digitoxin and Arrhythmias--Cardiac

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 concept that antiarrhythmic drugs can exacerbate the cardiac rhythm disturbance being treated, or generate entirely new clinical arrhythmia syndromes, is not new. Abnormal cardiac rhythms due to digitalis or quinidine have been recognized for decades. This phenomenon, termed "proarrhythmia," was generally viewed as a clinical curiosity, since it was thought to be rare and unpredictable. However, the past 20 years have seen the recognition that proarrhythmia is more common than previously appreciated in certain populations, and can in fact lead to substantially increased mortality during long-term antiarrhythmic therapy. These findings, in turn, have moved proarrhythmia from a clinical curiosity to the centerpiece of antiarrhythmic drug pharmacology in at least two important respects. First, clinicians now select antiarrhythmic drug therapy in a particular patient not simply to maximize efficacy, but very frequently to minimize the likelihood of proarrhythmia. Second, avoiding proarrhythmia has become a key element of contemporary new antiarrhythmic drug development. Further, recognition of the magnitude of the problem has led to important advances in understanding basic mechanisms. While the phenomenon of proarrhythmia remains unpredictable in an individual patient, it can no longer be viewed as "idiosyncratic." Rather, gradations of risk can be assigned based on the current understanding of mechanisms, and these will doubtless improve with ongoing research at the genetic, molecular, cellular, whole heart, and clinical levels.

Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digitalis; Humans; Ion Channels; Sodium Channel Blockers; Torsades de Pointes

Inverted T waves produced by myocardial ischemia are classically narrow and symmetric. T-wave inversion (TWI) associated with an acute coronary syndrome (ACS) is morphologically characterized by an isoelectric ST segment that is usually bowed upward (ie, concave) and followed by a sharp symmetric downstroke. The terms coronary T wave and coved T wave have been used to describe these ischemic TWIs. Prominent, deeply inverted, and widely splayed T waves are more characteristic of non-ACS conditions such as juvenile T-wave patterns, left ventricular hypertrophy, acute myocarditis, Wolff-Parkinson-White syndrome, acute pulmonary embolism, cerebrovascular accident, bundle branch block, and later stages of pericarditis.

Topics: Adult; Aged; Arrhythmias, Cardiac; Bundle-Branch Block; Chest Pain; Coronary Disease; Diagnosis, Differential; Digitalis; Electrocardiography; Female; Humans; Male; Middle Aged; Pre-Excitation Syndromes; Pulmonary Embolism; Stroke

The experimental and clinical evidence on the decreased efficacy of digitalis on old age are reviewed. The trials on the efficacy of digitalis on elderly in heart failure and sinus rythm, are analysed and we try to characterize the sub-group of responders. So we try to explain the criteria to choose the therapeutic dose, to avoid intoxication and to interpret the seric concentrations. We describe the pharmacocynetics of digitalis on old people on heart failure which can explain the susceptibility to intoxication. We reviewed the incidence of digitalis intoxication on old age and the difficulties on its recognition.

Topics: Aged; Arrhythmias, Cardiac; Cardiac Output, Low; Digitalis; Digitalis Glycosides; Humans; Plants, Medicinal; Plants, Toxic

Congestive heart failure (CHF) is a disorder characterized by a variety of clinical, biochemical, electrophysiological, and hemodynamic abnormalities. During the past two decades, numerous drugs have been employed in the treatment of this complex syndrome, and many agents have been shown to improve symptoms and ventricular function in patients with CHF. Because CHF is associated with a high risk of death, treatment should be directed not only toward the relief of symptoms, but also toward a reduction in mortality. Many variables have been shown to be related to survival; taken individually, however, each is limited in its utility in predicting prognosis. In recent years, large-scale studies with large sample sizes have directly assessed the effects of treatment on mortality in CHF. Results from these trials indicate that vasodilators and angiotensin-converting enzyme (ACE) inhibitors may improve mortality in patients with symptoms of heart failure. Additional trials are now in progress to evaluate the effect of treatment on patients with asymptomatic left ventricular dysfunction.

Topics: Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Cardiotonic Agents; Digitalis; Exercise Test; Heart Failure; Humans; Myocardial Contraction; Plants, Medicinal; Plants, Toxic; Prognosis; Renin-Angiotensin System; Sympathetic Nervous System; Treatment Outcome; Vasodilator Agents; Ventricular Function, Left

The authors consider the ever-increasing number of depressed patients, related to the stress of modern life and to the prolongation of life span. They stress that these patients are often cardiopathic or impaired by the senile heart. Finally they illustrate the cardiovascular effects of antidepressant drugs and how to avoid them.

Topics: Aged; Animals; Anti-Arrhythmia Agents; Antidepressive Agents; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Cardiovascular System; Depression; Digitalis; Drug Interactions; Heart Diseases; Heart Rate; Humans; Hypotension; Plants, Medicinal; Plants, Toxic

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Death, Sudden; Digitalis; Diuretics; Heart Failure; Humans; Phosphodiesterase Inhibitors; Plants, Medicinal; Plants, Toxic; Vasodilator Agents

The association between marked hypomagnesemia and arrhythmias, particularly those associated with digitalis intoxication, has long been recognized. More recently, acute intervention with magnesium in patients who are not hypomagnesemic has demonstrated arrhythmia suppression in 3 settings: digitalis intoxication, long QT-related arrhythmias and arrhythmias after acute myocardial infarction. Although the electrophysiologic effects of magnesium are not clearly understood, magnesium treatment is emerging as an important adjunct in managing certain serious ventricular arrhythmias.

Topics: Arrhythmias, Cardiac; Digitalis; Electrophysiology; Heart Ventricles; Humans; Long QT Syndrome; Magnesium; Myocardial Infarction; Plants, Medicinal; Plants, Toxic; Potassium

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

Topics: Adrenergic alpha-Agonists; Adrenergic beta-Antagonists; Angina Pectoris; Arrhythmias, Cardiac; Calcium Channel Blockers; Cardiovascular Agents; Digitalis; Diuretics; Hemodynamics; Humans; Hypertension; Isometric Contraction; Nitroglycerin; Physical Exertion; Plants, Medicinal; Plants, Toxic

Depletion of K and Mg appears to play a significant role in the ventricular tachyarrhythmias seen in alcoholic patients, patients treated with diuretics and/or patients with digitalis toxicity. A therapeutic strategy is suggested by the observation that hypokalemic patients have a 38-42% incidence of concurrent hypomagnesemia: that Mg as well as K should be replenished in all hypokalemic patients who suffer from alcoholism or who are receiving diuretics and/or digitalis because of the ventricular tachyarrhythmias which accompany these clinical states. Routine serum Mg determination will contribute significantly towards identifying patients at risk for cardiac arrhythmias due to Mg depletion.

Topics: Alcoholism; Animals; Arrhythmias, Cardiac; Digitalis; Diuretics; Electrocardiography; Humans; Magnesium; Magnesium Deficiency; Plants, Medicinal; Plants, Toxic; Potassium Deficiency; Rats

The antiarrhythmic potency of Mg has been described repeatedly since 1935, both as a factor in human disease and in animal experiments. Nevertheless, this therapeutic efficacy is rarely mentioned in textbooks. Both the pharmacological effect of Mg and the correction of Mg deficiency have been used in treatment of digitalis toxicity, variant angina, Torsades de Pointes, as well as in arrhythmia of unknown origin. Mg-deficiency can be caused by malabsorption or by excessive urinary loss. Both situations can occur on a congenital basis. The most frequent cause is probably alcoholism. Iatrogenic factors include digitalis, diuretics, gentamicin, as well as cisplatinum, which appreciably enhance urinary Mg loss. Correction of Mg-deficiency by parental and/or oral administration should lead to recovery. If the cause of the deficiency can be eliminated, once the deficit is repaired it may be acceptable to discontinue the supplement. However, the cause is often multifactorial, requiring further evaluation and treatment.

Topics: Animals; Arrhythmias, Cardiac; Diet; Digitalis; Electrophysiology; Humans; Magnesium; Magnesium Deficiency; Plants, Medicinal; Plants, Toxic; Potassium

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

Ventricular fibrillation is the most common mechanism of sudden unexpected cardiac death in persons with asymptomatic or symptomatic coronary artery disease. The electrophysiologic mechanisms reviewed in this article include: automaticity of pacemaker fibers, transformation of nonpacemaker into pacemaker fibers, "injury" currents and reentry. Some of the conditions facilitating ventricular fibrillation include bradycardia, long QT syndrome, electrocution, electrolyte imbalance, drugs, sympathetic stimulation and myocardial ischemia. Electrophysiologic studies during acute myocardial ischemia suggest that the earliest activity at the onset of arrhythmia may originate at the sites of the surviving Purkinje fibers or at the epicardial rim. Reentrant arrhythmias arising in ischemic myocardium are attributed to nonhomogeneous distribution of local hyperkalemia and acidosis.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Disease; Death, Sudden; Digitalis; Electric Stimulation; Electrocardiography; Electrophysiology; Heart Conduction System; Heart Rate; Heart Ventricles; Humans; Hypokalemia; Membrane Potentials; Pacemaker, Artificial; Phenothiazines; Plants, Medicinal; Plants, Toxic; Sympathetic Nervous System; Syndrome; Vagus Nerve; Ventricular Fibrillation

Cardiac arrhythmias are commonly associated with chronic obstructive lung disease and these arrhythmias can impair arterial blood oxygenation. The etiology of the arrhythmias is multifactorial. The treatment of the arrhythmias is largely the treatment of the deranged physiology and the underlying pulmonary disease. The association of arrhythmias with chronic obstructive lung disease portends a poor prognosis.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Disease; Digitalis; Drug Therapy, Combination; Humans; Hypoxia; Lung Diseases, Obstructive; Plants, Medicinal; Plants, Toxic; Pulmonary Heart Disease

Although digitalis glycosides were introduced for the treatment of cardiac disorders almost 200 years ago, controversy persists regarding the relative role of these inotropic agents, particularly in patients with coronary artery disease in sinus rhythm. With the advent of more potent diuretics and the demonstrated benefit of vasodilators in left ventricular unloading, the relative worth of digitalis in patients with coronary artery disease and myocardial infarction is being re-examined.

Topics: Angina Pectoris; Arrhythmias, Cardiac; Clinical Trials as Topic; Coronary Disease; Coronary Vessels; Digitalis; Heart Failure; Humans; Myocardial Infarction; Oxygen Consumption; Plants, Medicinal; Plants, Toxic; Substance Withdrawal Syndrome; Vascular Resistance

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

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

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; 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: 1-Propanol; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Autonomic Nervous System; Bretylium Compounds; Cardiac Glycosides; Digitalis; Drug Interactions; Electrolytes; Ethanolamines; Heart Conduction System; Humans; Lidocaine; Magnesium; Membrane Potentials; Phenytoin; Plants, Medicinal; Plants, Toxic; Potassium; Procainamide; Quinidine; Refractory Period, Electrophysiological; Sinoatrial Node

Topics: Age Factors; Aged; Angina Pectoris; Arrhythmias, Cardiac; Bundle-Branch Block; Digitalis; Electrocardiography; Female; Heart Diseases; Heart Failure; Hemodynamics; Humans; Hypertension; Male; Myocardial Infarction; Plants, Medicinal; Plants, Toxic; Prognosis

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: 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; Arrhythmias, Cardiac; Blood Pressure; Cardiovascular System; Catecholamines; Digitalis; Drug Interactions; Plants, Medicinal; Plants, Toxic; Sympathetic Nervous System

Topics: Animals; Antibodies; Arrhythmias, Cardiac; Cardiac Glycosides; Cholestyramine Resin; Digitalis; Digitalis Glycosides; Dogs; Electric Countershock; Half-Life; Heart Conduction System; Heart Rate; Humans; Immunoglobulin Fab Fragments; Lidocaine; Neurologic Manifestations; Phenytoin; Plants, Medicinal; Plants, Toxic; Potassium; Procainamide; Propranolol; Quinidine

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: Animals; Arrhythmias, Cardiac; Blood Pressure; Blood Pressure Determination; Digitoxin; Female; Glucocorticoids; Heart; Humans; Male; Myocardial Infarction; Oxygen Inhalation Therapy; Posture; Pulmonary Edema; Shock; Sympathomimetics; Vascular Resistance

Topics: Adult; Aged; Arrhythmias, Cardiac; Central Nervous System Diseases; Digitalis; Female; Gastrointestinal Diseases; Heart Block; Humans; Male; Middle Aged; Plants, Medicinal; Plants, Toxic

Topics: Anesthesia; Animals; Arrhythmias, Cardiac; Cardiac Catheterization; Cardiac Surgical Procedures; Cardiovascular System; Central Nervous System; Digitalis; Dogs; Heart; Heart Diseases; Heart Failure; Humans; Parasympatholytics; Phenytoin; Plants, Medicinal; Plants, Toxic; Procaine; Quinidine

Topics: Arrhythmias, Cardiac; Digitalis; Humans; Plants, Medicinal; Plants, Toxic

Topics: Arrhythmia, Sinus; Arrhythmias, Cardiac; Calcium; Digitalis; Digitalis Glycosides; Digitoxin; Dogs; Electrocardiography; Heart Arrest; Heart Block; Heart Conduction System; Humans; Pharmacology; Potassium; Research; Strophanthins; Toxicology

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digitalis; Digitalis Glycosides; Drug Therapy; Heart Block; Humans; Tachycardia; Tachycardia, Paroxysmal; Wolff-Parkinson-White Syndrome

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Heart Failure; Humans; Postoperative Period; Surgical Procedures, Operative

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Electric Stimulation Therapy; Procainamide; Quinidine; Tachycardia; Toxicology; Ventricular Fibrillation

Topics: Acetylcholine; Arrhythmias, Cardiac; Atropine; Digitalis; Digitalis Glycosides; Ephedrine; Epinephrine; Guanethidine; Humans; Isoproterenol; Lactates; Metaraminol; Methacholine Compounds; Methantheline; Neostigmine; Norepinephrine; Procainamide; Quaternary Ammonium Compounds; Quinidine; Reserpine; Sympatholytics

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Humans; Toxicology

The efficacy of magnesium in the prevention of arrhythmias in pediatric patients after heart surgery remains unknown. Therefore we prospectively examined the effect of magnesium treatment on the incidence of postoperative arrhythmias in pediatric patients undergoing surgical repair of congenital heart defects.. Twenty-eight pediatric patients undergoing heart surgery with cardiopulmonary bypass were prospectively, randomly assigned in a double-blind fashion to receive intravenous magnesium (magnesium group, n = 13; 30 mg/kg) or saline (placebo group, n = 15) immediately after cessation of cardiopulmonary bypass. Magnesium, potassium, and calcium levels were measured at defined intervals during surgery and 24 hours after surgery. Continuous electrocardiographic documentation by Holter monitor was performed for 24 hours after surgery. Magnesium levels were significantly decreased below the normal reference range for patients in the placebo group compared with the magnesium group on arrival in the intensive care unit and for 20 hours after surgery. Magnesium levels remained in the normal range for patients in the magnesium group after magnesium supplementation. In 4 patients in the placebo group (27%), junctional ectopic tachycardia developed within the initial 20 hours in the intensive care unit. No junctional ectopic tachycardia was observed in the magnesium group (P =.026).. Although this study was originally targeted to include 100 patients, the protocol was terminated because of the unacceptable incidence of hemodynamically significant junctional ectopic tachycardia that was present in the placebo group. Thus low magnesium levels in pediatric patients undergoing heart surgery are associated with an increased incidence of junctional ectopic tachycardia in the immediate postoperative period.

