digitalis Glycosides; Digitoxin; Digoxin; Dose-Response Relationship, Drug; Humans; Injections; Kidney; Kinetics; Lanatosides; Myocardium

Topics: Age Factors; Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Electrocardiography; Female; Humans; Male; Poisoning

Topics: Adult; Aged; Arrhythmias, Cardiac; Bradycardia; Coronary Care Units; Digoxin; Diuretics; Electrocardiography; Female; Heart Atria; Heart Block; Heart Failure; Heart Ventricles; Hospitals, Teaching; Humans; Male; Middle Aged; Myocardial Infarction; Prognosis; Shock, Cardiogenic; Tachycardia; Ventricular Fibrillation

Topics: Arrhythmias, Cardiac; Benzoates; Coronary Disease; Digoxin; Drug Combinations; Heart Diseases; Heart Failure; Humans; Morpholines; Tranquilizing Agents; Verapamil

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Female; Heart Rate; Humans; Male; Middle Aged; Pindolol; Tachycardia; Tachycardia, Paroxysmal

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Atrial Fibrillation; Cardiac Catheterization; Digoxin; Electrocardiography; Female; Heart Rate; Humans; Male; Methods; Middle Aged; Phenytoin; Procainamide; Propranolol; Quinidine; Tachycardia, Paroxysmal; Time Factors; Wolff-Parkinson-White Syndrome

Topics: Adult; Anesthesia; Anesthesia, General; Anesthesia, Inhalation; Anesthesia, Spinal; Arrhythmias, Cardiac; Digoxin; Drug Interactions; Electric Countershock; Extracorporeal Circulation; Humans; Methods; Postoperative Complications; Radioimmunoassay; Time Factors

Topics: ABO Blood-Group System; Age Factors; Aged; Arrhythmias, Cardiac; Boston; Digoxin; Electrocardiography; Female; Heart Block; Humans; Male; Middle Aged; Population Surveillance

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Atrial Flutter; Digitalis Glycosides; Digoxin; Electrocardiography; Female; Humans; Male; Middle Aged; Propranolol

Topics: Adult; Aged; Aortic Valve; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Blood Urea Nitrogen; Digoxin; Female; Heart Block; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Prospective Studies; Tachycardia, Paroxysmal; Tricuspid Valve; Ventricular Fibrillation

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Catecholamines; Diagnosis, Differential; Digoxin; Electric Countershock; Electrocardiography; Heart Conduction System; Humans; Lidocaine; Myocardial Infarction; Potassium; Procainamide; Quinidine; Tachycardia; Time Factors

Topics: Arrhythmias, Cardiac; Arteriosclerosis; Cardiac Output; Coronary Disease; Digoxin; Heart Rate; Humans; Intestinal Absorption; Rheumatic Heart Disease

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Electrocardiography; Humans; Poisoning; Potassium; Radioimmunoassay; Time Factors; Tritium; Urea

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Electrocardiography; Female; Heart Block; Heart Rate

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Female; Heart Atria; Humans; Lung Diseases; Male; Middle Aged; Myocardial Infarction; Quinidine; Time Factors

Topics: Animals; Antiemetics; Arrhythmias, Cardiac; Benzene Derivatives; Blood Flow Velocity; Blood Pressure; Butanols; Cardiac Output; Cats; Digoxin; Dogs; Electric Conductivity; Electrocardiography; Female; Heart Rate; Hemodynamics; In Vitro Techniques; Male; Ouabain; Papillary Muscles; Piperidines; Propranolol; Sinoatrial Node; Vascular Resistance

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digitoxin; Digoxin; Electrocardiography; Humans; Injections, Intravenous; Methods; Pulse; Radioimmunoassay; Time Factors

Topics: Acute Disease; Aged; Arrhythmias, Cardiac; Blood Pressure Determination; Coronary Care Units; Digitalis Glycosides; Digoxin; Drug Hypersensitivity; Electrocardiography; Female; Heart Block; Humans; Male; Middle Aged; Myocardial Infarction; Ouabain; Strophanthins

