digoxin and Coronary-Disease

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

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

The evidence suggests that digitalis glycosides do indeed improve ventricular performance through a sustained but moderate positive inotropic effect. This effect is more marked in failing than in nonfailing myocardium. The clinical studies suggest a moderate salutary effect in patients with chronic CHF who are in sinus rhythm. The drug can be given safely to patients with CAD and in combination with other medications when the physician is aware of those factors leading to increased sensitivity to digitalis.

Topics: Cardiotonic Agents; Clinical Trials as Topic; Coronary Disease; Digitalis Glycosides; Digoxin; Drug Therapy, Combination; Heart Failure; Humans; Myocardial Contraction; Time Factors; Vasodilator Agents

Topics: Anesthesia; Calcium Chloride; Coronary Artery Bypass; Coronary Circulation; Coronary Disease; Digoxin; Dobutamine; Drug Combinations; Enflurane; Fentanyl; Halothane; Hemodynamics; Humans; Isoflurane; Monitoring, Physiologic; Morphine; Myocardium; Nitroglycerin; Nitroprusside; Nitrous Oxide; Oxygen Consumption; Propranolol; Protamines

The electrical stability of the heart is more sensitive to the extracellular than to the intracellular potassium concentration. During exercise, extracellular potassium varies rapidly. Catecholamines also modulate the plasma potassium concentration. Hypokalaemia of any cause can precipitate arrhythmias. Ischaemic myocardium loses potassium into the extracellular space within seconds and the cell becomes depolarized. The rise of the extracellular potassium ion concentration accounts for many of the early electrophysiological changes. Abrupt changes of plasma potassium concentration in normal myocardium and a high potassium concentration in ischaemic myocardium can set up electrical forces which initiate arrhythmias. The same phenomenon can account for changes on the electrocardiogram early after the cessation of an exercise test in a patient with ischaemic heart disease. Accumulation of potassium between cells in response to an increase of heart rate is a possible mechanism for false positive exercise tests and Syndrome X.

Topics: Acidosis; Action Potentials; Angioplasty, Balloon; Animals; Catecholamines; Coronary Disease; Digoxin; Diuretics; Exercise Test; False Positive Reactions; Heart; Heart Rate; Humans; Hyperkalemia; Hypokalemia; Myocardium; Physical Exertion; Potassium; Syndrome

Topics: Age Factors; Aged; Blood Pressure; Blood Proteins; Body Weight; Coronary Disease; Digoxin; Electrolytes; Female; Heart Diseases; Heart Rate; Humans; Kidney Function Tests; Male; Middle Aged

Topics: Adolescent; Adult; Age Factors; Aged; Animals; Child; Child, Preschool; Coronary Disease; Digitalis Glycosides; Digoxin; Dogs; Drug Administration Schedule; Drug Interactions; Female; Humans; Infant; Infant, Newborn; Kinetics; Lung Diseases, Obstructive; Male; Middle Aged; Pregnancy

Topics: Adenosine Triphosphatases; Animals; Calcium; Cats; Cell Membrane; Coronary Disease; Cymarine; Digitalis Glycosides; Digoxin; Dose-Response Relationship, Drug; Energy Metabolism; Guinea Pigs; Humans; Myocardial Contraction; Myocardium; Potassium; Rats; Strophanthins

Topics: Adenosine Triphosphatases; Animals; Calcium; Cardiac Glycosides; Coronary Disease; Digitoxin; Digoxin; Dogs; Guinea Pigs; Heart; Humans; Myocardium; Potassium; Sodium; Strophanthins

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

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

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

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

The aim of this study was to investigate the influences of Simvastatin (Zocor) on nitric oxide (NO), calcitonin gene related peptide (CGRP) and endothelin (ET) in blood plasma of patients with coronary heart disease (CHD) complicated with congestive heart failure (CHF).. 80 cases of patients with CHD complicated with CHF were randomly divided into two groups: the conventional treatment (control) group (Digoxin, Dihydrochlorothiazide, Isosorbide dinitrate) containing 40 cases and the conventional treatment and Simvastatin (combination) combination group containing 40 cases. In addition, there were 40 healthy persons in the normal group. Greiss method was used for NO detection, and immunoradiometry method was used to detect CGRP and ET levels in blood before and after treatment.. NO and CGRP levels in blood of patients with CHD complicated with CHF was apparently lower than those of the normal group, and there were significant differences (p < 0.01). Also, ET was significantly higher than that of the normal group (p < 0.01). After treatment, all indicators were significantly improved (p < 0.01). Also, the improvement of the conventional treatment plus Simvastatin group was more significant. Compared with the conventional treatment group after treatment, there was a significant difference (p < 0.05).. The combination of conventional treatment and Simvastatin could significantly improve metabolic disturbances of NO, CGRP and ET of patients with CHD complicated with CHF.