Topics: Arrhythmias, Cardiac; Calcium; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Child, Preschool; Digitalis; Double-Blind Method; Electrocardiography, Ambulatory; Female; Heart Defects, Congenital; Humans; Infusions, Intravenous; Magnesium; Magnesium Deficiency; Male; Phytotherapy; Plants, Medicinal; Plants, Toxic; Postoperative Complications; Potassium; Prospective Studies; Tachycardia, Ectopic Junctional; Treatment Outcome

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

Digitoxin is considered a risk factor for ventricular arrhythmias in hemodialysis patients. In a randomized, crossover controlled study, 55 hemodialysis outpatients with sinus rhythm were prospectively investigated in two 48-h periods of electrocardiographic monitoring, one on and one off digitoxin or vice versa. The frequency of ventricular ectopic beats (mean +/- SD) which were found in 31 of 55 patients (56%), was slightly higher on hemodialysis (10 +/- 28 beats/h) than in the following 20 h (5.4 +/- 10 beats/h) and the next day off hemodialysis (3.6 +/- 6.6 beats/h); however, no difference was seen in patients on digitoxin during hemodialysis (10 +/- 29 beats/h), in the following 20 h (4.8 +/- 15 beats/h) and on the next day off hemodialysis (1.2 +/- 6.6 beats/h). The frequency of ventricular bigemini, polymorphous ectopies, couplets, more than 30 ectopies/h, salvos and tachycardias (10 vs 9 patients) on and off digitoxin was about the same (n.s., Fisher test). Supraventricular bigemini, salvos, tachycardias, and atrial fibrillation, however, occurred in significantly fewer patients on digitoxin (3 vs 13) than in those off digitoxin (P = 0.01, Fisher test). It is concluded that digitoxin does not increase the risk of ventricular arrhythmias in hemodialysis patients. Digitoxin, however, may have a beneficial effect on the supraventricular arrhythmias frequently observed in these patients.

Topics: Adult; Aged; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Clinical Trials as Topic; Digitoxin; Electrocardiography; Female; Heart Ventricles; Humans; Male; Middle Aged; Monitoring, Physiologic; Random Allocation; Renal Dialysis; Risk Factors; Tachycardia, Supraventricular

Although digitalis glycosides were introduced for the treatment of cardiac disorders almost 200 years ago, controversy persists regarding the relative role of these inotropic agents, particularly in patients with coronary artery disease in sinus rhythm. With the advent of more potent diuretics and the demonstrated benefit of vasodilators in left ventricular unloading, the relative worth of digitalis in patients with coronary artery disease and myocardial infarction is being re-examined.

Topics: Angina Pectoris; Arrhythmias, Cardiac; Clinical Trials as Topic; Coronary Disease; Coronary Vessels; Digitalis; Heart Failure; Humans; Myocardial Infarction; Oxygen Consumption; Plants, Medicinal; Plants, Toxic; Substance Withdrawal Syndrome; Vascular Resistance

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

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: 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: Acetates; Aged; Arrhythmias, Cardiac; Clinical Trials as Topic; Digitalis Glycosides; Digitoxin; Drug Tolerance; Electrocardiography; Female; Heart Failure; Humans; Intestinal Absorption; Male; Middle Aged; Time Factors

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Bradycardia; Cardiac Complexes, Premature; Cardiomegaly; Clinical Trials as Topic; Coronary Disease; Digitalis Glycosides; Digitoxin; Heart Aneurysm; Heart Failure; Heart Valve Diseases; Humans; Hypertension; Kidney Diseases; Lung Diseases; Middle Aged; Spinal Diseases; Tablets; Tachycardia

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

Recent studies suggest that proarrhythmic effects of cardiac glycosides (CGs) on cardiomyocyte Ca(2+) handling involve generation of reactive oxygen species (ROS). However, the specific pathway(s) of ROS production and the subsequent downstream molecular events that mediate CG-dependent arrhythmogenesis remain to be defined.. We examined the effects of digitoxin (DGT) on Ca(2+) handling and ROS production in cardiomyocytes using a combination of pharmacological approaches and genetic mouse models. Myocytes isolated from mice deficient in NADPH oxidase type 2 (NOX2KO) and mice transgenically overexpressing mitochondrial superoxide dismutase displayed markedly increased tolerance to the proarrhythmic action of DGT as manifested by the inhibition of DGT-dependent ROS and spontaneous Ca(2+) waves (SCW). Additionally, DGT-induced mitochondrial membrane potential depolarization was abolished in NOX2KO cells. DGT-dependent ROS was suppressed by the inhibition of PI3K, PKC, and the mitochondrial KATP channel, suggesting roles for these proteins, respectively, in activation of NOX2 and in mitochondrial ROS generation. Western blot analysis revealed increased levels of oxidized CaMKII in WT but not in NOX2KO hearts treated with DGT. The DGT-induced increase in SCW frequency was abolished in myocytes isolated from mice in which the Ser 2814 CaMKII phosphorylation site on RyR2 is constitutively inactivated.. These results suggest that the arrhythmogenic adverse effects of CGs on Ca(2+) handling involve PI3K- and PKC-mediated stimulation of NOX2 and subsequent NOX2-dependent ROS release from the mitochondria; mitochondria-derived ROS then activate CaMKII with consequent phosphorylation of RyR2 at Ser 2814.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Calcium; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Digitoxin; Male; Membrane Potential, Mitochondrial; Mice; Mice, Knockout; Myocytes, Cardiac; NADPH Oxidases; Phosphorylation; Reactive Oxygen Species; Ryanodine Receptor Calcium Release Channel; Superoxide Dismutase

The therapeutic use of cardiac glycosides (CGs), agents commonly used in treating heart failure (HF), is limited by arrhythmic toxicity. The adverse effects of CGs have been attributed to excessive accumulation of intracellular Ca(2+) resulting from inhibition of Na(+)/K(+)-ATPase ion transport activity. However, CGs are also known to increase intracellular reactive oxygen species (ROS), which could contribute to arrhythmogenesis through redox modification of cardiac ryanodine receptors (RyR2s). Here we sought to determine whether modification of RyR2s by ROS contributes to CG-dependent arrhythmogenesis and examine the relevant sources of ROS. In isolated rat ventricular myocytes, the CG digitoxin (DGT) increased the incidence of arrhythmogenic spontaneous Ca(2+) waves, decreased the sarcoplasmic reticulum (SR) Ca(2+) load, and increased both ROS and RyR2 thiol oxidation. Additionally, pretreatment with DGT increased spark frequency in permeabilized myocytes. These effects on Ca(2+) waves and sparks were prevented by the antioxidant N-(2-mercaptopropionyl) glycine (MPG). The CG-dependent increases in ROS, RyR2 oxidation and arrhythmogenic propensity were reversed by inhibitors of NADPH oxidase, mitochondrial ATP-dependent K(+) channels (mito-K(ATP)) or permeability transition pore (PTP), but not by inhibition of xanthine oxidase. These results suggest that the arrhythmogenic adverse effects of CGs involve alterations in RyR2 function caused by oxidative changes in the channel structure by ROS. These CG-dependent effects probably involve release of ROS from mitochondria possibly mediated by NADPH oxidase.

Topics: Animals; Antioxidants; Arrhythmias, Cardiac; Calcium; Cardiac Glycosides; Digitoxin; Glycine; Male; Membrane Potentials; Mitochondria; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Myocytes, Cardiac; NADPH Oxidases; Oxidation-Reduction; Rats; Reactive Oxygen Species; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum; Sulfhydryl Compounds

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

Topics: Arrhythmias, Cardiac; Digitalis; Electrocardiography; Humans; Plant Poisoning

Three cases of patients with symptoms of digitalis overdosage were presented. The principal manifestations included complex supraventricular dysrhythmias and atrio-ventricular conduction disturbances. In the discussion a special attention was paid to digitalis dosage. Multiple factors influencing plasma concentration of digitalis including pharmacokinetics, bioavailability and drug interactions with glycosides were described. Short review of toxic manifestations of digitalis was made and the treatment of digitalis intoxication was outlined.

Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Atrioventricular Node; Captopril; Digitalis; Digitalis Glycosides; Drug Interactions; Drug Overdose; Drug Therapy, Combination; Female; Heart Conduction System; Humans; Male; Medigoxin; Middle Aged; Pentoxifylline; Plants, Medicinal; Plants, Toxic; Tachycardia, Supraventricular

Topics: Adrenergic beta-Antagonists; Anticoagulants; Arrhythmias, Cardiac; Cardiomyopathy, Dilated; Cardiotonic Agents; Digitalis; Diuretics; Humans; Vasodilator Agents

The antiarrhythmic effects of a novel antiarrhythmic drug AP-792, 4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-[4-cyclohexylbutyl]piperidine hydrochloride, were analyzed using the epinephrine-, digitalis- and two-stage coronary ligation-induced canine ventricular arrhythmia models. Intravenous administration of AP-792 (0.3 or 1.0 mg/kg) effectively suppressed each of the ventricular arrhythmias, an action that resembles that of a typical cardioselective Ca2+ channel blocker, AH-1058. The antiarrhythmic action of AP-792 was slow in onset and longer-lasting than those in our previous studies using more than 50 antiarrhythmic drugs, including Na+ and Ca2+ channel blockers. These results suggest that AP-792 can become a unique long-acting antiarrhythmic drug.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Calcium Channel Blockers; Digitalis; Disease Models, Animal; Dogs; Electrocardiography; Epinephrine; Heart Ventricles; Injections, Intravenous; Ligation; Piperidines; Sodium Channel Blockers

Topics: Aged; Arrhythmias, Cardiac; Cardiotonic Agents; Digitoxin; Electrocardiography; Humans; Male; Pacemaker, Artificial

The antiarrhythmic profile and cardiohemodynamic effect of a novel Ca(2+) channel blocker, 4-(5H-Dibenzo[a, d]cyclohepten-5-ylidene)-1-[(E)-3-(3-methoxy-2-nitro)phenyl-2-p ropeny l]piperidine hydrochloride (AH-1058), were analyzed using the epinephrine-, digitalis- and two-stage coronary ligation-induced canine ventricular arrhythmia models. Intravenous administration of AH-1058 (100 microg/kg) effectively suppressed each of the ventricular arrhythmias accompanied by weak hypotensive effects. The results contrast well with those of a typical Ca(2+) channel blocker, verapamil, which suppresses only the epinephrine-induced ventricular arrhythmia with severe hypotension. These results indicate that AH-1058 may possess a more selective inhibitory action on Ca(2+) channels in the heart than on those in the vessels. Furthermore, the antiarrhythmic actions of AH-1058 were slower in onset and longer-lasting, than those in our previous studies using other antiarrhythmic drugs, including Na(+) and Ca(2+) channel blockers. The antiarrhythmic effects of AH-1058 did not correlate with its plasma concentrations when administered either intravenously or orally. These results suggest that AH-1058 can become a long-acting Ca(2+) channel blocker with unique antiarrhythmic properties, and that AH-1058 may be used in certain pathological processes, for which selective inhibition of the cardiac Ca(2+) channels is essential.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Bridged Bicyclo Compounds; Calcium Channel Blockers; Cardiovascular Agents; Coronary Vessels; Digitalis; Disease Models, Animal; Dogs; Epinephrine; Ligation; Piperidines; Plants, Medicinal; Plants, Toxic

Two miniature Shetland ponies showing clinical signs of Digitalis purpurea (foxglove) poisoning were examined. One animal died shortly afterwards, but the second was treated successfully with the anti-arrhythmic agent, phenytoin, and was discharged after 16 days.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digitalis; Female; Horse Diseases; Horses; Phenytoin; Plant Poisoning; Plants, Medicinal; Plants, Toxic

Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Cardiotonic Agents; Digitalis; Electrocardiography; Female; Humans; Plants, Medicinal; Plants, Toxic

KCB-328 is a newly synthesized class III drug. To determine whether this drug has antiarrhythmic or proarrhythmic effects, we used canine ventricular arrhythmia models induced by coronary ligation and reperfusion, programmed electrical stimulation (PES), two-stage coronary ligation, digitalis, or epinephrine. KCB-328, in an intravenous infusion of 0.5 mg/kg/30 min, prolonged the QTc interval only 11%, but had antiarrhythmic effects on the reentry arrhythmias induced by PES (12 of 12 dogs with old myocardial infarction; p < 0.05). KCB-328, in an infusion of 1 mg/kg/h, suppressed the occurrence of fatal ventricular fibrillation (VF) induced by coronary ligation and reperfusion under either halothane anesthesia (p < 0.05) or pentobarbital anesthesia (p < 0.05). Under the halothane anesthesia, KCB-328 alone showed proarrhythmic effects [i.e., induction of ventricular premature contractions (VPCs)], but it did not induce a more severe effect such as torsades de pointes-type ventricular tachycardia (VT). In addition, KCB-328 had weak antiarrhythmic effects on the automaticity arrhythmias induced by 24-h coronary ligation but was effective neither on 48-h coronary ligation arrhythmias nor on the digitalis- and epinephrine-induced arrhythmias. Our results indicate that KCB-328 has powerful antiarrhythmic effects with fewer proarrhythmic potencies.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digitalis; Disease Models, Animal; Dogs; Electric Stimulation; Epinephrine; Female; Ligation; Male; Myocardial Reperfusion; Phenethylamines; Plants, Medicinal; Plants, Toxic; Sulfonamides

Dofetilide, a new class III antiarrhythmic agent, was tested in various kinds of canine ventricular arrhythmias to compare its effects with those of other class III agents. Ventricular arrhythmia models used were induced by two-stage coronary ligation, digitalis, epinephrine, coronary ligation and reperfusion, and programmed electrical stimulation (PES). Dofetilide (100 micrograms/kg intravenously) did not suppress automaticity arrhythmias induced by two-stage coronary ligation and epinephrine or the coronary ligation and reperfusion arrhythmias, but suppressed the reentry arrhythmia induced by PES in dogs with old myocardial infarction (MI). This effect was associated with a prolongation of QT interval. Dofetilide also showed antiarrhythmic effect in some dogs with digitalis arrhythmia. Dofetilide increased QT interval and showed negative chronotropic effect like that of other class III drugs, but was different in antiarrhythmic profiles from those of other class III agents such as D-sotalol, E-4031, and MS-551 in that it did not prevent the occurrence of ventricular fibrillation (VF) immediately after coronary reperfusion and had some antiarrhythmic effects on digitalis arrhythmia.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Vessels; Digitalis; Disease Models, Animal; Dogs; Electric Stimulation; Electrocardiography; Epinephrine; Female; Male; Myocardial Infarction; Myocardial Reperfusion; Phenethylamines; Plants, Medicinal; Plants, Toxic; Sulfonamides; Tachycardia, Ventricular; Ventricular Fibrillation

Disopyramide is an effective class I antiarrhythmic drug and widely used for the treatment of arrhythmias, but it has anticholinergic side effects. In vitro studies demonstrated that dextrorotatory (D-) disopyramide has a stronger anticholinergic action, whereas the levorotatory (L-) isomer has a stronger Na channel blocking action. Because the antiarrhythmic mechanism of disopyramide suppressing digitalis- and two-stage coronary ligation-induced canine ventricular arrhythmias is the drug-induced Na channel block, we examined the antiarrhythmic efficacy of D- and L-disopyramide on two arrhythmia models. On ouabain-induced ventricular tachycardia (VT), L-disopyramide 3 mg/kg decreased the arrhythmic ratio (number of ectopic beats/total heart rate), whereas the same dose of the D-isomer was ineffective and a higher dose (5 mg/kg) was needed to suppress the arrhythmia. The effective plasma concentrations (IC50) decreasing the arrhythmic ratio to 50% of the control were 5.3 and 11.3 mu g/ml for L- and D-disopyramide, respectively. We obtained similar results using 24-h two-stage coronary ligation VT. The IC50 were 8.9 and 22.2 mu g/ml for the L- and D-isomers, respectively. Our results indicate that L-disopyramide is about twice as strong an antiarrhythmic drug as the D-isomer.

Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Disease; Digitalis; Disopyramide; Dogs; Electrocardiography; Female; Male; Plants, Medicinal; Plants, Toxic; Stereoisomerism

We examined the effects of an aconitine-like compound, TJN-505 (1alpha-16beta-dimethoxy-20-ethyl-14alpha-(4-methox ybenzoyloxy)-aconitan-8,13-diol hydrochloride), on canine arrhythmias provoked by digitalis, two-stage coronary ligation, adrenaline, programmed electrical stimulation, or aconitine. TJN-505 (2-2.5 mg/kg i.v.) suppressed digitalis-, two-stage coronary ligation- and adrenaline-induced ventricular arrhythmias. The antiarrhythmic plasma concentrations (IC50) of TJN-505 for these arrhythmia models were 1.26, 0.94 and 1.31 microg/ml, respectively. TJN-505 (2 mg/kg i.v. followed by the infusion of 0.1 mg/kg per min) prolonged PR, QRS, QTc and JTc intervals and the ventricular effective refractory period and reduced the incidence of programmed electrical stimulation-induced arrhythmias in dogs with 7-day-old myocardial infarction (P < 0.05). TJN-505 (2 mg/kg i.v.) also suppressed the aconitine-induced atrial arrhythmias. In conclusion, TJN-505 suppressed various canine ventricular and atrial arrhythmias and seems to act as a blocker of multiple channels.

Topics: Aconitine; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Calcium Channels; Digitalis; Dogs; Electrocardiography; Epinephrine; Female; Male; Plants, Medicinal; Plants, Toxic; Potassium Channels; Sodium Channels

We investigated antiarrhythmic effects of intravenously (i.v.) administered amiodarone using four canine ventricular arrhythmia models. Bolus injections of amiodarone 3 mg/kg suppressed epinephrine (EPI)-induced arrhythmia and 5-mg/kg bolus injections of amiodarone suppressed digitalis- and two-stage coronary ligation-induced arrhythmia models, but the antiarrhythmic effects did not correlate with the amiodarone plasma concentrations. The infusion of amiodarone 6.67 mg/kg/h did not prolong the QTc interval or produce antiarrhythmic effects in coronary ligation and reperfusion experiments. Amiodarone significantly decreased the mean blood pressure (MAP), and this effect lasted throughout the observation period. The results indicate that the antiarrhythmic effects of intravenously administered amiodarone may not be due to its class III action, but to other actions, such as class I, II and IV actions.

Topics: Amiodarone; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Disease; Digitalis; Dogs; Electrocardiography; Epinephrine; Female; Injections, Intravenous; Male; Plants, Medicinal; Plants, Toxic

1. KRN2391 (3-30 micrograms/kg, i.v.) produced a decrease in mean blood pressure (MBP) with concomitant increase in heart rate (HR) and change in electrocardiogram (ECG) such as the shortening of PP and PQ intervals and the prolongation of QTc and these changes in HR and ECG were attenuated by pretreatment with propranolol (1 mg/kg) in normal dogs. 2. KRN2391 at 30 micrograms/kg induces neither suppression nor aggravation of ventricular arrhythmias caused by adrenaline and digitalis. 3. In two-stage coronary ligation-induced arrhythmia, KRN2391 inhibited arrhythmia at 48 hr. 4. These results suggest that KRN2391 may be effective on arrhythmia related to ischemia. In addition, it is considered that arrhythmia is not induced even by a high dose of KRN2391 in the normal condition.

Topics: Animals; Arrhythmias, Cardiac; Coronary Disease; Digitalis; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Electrocardiography; Epinephrine; Female; Male; Plants, Medicinal; Plants, Toxic; Pyridines; Vasodilator Agents; Ventricular Function

Peri-operative arrhythmia is one of the major complications in anaesthesia for valve replacement surgery in patients with aortic stenosis. In this retrospective study, 58 patients with sinus rhythm were investigated from induction of anaesthesia until arrival at the recovery room by close haemodynamic monitoring and Holter ECG recording. After cardiopulmonary bypass (CPB), they received either lidocaine (L, n = 35) or mexiletine (M, n = 23) via infusion for 24 hours. Pre-bypass incidence was 14% for supraventricular (SPBs) and 19% for ventricular serious arrhythmia (VPBs), i.e. high-grade forms which indicate possible deterioration and may require therapy (for all arrhythmia, incidences were 45 resp. 28%). VPBs was independently related to impaired left ventricular function (11 patients) and preoperative digitalis therapy (20 patients) but not to severity of stenosis, serum concentration of potassium (between 3.3 and 5.2 meq/l), or any other clinical parameters. Post-bypass incidence was SPBs 11% and VPBs 33%, the latter representing a significant increase compared to the first period (p < 0.03)--(all arrhythmia: 26 resp. 40%). VPBs was related to the need for multiple therapy including catecholamines and antiarrhythmic agents other than L or M, but no longer to preoperative parameters nor duration of intraoperative ischaemia. Incidences of arrhythmia for L and M were identical. While in these patients digitalis therapy may account for arrhythmia also in general anaesthesia, in valve replacement there is a post-bypass increase in VPBs which is not fully explained. Since the incidence is 33% in spite of anti-arrhythmic therapy, both administered class IB drugs may not be the best therapeutic approach.

Topics: Aged; Aortic Valve Stenosis; Arrhythmias, Cardiac; Digitalis; Diuretics; Female; Hemodynamics; Humans; Intraoperative Complications; Male; Middle Aged; Plants, Medicinal; Plants, Toxic; Postoperative Complications

The antiarrhythmic effects of a new antiarrhythmic agent, SD-3212, (-)-(S)-3,4-Dihydro-2-[5-methoxy-2-[3-[N-methyl-N-[2-[(3,4- methylene dioxy)phenoxy]ethyl]amino]propoxy]phenyl]-4-methyl-3-oxo-2H-1, 4-benzothiazine hydrogen fumarate, were investigated using canine models of ventricular arrhythmias, i.e. spontaneously occurring digitalis-, two-stage coronary ligation- and adrenaline-induced arrhythmias. SD-3212 suppressed adrenaline-induced arrhythmia and showed some antiarrhythmic effect on digitalis- and 48 hr coronary ligation-arrhythmias. These results indicate that SD-3212 has antiarrhythmic effects common among class IV antiarrhythmic drugs and also has additional efficacy common among class I antiarrhythmic drugs, thus when considering the level of experimental arrhythmias it somewhat resembles propafenone. It may therefore become a clinically useful antiarrhythmic drug among typical class I or class IV antiarrhythmic drugs.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Vessels; Digitalis; Dogs; Epinephrine; Female; Ligation; Male; Osmolar Concentration; Plants, Medicinal; Plants, Toxic; Thiazoles

The antiarrhythmic and direct cardiovascular effects of the new antiarrhythmic agent KW-3407, 5-[[2-(diethylamino)ethyl]amino]-7-methoxy-5,11- dihydro[1]benzoxepino[3,4-b]pyridine 1.5 fumarate, were examined. To evaluate antiarrhythmic effects, two-stage coronary ligation-, digitalis- and adrenaline-induced spontaneously occurring arrhythmias were used. KW-3407, 20 mg/kg/10 min, suppressed these three arrhythmia models, similar to flecainide, mexiletine and phenytoin. The antiarrhythmic plasma concentrations, IC50, of KW-3407 for 24-hr and 48-hr coronary ligation-, digitalis- and adrenaline-induced arrhythmias were 18.1, 14.4, 18.3 and 21.4 micrograms/ml, respectively; and these values were similar to one another. In the canine blood perfused atrioventricular (AV) node, sinoatrial node and papillary muscle preparations, KW-3407 decreased the sinoatrial rate and contractile force, and increased the coronary blood flow and AV conduction times, but these effects were weaker than those of disopyramide and flecainide and were short-lived. These results indicate that KW-3407 can be expected to become a clinically useful antiarrhythmic drug.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzoxepins; Coronary Vessels; Digitalis; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Epinephrine; Female; Heart Conduction System; In Vitro Techniques; Ligation; Male; Myocardial Contraction; Papillary Muscles; Plants, Medicinal; Plants, Toxic; Sinoatrial Node

In order to compare and clarify the effects of various antiarrhythmic drugs when given as monotherapy, we reevaluated our previous data on antiarrhythmic drugs and recalculated antiarrhythmic plasma concentrations of drugs for several canine arrhythmia models. We used three spontaneously occurring arrhythmias: a) digitalis-, b) two-stage coronary ligation-, and c) adrenaline-induced arrhythmias. All antiarrhythmic drugs of class I suppressed digitalis arrhythmia, and, except for lidocaine, also suppressed coronary ligation arrhythmia. Class II antiarrhythmic drugs, beta blockers, and class IV antiarrhythmic drugs, Ca antagonists, had common features of effectiveness and suppressed adrenaline arrhythmia in relatively low concentrations. Class III drugs were not effective on these three arrhythmias. Differences among the antiarrhythmic effects of class I drugs could not be explained by their subclassification based either on action potential duration or kinetic properties of dissociation or association with Na channels. New triggered arrhythmia models in vivo and in vitro canine hearts were developed, and drug effects were not the same as those on the three spontaneously occurring arrhythmia models.

Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digitoxin; Dogs; Electrophysiology; Female; Heart; Heart Ventricles; Humans; Male; Models, Cardiovascular; Myocardial Contraction; Papillary Muscles; Sodium Channels

Topics: Aortic Valve; Arrhythmias, Cardiac; Aspirin; Digitalis; Echocardiography; Electrocardiography, Ambulatory; Heart Valve Diseases; Hemodynamics; Mitral Valve; Plants, Medicinal; Plants, Toxic; Warfarin

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Digitalis; Electrocardiography; Humans; Plants, Medicinal; Plants, Toxic

Topics: Arrhythmias, Cardiac; Cardiac Glycosides; Catecholamines; Chronic Disease; Digitalis; Heart Failure; Humans; Physical Endurance; Plants, Medicinal; Plants, Toxic; Prognosis; Vasodilator Agents; Ventricular Function, Left

Topics: Administration, Oral; Arrhythmias, Cardiac; Biological Availability; Digitoxin; Dosage Forms; Humans; Immunoenzyme Techniques; Kidney Diseases; Liver Diseases; Radioimmunoassay; Specimen Handling

A 36 year old male was admitted to the intensive care unit with acute digitalis intoxication after ingestion of 350 digitoxin tablets (= 35 mg digitoxin). He was treated with Fab fragments of a digitalis antiserum raised in sheep, the concentrations of digitoxin in serum, urine and dialysates being measured with two automated digitoxin immunoassays based on fluorescence labelling techniques. Whereas one assay reflected the total digitoxin concentrations, including that bound to the antidote, the other measured only the bioactive "free" form of the drug. This article examines the use and limitations of both assay systems in assessing and monitoring cases of digitalis poisoning.

Topics: Adult; Arrhythmias, Cardiac; Combined Modality Therapy; Digitoxin; Electric Countershock; Electrocardiography; Humans; Immunoglobulin Fab Fragments; Male; Metabolic Clearance Rate; Suicide, Attempted

The possible chronotropic and arrhythmogenic effects of newly-developed oral inotropic agents were studied in 60 patients with idiopathic dilated cardiomyopathy (NYHA class II-IV). Changes in heart rates and the incidence of arrhythmias were evaluated using ambulatory electrocardiography. Denopamine 30 and 60 mg (beta 1 agonist), xamoterol 200 and 400 mg (beta 1 partial agonist) and OPC-8212 60, 90 and 120 mg (non-catecholamine) were sequentially administered for 10 +/- 2 months. Denopamine slightly increased heart rate throughout the day. Denopamine 60 mg caused excessive tachycardia in patients with atrial fibrillation, and could be used without digoxin. With xamoterol, maximum heart rate decreased during the daytime, while heart rate increased at night. Xamoterol was highly effective in patients with atrial fibrillation who not only had excessive tachycardia during exercise but marked bradycardia at night. Xamoterol increased the severity of heart failure in two patients who belonged to NYHA class IV, whose heart rates at rest had exceeded 100 beats/min. OPC-8212 did not affect heart rate, and was considered an ideal inotropic agent. None of these agents aggravated arrhythmias or caused sustained ventricular tachycardia. It was concluded that not only the severity of heart failure but the chronotropic and arrhythmogenic effects should be considered when choosing inotropic agents.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Atrial Fibrillation; Cardiomyopathy, Dilated; Cardiotonic Agents; Circadian Rhythm; Digitalis; Drug Evaluation; Electrocardiography, Ambulatory; Ethanolamines; Female; Heart Rate; Humans; Male; Middle Aged; Plants, Medicinal; Plants, Toxic; Propanolamines; Pyrazines; Quinolines; Xamoterol

Between 1986 and 1988 within our therapeutic drug monitoring plasma concentrations were estimated in 1,442 plasma samples by radioimmunoassay. Plasma levels between 0 and 84.2 ng.ml-1 with a mean of 20.8 ng.ml-1 were measured. If the maintenance dose was reduced from 0.1 to 0.07 mg the frequency distribution of the plasma samples was shifted to the left, and the mean value decreased by 5.8 ng.ml-1 (23.5 vs. 17.7 ng.ml-1). The physician's assumptions underdosage?, optimum dosage schedule? or overdosage? were confirmed by the laboratory results in 22.3, 63.6, or 23.0% of the requests, respectively. In 61.2% of all plasma samples were digitoxin concentrations in the range between 10 and 30 ng.ml-1, i.e. in the optimum therapeutic range. Main reasons for the divergent results are non-compliance of the patients and inter-individual differences in the pharmacokinetics of digitoxin. Furthermore, incomplete filling of the forms by the physicians aggravates the assessment of the results. Therefore, a permanent dialogue between clinician and clinical pharmacologist is necessary for an improvement of digitalis therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Child; Child, Preschool; Digitoxin; Dose-Response Relationship, Drug; Heart Failure; Humans; Infant; Middle Aged; Radioimmunoassay

Using two-stage coronary-ligation-, digitalis- and adrenaline-induced ventricular arrhythmias in beagles, antiarrhythmic effects of AN-132 were examined, and the minimum effective plasma concentration for each arrhythmia model was determined. AN-132 suppressed all the arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by 24-hour coronary ligation, 48-hour coronary ligation, digitalis, and adrenaline were 3.4-4.6, 1.5-2.3, 0.83, and 9.3 micrograms/ml, respectively. The concentration for adrenaline-induced arrhythmia was significantly higher than that of 24-hour coronary ligation arrhythmia, and it was also higher than that of digitalis arrhythmia. This pharmacologic profile is similar to those of pirmenol and mexiletine. Since AN-132 had no deleterious effects on the hemodynamics and the central nervous system, it may become a clinically useful antiarrhythmic drug.