Topics: Aged; Arrhythmias, Cardiac; Cardiac Output; Digoxin; Electrocardiography; Heart Failure; Heart Ventricles; Humans; Male; Pacemaker, Artificial; Pulse

Topics: Adult; Aged; Angina Pectoris; Arrhythmias, Cardiac; Blood Pressure; Cardiac Complexes, Premature; Coronary Disease; Digoxin; Geriatrics; Heart Diseases; Heart Failure; Humans; Hypertension; Middle Aged; Morpholines; Myocardial Infarction; Phenethylamines; Pulmonary Heart Disease; Pulse; Tachycardia

Topics: Adult; Aged; Antibody Specificity; Arrhythmia, Sinus; Arrhythmias, Cardiac; Atrial Fibrillation; Cholesterol; Dehydroepiandrosterone; Digitoxin; Digoxin; Electrocardiography; Estradiol; Female; Heart Block; Heart Failure; Humans; Hydrocortisone; Male; Mathematics; Methods; Middle Aged; Progesterone; Radioimmunoassay; Tachycardia; Testosterone; Tritium

Topics: Adenosine Triphosphatases; Animals; Arrhythmias, Cardiac; Chemical Phenomena; Chemistry; Digoxin; False Positive Reactions; Humans; Methods; Potassium; Sodium; Solvents; Swine; Tritium; Vomiting

Topics: Acidosis, Respiratory; Age Factors; Arrhythmias, Cardiac; Cardiac Catheterization; Cardiomegaly; Cyanosis; Diagnosis, Differential; Digoxin; Dyspnea; Electrocardiography; Ethacrynic Acid; Heart Defects, Congenital; Heart Failure; Hemodynamics; Hepatomegaly; Humans; Infant; Infant Care; Infant, Newborn; Lung Diseases; Monitoring, Physiologic; Oxygen; Parenteral Nutrition; Radiography

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Guinea Pigs; Heart Atria; Hydroxysteroids; Ketosteroids; Mineralocorticoid Receptor Antagonists; Pregnanes; Propionates

Topics: Adrenergic beta-Antagonists; Antidotes; Arrhythmias, Cardiac; Calcium; Digitalis Glycosides; Digoxin; Heart Conduction System; Humans; Lidocaine; Phenytoin; Potassium Chloride

Topics: Administration, Oral; Arrhythmias, Cardiac; Cardiac Glycosides; Diet Therapy; Digitoxin; Digoxin; Diuresis; Drug Tolerance; Edetic Acid; Electrocardiography; Gastrointestinal Diseases; Heart Failure; Heart Rate; Humans; Injections, Intravenous; Lanatosides; Nervous System Diseases; Phytotherapy; Plants, Medicinal; Poisoning; Potassium; Rest; Strophanthins

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Carbamazepine; Digitalis Glycosides; Digoxin; Dogs; Electrocardiography; Injections, Intramuscular; Injections, Intravenous; Time Factors

Using the radioimmunoassay technique for measuring serum digoxin, it was found that patients who were given 0.25 mg. digoxin orally per day had a mean serum level of 0.83 +/- 0.06 ng. per ml. In patients given 0.5 mg. daily the mean level was 1.30 +/- 0.14 ng. A higher 24-hour urinary excretion of digoxin was associated with the higher serum levels in the latter group. Individuals who exhibited electrocardiographic evidence of digoxin toxicity had a mean serum level of 2.81 +/- 0.21 ng. The majority of patients with high serum levels had evidence of impaired renal function, and it is in this clinical situation that knowledge of serum digoxin levels is likely to be most helpful in determining dose schedules.The method is specific, sensitive and reproducible. Repeated measurements on the same patient on maintenance therapy showed little variation. To obtain dependable serum levels blood should be drawn at least five hours after oral, and three hours after intravenous administration.