Topics: Adult; Aged; Calcitonin Gene-Related Peptide; Coronary Disease; Digoxin; Drug Therapy, Combination; Endothelins; Endothelium, Vascular; Female; Heart Failure; Humans; Hydrochlorothiazide; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Isosorbide Dinitrate; Male; Middle Aged; Nitric Oxide; Simvastatin

To compare the clinical effect of three TCM therapeutic methods, Yiqi (YQ, supplementing Qi), Huoxue (HX, activating blood circulation) and Yiqi Huoxue (YQHX) method on congestive heart failure and heart function.. Eighty patients were divided into 3 groups randomly, they were treated by conventional therapy and with the additional TCM drugs for YQHX to group A (n = 36), drugs for YQ to group B (n = 24), and drugs for HX to group C (n = 20). After 2 weeks' treatment, clinical effect was observed and cardiac function was detected and compared.. The total effective rate was 91.7% in group A, which was superior to that in group B (66.7%) and group C (65.0%) respectively. Cardiac function was improved remarkably after treatment in all groups, the optimal effect was shown in group A.. All the 3 methods could improve clinical symptoms and cardiac function in patients with congestive heart failure, among which YQHX method has the optimal effect.

Topics: Aged; Astragalus Plant; Astragalus propinquus; Coronary Disease; Digoxin; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Heart; Heart Failure; Humans; Male; Middle Aged; Phytotherapy; Salvia miltiorrhiza; Stroke Volume

A comparative randomized clinical study was conducted to evaluate the diagnostic and prognostic value of the activation of proinflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1alpha, IL-2, IL-6, IL-8)] and the increased production of autoimmune complexes in the pathogenesis of chronic heart failure (CHF) in patients with coronary heart disease (CHD). The study included 47 patients with CHD who had a more than 6-month history of Q-forming myocardial infarction. The patients were randomized into 3 groups: 1) 21 patients with NYHA Functional Class (FC) II heart failure (HF); 2) 16 patients with FC III HF; and 3) 10 with FC IV HF. Basic therapy involved angiotensin-converting enzyme (ACE) inhibitors, nitrates, diuretics, beta-adrenoblockers; 27.6% received digoxin, disaggregatory agents. A study protocol involved the estimation of the parameters of EchCG, paired bicycle ergometric tests, 6-min walking test, ECG daily monitoring, the levels of proinflammatory cytokines in the serum and IgG autoantibodies to cardiolipin. The findings suggest that with the higher expression of autoimmune complexes, the activation of cytokines (primarily TNF-alpha, IL-1alpha, IL-2) plays an important role in the pathogenesis of CHF in patients with postinfarct cardiac dysfunction: the high activation of cytokines and the elevated level of autoimmune complexes are associated with moderate or severe NYHA FC II-IV HF, depressed left ventricular contractility (ejection fraction, 23-38%), low exercise tolerance, and cardiac remodeling.

Topics: Adrenergic beta-Antagonists; Adult; Angiotensin-Converting Enzyme Inhibitors; Antigen-Antibody Complex; Coronary Disease; Cytokines; Digoxin; Diuretics; Heart Failure; Humans; Middle Aged; Myocardial Infarction; Nitrates; Platelet Aggregation Inhibitors; Stroke Volume

To investigate the effect of Shengmai Injection (SMI) on serum concentration and pharmacokinetic parameters of digoxin in patients with congestive heart failure.. Forty in-patients with congestive heart failure were selected and randomly divided into 4 groups, the three treated groups I, II and III treated with digoxin combined with 20 ml, 40 ml and 60 ml of SMI respectively, and the control group, 10 patients in each group. The serum concentration of digoxin at different time points was determined with radioimmunoassay and the pharmacokinetical parameters were calculated with 3P97 pharmacokinetic software.. The serum concentration of digoxin in the treated group I was significantly lower than that in the control group (P < 0.05), with the pharmacokinetical parameters, including the elimination half-life time (T1/2), elimination rate constant (Ke), apparent volume of distribution (Vd), plasma clearance (CL) and area under curve (AUC), significantly different to those in the control group (P < 0.05 or P < 0.01). But the serum concentration of digoxin with its pharmacokinetical parameters in the other two treated groups were not different significantly to those in the control group respectively (P > 0.05).. SMI could influence the metabolism of digoxin in patients with congestive heart failure. This study has provided an important reference for safe and rational combined use of digoxin and SMI in clinical practice.

Topics: Adult; Aged; Coronary Disease; Digoxin; Drug Combinations; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Heart Failure; Humans; Infusions, Intravenous; Male; Middle Aged; Phytotherapy

A multicenter, placebo-controlled, randomized, double-blind trial compared the preventive effect of aprindine and digoxin on the recurrence of atrial fibrillation (AF) with placebo, and also compare the effectiveness of these 2 drugs in the prevention of AF. Patients with symptomatic paroxysmal or persistent AF who had converted to sinus rhythm (SR) were randomly assigned aprindine (40 mg/day), digoxin (0.25 mg/day) or placebo and followed up on an outpatient basis every 2 weeks for 6 months. Of the 141 patients from 36 participating centers, 47 were given aprindine, 47 digoxin, and 47 were on placebo. After the 6-month follow-up, the Kaplan-Meier estimates of the percentage of patients remaining free of recurrent symptomatic AF on aprindine, digoxin and placebo were 33.3%, 29.2% and 21.5%, respectively. In patients remaining in SR for 15 days after from the start of follow-up, freedom from recurrence was significantly more prevalent in the aprindine group than in the placebo group (p=0.0414), but there was no significant difference between the digoxin and placebo groups. The rate of adverse events was similar in the 3 groups. In conclusion, neither aprindine nor digoxin had a significant effect on preventing relapse of symptomatic AF; however, recurrence of AF occurred later with aprindine than with placebo or digoxin.