Topics: Anilides; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Vessels; Digitalis; Dogs; Dose-Response Relationship, Drug; Epinephrine; Ethylenediamines; Female; Ligation; Male; Plants, Medicinal; Plants, Toxic; Tachycardia; Ventricular Function

The effects of OPC-88117, a new investigational antiarrhythmic drug, on early and delayed afterdepolarizations (EAD and DAD, respectively) were assessed in vitro in canine Purkinje fibers and in vivo in the canine right ventricle. OPC-88117 had similar electrophysiologic properties to class I antiarrhythmic agents in that it decreased Vmax. OPC-88117 decreased the amplitude and prolonged the coupling interval of DAD induced by acetylstrophanthidin. Likewise, OPC-88117 suppressed EAD induced in vitro by 4-aminopyridine. In vivo, cesium-induced EAD, ventricular arrhythmia, and atrioventricular block were suppressed by OPC-88117. In summary, OPC-88117 suppressed DAD and EAD in vitro and inhibited EAD and triggered activity in the in situ canine heart.

Topics: 4-Aminopyridine; Action Potentials; Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Cesium; Digitalis; Dogs; Electrocardiography; Heart; Heart Block; Heart Conduction System; Membrane Potentials; Piperazines; Plants, Medicinal; Plants, Toxic; Purkinje Fibers; Quinolones

Antiarrhythmic effects of the new drug KT-362, which was reported to suppress Na and Ca currents of cardiac cells and also to suppress intracellular Ca release in isolated smooth muscle preparations, were examined using two-stage coronary ligation-, digitalis- and adrenaline-induced ventricular arrhythmias in the dog. Intravenous KT-362 at 10 mg/kg suppressed coronary ligation arrhythmia both at 24 and 48 hr after ligation, and the minimum effective plasma concentrations for arrhythmias induced by 24 hr coronary ligation and 48 hr coronary ligation were 6.1 +/- 1.7 and 8.6 +/- 2.7 micrograms/ml, respectively. Antiarrhythmic effects were accompanied by transient hypotension. Oral administration of 70-100 mg/kg was also effective on 24 hr coronary ligation arrhythmia. However, there was no prominent hypotension in these experiments. Intravenous KT-362 at 3 mg/kg suppressed digitalis arrhythmia; and the minimum effective plasma concentration was 3.3 +/- 1.2 micrograms/ml, which was lower than the effective plasma concentrations for coronary ligation arrhythmias. Intravenous KT-362 at 1 mg/kg also suppressed adrenaline arrhythmia; and the minimum effective plasma concentration was 1.0 +/- 0.1 microgram/ml, the lowest among the effective plasma concentrations. These pharmacological profiles of KT-362 are quite different from those of class 4 Ca antagonists, but similar to those of class 1 drugs such as propafenone. Though KT-362 has a hypotensive effect, it is effective on canine ventricular arrhythmias; thus its clinical usefulness for supraventricular and ventricular arrhythmias is expected.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Calcium Channel Blockers; Coronary Vessels; Digitalis; Dogs; Epinephrine; Female; Male; Plants, Medicinal; Plants, Toxic; Sodium Channels; Thiazepines

Using two-stage coronary ligation-, digitalis- and adrenaline-induced canine ventricular arrhythmias, antiarrhythmic effects of pirmenol were examined, and the minimum effective plasma concentration for each arrhythmia model was determined. Pirmenol suppressed all the arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by 24 hr coronary ligation, 48 hr coronary ligation, digitalis and adrenaline were 1.1 +/- 0.3 (by 3 mg/kg, i.v.), 1.1 +/- 0.3 (by 3 mg/kg, i.v.), 1.1 +/- 0.2 (by 3 mg/kg, i.v.) and 2.5 +/- 1.5 (by 3 mg/kg, i.v.) microgram/ml, respectively (mean +/- S.D.M., n = 6-7). The concentration for adrenaline-induced arrhythmia was significantly higher than those for the other types of arrhythmias. This pharmacological profile is similar to those of mexiletine, tocainide and cibenzoline. Since pirmenol had no deleterious effects on the blood pressure and sinus node activity, its clinical usefulness is expected.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Vessels; Digitalis; Dogs; Epinephrine; Female; Ligation; Male; Piperidines; Plants, Medicinal; Plants, Toxic

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

Although triggered activity has been identified in isolated atrial tissue with the use of cellular electrophysiologic techniques, there has been no identification of triggered atrial arrhythmias in situ. Moreover, it is unclear whether triggered rhythms of different causes and sites of origin in the heart exhibit uniform responses to pacing that might aid in their identification. We therefore studied arrhythmias induced by overdrive pacing in three canine preparations, and based the analysis of our results on guidelines derived from microelectrode studies. We studied ventricular tachycardias induced by ouabain or by anterior wall myocardial infarction and atrial (coronary sinus) arrhythmias induced by the infusion of epinephrine into the great cardiac vein. In the ouabain and postinfarction preparations, right ventricular epicardial pacing induced ventricular premature beats or tachycardias whose recovery intervals after cessation of pacing shortened and showed overdrive acceleration as pacing rate increased. The first postpacing beat displayed progressive fusion with the paced beats but transient entrainment could not be induced. In the coronary sinus, the recovery intervals of impulses induced by epinephrine and pacing decreased as the drive rate increased, and inducibility of the paced rhythms increased at faster drive rates. Thus, the recovery intervals of triggered activity induced in the coronary sinus are phenomenologically similar to those of infarct- and digitalis-induced triggered rhythms. This is the first demonstration of consistent behavior in response to pacing of diverse types of triggered activity. Considered in light of the failure to induce transient entrainment, the results emphasize the potential utility of pacing in clinical identification of triggered rhythms and their differentiation from reentry.

Topics: Animals; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Coronary Vessels; Digitalis; Disease Models, Animal; Dogs; Electrophysiology; Epinephrine; Female; Heart Atria; Heart Rate; Heart Ventricles; Ligation; Male; Myocardial Infarction; Plants, Medicinal; Plants, Toxic

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

We studied the effects of Ca channel blockers and 3 antiarrhythmic drugs on the digitalis-induced oscillatory afterpotential (OAP). The OAP was observed in Purkinje fibers stimulated by pulse trains, with cycle lengths ranging from 1,000 to 300 msec. The Ca channel blockers verapamil, diltiazem and nifedipine (2.0 x 10(-6) M) depressed OAP significantly and abolished triggered activity. Verapamil was more effective than diltiazem. However, nicardipine and nitrendipine (2.0 x 10(-6) M) had no depressant effects on OAP or triggered activity. The antiarrhythmic drugs procainamide (1.0 x 10(-4) M), mexiletine (1.0 x 10(-5) M) and propranolol (1.0 x 10(-4) M) depressed both OAP and triggered activity. There were no significant differences in the depressant effects between the Ca2+ antagonists (except for nitrendipine and nicardipine) and the other antiarrhythmic drugs. The OAP coupling interval was prolonged by verapamil, diltiazem, propranolol, procainamide and mexiletine. Although the APD50 was shortened by verapamil, diltiazem and nifedipine, it was prolonged by propranolol. It is concluded that nifedipine, verapamil, diltiazem, procainamide, mexiletine and propranolol may be effective for digitalis-related arrhythmia.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Calcium Channel Blockers; Digitalis; Diltiazem; Dogs; Electric Stimulation; Female; Heart Conduction System; Male; Mexiletine; Nicardipine; Nifedipine; Nitrendipine; Plants, Medicinal; Plants, Toxic; Procainamide; Propranolol; Purkinje Fibers; Verapamil

Topics: Arrhythmias, Cardiac; Coronary Disease; Digitalis; Drug Utilization; Heart; Heart Diseases; Humans; Kinetics; Plants, Medicinal; Plants, Toxic

The antagonistic effect of triamterene on the toxicity of cardiac glycosides was investigated in conscious rabbits using the infusion method. Pretreatment with triamterene (5 mg/kg and 10 mg/kg) significantly reduces the ouabain toxicity indicated by an increase of the dose producing arrhythmia (from 61 +/- 14 to 121 +/- 17 and 178 +/- 22 micrograms/kg, resp.) and lethality (from 114 +/- 18 to 236 +/- 5 and 329 +/- 11 micrograms/kg, resp.). The triamterene induced increase of plasma potassium concentration may contribute to the antitoxic effect, however, the effect persisted after the decrease of plasma potassium concentration (by addition of NaHCO3) to pretreatment values. Under the influence of digitoxin the antitoxic effect of triamterene (10 mg/kg) is also demonstrated by the delayed appearance of arrhythmias (113 +/- 3 min compared to 78 +/- 5 min) and of lethality (125 +/- 4 min compared to 92 +/- 6 min). Triamterene is not only a prophylactic but also a curative antitoxic agent in the digitalis intoxicated rabbit.

Topics: Animals; Arrhythmias, Cardiac; Cardiac Glycosides; Digitoxin; Electrocardiography; Potassium; Rabbits; Strophanthins; Time Factors; Triamterene

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

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Digitalis; Heart Failure; Humans; Myocardial Infarction; Plants, Medicinal; Plants, Toxic

Percutaneous cholecystostomy was employed successfully as an alternative to cholecystectomy for the treatment of acute cholecystitis with perforation in an elderly woman. The procedure, performed portably in the cardiac care unit, was selected because progressive cardiac and renal decompensation made the patient an extremely poor surgical risk.

Topics: Aged; Arrhythmias, Cardiac; Cholecystitis; Digitoxin; Drainage; Female; Humans; Risk; Tomography, X-Ray Computed; Ultrasonography

Investigations by various teams have shown that combined treatment with verapamil and digoxin may result in a marked increase in digoxin plasma concentrations, necessitating a reduction in the dose of digoxin. This is mainly due to an impairment of the renal digoxin excretion. Unlike digoxin, the excretion of digitoxin is independent of renal function. A prospective clinical study was therefore planned to investigate the influence of a daily dose of 240 mg of verapamil on pharmacokinetics and the cardiac effect of digitoxin after a single dose (n = 3) and under steady-state conditions (n = 10). While pretreatment with verapamil did not alter pharmacokinetics of digitoxin in the single-dose study, there was a slight rise of digitoxin plasma concentrations (an average of 35% in 8 out of 10 patients) following administration of verapamil for a period of 4 to 6 weeks. Renal excretion of digitoxin, however, was not changed significantly. Simultaneous with a rise of digitoxin plasma concentrations and until a new steady state was reached, PQ interval was prolonged and T wave flattening intensified. On the other hand, the antagonistic effect on contractility which was initially observed after verapamil administration was diminished. Based on these observations, it can be concluded that the risk of digitalis overdose after combined treatment with verapamil and digitoxin may be less pronounced than after digoxin, and that this glycoside can prove a valuable alternative.

Topics: Aged; Arrhythmias, Cardiac; Digitoxin; Drug Therapy, Combination; Electrocardiography; Heart Diseases; Humans; Intestinal Absorption; Kinetics; Metabolic Clearance Rate; Middle Aged; Myocardial Contraction; Systole; Verapamil

Topics: Arrhythmias, Cardiac; Digitalis; England; History, 16th Century; History, 17th Century; History, 18th Century; History, 19th Century; Humans; Myocardial Contraction; Plants, Medicinal; Plants, Toxic

Enhanced susceptibility to toxic arrhythmias by digitalis administration has been reported in clinical and experimental myocardial infarction. To investigate the mechanism responsible for this phenomenon, the effects of superfusion with normal Tyrode's solution and superfusion with Tyrode's solution containing 4 X 10(-8)M of ouabain in ischemic Purkinje fibers were compared. Ischemic Purkinje fibers of small endocardial preparations from 1 day old myocardial infarcts in 18 dogs were used for the study. During control conditions, these endocardial preparations demonstrated delayed afterdepolarizations and triggered activity. Superfusion with normal Tyrode's solution resulted in a gradual increase in maximal diastolic potential and action potential amplitude, a decrease in delayed afterdepolarizations amplitude and slowing and termination of triggered activity. Superfusion for 90 minutes with Tyrode's solution containing ouabain resulted in: 1) an increase in the magnitude of delayed afterdepolarizations in preparations demonstrating subthreshold delayed afterdepolarizations, 2) sustainment of triggered activity in preparations showing nonsustained triggered activity, and 3) shortening of cycle lengths of the triggered activity in preparations demonstrating sustained triggered activity before superfusion with ouabain. These effects occurred despite the gradual increase in maximal diastolic potential and action potential amplitude. Superfusion of normal Purkinje fibers with Tyrode's solution containing 4 X 10(-8)M of ouabain for 90 minutes did not result in delayed afterdepolarizations or triggered activity. Thus, ouabain at a concentration that has no toxic effect on normal Purkinje fibers may enhance arrhythmias in ischemic Purkinje fibers by increasing the magnitude of delayed afterdepolarizations and enhancing triggered activity.

Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Coronary Disease; Digitalis; Dogs; Dose-Response Relationship, Drug; Heart Conduction System; Isotonic Solutions; Myocardial Infarction; Ouabain; Perfusion; Plants, Medicinal; Plants, Toxic; Purkinje Fibers; Time Factors

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

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Drug Interactions; Heart Diseases; Heart Failure; Humans; Myocardial Infarction; Plants, Medicinal; Plants, Toxic

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

Atrial and ventricular arrhythmias were characterized by ambulatory electrocardiography in 31 patients with nonischemic mitral regurgitation (MR), 17 of whom had echocardiographic evidence of mitral valve prolapse (MVP) and 14 of whom had other causes of MR. Frequent and complex arrhythmias were common and equally prevalent in each MR subgroup, whether or not MVP was present. Multiform ventricular ectopy was found in 77% (24 of 31), ventricular couplets in 61% (19 of 31), and ventricular salvos or ventricular tachycardia in 35% (11 of 31) of patients with MR. Arrhythmias in patients with MR were significantly more prevalent than in 63 patients with MVP who had no evidence of MR. Among patients with MVP, excess arrhythmias associated with MR were most striking with respect to frequent ventricular premature complexes (41% with MR vs 3% without MR), multiform ventricular ectopic activity (88% vs 43%), ventricular couplets (65% vs 6%), and ventricular salvos or ventricular tachycardia (35% vs 5%) (p less than 0.005 for each comparison). These data demonstrate that complex arrhythmias are common in patients with nonischemic MR irrespective of etiology, and that these arrhythmias are more strongly associated with hemodynamically important MR than with MVP alone.