Topics: Administration, Oral; Animals; Antigen-Antibody Reactions; Arrhythmias, Cardiac; Blood Urea Nitrogen; Dialysis; Digoxin; Electrocardiography; Humans; Immune Sera; Injections, Intravenous; Kidney Function Tests; Rabbits; Radioimmunoassay; Time Factors; Tritium

Topics: Aged; Arrhythmias, Cardiac; Blood Urea Nitrogen; Calcium; Centrifugation; Digitalis Glycosides; Digitoxin; Digoxin; Humans; Middle Aged; Potassium; Radioimmunoassay; Saliva; Spectrophotometry

Topics: Arrhythmias, Cardiac; Digoxin; Electrocardiography; Heart Conduction System; Heart Failure; Humans; Male; Middle Aged; Mitral Valve Stenosis; Propranolol; Wolff-Parkinson-White Syndrome

Topics: Arrhythmias, Cardiac; Digoxin; Humans; Lidocaine

Topics: Acetanilides; Amino Alcohols; Arrhythmias, Cardiac; Digitalis Glycosides; Digitoxin; Digoxin; Heart; Humans; Muscle Contraction; Propranolol; Propylamines

Topics: Arrhythmias, Cardiac; Creatinine; Digoxin; Heart; Humans; Kidney; Potassium

Topics: Ajmaline; Arrhythmias, Cardiac; Digoxin; Electric Countershock; Female; Glucagon; Heart Failure; Humans; Lanatosides; Middle Aged; Mitral Valve Insufficiency; Phenytoin; Phytotherapy; Plants, Medicinal; Pulmonary Edema; Quinidine; Rauwolfia; Water-Electrolyte Balance

Topics: Acute Disease; Aged; Arrhythmias, Cardiac; Coronary Disease; Digitalis Glycosides; Digitoxin; Digoxin; Electrocardiography; Female; Humans; Lung Diseases; Male; Myocardial Infarction; Poisoning; Prognosis; Prospective Studies; Radioimmunoassay

Topics: Administration, Oral; Adult; Age Factors; Aged; Arrhythmias, Cardiac; Coronary Disease; Digoxin; Electrocardiography; Female; Humans; Hypothyroidism; Male; Middle Aged; Nausea; Potassium; Radioimmunoassay; Rheumatic Heart Disease; Urea; Vomiting

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Drug Synergism; Heart Diseases; Humans; Middle Aged; Nitriles; Tranquilizing Agents

Topics: Arrhythmias, Cardiac; Bradycardia; Digoxin; Electric Countershock; Electrocardiography; Humans; Isoproterenol; Lidocaine; Pacemaker, Artificial; Tachycardia

Topics: Arrhythmias, Cardiac; Biliary Tract; Digitalis Glycosides; Digitoxin; Digoxin; Gastrointestinal Diseases; Heart Diseases; Humans; Intestinal Absorption; Kidney; Lanatosides; Liver; Lung; Muscles; Myocardium; Nervous System Diseases; Strophanthins; Vision Disorders

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Cardiac Complexes, Premature; Diagnosis, Differential; Digoxin; Electrocardiography; Heart Block; Humans; Middle Aged; Poisoning; Tachycardia

Topics: Animals; Antibodies; Arrhythmias, Cardiac; Digoxin; Dogs; Humans; Rabbits; Radioimmunoassay

Topics: Adrenergic beta-Antagonists; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Hypoxia

Topics: Animals; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Dogs; Furaldehyde; Rats

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Cardiac Glycosides; Digitoxin; Digoxin; Heart Rate; Humans; Mathematics; Strophanthins; Tachycardia

Topics: Age Factors; Aged; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Female; Humans; Tachycardia

Topics: Aged; Arrhythmias, Cardiac; Bradycardia; Coronary Disease; Digoxin; Electrocardiography; Heart Block; Humans; Hypertension; Ischemic Attack, Transient; Middle Aged; Rheumatic Heart Disease; Syncope; Tachycardia