Topics: Aged; Anti-Arrhythmia Agents; Aprindine; Atrial Fibrillation; Coronary Disease; Diabetic Angiopathies; Digoxin; Double-Blind Method; Electric Countershock; Female; Heart Valve Diseases; Humans; Hypertension; Male; Middle Aged; Placebos; Safety; Time Factors

Twelve patients with refractory chronic congestive heart failure (Class IV NYHA), related to idiopathic dilated cardiomyopathy (10 patients); previous myocardial infarction (one patient) and peripartum cardiomyopathy (one patient), received Terminalia Arjuna, an Indian medicinal plant, as bark extract (500 mg 8-hourly) or matching placebo for 2 weeks each, separated by 2 weeks washout period, in a double blind cross over design as an adjuvent to maximally tolerable conventional therapy (Phase I). The clinical, laboratory and echocardiographic evaluation was carried out at baseline and at the end of Terminalia Arjuna and placebo therapy and results were compared. Terminalia Arjuna, compared to placebo, was associated with improvement in symptoms and signs of heart failure, improvement in NYHA Class (Class III vs. Class IV), decrease in echo-left ventricular enddiastolic (125.28 +/- 27.91 vs. 134.56 +/- 29.71 ml/m2; P < 0.005) and endsystolic volume (81.06 +/- 24.60 vs. 94.10 +/- 26.42 ml/m2; P < 0.005) indices, increase in left ventricular stroke volume index (44.21 +/- 11.92 vs. 40.45 +/- 11.56 ml/m2; P < 0.05) and increase in left ventricular ejection fractions (35.33 +/- 7.85 vs. 30.24 +/- 7.13%; P < 0.005). On long term evaluation in an open design (Phase II), wherein Phase I participants continued Terminalia Arjuna in fixed dosage (500 mg 8-hourly) in addition to flexible diuretic, vasodilator and digitalis dosage for 20-28 months (mean 24 months) on outpatient basis, patients showed continued improvement in symptoms, signs, effort tolerance and NYHA Class, with improvement in quality of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Cardiomyopathy, Dilated; Chemotherapy, Adjuvant; Chronic Disease; Coronary Disease; Cross-Over Studies; Digoxin; Double-Blind Method; Female; Furosemide; Heart Failure; Heart Function Tests; Humans; Hypertension; India; Male; Middle Aged; Plants, Medicinal; Quality of Life; Spironolactone; Treatment Outcome; Ventricular Function, Left; Weight Loss

Heart diseases requiring glycoside therapy are often associated with coronary artery disease. This study evaluated quantitatively the effect of an intravenous bolus injection of digoxin (0.8 mg) on diameters of epicardial coronary arteries in 11 patients with coronary artery disease. Coronary angiograms were taken up to 30 min following intravenous administration of glycosides. The maximum decrease in mean diameters of angiographically normal coronary segments was 10.0 +/- 3.5% (p < or = 0.001) compared to control. Maximum reduction in minimal diameters of stenotic segments was 22.1 +/- 13.1% (p < or = 0.001). This vasoconstriction could be reversed with nitroglycerin. Thus, intravenous administration of digoxin induces vasoconstriction of normal and stenotic coronary arteries, which could cause ischemic complications in the presence of high-grade stenoses. Since digoxin-induced vasoconstriction could be reversed with nitroglycerin, concomitant vasodilator therapy is recommended.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Circulation; Coronary Disease; Coronary Vasospasm; Digoxin; Drug Therapy, Combination; Female; Hemodynamics; Humans; Injections, Intravenous; Male; Middle Aged; Nitroglycerin; Recurrence

In order to compare the acute hemodynamic effects of digoxin (0.01 mg/kg) and enoximone (1 mg/kg), a phosphodiesterase inhibitor inotropic agent, in severe chronic congestive heart failure, 8 patients (male, mean age 56.7 years, sinus rhythm) were investigated with a randomized cross-over study. Peak effect of enoximone (30 min) in comparison to that of digoxin (90 min) resulted in a similar reduction of left-ventricular filling pressure (-27 vs. -28%) and mean pulmonary artery pressure (-23 vs. -24%). Pulmonary (-39 vs. -16%; p < 0.01) and systemic vascular resistance (-27 vs. -4%; p < 0.001) were significantly lowered by enoximone. Cardiac index (+30 vs. +6%; p < 0.001) and heart rate (+11 vs. -3%; p < 0.05) were increased significantly more by enoximone than by digoxin. Since enoximone resulted in an enhancement of cardiac performance greater than that produced by digoxin, enoximone could be a useful and powerful substitute for digoxin in the acute therapy of severe chronic congestive heart failure with sinus rhythm.