Topics: Adult; Aged; Arrhythmias, Cardiac; Cineangiography; Digitalis; Echocardiography; Electrocardiography; Female; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Mitral Valve Prolapse; Plants, Medicinal; Plants, Toxic

Sideris et al followed 91 patients aged 25 to 82 (mean age 55) with respiratory failure due to severe asthma, emphysema, or chronic bronchitis. They found that patients with ventricular arrhythmias were significantly older than those without them. Although arrhythmias associated with myocardial infarction are managed primarily with drug therapy, those associated with acute respiratory failure respond best to adequate oxygenation and correction of metabolic and hemodynamic abnormalities.

Topics: Adult; Aged; Arrhythmias, Cardiac; Asthma; Cardiovascular Diseases; Digitalis; Digitalis Glycosides; Humans; Lung Diseases, Obstructive; Middle Aged; Parasympatholytics; Plants, Medicinal; Plants, Toxic; Risk; Sympathomimetics; Theophylline

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

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

In 9 (of 17 attempted) experiments (8 aborted due to premature tissue death), transmembrane electrical activity was recorded from canine false tendons superfused with Mg-free Tyrode's solution to simulate hypomagnesemia. Oscillatory after-potentials (OAP) developed similar to those seen after exposure to 2 X 10(-7) M ouabain, a short-lasting (0.5-1 time the duration of an action potential) OAP that often reached threshold superimposed on a long-lasting (3-4 times as long as the short) OAP. Both forms of OAP were shown to be Ca2+-dependent, as both were prevented by 10(-7) M nifedipine, but only the short OAP were abolished by nifedipine once they had appeared, while high (5 mM = 10 times normal) Mg2+ both prevented and terminated short and long OAP in digitoxic preparations. Results suggest that cardiac glycosides may deplete Mg from the myocardium. The mechanism of the therapeutic action of Mg2+ in digitalis intoxication is discussed in light of its involvement in Ca2+ sequestration by the sarcoplasmic reticulum.

Topics: Animals; Arrhythmias, Cardiac; Calcium; Cardiac Glycosides; Digitoxin; Dogs; Female; Heart; Magnesium; Magnesium Deficiency; Male; Nifedipine; Purkinje Fibers

Topics: Arrhythmias, Cardiac; Digitalis; Heart Failure; Humans; Magnesium; Plants, Medicinal; Plants, Toxic

To clarify the cause of hypersensitivity to digitoxin, an experiment was carried out with cats. The most potent hypersensitivity to digitoxin has been observed 48 hr after the injection of a loading dose. However, 1 hr after this injection, the cats failed to show the hypersensitivity. One, 24 and 48 hr after the injection of 3H-digitoxin, the contents of digitoxin and its metabolites in subcellular fractions of hearts were measured. Digitoxin contents in microsomal fractions 48 hr after the injection only slightly decreased. while those in mitochondrial and nuclear fractions markedly decreased as compared with the check at 1 hr. An increase of sodium ions and a decrease of potassium ions in the hearts were seen 48 hr after the injection. These facts may be related to the cause of hypersensitivity.

Topics: Animals; Arrhythmias, Cardiac; Biotransformation; Cats; Cell Nucleus; Digitoxin; Drug Hypersensitivity; Female; Male; Myocardium; Sodium-Potassium-Exchanging ATPase; Subcellular Fractions; 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

The narrow therapeutic range of digitalis glycosides and the danger of intoxication has prompted a search for alternative medication in recent years. Substances reducing the pre- and afterload of the heart are suitable therapeutic agents and vasodilators are, therefore, used as adjuvant or alternative therapy. Of all positive inotropic substances only the catecholamines play an established part in the treatment of acute myocardial failure. Pilot studies testing orally administrable positive inotropic substances are being conducted, but for the moment no such drugs are available for routine use. Digitalis still remains the drug of choice for all forms of primary impairment of contractility and/or supraventricular tachyarrhythmias. The appropriate dosage has to be adapted to the estimated lean body mass and, if necessary, reduced in a thin person, Digitoxin is preferentially used in cases with suspected renal insufficiency (especially in elderly patients).

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digitoxin; Diuretics; Heart Failure; Heart Rate; Humans; Hyperkalemia; Myocardial Contraction; Vasodilator Agents

Digitalis toxicity in vivo generally is recognized by the appearance of cardiac arrhythmias but in vitro by a decline in myocardial performance. To determine whether concentrations of digitoxin producing cardiac arrhythmias in intact animals also produce a decline in myocardial performance directly, three groups of adult cats were studied. One received digitoxin daily until arrhythmias developed (toxic group), the second sufficient digitoxin to produce an inotropic effect without arrhythmias (nontoxic group), and the third was untreated. Peak isometric force and maximal dF/dt of isolated right ventricular papillary muscles were significantly greater in nontoxic muscles (3.9 +/- 0.4 gm/mm2 and 21.3 +/- 1.7 gm/mm2 . sec-1). Values in toxic muscles were similar to untreated ones (2.8 +/- -.6 gm/mm2 and 19.0 +/- 3.2 gm/mm2 . sec-1). Acetylstrophanthidin (2 X 10(-8) M) resulted in an increase in peak force and max dF/dt in nontoxic muscles, whereas myocardial performance changed minimally in untreated muscles and declined in 8 of 10 toxic muscles. We conclude that electrical and mechanical toxicity induced by digitoxin frequently coexist.

Topics: Animals; Arrhythmias, Cardiac; Cats; Digitoxin; Myocardial Contraction; Papillary Muscles; Stimulation, Chemical; Strophanthidin

Topics: Arrhythmias, Cardiac; Cardiology; Digitalis; Digitalis Glycosides; England; Heart Conduction System; History, 18th Century; History, 19th Century; History, 20th Century; Humans; Myocardial Contraction; Plants, Medicinal; Plants, Toxic

Topics: Anti-Arrhythmia Agents; Anti-Bacterial Agents; Antihypertensive Agents; Antineoplastic Agents; Arrhythmias, Cardiac; Digitalis; Diuretics; Drug-Related Side Effects and Adverse Reactions; Humans; Plants, Medicinal; Plants, Toxic; Psychotropic Drugs; Vasodilator Agents

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Digitalis; Emergencies; Humans; Plants, Medicinal; Plants, Toxic; Tachycardia; Wolff-Parkinson-White Syndrome

Nine infants with episodic or continuous chaotic atrial rhythm (CAR) are presented. In addition to 3 or more different P-wave contours, atrial rates greater than 100 per minute, variable PP, RR, and PR intervals, and a discrete isoelectric baseline, findings included atrial rates that varied from a low of 50 to 120 to a high of 140 to 270 per minute, ventricular rates that varied from a low of 40 to 50 to a high of 180 to 270 per minute, and periodic sinus arrest with junctional escape rhythm. Except for the arrhythmia, all had a normal cardiac examination, ECG, chest x-ray film, and echocardiogram. Six infants were otherwise normal; one had an orbital rhabdomyosarcoma; one had neonatal asphyxia; and one had respiratory distress, bronchopulmonary dysplasia, and an intraventricular cerebral hemorrhage. The CAR persisted from 3 days to 20 months; it spontaneously reverted to normal sinus rhythm in 8 infants and persists in 1 infant at age 7 months. Digoxin (4 patients), propranolol hydrochloride (3 patients), quinidine sulfate (2 patients), and lidocaine (1 patient) did not alter the CAR. No patient had heart failure secondary to the CAR, although three also had episodes of sustained atrial tachycardia, which while present caused heart failure. All patients are functioning normally at home and have normal findings on cardiac examination and have normal ECGs at ages 3 to 38 months. Seven are in normal sinus rhythm, one has rare atrial premature contractions, and one has persistent CAR. We conclude that specific treatment was not necessary in these infants with CAR, except in those with associated sustained atrial tachycardia, which itself may cause heart failure.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digitoxin; Electrocardiography; Female; Follow-Up Studies; Heart Atria; Humans; Infant; Infant, Newborn; Male; Tachycardia; Tachycardia, Paroxysmal

Topics: Aged; Antibodies; Antibody Specificity; Arrhythmias, Cardiac; Digitoxin; Hemodynamics; Humans; Immunoglobulin Fab Fragments; Male; Prognosis; Time Factors

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

Topics: Arrhythmias, Cardiac; Digitalis; Erythrocytes; Humans; Plants, Medicinal; Plants, Toxic; Potassium; Sodium

Topics: Adult; Arrhythmias, Cardiac; Digitalis; Digitoxin; Humans; Male; Plant Poisoning; Plants, Medicinal; Plants, Toxic

Severe digitoxin poisoning in seven patients is reported. Doses taken varied from 2 to 20 mg, and maximal plasma concentrations of digitoxin from 50 to 237 nmol/L. One patient died from ventricular fibrillation, and the course in another was considerably protracted due to severe complications. The course in all patients was more dependent on underlying heart disease than on the plasma digitoxin concentration. Based on our own experiences and survey of the literature the following treatment is proposed: Gastric aspiration and lavage followed by instillation of activated charcoal should even be performed many hours after drug intake. In order to interrupt the enterohepatic circulation of digitoxin, repeated doses of charcoal should be given. Charcoal is preferable to cholestyramine because of its better tolerability. Ventricular arrhythmias should not be treated unless they are serious, because most antiarrhythmic drugs may further impede the AV-conduction. Phenytoin is the drug of choice, because the AV-conduction is less affected or even improved, and because the metabolism of digitoxin is accelerated. Conduction disturbances with bradycardia are frequently seen and may occur suddenly. Prophylactic introduction of a transvenous pacing catheter is therefore recommended as a routine procedure.

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Charcoal; Digitoxin; Electrocardiography; Female; Gastric Lavage; Humans; Male; Middle Aged

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Coronary Disease; Digitoxin; Echocardiography; Female; Humans; Middle Aged; Mitral Valve Prolapse; Phonocardiography; Quinidine

Topics: Adult; Aged; Arrhythmias, Cardiac; Digitalis; Heart Failure; Humans; Long-Term Care; Male; Middle Aged; Oxygen Inhalation Therapy; Plants, Medicinal; Plants, Toxic; Respiratory Insufficiency; Spironolactone

Topics: Action Potentials; Anesthesia; Arrhythmias, Cardiac; Cardiovascular Diseases; Digitalis; Digitalis Glycosides; Heart; Humans; Myocardial Contraction; Plants, Medicinal; Plants, Toxic; Water-Electrolyte Imbalance

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Digitalis; Electrocardiography; Humans; Plants, Medicinal; Plants, Toxic

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

Topics: Aged; Arrhythmias, Cardiac; Digitalis; Electrocardiography; Female; Heart Failure; Heart Ventricles; Humans; Plants, Medicinal; Plants, Toxic

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

Two case reports describing the treatment of digitoxin toxicity with cholestyramine resin are presented. Both female patients were receiving 100 microgram/day of digitoxin when toxicity occurred. In both patients, digitoxin was discontinued and hypokalemia was corrected. In patient 1, lidocaine hydrochloride and phenytoin sodium also were administered. Serum digitoxin levels were decreased from 43 ng/ml to 21.8 ng/ml and from 42 ng/ml to 29 ng/ml in patients 1 and 2, respectively, following administration of three 4-g doses of cholestyramine resin over a one-day period. Previous studies on the treatment of digitoxin intoxication with potassium chloride, phenytoin sodium, lidocaine hydrochloride, digitoxin-specific antibodies, colestipol hydrochloride and cholestyramine resin are discussed. Ion-exchange resins may be valuable adjuncts in the treatment of digitoxin intoxication but further studies of their utility are needed.

Topics: Aged; Arrhythmias, Cardiac; Cholestyramine Resin; Digitoxin; Female; Humans; Hypokalemia

Topics: Aged; Anorexia; Arrhythmias, Cardiac; Deglutition Disorders; Digitalis Glycosides; Digitoxin; Digoxin; Female; Heart Failure; Humans; Male

This study examined nonuniform postganglionic cardiac sympathetic neural discharge as a possible mechanism involved in the production of coronary occlusion or ouabain-induced arrhythmias. After acute occlusion of the left anterior descending coronary artery in 12 cats, anesthetized with alpha-chloralose and pretreated with atropine, arrhythmia occurred within 3 min in eight animals; three of these died in ventricular fibrillation. In recordings from 15 nerves in the eight animals with arrhythmia, spontaneous discharge increased in nine nerves, decreased in five nerves, and showed no change in one nerve. This nonuniform neural discharge was associated with the development of arrhythmia after occlusion. In four of the cats, neural discharge did not change within the first 3 min after coronary artery occlusion and arrhythmia did not occur. Development of ouabain-induced arrhythmia was accompanied by a nonuniform pattern in the neural discharge (13 cats). This discharge may alter ventricular excitation and conduction to produce arrhythmia.

Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Arterial Occlusive Diseases; Blood Pressure; Cats; Coronary Vessels; Digitalis; Heart; Heart Conduction System; Heart Rate; Ouabain; Plants, Medicinal; Plants, Toxic; Sympathetic Nervous System; Time Factors

In order to determine if there is a relationship between Na+, K+-ATPase inhibition and cardiac glycoside-induced arrhythmia, the time course of the onset and offset of the arrhythmia induced by the semi-synthetic glycoside, actodigin, and the enzyme activity during arrhythmia and following reversion to normal sinus rhythm was studied in the intact, anethetized dog. An infusion of actodigin(AY22,241) at the rate of 0.1 micronmol/kg/min for 30 min induced a severe and persistent arrhythmia within 13.1 +/- 192 min of 9 dogs. Upon termination of the actodigin infusion, the arrhythmia spontaneously converted to sinus rhythm within 17.5 +/- 2.3 min. Left ventricular tissue was taken from dogs sacrificed at the peak of the actodigin-induced arrhythmic periods or from the dogs that were allowed to recover from the actodigin-induced arrhythmia. These samples were homogenized and the membrane-containing fraction was passed through a Millipore filter. The membrane fraction trapped in the filter was then assayed for Na+ + K+ stimulated, Mg2+ dependent ATPase acctivity. The results showed that, in comparison to the time matched control dogs, the cardiac microsomes prepared from the arrhythmic dogs had a markedly reduced Na+, K+-ATPase activity. On the other hand, actodigin-treated dogs that were allowed to recover from the arrhythmic episode had Na+, K+-ATPase activity that was not significantly different from the control values. The amount of 3H-actodigin bound by the cardiac muscle microsomal fraction was also investigated. The microsomes from left ventricle were isolated with a slight modification of the method of Dutta et al. (1968). The microsomal binding of 3H-actodigin was maximum at 30 min (26.6 mol/mg protein) when the sample was prepared from the dogs at the peak of the arrhythmic effect. However, the binding was significantly reduced (11.5pmol/mg protein) in the microsomal fraction from hearts that had returned to sinus rhythm. These data provide direct evidence that inhibition of Na+, K+-ATPase and cardiac glycosideinduced arrhythmia may have some cause and effect relationship.