A radioimmunoassay for serum digoxin concentration has been used to study the interrelationships of circulating levels of the drug and various factors in the clinical setting in 48 hospitalized patients with cardiac rhythm disturbances due to digoxin intoxication. 131 patients on maintenance doses of digoxin without toxicity and 48 patients with equivocal evidence of digoxin excess were also studied and compared with the toxic group. Patients with cardiac rhythm disturbances due to digoxin intoxication tended to be older and to have diminished renal function compared with the nontoxic group; body weight, serum potassium concentration, underlying cardiac rhythm, and nature of cardiac disease were not significantly different for the groups as a whole. Despite comparable mean daily digoxin dosages, digoxin intoxicated patients had a mean serum digoxin concentration of 3.7 +/-1.0 (SD) ng/ml, while nontoxic patients had a mean level of 1.4 +/-0.7 ng/ml (P < 0.001), 90% of patients without evidence of toxicity had serum digoxin concentrations of 2.0 ng/ml or less, while 87% of the toxic group had levels above 2.0; the range of overlap between the two groups extended from 1.6 to 3.0 ng/ml. Patients with atrioventricular block as their principal toxic manifestation had a significantly lower mean serum digoxin concentration than those in whom ectopic impulse formation was the chief rhythm disturbance. Patients with equivocal evidence of digoxin excess had received comparable daily maintenance doses of digoxin but had a mean serum concentration of 1.9 +/-0.8 ng/ml, intermediate between those of the nontoxic (P < 0.005) and toxic (P < 0.001) groups. Renal function as judged by mean blood urea nitrogen concentration was also intermediate. The data indicate that knowledge of the serum digoxin concentration, weighed in the clinical context, is useful in the management of patients receiving this drug.

Topics: Age Factors; Arrhythmias, Cardiac; Body Weight; Computers; Digoxin; Heart Failure; Humans; Kidney; Potassium; Radioimmunoassay; Tachycardia; Tritium

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Atropine; Digoxin; Electrocardiography; Female; Humans; Male; Pacemaker, Artificial; Poisoning; Potassium Chloride; Propranolol; Suicide

Topics: Arrhythmias, Cardiac; Coronary Disease; Digoxin; Heart Diseases; Humans

Topics: Adult; Aged; Ajmaline; Arrhythmias, Cardiac; Digitoxin; Digoxin; Humans; Lidocaine; Metaproterenol; Middle Aged; Phenytoin; Procainamide; Quinidine; Reserpine; Verapamil

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Drug Synergism; Histamine H1 Antagonists; Humans; Phytotherapy; Plants, Medicinal; Rauwolfia; Sparteine

Topics: Anti-Bacterial Agents; Antilymphocyte Serum; Arrhythmias, Cardiac; Australia; Azathioprine; Betamethasone; Blood Pressure; Blood Sedimentation; Digoxin; Edema; Electrocardiography; Furosemide; Glycosuria; Heart Auscultation; Heart Transplantation; Hemorrhage; Humans; Hydrocortisone; Hydroxybutyrate Dehydrogenase; Immunosuppressive Agents; Infections; Infusions, Parenteral; Injections, Intramuscular; Injections, Intravenous; Intensive Care Units; Isoproterenol; Male; Middle Aged; Postoperative Complications; Respiration; Transplantation Immunology; Transplantation, Homologous; Veins

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Humans; Hydrochlorothiazide; Male; Tachycardia

Topics: Adult; Aged; Arrhythmias, Cardiac; Digoxin; Diuretics; Electrocardiography; Female; Heart Conduction System; Heart Diseases; Heart Failure; Humans; Lidocaine; Male; Middle Aged; Phenytoin; Potassium; Radiography, Thoracic

Topics: Animals; Arrhythmias, Cardiac; Cardanolides; Cardiac Surgical Procedures; Digitalis Glycosides; Digoxin; Dogs; Drug Tolerance; Extracorporeal Circulation; Heart; Postoperative Care; Preoperative Care

Topics: Arrhythmias, Cardiac; Cardiac Surgical Procedures; Digitalis Glycosides; Digitoxin; Digoxin; Electric Stimulation Therapy; Extracorporeal Circulation; Humans; Lidocaine; Myocardium; Perfusion; Phenytoin; Postoperative Complications; Potassium; Tachycardia