Topics: Adult; Aged; Chronic Disease; Coronary Disease; Cross-Over Studies; Digoxin; Enoximone; Heart Failure; Hemodynamics; Humans; Injections, Intravenous; Male; Middle Aged; Severity of Illness Index; Ventricular Function, Left

We conducted a prospective, double-blind, placebo-controlled multicenter trial in order to evaluate the long-term effects of captopril (50 mg/day), digoxin (0.25 mg/day) and placebo on quality of life, cardiovascular events, clinical symptoms and exercise tolerance in patients with documented myocardial infarction, resulting in regional wall motion abnormalities, and with mild heart failure (NYHA class II to III without treatment) and exercise not limited by angina. 222 patients were studied, 63 were randomized to captopril, 66 to digoxin, 67 to placebo. Follow-up was conducted for two years. Base line characteristics in the three treatment groups were similar. After one year of therapy, digoxin had significantly improved general well-being (p < 0.01 vs captopril), symptom score (p < 0.05 vs captopril and placebo), and vitality (p < 0.05 vs captopril). Digoxin improved NYHA class in 45% as compared to placebo (28%, p < 0.05). Worsening of angina was more frequent with captopril as compared to digoxin (p < 0.05). However, cardiovascular events during follow-up were lower in the captopril group as compared to placebo and digoxin (p < 0.01 captopril vs placebo). No differences between groups were observed in baseline and follow-up exercise tolerance between the three groups. Dizziness during upright tilt and cough were more frequent with captopril as compared to digoxin or placebo. After two years of follow-up (captopril n = 32, digoxin n = 29, placebo n = 27) general well-being was improved with both digoxin and captopril (p < 0.004 and p < 0.03 vs placebo).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Angina Pectoris; Captopril; Coronary Disease; Digoxin; Double-Blind Method; Drug Therapy, Combination; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Nitroglycerin; Prospective Studies; Quality of Life; Survival Rate

Despite 200 years of use, the ability of digitalis glycosides to improve exercise capacity in patients with congestive heart failure remains controversial, partly because of imprecise end points and suboptimal study design. Therefore, this question was examined in 10 ambulatory patients (8 men and 2 women) aged 46 to 70 years (mean 57.8) in sinus rhythm with mild to moderate chronic stable congestive heart failure due to coronary artery disease and systolic left ventricular dysfunction (ejection fraction 32 +/- 12). All underwent maximal treadmill exercise with respiratory gas analysis and upright cycle ergometry with gated radionuclide angiography after 4 weeks of digoxin or placebo therapy, administered in a randomized double-blind crossover protocol. Neither treadmill exercise duration (7.7 +/- 2.3 versus 7.3 +/- 2.7 min) nor peak oxygen consumption (18.7 +/- 3.7 versus 18.4 +/- 5.4 ml/kg per min) differed between digoxin and placebo regimens. However, the change in peak oxygen consumption induced by digoxin was inversely related to the peak oxygen consumption during placebo therapy (r = -0.64, p less than 0.05). At maximal treadmill effort, heart rate (138 +/- 16 versus 141 +/- 21 beats/min), oxygen pulse (10.3 +/- 2.1 versus 9.9 +/- 2.2 ml/beat), ventilation (40.3 +/- 10.6 versus 42.0 +/- 10.8 liters/min) and ventilatory equivalent (29.4 +/- 4.8 versus 31.5 +/- 6.8) did not differ between digoxin and placebo treatment, although systolic blood pressure was higher during digoxin therapy (163.0 +/- 23.1 versus 153.2 +/- 25.3 mm Hg, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Chronic Disease; Coronary Disease; Digoxin; Exercise Test; Female; Heart Failure; Humans; Male; Middle Aged; Oxygen Consumption; Pulmonary Gas Exchange; Stroke Volume; Vasodilator Agents; Ventricular Function, Left

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

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

A total of 153 coronary patients with congestive heart failure, stage IIA and IIB, were investigated. Thirty patients underwent a three-week course of treatment with cardiac glycosides, plus diuretics and potassium preparations where necessary. In addition to conventional treatment, 123 patients were treated with vasodilating agents (2% nitroglycerin ointment, nitrosorbide or molsidomin) with the doses adjusted individually on the basis of acute drug testing. Those patients with congestive heart failure who received combined treatment with cardiac glycosides and vasodilators demonstrated a more obvious improvement of clinical parameters and instrumental findings as compared to the patients, treated with cardiac glycosides alone.