Topics: Adenosine Triphosphatases; Animals; Arrhythmias, Cardiac; Cardenolides; Digitalis Glycosides; Digitoxin; Dogs; Female; History, 18th Century; Microsomes; Myocardial Contraction; Myocardium; Potassium; Protein Binding; Sodium

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

In a prospective study of digitalis intoxication in 649 patients on maintenance treatment with digitoxin a low incidence of digitalis toxicity was found, namely, 5.8 per cent. This is mainly due to a more careful use to digitalis glycosides. It is especially important to reduce the dose of digitoxin in the liver and partly excreted metabolized in the liver and partly excreted through the kidneys as metabolities. Serum half-time of digitoxin is shortened in patients with impaired renal function. Patients with reduced renal function may be treated with digitoxin in the same doses as individuals with normal renal function. This is in contrast to patients treated with digoxin. Digitoxin should therefore be the cardiac glycoside of choice in treatment of patients with renal failure. Digitoxin is further rapidly eliminated in patients with reduced liver function in spite of its extensive hepatic metabolism. In this study extracardia symptoms were found equally often as cardiac signs of toxicity. Patients intoxicated usually had several symptoms and signs of toxicity at the same time. The specificity of commonly used symptoms and signs a digitalis intoxication is very low. In this study atrial tachycardia with block, which has been considered to be an important cardiotoxic arrhythmia, very seldom was found in digitalis intoxication. There is an overlap in digitalis serum concentration between toxic and nontoxic patients. The diagnosis of toxicity was made on clinical grounds. Most of the intoxicated patients had high serum concentrations, but some had concentrations in the normal or low range. Apart from being a guide to the diagnosis of digitalis intoxication, serum digitalis levels may further be a guide to underdigitalization of cardiac patients, especially patients in sinus rhythm.

Topics: Age Factors; Aged; Arrhythmias, Cardiac; Body Weight; Digitoxin; Female; Humans; Kidney Diseases; Liver; Male; Middle Aged; Prospective Studies

Topics: Age Factors; Arrhythmias, Cardiac; Child; Child, Preschool; Digitalis Glycosides; Digitoxin; Electrocardiography; Humans; Infant

Out of 124 patients who had taken massive doses of digitoxin in attempted suicide, emergency endocardial pacing was performed in the 68 with the worst prognosis. The mortality (13%) in the 124 patients compared favorably with the mortality (20%) in a previous series of 70 similar patients none of whom were paced. Sixteen (23%) of the 68 paced patients died. The causes of death were: asystole (two); cardiogenic shock (two); septicemia (one); and ventricular fibrillation (eleven). Ventricular fibrillation occurred during introduction of the pacing catheter in two patients, as a result of electrode displacement in these patients, because of premature withdrawal of the catheter in one patient, and for no detectable reason, during normally proceeding pacing, in five patients. Endocardial pacing has a place in the emergency treatment of massive digitoxin poisoning. Its chief hazards are mechanical, and one of the commonest is electrode displacement.

Topics: Adolescent; Adult; Age Factors; Aged; Arrhythmias, Cardiac; Catheterization; Digitoxin; Electrocardiography; Female; Humans; Male; Middle Aged; Pacemaker, Artificial; Potassium; Time Factors

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

Topics: Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digitoxin; Dyspnea; Edema; Humans; Male

The effect of colestipol (colestipol hydrochloride; U-26 597 A), a copolymer of tetraethylenepentamine and epichlorhydrine, on plasma digitoxin levels has been investigated. Recently, it has been stated that colestipol decreases the enterohepatic circulation and the plasma half-life of digitoxin. Colestipol was administered to 11 patients having a digitoxin plasma level which is generally accepted to be above the therapeutic range (greater than 40 ng/ml). The elimination rate of digitoxin measured by serial radioimmunoassay in these colestipol treated patients was compared with the elimination rate of digitoxin in 11 patients not treated with colestipol. The results of this study did not demonstrate a significant difference in the mean (+/- S.D.) digitoxin plasma half-life between the colestipol treated (6.3 +/- 1.3 days) and the non-colestipol treated patients (6.8 +/- 1.0 days).

Topics: Antidotes; Arrhythmias, Cardiac; Colestipol; Digitoxin; Electrocardiography; Half-Life; Humans; Polyamines

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

Ajmaline, a rauwolfia derivative, has been found to possess potent antiarrhythmic effects. The present study has been designed to define the cardiovascular effects of this drug. Hemodynamic studies performed in anesthetized and conscious dogs demonstrated no significant changes in measured hemodynamic parameters at doses equal to or less than 2 mg. per kilogram. Studies in isolated papillary muscle demonstrated no negative inotropic effects until concentrations of 1 X 10(-4). Disparate results were obtained with regard to heart rate reflecting the state of autonomic tone. Electrophysiologic studies in both anesthetized and conscious dogs demonstrated a significant depression of intraventricular conduction with no significant effect on AV nodal conduction; ventricular automaticity was not affected. Ajmaline did not alter digitalis-induced AV nodal conduction prolongation. However, ajmaline dramatically altered or abolished ventricular arrhythmias secondary to acute ischemia. In conclusion, these studies demonstrate that ajmaline specifically depresses intraventricular conduction, suggesting that this drug would be particularly effective in the treatment of re-entrant ventricular arrhythmias.

Topics: Ajmaline; Animals; Arrhythmias, Cardiac; Atrioventricular Node; Cardiovascular System; Cats; Depression, Chemical; Digitalis; Dogs; Heart Conduction System; Heart Rate; Hemodynamics; In Vitro Techniques; Myocardial Contraction; Papillary Muscles; Plants, Medicinal; Plants, Toxic

Topics: Administration, Oral; Adrenergic beta-Antagonists; Antidepressive Agents, Tricyclic; Arrhythmia, Sinus; Arrhythmias, Cardiac; Atrioventricular Node; Coronary Disease; Digitoxin; Drug Therapy, Combination; Humans; Injections, Intravenous; Myocardial Infarction; Practolol; Propranolol; Quinidine

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digitoxin; Digoxin; Gastrointestinal Diseases; Humans; Neurologic Manifestations

Serum digitoxin levels were measured in 18 infants (under two years) and in 23 children (aged 2-13 years) receiving maintenance therapy. Digitalization was carried out because of heart failure in 17 infants and 13 children and for control of dysrhythmia in one infant and 10 children. Mean maintenance dosage for infants was 0.0042 plus or minus 0.0008 (sd) mg/kg/day and for children was 0.0031 plus or minus 0.0012 mg/kg/day. The mean serum digitoxin level was not significantly different in infants (30 plus or minus 10 ng/ml, range 14-58) from that found for children (34 plus or minus 11 ng/ml, range 19-61). Both values were significantly different (P smaller than 0.001) from those determined in this laboratory for adults (mean 24 plus or minus 7 ng/ml, range 5-39). In four infants with electrocardiographic or other evidence of toxicity, the mean serum level was 71 plus or minus 2 ng/ml (range 68-72), and in four children with electrocardiographic or other evidence of toxicity, the mean serum level for digitoxin was 72 plus or minus 14 ng/ml (range 53-84). The data suggest that infants and children tolerate a higher serum digitoxin concentration without any evidence of toxicity and may require more digitoxin (mg/kg) for therapeutic effect than do adults. Serum digitoxin levels may serve as an important guide in determining the adequacy of digitalization and in the recognition and management of digitalis toxicity.

Topics: Adolescent; Age Factors; Arrhythmias, Cardiac; Body Weight; Child; Child, Preschool; Digitoxin; Electrocardiography; Heart; Heart Failure; Humans; Infant; Radioimmunoassay

Topics: Age Factors; Arrhythmias, Cardiac; Digitoxin; Humans; 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

Extensive clinical experience indicates that cardioversion is the most effective method now available for terminating cardiac tachyarrhythmias. This procedure is not accompanied by depression of myocardial contractility, conductivity, or excitability, a common sequel to the use of antiarrhythmic drugs. Furthermore, the incidence of complications with cardioversion is low. These features of effectiveness, safety, and simplicity permit cardioversion to be used by the noncardiologist physician, who may be less experienced than a cardiologist in recognizing arrrhythmias. Cardioversion has not reduced the need for antiarrhythmic agents; on the contrary, more such drugs are required to maintain normal sinus rhythm. The problem at present is not the terminating a tachyarrhythmia but in preventing its recurrence.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Choice Behavior; Digitalis; Electric Countershock; Electricity; Emergencies; Heart Valve Prosthesis; Humans; Pacemaker, Artificial; Plants, Medicinal; Plants, Toxic; Quinidine; Tachycardia; Ventricular Fibrillation

Topics: Adult; Aged; Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Electric Countershock; Female; Heart; Heart Diseases; Humans; Male; Middle Aged; Plants, Medicinal; Plants, Toxic

Topics: Administration, Oral; Adrenergic beta-Antagonists; Animals; Antibody Formation; Antigens; Arrhythmias, Cardiac; Biopharmaceutics; Digitalis Glycosides; Digitoxin; Digoxin; Drug Interactions; Humans; Rabbits; Radioimmunoassay

Topics: Adenosine Triphosphatases; Animals; Arrhythmias, Cardiac; Cardanolides; Cardiac Glycosides; Digitoxin; Dogs; Dose-Response Relationship, Drug; Enzyme Activation; Glucose; Heart; Myocardium; Ouabain; Potassium; Sodium; Species Specificity; Stimulation, Chemical; Structure-Activity Relationship; Subcellular Fractions; Swine; Time Factors

Topics: Acetyldigitoxins; Administration, Oral; Adolescent; Adult; Arrhythmias, Cardiac; Calcium; Digitoxin; Female; Humans; Injections, Intravenous; Male; Phenytoin; Phosphotransferases; Potassium; Saliva

Topics: Administration, Oral; Adult; Age Factors; Animals; Arrhythmias, Cardiac; Digitalis; Digitoxin; Digoxin; Heart; Humans; Infant; Methods; Myocardium; Plants, Medicinal; Plants, Toxic; Radioimmunoassay

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: 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: Aged; Arrhythmias, Cardiac; Digitalis Glycosides; Digitoxin; Digoxin; Heart Block; Heart Failure; Heart Valve Diseases; Humans; Middle Aged; Myocardial Infarction; Potassium Deficiency; Strophanthins

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

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Cats; Digitoxin; Dose-Response Relationship, Drug; Electrocardiography; Female; Heart; Heart Atria; Heart Rate; Male; Myocardium; Spinal Cord; Tachycardia; Time Factors; Tritium; Ventricular Fibrillation

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Blood Pressure; Digitalis; Drug Synergism; Heart; Heart Conduction System; Heart Rate; Hemodynamics; Humans; Injections, Intravenous; Phenytoin; Plants, Medicinal; Plants, Toxic

Topics: Adrenal Gland Diseases; Adult; Arrhythmias, Cardiac; Athletic Injuries; Autopsy; Cardiomegaly; Cholelithiasis; Coronary Vessel Anomalies; Coronary Vessels; Death, Sudden; Digitalis; Electrocardiography; Heart Conduction System; Heart Diseases; Humans; Male; Military Medicine; Myocarditis; Myocardium; Phytotherapy; Plants, Medicinal; Plants, Toxic; Pulmonary Edema; Quinidine; Thymus Gland

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: Adult; Aged; Arrhythmias, Cardiac; Cardiomyopathies; Digitalis; Digitalis Glycosides; Fatty Acids, Nonesterified; Female; Glycerol; Humans; Hypertension; Lactates; Male; Middle Aged; Plant Extracts; Plants, Medicinal; Plants, Toxic

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: Animals; Arrhythmias, Cardiac; Blood Pressure; Cats; Digitoxin; Digoxin; Ethanolamines; Female; Heart; Heart Rate; Male; Nitrobenzenes; Oxygen; Partial Pressure; Phenethylamines; Tachycardia

Topics: Adolescent; Aged; Arrhythmias, Cardiac; Child; Digitalis Glycosides; Digitoxin; Digoxin; Humans; Radioimmunoassay; Radioisotopes; Rubidium; 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: Action Potentials; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cats; Digitalis Glycosides; Digitoxin; Heart; Practolol; Sympathetic Nervous System

Topics: Adult; Age Factors; Angiography; Arrhythmias, Cardiac; Atrial Fibrillation; Cardiac Complexes, Premature; Cardiomyopathies; Coronary Disease; Digitalis; Exercise Test; Female; Heart Diseases; Heart Rate; Heart Valve Diseases; Hemodynamics; Humans; Hypoxia; Male; Middle Aged; Phytotherapy; Plants, Medicinal; Plants, Toxic; Statistics as Topic; Tachycardia; Ventricular Fibrillation

Topics: Acetanilides; Adrenergic beta-Antagonists; Amino Acids; Arrhythmias, Cardiac; Asthma; Digitalis; Drug Synergism; Humans; Phytotherapy; Plants, Medicinal; Plants, Toxic; Propylamines

Topics: Adrenergic beta-Agonists; Ajmaline; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Bradycardia; Digitalis; Electrocardiography; Heart; Hemodynamics; Humans; Lidocaine; Phenytoin; Phytotherapy; Plants, Medicinal; Plants, Toxic; Procainamide; Propranolol; Quinidine; Tachycardia

Topics: Administration, Oral; Arrhythmias, Cardiac; Body Weight; Computers; Digitalis Glycosides; Digitoxin; Digoxin; Dose-Response Relationship, Drug; Humans; Injections; Kidney; Kinetics; Lanatosides; Myocardium

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digitoxin; Digoxin; Electrocardiography; Humans; Injections, Intravenous; Methods; Pulse; Radioimmunoassay; Time Factors

Topics: Adult; Aged; Arrhythmias, Cardiac; Coronary Disease; Diagnosis, Differential; Digitalis; Electrocardiography; Female; Heart; Heart Atria; Heart Diseases; Heart Failure; Humans; Hypertension; Male; Middle Aged; Muscle Contraction; Plants, Medicinal; Plants, Toxic

Topics: Alkaloids; Anesthetics, Local; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atropine; Barium; Cardiac Complexes, Premature; Digitoxin; Dogs; Electrocardiography; Epinephrine; Guinea Pigs; Heart Atria; In Vitro Techniques; Ouabain; Petroleum; Tachycardia

To determine whether digoxin-specific antibodies can reverse established digoxin toxicity in the dog, digoxin intoxication was produced by the intramuscular administration of digoxin, 0.09 mg/kg, on each of 3 consecutive days. All animals developed toxic arrhythmias (atrioventricular block, ventricular premature contractions and/or ventricular tachycardia). In control animals not receiving antidigoxin antibodies, the arrhythmias persisted throughout a 6 hr study period. Seven of the nine control dogs were dead within 24 hr and one moribund animal was sacrificed at that time; the last animal died within 48 hr.In contrast, in six of eight dogs given digoxin-specific antibodies in canine plasma and/or rabbit serum, the arrhythmias reverted to a sinus mechanism within 30-90 min after the start of the infusion. At the end of a 6 hr period of study, these six dogs were in normal sinus rhythm and all eight were alive and in normal sinus rhythm at the end of 72 hr. This study provides evidence that digoxin-specific antibodies can reverse severe established digoxin toxicity in the dog.