Topics: Animals; Arrhythmias, Cardiac; Cardiac Glycosides; Digitalis Glycosides; Digitoxin; Digoxin; Dogs; Humans; Myocardium; Radioimmunoassay

Topics: Age Factors; Aged; Aminophylline; Arrhythmias, Cardiac; Body Weight; Digoxin; Epidemiologic Methods; Female; Furosemide; Heparin; Humans; Male; Massachusetts; Meperidine; Middle Aged; Morphine; Prochlorperazine; Statistics as Topic; Tachycardia

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Female; Male; Phenytoin; Wolff-Parkinson-White Syndrome

Topics: Adult; Aged; Arrhythmias, Cardiac; Digoxin; Female; Humans; Male; Middle Aged

Topics: Animals; Antibodies; Arrhythmias, Cardiac; Binding Sites; Blood Urea Nitrogen; Creatinine; Digoxin; Humans; Methods; Middle Aged; Rabbits; Radioimmunoassay; Tritium

Topics: Animals; Arrhythmias, Cardiac; Cats; Digoxin; Male; Phosphocreatine

Topics: Animals; Arrhythmias, Cardiac; Cats; Digoxin; Drug Synergism; Electric Countershock; Electrocardiography; Humans; Tachycardia; Ventricular Fibrillation

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Heart Failure; Humans; Intensive Care Units; Myocardial Infarction; Pacemaker, Artificial; Phenytoin

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Computers; Digitalis Glycosides; Digoxin; Electrocardiography; Heart Conduction System; Heart Rate; Humans; Ventricular Fibrillation

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Female; Male; Phenytoin

Topics: Animals; Arrhythmias, Cardiac; Digitoxin; Digoxin; Dogs; Electrocardiography; Phytotherapy; Plants, Medicinal; Rauwolfia

Topics: Arrhythmia, Sinus; Arrhythmias, Cardiac; Digoxin; Drug Synergism; Humans; Propranolol

Topics: Aged; Arrhythmias, Cardiac; Aspartate Aminotransferases; Biophysical Phenomena; Biophysics; Blood Flow Velocity; Blood Pressure; Cardiac Output; Coronary Disease; Digoxin; Electrocardiography; Heart; Heart Failure; Humans; Hydrocortisone; Hypotension; Isoproterenol; Lidocaine; Male; Methyldopa; Middle Aged; Models, Biological; Propranolol; Stress, Psychological; Veins

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atropine; Bradycardia; Cardiac Complexes, Premature; Digoxin; Drug Hypersensitivity; Dyspnea; Heart Rate; Humans; Male; Middle Aged; Propranolol; Tachycardia; Uremia

Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digoxin; Guinea Pigs; Heart; Heart Atria; In Vitro Techniques; Perfusion; Phenytoin; Strophanthins

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Cats; Digoxin; Ouabain; Pentobarbital; Ventricular Function

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Ethanolamines; Extracorporeal Circulation; Heart; Heart Conduction System; In Vitro Techniques; Mephentermine; Ouabain; Sympathectomy; Ventricular Fibrillation

Topics: Animals; Arrhythmias, Cardiac; Citrates; Digoxin; Dogs; Electrocardiography; Female; Heart Conduction System; Histamine H1 Antagonists; Imipramine; Injections, Intravenous; Male; Propranolol; Sodium

Topics: Anticoagulants; Arrhythmias, Cardiac; Atropine; Digoxin; Electric Countershock; Heart Arrest; Humans; Intensive Care Units; Isoproterenol; Levallorphan; Lidocaine; Medical Staff, Hospital; Meperidine; Myocardial Infarction; New Zealand; Nursing Service, Hospital; Oxygen Inhalation Therapy; Procainamide; Quinidine; Sympathomimetics; Ventricular Fibrillation

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Heart Failure; Humans; Hydrochlorothiazide; Male