Topics: Aged; Cardiomyopathy, Dilated; Clinical Trials as Topic; Coronary Disease; Digoxin; Drug Synergism; Drug Therapy, Combination; Female; Furosemide; Hemodynamics; Humans; Male; Middle Aged; Molsidomine; Myocardial Contraction; Nitrates

The evidence suggests that digitalis glycosides do indeed improve ventricular performance through a sustained but moderate positive inotropic effect. This effect is more marked in failing than in nonfailing myocardium. The clinical studies suggest a moderate salutary effect in patients with chronic CHF who are in sinus rhythm. The drug can be given safely to patients with CAD and in combination with other medications when the physician is aware of those factors leading to increased sensitivity to digitalis.

Topics: Cardiotonic Agents; Clinical Trials as Topic; Coronary Disease; Digitalis Glycosides; Digoxin; Drug Therapy, Combination; Heart Failure; Humans; Myocardial Contraction; Time Factors; Vasodilator Agents

A direct and objective method of measuring compliance to medication is presented. Digoxin is used as a marker in capsules of either gemfibrozil or placebo with a minimal dose of 4.4 micrograms twice a day. Compliance is estimated by measuring the ratio of urinary digoxin to creatinine concentration. By choosing two cut-off points of this ratio patients who are taking their capsules regularly and those who have taken no capsules at all could be distinguished from others. Reduced dosage was easily detected in the marker results. During regular intake of three quarters of the dose, 53% of the samples would have classified the patient to the good compliance group. With half of the dose, 24% of samples and with a quarter of the dose, 5% of samples would have classified the subject to good compliance. Since the digoxin marker was planned for compliance measurements in the Helsinki Heart Study, a primary prevention study of coronary heart disease, it was tested under the conditions of a clinical trial. Digoxin concentrations were measured using a routine method normally applied to serum but shown to be valid for urine. The results of the urinary assays were not affected by storage at room temperature, as occurs during postal transport of samples, nor were they affected by freezing, routinely used for the storage of samples in clinical trials. The results therefore suggest that the digoxin marker represents a particularly effective method to study compliance to medication during such long-lasting clinical investigations.

Topics: Clinical Trials as Topic; Coronary Disease; Creatinine; Digoxin; Double-Blind Method; Finland; Follow-Up Studies; Gemfibrozil; Humans; Hypolipidemic Agents; Male; Middle Aged; Patient Compliance; Pentanoic Acids; Random Allocation; Valerates

During the last quarter of the third year of follow-up in the Helsinki Heart Study, compliance to medication was measured in 1739 patients with digoxin used as a marker substance, capsule counting and a compliance questionnaire. The estimates for good and poor compliers were found to be highly dependent on the method and the cut-off points chosen for the compliance allocation. The methods studied here were more reliable for the detection of poor rather than good compliance. In the poor compliance group, defined with the use of the digoxin marker, there was 39% of subjects who returned less than 5% of their capsule dosage or reported a deviation less than 5%. In the good compliance group, defined by the digoxin marker, only 11.8% of patients either returned or reported a deviation of at least 25% of their dose. The compliance was better when measured by the questionnaire than by capsule counting. The size of the poor compliance group, defined by the use of the digoxin marker, was as large as a group who had returned at least 27% of their capsule dose and a group who had reported a deviation of 11% or more from their dosing schedule. The size of the group allocated to the good compliance category by the use of the digoxin marker was equivalent in size to a group of patients who had returned less than 15% of their prescribed dose or reported a deviation of less than 6% from their prescription. When the strictest criteria for the combination of all three methods were used, 57% of subjects were classified as good and 31% as poor compliers to medication in the third year of the primary prevention trial designed to reduce the incidence of coronary heart disease.

Topics: Capsules; Clinical Trials as Topic; Coronary Disease; Creatinine; Digoxin; Double-Blind Method; Finland; Follow-Up Studies; Gemfibrozil; Humans; Hypolipidemic Agents; Male; Middle Aged; Patient Compliance; Pentanoic Acids; Random Allocation; Valerates

Topics: Aged; Benzazepines; Bradycardia; Clinical Trials as Topic; Coronary Disease; Digoxin; Diltiazem; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Placebos

Topics: Clinical Trials as Topic; Coronary Disease; Digitalis Glycosides; Digoxin; Heart Failure; Heart Rate; Hemodynamics; Humans; Hypertension; Long-Term Care; Myocardial Contraction; Substance Withdrawal Syndrome

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

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

In 10 patients with postoperative cardiac dysfunction which required dopamine for inotropic and hemodynamic support, we observed the cardiovascular effects of short-term digoxin administration. The average dosage of dopamine was 7.45 micrograms/kg per minute and was maintained while the patients were given 1 mg of digoxin over 8 hours. The dosage of dopamine was then tapered over the next 4 hours. We observed a significant increase in the cardiac index (4 hours) and a reduction in the heart rate (8 hours) before the dopamine dosage was reduced. After a reduction in dopamine dosage to 2.28 micrograms/kg per minute, these effects persisted. No significant changes were noted in systemic vascular resistance or pulmonary artery diastolic pressure during digoxin administration. These results indicate that the inotropic effects of dopamine and digoxin are additive when given in combination and that digoxin can be used to significantly reduce the dopamine dosage in patients with postoperative cardiac failure. Thus, the combination of an acute inotropic agent, dopamine, and a chronic inotropic agent, digoxin, appears to be clinically useful in postoperative cardiac dysfunction.