Topics: Animals; Antibodies; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Digitoxin; Disease Models, Animal; Dogs; Heart Block; Hemagglutination Tests; Immunization, Passive; Poisoning; Potassium; Protein Binding; Serum Albumin; 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: 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: Aged; Arrhythmias, Cardiac; Blood Urea Nitrogen; Calcium; Centrifugation; Digitalis Glycosides; Digitoxin; Digoxin; Humans; Middle Aged; Potassium; Radioimmunoassay; Saliva; Spectrophotometry

Topics: Acetanilides; Amino Alcohols; Arrhythmias, Cardiac; Digitalis Glycosides; Digitoxin; Digoxin; Heart; Humans; Muscle Contraction; Propranolol; Propylamines

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: Adult; Aged; Arrhythmias, Cardiac; Digitoxin; Follow-Up Studies; Heart Diseases; Heart Failure; Humans; Middle Aged

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: Aged; Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Electrocardiography; Heart; Humans; Male; Medication Errors; Nephritis; Phytotherapy; Plants, Medicinal; Plants, Toxic; Self Medication

Topics: Arrhythmia, Sinus; Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Electrocardiography; Humans; Plants, Medicinal; Plants, Toxic; Tachycardia

Topics: Arrhythmia, Sinus; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Diagnosis, Differential; Digitalis; Edrophonium; Electrocardiography; Heart Conduction System; Heart Rate; Humans; Plants, Medicinal; Plants, Toxic; Tachycardia; Time Factors

Topics: Aged; Arrhythmias, Cardiac; Bradycardia; Digitoxin; Electric Stimulation; Electrocardiography; Female; Heart Ventricles; Humans; Male; Quinidine; Syncope; Ventricular Fibrillation

Because of an error in the manufacture of digoxin tablets a large number of patients took tablets that contained 0.20 mg. of digitoxin and 0.05 mg. of digoxin instead of the prescribed 0.25 mg. of digoxin. The symptoms are described of 179 patients who took these tablets and suffered from digitalis intoxication. Of these patients, 125 had taken the faultily composed tablets for more than three weeks. In 48 patients 105 separate disturbances in rhythm or in atrioventricular conduction were observed on the electrocardiogram. Extreme fatigue and serious eye conditions were observed in 95% of the patients. Twelve patients had a transient psychosis. Extensive ophthalmological observations indicated that the visual complaints were most probably caused by a transient retrobulbar neuritis.

Topics: Aged; Arrhythmias, Cardiac; Depression; Digitoxin; Fatigue; Feeding and Eating Disorders; Female; Gastrointestinal Diseases; Heart Block; Humans; Male; Medication Errors; Muscular Diseases; Nausea; Tachycardia; Vision Disorders

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Cardiac Glycosides; Digitoxin; Digoxin; Heart Rate; Humans; Mathematics; Strophanthins; Tachycardia

Topics: Adult; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digitalis Glycosides; Digitoxin; Female; Humans; Lanatosides; Male; Middle Aged; Pyridines; Strophanthins

Topics: Anesthetics, Local; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Barbiturates; Barium; Blood Pressure; Bradycardia; Chlorides; Conjunctiva; Cornea; Depression, Chemical; Digitoxin; Dogs; Electrocardiography; Epinephrine; Heart Rate; Hydrochloric Acid; Hypotension; Imipramine; Irritants; Ouabain; Petroleum; Proadifen; Rabbits; Reflex

Topics: Adolescent; Age Factors; Arrhythmias, Cardiac; Blood Circulation; Child; Child, Preschool; Digitoxin; Drug Tolerance; Heart Defects, Congenital; Humans; Infant; Pneumonia; Time Factors; Vascular Diseases

Topics: Aged; Arrhythmias, Cardiac; Bradycardia; Digitoxin; Electrocardiography; Female; Humans; Lidocaine; Pacemaker, Artificial; Postoperative Complications; Potassium Chloride; Procaine; Propranolol; Tachycardia; Ventricular Fibrillation

Topics: Adams-Stokes Syndrome; Arrhythmias, Cardiac; Cardiac Glycosides; Digitoxin; Heart Block; Heart Failure; Heart Rate; Humans; Pacemaker, Artificial; Procainamide; Sympatholytics; Tachycardia

Topics: Adult; Aged; Ajmaline; Arrhythmias, Cardiac; Digitoxin; Digoxin; Humans; Lidocaine; Metaproterenol; Middle Aged; Phenytoin; Procainamide; Quinidine; Reserpine; Verapamil

Topics: Animals; Arrhythmias, Cardiac; Cardiac Glycosides; Cats; Digitoxin; Female; Heart; Heart Failure; Lanatosides; Male; Strophanthins

Topics: Arrhythmias, Cardiac; Cardiac Glycosides; Digitalis; Edetic Acid; Electric Countershock; Electrocardiography; Heart Diseases; Humans; Phenytoin; Plants, Medicinal; Plants, Toxic; Procainamide; Propranolol; Strophanthins; Ventricular Fibrillation

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digitalis; Electric Countershock; Embolism; Female; Humans; Lidocaine; Male; Phytotherapy; Plants, Medicinal; Plants, Toxic; Quinidine; Tachycardia

Topics: Adult; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Bradycardia; Cardiac Complexes, Premature; Digitoxin; Electric Countershock; Electrocardiography; Electrolytes; Embolism; Female; Heart Failure; Heart Septal Defects, Atrial; Heparin; Humans; Hypokalemia; Intracranial Embolism and Thrombosis; Male; Middle Aged; Mitral Valve Stenosis; Postoperative Complications; Pulmonary Embolism; Quinidine; Spironolactone; Water-Electrolyte Balance

Topics: Adult; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Azathioprine; Cardiomyopathies; Digitoxin; Heart Transplantation; Heart Valve Diseases; Histocompatibility; Humans; Hydrocortisone; Hydroquinones; Male; Methods; Phlebitis; Postoperative Complications; Serum Globulins; Transplantation, Homologous

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Child; Digitoxin; Female; Heart Failure; Humans; Male; Middle Aged

Topics: Aged; Arrhythmias, Cardiac; Digitoxin; Electrocardiography; Female; Heart Conduction System; Humans; Hypotension; Male; Middle Aged; Peritoneal Cavity; Postoperative Care; Postoperative Complications; Time Factors

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: Adult; Aged; Arrhythmias, Cardiac; Digitoxin; Drug Compounding; Female; Humans; Male; Medication Errors; Middle Aged; Netherlands; Poisoning

Topics: Animals; Arrhythmias, Cardiac; Cardiac Glycosides; Digitalis Glycosides; Digitoxin; Digoxin; Dogs; Humans; Myocardium; Radioimmunoassay

Topics: Animals; Arrhythmias, Cardiac; Digitoxin; Digoxin; Dogs; Electrocardiography; Phytotherapy; Plants, Medicinal; Rauwolfia

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Cardiac Glycosides; Cats; Digitoxin; Electrophysiology; Female; Heart Rate; Injections, Intravenous; Male; Neural Conduction; Neurons; Neurons, Efferent; Ouabain; Stellate Ganglion; Sympathetic Nervous System; Vagus Nerve

Topics: Acute Disease; Adult; Aged; Anticoagulants; Arrhythmias, Cardiac; Digitoxin; Electrocardiography; Female; Furosemide; Heart Arrest; Heart Block; Heart Massage; Humans; Intensive Care Units; Isoproterenol; Male; Middle Aged; Myocardial Infarction; Nitroglycerin; Pacemaker, Artificial; Ventricular Fibrillation

Topics: Acid-Base Equilibrium; Animals; Arrhythmias, Cardiac; Calcium; Carbon Dioxide; Digitoxin; Dogs; Electrocardiography; Female; Hydrogen-Ion Concentration; Infusions, Parenteral; Phosphates; Potassium

Topics: Age Factors; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digitoxin; Digoxin; Female; Humans; Lung; Lung Neoplasms; Male; Middle Aged; Postoperative Complications

Topics: Animals; Arrhythmias, Cardiac; Digitoxin; Electrocardiography; Guinea Pigs; Heart Atria; Ouabain; Phenytoin

Topics: Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Coronary Disease; Digitoxin; Drug Tolerance; Electric Conductivity; Female; Heart Block; Heart Rate; Humans; Male; Middle Aged

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Child; Digitoxin; Electric Countershock; Female; Follow-Up Studies; Heart; Heart Function Tests; Humans; Male; Middle Aged; Quinidine; Rheumatic Heart Disease; Tachycardia

Topics: Anesthesia, General; Animals; Arrhythmias, Cardiac; Blood Pressure; Bradycardia; Cats; Digitoxin; Dimethyl Sulfoxide; Drug Synergism; Electrocardiography; Female; Glycosides; Heart Rate; Infusions, Parenteral; Male; Ouabain; Plants, Medicinal; Ventricular Fibrillation

Topics: Animals; Arrhythmias, Cardiac; Cats; Digitalis Glycosides; Digitoxin; Digoxin; Female; Lanatosides; Male; Ouabain; Reserpine; Vagus Nerve; Ventricular Fibrillation

Topics: Animals; Arrhythmias, Cardiac; Digitalis; Digitoxin; Ecology; Heart; Plant Extracts; Plants, Medicinal; Plants, Toxic; Rats

Topics: Adult; Arrhythmias, Cardiac; Digitoxin; Electrocardiography; Female; Humans; Isoproterenol; Male; Middle Aged; Propranolol; Quinidine

Topics: Animals; Arrhythmias, Cardiac; Barium; Calcium Chloride; Digitoxin; Electrophysiology; Guinea Pigs; Heart Conduction System; Magnesium; Membrane Potentials; Potassium; Propranolol; Solutions

Topics: Aftercare; Aged; Ambulatory Care; Arrhythmias, Cardiac; Coronary Disease; Digitoxin; Electrocardiography; Female; Humans; Male; Middle Aged

Topics: Anesthesia, General; Animals; Arrhythmias, Cardiac; Autonomic Nervous System; Catecholamines; Cocaine; Denervation; Digitoxin; Dogs; Electric Countershock; Ethanolamines; Heart; Isoproterenol; Ouabain; Propranolol; Reserpine

Topics: Adult; Arrhythmias, Cardiac; Asparagine; Atropine; Digitoxin; Diuretics; Edetic Acid; Female; Heart; Humans; Hypocalcemia; Magnesium; Potassium; Potassium Deficiency; Salts; Suicide; Toxicology

Topics: Arrhythmias, Cardiac; Digitalis Glycosides; Digitoxin; Electric Countershock; Humans; Tachycardia, Paroxysmal

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digitalis; Electrocardiography; Heart Rate; Humans; Middle Aged; Monitoring, Physiologic; Plants, Medicinal; Plants, Toxic; Quinidine; Tachycardia

Topics: Arrhythmias, Cardiac; Atropine; Child; Deafness; Digitalis; Electrocardiography; Female; Heart Diseases; Humans; Plants, Medicinal; Plants, Toxic; Potassium Chloride; Ventricular Fibrillation

Topics: Animals; Arrhythmias, Cardiac; Digitalis; Dogs; Electrocardiography; Heart; Heart Block; Heart Conduction System; Heart Rate; Phenytoin; Plants, Medicinal; Plants, Toxic; Procainamide

Topics: Arrhythmias, Cardiac; Digitalis; Electric Countershock; Humans; Isoproterenol; Lidocaine; Metaraminol; Myocardial Infarction; Norepinephrine; Phenytoin; Plants, Medicinal; Plants, Toxic; Procainamide; Quinidine

Topics: Animals; Arrhythmias, Cardiac; Catecholamines; Cats; Digitalis; Ethanolamines; Muscle Contraction; Neuromuscular Junction; Neurons; Plants, Medicinal; Plants, Toxic; Sensory Receptor Cells

Topics: Arrhythmias, Cardiac; Digitalis; Ethanolamines; Heart; Heart Conduction System; Nerve Endings; Plants, Medicinal; Plants, Toxic; Sympatholytics

Topics: Arrhythmias, Cardiac; Atrial Flutter; Bradycardia; Digitalis; Digitalis Glycosides; Electrocardiography; Humans; Phytotherapy; Plants, Medicinal; Plants, Toxic; Procainamide; Quinidine; Rauwolfia; Tachycardia; Tachycardia, Paroxysmal

Topics: Arrhythmias, Cardiac; Chlorthalidone; Digitoxin; Drug Synergism; Heart Function Tests; Humans; Hypertension; Hypokalemia; Methyldopa; Myocardial Infarction; Quinidine; Reserpine

Topics: Arrhythmia, Sinus; Arrhythmias, Cardiac; Cardiac Glycosides; Digitalis Glycosides; Digitoxin; Heart Diseases; Heart Failure; Humans; Pulse; Strophanthins; Tachycardia, Paroxysmal

Topics: Adult; Arrhythmias, Cardiac; Death, Sudden; Digitalis; Electric Countershock; Embolism; Female; Heart Arrest; Heart Diseases; Humans; Intracranial Embolism and Thrombosis; Male; Middle Aged; Myocardial Infarction; Plants, Medicinal; Plants, Toxic; Popliteal Artery; Quinidine; Ventricular Fibrillation

Topics: Arrhythmias, Cardiac; Digitoxin; Drug Therapy; Electrocardiography; Heart; Heart Failure; Humans; Strophanthins

Topics: Arrhythmias, Cardiac; Blood; Carbon Dioxide; Digitalis; Dogs; Electrocardiography; Extracorporeal Circulation; Heart, Artificial; Hypokalemia; Lactates; Phosphates; Research; Toxicology

Topics: Aged; Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Digoxin; Diuretics; Geriatrics; Gynecomastia; Heart Failure; Humans; Male; Psychoses, Substance-Induced; Psychotic Disorders; Toxicology

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Drug Therapy; Ethanolamines; Sympatholytics; Toxicology

Topics: Arrhythmias, Cardiac; Child; Digitalis; Digitalis Glycosides; Drug Therapy; Eye Manifestations; Fatigue; Gastrointestinal Diseases; Geriatrics; Humans; Mental Disorders; Poisoning; Statistics as Topic; 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: Arrhythmias, Cardiac; Blood Volume; Calcium; Carbon Dioxide; Cations; Chlorides; Digitalis; Digitalis Glycosides; Dogs; Drug Synergism; Edetic Acid; Electrocardiography; Heart Arrest; Myocardium; Pacemaker, Artificial; Pharmacology; Potassium; Research; Sodium; Toxicology

Topics: Alkaloids; Arrhythmias, Cardiac; Digitalis; Dogs; Electrocardiography; Muscle Contraction; Myocardium; Ouabain; Pharmacology; Potassium; Rauwolfia; Research; Reserpine; Strophanthins; Toxicology; Tyramine

Topics: Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Digitalis; Digitalis Glycosides; Electrocardiography; Heart Conduction System; Humans; Pulmonary Heart Disease; Quinidine; Wolff-Parkinson-White Syndrome