Topics: Adult; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Female; Fetal Heart; Heart Atria; Humans; Infant; Infant, Newborn; Pregnancy

Topics: Age Factors; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digitoxin; Digoxin; Female; Humans; Lung; Lung Neoplasms; Male; Middle Aged; Postoperative Complications

Topics: Arrhythmias, Cardiac; Digoxin; Humans; Propranolol

Topics: Adolescent; Arrhythmias, Cardiac; Atrial Fibrillation; Digoxin; Electric Countershock; Female; Heart Ventricles; Humans; Male; Middle Aged; Pulmonary Edema; Quinidine; Thromboembolism

Topics: Aged; Arrhythmias, Cardiac; Digoxin; Heart Ventricles; Humans; Male; Methods

Topics: Adult; Aged; Arrhythmias, Cardiac; Coronary Disease; Digoxin; Female; Humans; Male; Middle Aged; Rheumatic Heart Disease

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Child; Coronary Disease; Digoxin; Female; Heart Defects, Congenital; Heart Diseases; Heart Valve Diseases; Humans; Male; Middle Aged; Pulmonary Heart Disease; Rheumatic Heart Disease; Tachycardia, Paroxysmal

Topics: Animals; Arrhythmias, Cardiac; Cats; Digitalis Glycosides; Digitoxin; Digoxin; Female; Lanatosides; Male; Ouabain; Reserpine; Vagus Nerve; Ventricular Fibrillation

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Heart Block; Plants, Medicinal; Rauwolfia; Strophanthins

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Child; Child, Preschool; Digoxin; Electric Countershock; Electrocardiography; Female; Heart Block; Heart Septal Defects, Atrial; Humans; Hypertension, Pulmonary; Hypothermia, Induced; Male; Postoperative Complications; Quinidine

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digoxin; Electric Countershock; Heart Diseases; Humans

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Child; Child, Preschool; Digoxin; Heart Defects, Congenital; Heart Diseases; Heart Septal Defects, Atrial; Humans; Lanatosides; Middle Aged; Postoperative Complications; Preoperative Care; Retrospective Studies; Tachycardia

Topics: Adult; Arrhythmias, Cardiac; Atrial Flutter; Bundle-Branch Block; Cardiac Complexes, Premature; Digoxin; Humans; Male; Sympathomimetics

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Electrocardiography; Guinea Pigs; Male; Quinidine

Topics: Animals; Arrhythmias, Cardiac; Chick Embryo; Culture Techniques; Digoxin; Heart; Microscopy, Phase-Contrast; Myocardium; Phenytoin; Television; Trypsin

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Electrocardiography; Guinea Pigs; Heart Rate; In Vitro Techniques; Isoproterenol; Mephentermine; Muscle Contraction

Topics: Adult; Aged; Arrhythmias, Cardiac; Digoxin; Diuretics; Ethanolamines; Female; Humans; Male; Middle Aged; Potassium

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Child; Child, Preschool; Digitalis Glycosides; Digoxin; Female; Heart Block; Humans; Infant; Infant, Newborn; Kidney Diseases; Male; Middle Aged; Potassium; Pulmonary Heart Disease; Tachycardia; Tachycardia, Paroxysmal

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Electric Countershock; Electric Stimulation; Electrocardiography; Electrophysiology; Heart Block; Heart Conduction System; Quinidine; Tachycardia; Ventricular Fibrillation

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digoxin; Female; Humans; Vertigo

Topics: Animals; Arrhythmias, Cardiac; Calcium; Cardiac Glycosides; Citrates; Digoxin; Dogs; Humans; Potassium Chloride; Sodium

Topics: Aged; Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Digoxin; Diuretics; Geriatrics; Gynecomastia; Heart Failure; Humans; Male; Psychoses, Substance-Induced; Psychotic Disorders; Toxicology

Topics: Arrhythmias, Cardiac; Autoimmune Diseases; Coombs Test; Diagnosis; Digoxin; Drug Therapy; Geriatrics; Humans; Joint Diseases; Lupus Erythematosus, Systemic; Prednisone; Procainamide; Splenomegaly; Toxicology