Topics: Cardiac Output; Cardiac Output, Low; Clinical Trials as Topic; Coronary Disease; Digoxin; Dopamine; Drug Therapy, Combination; Female; Heart Rate; Hemodynamics; Humans; Male; Middle Aged; Postoperative Care; Prospective Studies

Topics: Abdomen; Aged; Coronary Disease; Digoxin; Drug Evaluation; Echocardiography; Female; Hemodynamics; Humans; Male; Middle Aged; Premedication; Random Allocation

The effect of spironolactone on cardiac contractility indices was studied by externally recording systolic time intervals in four digitalized and four non-digitalized patients with ischaemic heart disease. A negative inotropic effect was found after spironolactone 100mg b.i.d. in all eight patients, as measured by an increase in pre-ejection period index PEPI (p less than 0.01), and the ratio between pre-ejection period and left ventricular ejection time PEP/LVET (p less than 0.001), while pre- and afterload remained constant. As expected, digoxin exerted a positive inotropic effect, as a decrease was observed in PEPI (p less than 0.01), and PEP/LVET (p less than 0.001). It was not possible to ascertain whether the observed effect was caused by a pharmacological interaction at receptor level between spironolactone and digoxin, or indirectly to changes in endogenous substances e.g. aldosterone. The results suggest that spironolactone may have unintended side effects in patients with severe heart failure and that its use be reevaluated.

Topics: Aged; Blood Pressure; Body Weight; Coronary Disease; Depression, Chemical; Digoxin; Drug Interactions; Humans; Middle Aged; Myocardial Contraction; Potassium; Spironolactone; Systole

Topics: Adolescent; Adult; Coronary Disease; Digoxin; Female; Heart Aneurysm; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Nitroglycerin; Propranolol; Radionuclide Imaging; Technetium; Theophylline; Verapamil

Topics: Clinical Trials as Topic; Coronary Disease; Digoxin; Double-Blind Method; Heart Failure; Heart Ventricles; Humans; Male; Middle Aged; Penbutolol; Propanolamines; Propranolol

The results of studying the clinical effect of the diuretic soldacton and its effect on a number of indices of water-electrolyte metabolism are discussed. The drug was used in 16 patients with IIB--III stage of circulatory insufficiency. It was found that soldacton possesses a moderate diuretic and natriuretic effect and produces a potassium-preserving effect. The drug is effective in various initial concentrations of plasma aldosterone which does not change significantly under its effect. Soldacton promotes improvement of tolerance to cardiac glycosides and diminishes the risk of the development of digitalis intoxication.

Topics: Adult; Aged; Aldosterone; Canrenoic Acid; Cardiovascular Diseases; Chronic Disease; Clinical Trials as Topic; Coronary Disease; Digoxin; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Pregnadienes; Pulmonary Heart Disease; Rheumatic Heart Disease; Water-Electrolyte Balance

Topics: Acute Disease; Clinical Trials as Topic; Coronary Disease; Digoxin; Drug Evaluation; Hemodynamics; Humans; Lanatosides; Mitral Valve Stenosis; Postoperative Period; Rheumatic Heart Disease; Strophanthins

The effect of nitroglycerin, digoxin and inderal on myocardial asynergy was studied in 108 patients with ischemic heart disease by means of echocardiography. The effect of nitroglycerin was studied in 32 patients; myocardial contractions were restored in the areas of asynergy in 15 patients, in 17 the character of myocardial asynergy did not change. The effect of digoxin was studied in 42 patients; intensification of myocardial contractions in the asynergic areas was noted in 18 patients in 16 the character of asynergy of the myocardium did not change, and in 8 paradoxical protrusion of the cardiac wall increased. Prescription of inderal for 34 patients did not lead to the development of additional areas of myocardial asynergy; proportionate decrease of the amplitude of the systolic myocardial movement in healthy areas and in areas with hypo-and dyskinesia was noted in such cases. The study showed changeability of the character of myocardial asynergy under the effect of the drugs investigated, which should be taken into account when these drugs are given to patients with ischemic heart disease.