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Cardiac Complexes, Premature; Digitoxin; Electrocardiography; Humans; Pacemaker, Artificial; Quinidine; Rauwolfia; Tachycardia; Tachycardia, Paroxysmal

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Brugada Syndrome; Cardiac Conduction System Disease; Cardiac Surgical Procedures; Digitoxin; Drug Therapy; Heart Block; Heart Conduction System; Humans; Mitral Valve Insufficiency; Mitral Valve Stenosis; Postoperative Complications; Rauwolfia; Tachycardia; Tachycardia, Paroxysmal; Thoracic Surgery

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Cardiac Surgical Procedures; Digitoxin; Drug Therapy; Mitral Valve Stenosis; Postoperative Complications; Thoracic Surgery

Topics: Anti-Arrhythmia Agents; Anura; Arrhythmias, Cardiac; Cardiac Glycosides; Cats; Digitoxin; Dogs; Ethylamines; Glycosides; Heart; Heart Rate; Intestinal Absorption; Lactones; Pharmacology; Procainamide; Research; Toxicology

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; Atrial Fibrillation; Digitalis; Electrocardiography; Geriatrics; Heart Block; Humans; Parasystole; Quinidine; Tachycardia; Wolff-Parkinson-White Syndrome

Topics: Arrhythmias, Cardiac; Atropine; Digitalis; Digitalis Glycosides; Epinephrine; Heart Block; Prednisolone; Pulse; Quinidine; Reserpine

Topics: Adrenal Cortex Hormones; Aortic Diseases; Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Diuretics; Electrocardiography; Female; Humans; Hypokalemia; Iatrogenic Disease; Mitral Valve Stenosis; Potassium Deficiency; Pregnancy; Pregnancy Complications; Pregnancy Complications, Cardiovascular; Toxicology

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Aspartic Acid; Digitalis; Digitalis Glycosides; Epinephrine; Humans; Isoproterenol; Pharmacology; Procainamide; Quinidine; Tranquilizing Agents

Topics: Antazoline; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Dogs; Electrocardiography; Geriatrics; Histamine H1 Antagonists; Humans; Myocardial Infarction; Research; Tachycardia; Tachycardia, Paroxysmal; Toxicology

Topics: Adolescent; Alkaloids; Anabolic Agents; Antithyroid Agents; Arrhythmias, Cardiac; Cardiovascular Diseases; Child; Chloroquine; Digitalis; Digitalis Glycosides; Drug Therapy; Humans; Hydrochlorothiazide; Infant; Procaine; Rauwolfia; Reserpine; Rheumatic Heart Disease; Steroids

Topics: Arrhythmias, Cardiac; Arteriosclerosis; Digitalis; Digitalis Glycosides; Electrocardiography; Geriatrics; Heart Failure; Toxicology

Topics: Arrhythmias, Cardiac; Blood Pressure Determination; Coronary Disease; Digitalis; Digitalis Glycosides; Drug Therapy; Electric Stimulation; Electric Stimulation Therapy; Electrocardiography; Heart Auscultation; Procainamide; Quinidine; Tachycardia; Tachycardia, Paroxysmal; Tachycardia, Ventricular; Toxicology

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Bradycardia; Digitalis; Digitalis Glycosides; Electrocardiography; Heart Arrest; Heart Block; Humans; Myocardial Infarction; Physiology; Sympathomimetics; Ventricular Fibrillation

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: Acidosis; Adolescent; Arrhythmias, Cardiac; Cardiac Surgical Procedures; Child; Digitalis; Heart Block; Heart Septal Defects; Heart Septal Defects, Ventricular; Humans; Hypoxia; Infant; Infant, Newborn; Postoperative Complications; Tetralogy of Fallot; Thoracic Surgery; Toxicology

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Brugada Syndrome; Cardiac Conduction System Disease; Chronic Disease; Digitalis; Digitalis Glycosides; Drug Therapy; Electrocardiography; Heart Conduction System; Quinidine; Syncope; Toxicology; Ventricular Fibrillation

Topics: Adolescent; Arrhythmias, Cardiac; Blood; Body Temperature; Calcium; Cardiac Surgical Procedures; Child; Digitalis; Digitalis Glycosides; Dogs; Drug Tolerance; Electrocardiography; Heart Defects, Congenital; Humans; Infant; Perfusion; Pharmacology; Potassium; Research; Surgical Procedures, Operative; Thoracic Surgery; Toxicology

Topics: Arrhythmias, Cardiac; Cardiomegaly; Digitalis; Digitalis Glycosides; Heart Valve Prosthesis; Humans; Hypokalemia; Mitral Valve; Toxicology; Ventricular Fibrillation

Topics: Adolescent; Aortic Valve Stenosis; Arrhythmias, Cardiac; Biomedical Research; Digitalis; Digitalis Glycosides; Drug Therapy; Drug Tolerance; Electrocardiography; Humans; Mitral Valve Insufficiency; Mitral Valve Stenosis; Rheumatic Heart Disease; Sex; Toxicology

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Electrocardiography; Emetics; Humans; Infant; Poisoning; Toxicology

Topics: Arrhythmias, Cardiac; Cations; Chlorides; Digitalis; Digitalis Glycosides; Dogs; Electric Stimulation; Electrocardiography; Hyperkalemia; Myocardium; Pacemaker, Artificial; Pharmacology; Potassium; Research; Toxicology

Topics: Alkaloids; Arrhythmias, Cardiac; Blood Circulation; Blood Pressure; Digitalis; Digitalis Glycosides; Dogs; Electrocardiography; Hemodynamics; Humans; Pharmacology; Research; Ryanodine; Toxicology

Topics: Animals; Arrhythmias, Cardiac; Breast; Diarrhea; Digitalis; Digitalis Glycosides; Dogs; Drug Hypersensitivity; Endocrine Glands; Eye Manifestations; Hyperkalemia; Hypertrophy; Neurologic Manifestations; Toxicology

Topics: Arrhythmias, Cardiac; Cardiotonic Agents; Digitalis; Digitalis Glycosides; Drug Therapy; Humans; Quinidine

Topics: Arrhythmias, Cardiac; Digitoxin; Digoxin; Heart Arrest; Humans; Infant

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Humans; Plant Extracts; Poisoning; Potassium

Topics: Acidosis; Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Humans; Hydrogen-Ion Concentration; Strophanthins

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

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Humans; Procainamide; Quinidine; Rauwolfia; Tachycardia; Tachycardia, Paroxysmal

Topics: Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Cardiomyopathies; Digitalis; Digitalis Glycosides; Heart Conduction System; Humans; Poisoning

Topics: Arrhythmias, Cardiac; Calcium; Calcium, Dietary; Digitalis; Digitalis Glycosides; Electrolytes; Humans; Magnesium; Potassium; Preoperative Care

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Electrocardiography; Esophageal Neoplasms; Geriatrics; Heart Failure; Humans; Lung Neoplasms; Mortality; Surgical Procedures, Operative; Thoracotomy; Thorax

Topics: Ammonium Compounds; Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Cats; Choline; Digitalis; Digitalis Glycosides; Heart Conduction System; Quaternary Ammonium Compounds; Research; Reserpine

Topics: Arrhythmias, Cardiac; Calcium; Cardiac Complexes, Premature; Cats; Digitalis; Digitalis Glycosides; Dogs; Edetic Acid; Electrocardiography; Pharmacology; Potassium; Procainamide; Research; Tachycardia; Toxicology

Topics: Arrhythmia, Sinus; Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Electric Countershock; Heart Block; Heart Failure; Humans; Hypokalemia; Potassium; Procainamide; Resuscitation; Tachycardia; Tachycardia, Paroxysmal; Toxicology

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Electrocardiography; Heart Block; Heart Conduction System; Humans; Toxicology; Vagus Nerve

Topics: Arrhythmias, Cardiac; Cardiotoxicity; Cardiovascular Diseases; Digitalis; Heart Block; Humans; Isoproterenol; Plant Extracts; Sympathomimetics

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Humans; Plant Extracts

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Heart Failure; Lanatosides

Topics: Animal Experimentation; Animals; Arrhythmias, Cardiac; Digitalis; Drug-Related Side Effects and Adverse Reactions; Hypertension; Reserpine

Topics: Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Digitalis; Digitalis Glycosides; Electrocardiography; Heart Conduction System

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Blood Pressure Determination; Digitalis; Dogs; Electrocardiography; Heart Block; Hemodynamics; Humans

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Edetic Acid; Electrolytes; Humans; Magnesium Sulfate; Potassium; Sodium

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Leadership; Plant Extracts

Topics: Arrhythmias, Cardiac; Biological Phenomena; Digitalis; Digitalis Glycosides; Physiological Phenomena

Topics: Arrhythmias, Cardiac; Chlorothiazide; Digitalis; Heart Arrest; Heart Block; Heart Defects, Congenital; Humans; Medical Records; Pacemaker, Artificial

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Disease; Digitalis; Digitalis Glycosides; Digoxin

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Humans; Plant Extracts; Procainamide; Quinidine; Triclosan

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Plant Extracts

Topics: Arrhythmias, Cardiac; Cardiovascular Diseases; Digitalis; Heart Block; Humans

Topics: Arrhythmias, Cardiac; Diagnosis, Differential; Digitalis; Heart Block; Humans

Topics: Arrhythmias, Cardiac; Biomedical Research; Calcium; Chelating Agents; Digitalis; Edetic Acid; Humans

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Humans; Magnesium; Plant Extracts

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Esophagus; Heart Failure; Humans; Lung; Pulmonary Surgical Procedures

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Heart; Humans; Physiological Phenomena; Ventricular Septum

Topics: Arrhythmias, Cardiac; Digitalis; Plant Extracts

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Plant Extracts

Topics: Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Digitalis; Heart Block; Heart Conduction System; Strophanthins

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Plant Extracts

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Brugada Syndrome; Cardiac Conduction System Disease; Digitalis; Digitalis Glycosides; Heart Conduction System; Humans; Quinidine

Topics: Arrhythmias, Cardiac; Digitalis; Humans

Topics: Arrhythmias, Cardiac; Chelating Agents; Digitalis; Edetic Acid; Humans

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Humans; Plant Extracts; Procainamide; Quinidine; Strophanthins

Topics: Arrhythmias, Cardiac; Digitalis; Humans

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Digoxin; Hostility; Phenothiazines

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Heart; Heart Diseases; Lactates; Sodium Lactate

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Brugada Syndrome; Cardiac Conduction System Disease; Digitalis; Heart Conduction System; Heart Rate; Potassium

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Brugada Syndrome; Cardiac Conduction System Disease; Digitalis; Digitalis Glycosides; Heart Conduction System; Humans; Quinidine

Topics: Arrhythmias, Cardiac; Digitalis; Humans; Quinidine

Topics: Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Digitalis; Heart Block; Heart Conduction System; Humans; Potassium; Seizures; Tachycardia; Tachycardia, Ventricular; Ventricular Fibrillation

Topics: Arrhythmias, Cardiac; Deslanoside; Digitalis; Humans; Plant Extracts

Topics: Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Digitalis; Digitalis Glycosides; Heart Conduction System; Niacin; Nicotinic Acids; Quinidine

Topics: Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Cardiovascular Agents; Digitalis; Heart Conduction System; Humans

Topics: Arrhythmias, Cardiac; Cardiac Surgical Procedures; Digitalis; Digitalis Glycosides; Mitral Valve Stenosis; Neostigmine; Ventricular Flutter

Topics: Arrhythmias, Cardiac; Cardiac Surgical Procedures; Digitalis; Heart Failure; Humans; Mitral Valve Stenosis

Topics: Arrhythmias, Cardiac; Deslanoside; Digitalis; Digitalis Glycosides; Emergencies; Heart Failure; Humans; Myocardial Infarction

Topics: Acetyldigitoxins; Arrhythmias, Cardiac; Digitalis; Tachycardia

Topics: Arrhythmias, Cardiac; Blood Vessels; Brugada Syndrome; Cardiac Conduction System Disease; Coronary Sinus; Digitalis; Electrocardiography; Epinephrine; Heart Conduction System; Humans

Topics: Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Digitalis; Electrocardiography; Heart Conduction System; Humans

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Humans; Physiological Phenomena

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Brugada Syndrome; Cardiac Conduction System Disease; Cinchona Alkaloids; Digitalis; Digitalis Glycosides; Heart Conduction System; Procaine; Sparteine; Ventricular Fibrillation

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Digitalis; Humans; Poisoning

Topics: Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Digitalis; Digitalis Glycosides; Heart Conduction System; Lanatosides; Tachycardia

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Heart Murmurs; Heart Sounds; Sound

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Heart; Hypersensitivity; Strophanthins

Topics: Arrhythmias, Cardiac; Brugada Syndrome; Carbohydrates; Cardiac Conduction System Disease; Digitalis; Digitalis Glycosides; Heart Conduction System; Humans; Poisoning

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Digitalis; Humans; Potassium; Tachycardia

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Plant Extracts

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Digitalis; Potassium

Topics: Arrhythmias, Cardiac; Digitalis; Electrocardiography; Humans

Topics: Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Digitalis; Heart Conduction System; Heart Failure; Humans; Lanatosides

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Plant Extracts

Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Digitalis; Dogs; Heart; Heart Conduction System; Membrane Potentials; Microelectrodes

Topics: Acetyldigitoxins; Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Heart Arrest; Heart Failure

Topics: 4-Butyrolactone; Angelica; Arrhythmias, Cardiac; Barium; Brugada Syndrome; Cardiac Conduction System Disease; Digitalis; Digitoxin; Heart Conduction System

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Heart Failure; Plant Extracts

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Plant Extracts; Procainamide; Procaine; Ventricular Premature Complexes

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Humans; Magnesium

Topics: Arrhythmias, Cardiac; Bradycardia; Digitalis; Digitalis Glycosides; Heart Rate; Humans; Myocardial Contraction; Reflex

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Brugada Syndrome; Cardiac Conduction System Disease; Digitalis; Digitalis Glycosides; Heart Conduction System; Humans; Lanatosides

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Drug-Related Side Effects and Adverse Reactions; Heart; Procainamide; Procaine

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Digitalis; Digitalis Glycosides; Digitoxin; Humans; Plant Extracts

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Humans; Lanatosides; Tachycardia, Supraventricular

Topics: Arrhythmias, Cardiac; Carotid Sinus; Digitalis; Digitalis Glycosides; Drug Overdose; Humans; Tachycardia

Topics: Arrhythmias, Cardiac; Digitalis; Digitalis Glycosides; Heart; Humans; Potassium; Potassium Compounds

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Autonomic Nervous System; Digitalis; Digitalis Glycosides; Echocardiography; Humans

Topics: Arrhythmias, Cardiac; Atrial Flutter; Digitalis; Digitalis Glycosides; Humans

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Digitalis; Digitalis Glycosides; Heart Failure

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

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

Topics: Arrhythmias, Cardiac; Digitalis; Glucans; Heart Rate; Humans; Tachycardia, Ventricular

Topics: Arrhythmias, Cardiac; Atrial Flutter; Digitalis; Heart; Humans; Quinidine