Topics: Arrhythmias, Cardiac; Bronchitis; Brugada Syndrome; Cardiac Conduction System Disease; Digitalis; Digoxin; Electrocardiography; Geriatrics; Heart Conduction System; Heart Failure; Humans; Hypertension; Poisoning; Toxicology

Topics: Animals; Arrhythmias, Cardiac; Digoxin; Dogs; Humans; Male; Middle Aged; Phenytoin

Topics: Aconitum; Alkaloids; Arrhythmias, Cardiac; Citrates; Citric Acid; Digitalis; Digoxin; Dogs; Edetic Acid; Humans; Injections; Injections, Intravenous; Research; Salts; Toxicology

Topics: Arrhythmia, Sinus; Arrhythmias, Cardiac; Blood Chemical Analysis; Blood Pressure; Blood Pressure Determination; Bradycardia; Calcium; Calcium, Dietary; Child; Digitalis; Digitalis Glycosides; Digoxin; Electrocardiography; Electroencephalography; Humans; Hydrogen-Ion Concentration; Infant; Potassium; Sodium; Toxicology; Urea; Water-Electrolyte Balance

Topics: Arrhythmias, Cardiac; Clinical Laboratory Techniques; Digoxin; Female; Goiter; Graves Disease; Hepatomegaly; Humans; Hyperthyroidism; Hypoprothrombinemias; Infant; Infant, Newborn; Infant, Newborn, Diseases; Iodides; Liver Diseases; Maternal-Fetal Exchange; Prednisolone; Pregnancy; Pregnancy Complications; Reserpine; Splenomegaly; Thrombocytopenia; Toxicology; Vitamin K

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digoxin; Electric Countershock; Electric Stimulation Therapy; Electrocardiography; Humans; Phenindione; Quinidine; Tachycardia

Topics: Adolescent; Arrhythmias, Cardiac; Child; Digoxin; Heart Defects, Congenital; Humans; Hypokalemia; Infant; Infant, Newborn; Rheumatic Heart Disease; Toxicology

Topics: Aged; Aortic Valve; Aortic Valve Stenosis; Arrhythmias, Cardiac; Cardiac Catheterization; Cardiac Surgical Procedures; Digoxin; Endocarditis; Endocarditis, Bacterial; Heart Failure; Heart Valve Diseases; Heart Valve Prosthesis; Heart, Artificial; Humans; Isoproterenol; Methicillin; Middle Aged; Postoperative Complications; Psychoses, Substance-Induced; Psychotic Disorders; Thoracic Surgery; Warfarin

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digitalis Glycosides; Digoxin; Drug Therapy; Electric Countershock; Electric Stimulation Therapy; Potassium; Procaine; Quinidine; Tachycardia; Toxicology

Topics: Adams-Stokes Syndrome; Arrhythmias, Cardiac; Barbiturates; Digoxin; Electrocardiography; Heart Block; Humans; Myocardial Infarction; Pacemaker, Artificial; Poisoning; Quinidine; Resuscitation; Toxicology

Topics: Adrenergic Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Digitalis; Digoxin; Electrocardiography; Ethanolamines; Geriatrics; Heart Block; Heart Failure; Hypotension; Myocardial Infarction; Nausea; Paresthesia; Sympatholytics; Toxicology; Vertigo; Vomiting

Topics: Arrhythmias, Cardiac; Cardiac Glycosides; Digoxin; Diuretics; Drug Therapy; Heart Failure; Humans; Rubiaceae

Topics: Arrhythmias, Cardiac; Digitoxin; Digoxin; Heart Arrest; Humans; Infant

Topics: Arrhythmia, Sinus; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Digoxin; Dogs; Electrocardiography; Oxytocin; Pharmacology; Quinidine; Research

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Disease; Digitalis; Digitalis Glycosides; Digoxin

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Digoxin; Hostility; Phenothiazines