Topics: Adult; Aged; Angina Pectoris; Clinical Trials as Topic; Coronary Disease; Digoxin; Drug Evaluation; Echocardiography; Female; Humans; Male; Middle Aged; Myocardial Contraction; Myocardial Infarction; Nitroglycerin; Propranolol

Topics: Adolescent; Adult; Blood Pressure; Cardiac Glycosides; Coronary Disease; Digoxin; Female; Heart Diseases; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Myocardial Contraction; Placebos; Pulmonary Artery; Time Factors

The effects of propranolol, digoxin and combination therapy (/D) on the resting and exercise ECG were studied in ten normal subjects and 20 patients with coronary artery disease (CAD) given a sequence of oral placebo, propranolol, P/D, digoxin and placebo, for two week periods. Digoxin produced a significant decrease in T-wave amplitude and often resulted in ST segment depression in the resting ECG. Propranolol, digoxin, and P/D tended to decrease the QTc interval and prolong the PR interval. However, CAD patients were more sensitive to PR prolongation than normals while receiving propranolol or digoxin alone. Propranolol therapy did not significantly affect the ST segment of the exercise ECG in the normal subjects or the CAD patients without an ischemic control exercise ECG. By contrast, 50 per cent of the normal subjects developed "false-positive" ischemic ST segment responses to exercise while receiving digoxin of P/D and three of eight CAD patients without ischemic control exercise ST segments had a similar response to digoxin or P/D. In 12 CAD patients with ischemic control exercise ST segments, propranolol did not affect the amount of ST segment depression at the onset of angina or the maximum amount of ST segment depression. Digoxin or P/D both uniformly increased the maximum amount of ST segment depression which was greater with digoxin than P/D. However, the maximum heart rate on P/D was significantly reduced as compared to that on digoxin. It is concluded that (1) CAD patients are more sensitive to propranolol or digoxin-induced AV block than normals, (2) propranolol does not change the magnitude of ischemic exercise ST segment depression, (3) digoxin increases ischemic exercise ST segment depression and results in a high incidence of false-positive exercise tests, and (4) the addition of propranolol to digoxin attenuates the effects of digoxin on the exercise ST segment.

Topics: Administration, Oral; Adult; Clinical Trials as Topic; Coronary Disease; Digoxin; Drug Therapy, Combination; Electrocardiography; Exercise Test; False Positive Reactions; Female; Heart Block; Humans; Male; Middle Aged; Placebos; Propranolol; Rest

Segontin-Digoxin and digoxin were tested in a cross-over double blind trial in 30 patients with coronary heart disease and concomitant organic insufficiency in a cardiological specialist practice. As far as the coronary symptoms were concerned, treatment with Segontin-Digoxin was clearly superior to digoxin therapy alone. With regard to the elimination or improvement of signs of myocardial insufficiency, no difference could be established between the two preparations. A distinct lowering of heart rate and blood pressure, especially in hypertensives, was observed with Segontin-Digoxin therapy compared with digoxin alone.

Topics: Adult; Aged; Clinical Trials as Topic; Coronary Disease; Digoxin; Drug Combinations; Drug Tolerance; Female; Humans; Male; Middle Aged; Prenylamine

Segontin-Digoxin and digoxin were tested in a cross-over double blind trial in 30 patients with coronary heart disease and concomitant organic insufficiency in a cardiological specialist practice. As far as the coronary symptoms were concerned, treatment with Segontin-Digoxin was clearly superior to digoxin therapy alone. With regard to the elimination or improvement of signs of myocardial insufficiency, no difference could be established between the two preparations. A distinct lowering of heart rate and blood pressure, especially in hypertensives, was observed with Segontin-Digoxin therapy compared with digoxin alone.

Topics: Adult; Aged; Blood Pressure; Clinical Trials as Topic; Coronary Disease; Digoxin; Drug Combinations; Drug Evaluation; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Placebos; Prenylamine; Tranquilizing Agents

Topics: Administration, Oral; Adult; Aged; Chromonar; Clinical Trials as Topic; Coronary Disease; Coumarins; Digoxin; Drug Combinations; Drug Evaluation; Female; Humans; Injections, Intravenous; Male; Middle Aged

Topics: Azepines; Clinical Trials as Topic; Coronary Disease; Digoxin; Dilazep; Drug Combinations; Heart Failure; Humans

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

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

The additive natriuretic effect of a single dose of bendroflumethiazide, 5 mg., has been studied in patients with advanced congestive heart failure in long-term treatment with bumetanide, 4 mg., daily. Three permutation trial tests were performed including six patients each. In the first trial, the response to supplementary bendroflumethiazide, 5 mg., was definitely superior to that of additional bumetanide, 4 mg., in terms of renal output of sodium, chloride, potassium, water, and osmolar clearance. In the second trial, a similar pattern was found in patients receiving a combination of bumetanide, 4 mg., and spironolactone, 100 mg., daily. The third trial compared the effects of bendroflumethiazide, 5 mg., plus bumetanide, 4 mg.; of bendroflumethiazide, 5 mg.; and of bumetanide, 4 mg. In terms of natriuresis and chloruresis, the response to the combination of two drugs was significantly larger than the sum of the effects of other treatments. It is concluded that the combined effects of the drugs represent a supra-additive effect addition for sodium and chloride. A tentative explanation of the mechanism of interaction in terms of inhibition of renal tubular supplementary spironolactone, involve a tendency to development of hypokalemia, hypochloremia, and alkalosis, it is recommended that supplementary use of bendroflumethiazide in this setting is combined with the administration of potassium chloride or potassium-saving diuretics.

Topics: Adult; Bendroflumethiazide; Benzoates; Butylamines; Chlorides; Clinical Trials as Topic; Coronary Disease; Creatine; Digoxin; Diuretics; Drug Synergism; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Natriuresis; Nephrons; Placebos; Potassium; Potassium Chloride; Sodium; Spironolactone; Sulfonamides

Topics: Azepines; Benzoates; Bilirubin; Blood Glucose; Blood Pressure; Blood Sedimentation; Cholesterol; Coronary Circulation; Coronary Disease; Digoxin; Drug Combinations; Drug Evaluation; Drug Tolerance; Heart Rate; Humans; L-Lactate Dehydrogenase; Transaminases; Vasodilator Agents

Topics: Azepines; Benzoates; Clinical Trials as Topic; Coronary Disease; Digoxin; Drug Combinations; Drug Evaluation; Humans; Male; Middle Aged; Vasodilator Agents

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

Topics: Coronary Disease; Digoxin; Electrocardiography; Humans; Hypoxia; Ouabain

Topics: Adult; Aged; Angina Pectoris; Blood Pressure; Clinical Trials as Topic; Coronary Disease; Digoxin; Electrocardiography; Female; Heart Rate; Humans; Hypertension; Hypnotics and Sedatives; Injections, Intravenous; Male; Middle Aged; Myocardial Infarction; Placebos; Respiration; Vasodilator Agents

Topics: Clinical Trials as Topic; Coronary Disease; Digitoxin; Digoxin; Electrocardiography; Heart Diseases; Heart Failure; Heart Valve Diseases; Humans; Strophanthins

Topics: Aged; Clinical Trials as Topic; Coronary Disease; Digoxin; Female; Heart Diseases; Humans; Hypertension; Male; Pulmonary Heart Disease; Rheumatic Heart Disease; Tachycardia, Paroxysmal

Topics: Adult; Aged; Animals; Cats; Coronary Disease; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Rats

Topics: Adult; Aged; Clinical Trials as Topic; Coronary Disease; Digoxin; Humans; Middle Aged; Vasodilator Agents

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

Topics: Acute Disease; Aged; Anti-Arrhythmia Agents; Blood Pressure; Cardiac Surgical Procedures; Coronary Angiography; Coronary Disease; Digoxin; Electrocardiography; Female; Hospital Mortality; Humans; Incidence; Male; Middle Aged; Patient Admission; Platelet Glycoprotein GPIIb-IIIa Complex; Prospective Studies; Sex Factors; Stroke Volume; Syndrome; Thrombolytic Therapy; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left

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

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

In patients taking digoxin, the exercise electrocardiogram has a lower specificity for detecting coronary artery disease. However, the effect of digoxin on adenosine-induced ST-segment depression is unknown. The purpose of this study was to evaluate the specificity of the electrocardiogram during adenosine myocardial perfusion imaging in patients taking digoxin.. Between May 1991 and September 1997, patients (n = 99) taking digoxin who underwent adenosine stress imaging with thallium-201 or technetium-99m sestamibi and coronary angiography within 3 months were retrospectively identified. Exclusion criteria included prior myocardial infarction, coronary artery angioplasty or bypass surgery, left bundle branch block, paced ventricular rhythm, or significant valvular disease. Twelve-lead electrocardiograms were visually interpreted at baseline, during adenosine infusion, and during the recovery period. The stress electrocardiogram was considered positive if there was > or =1 mm additional horizontal or downsloping ST-segment depression or elevation 0.08 seconds after the J-point compared with the baseline tracing.. ST-segment depression and/or elevation occurred in 24 of 99 patients. There were only 2 false-positive stress electrocardiograms, yielding a specificity of 87% and positive predictive value of 92%. All 8 patients with > or =2 mm ST segment depression had multivessel disease by coronary angiography.. ST-segment depression or elevation during adenosine myocardial perfusion imaging in patients taking digoxin is highly specific for coronary artery disease. Marked (> or =2 mm) ST-segment depression and/or ST-segment elevation is associated with a high likelihood of multivessel disease.

Topics: Adenosine; Aged; Atrial Fibrillation; Cardiotonic Agents; Coronary Disease; Diagnosis, Differential; Digoxin; Electrocardiography, Ambulatory; Exercise Test; Female; Heart Failure; Humans; Infusions, Intravenous; Male; Radionuclide Ventriculography; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Severity of Illness Index; Vasodilator Agents

We conducted this study to evaluate whether there is an association between preoperative drug therapy and in-hospital mortality in patients undergoing coronary artery graft surgery. We collected data on 1593 consecutive patients undergoing coronary artery surgery. The relative risk of in-hospital mortality was determined by logistic regression with in-hospital mortality as the dependent variable, and independent variables that included known risk factors and preoperative cardioactive or antithrombotic drug treatment, i.e., age; left ventricular function; left main coronary artery disease; urgent priority; gender; previous cardiac surgery; concurrent cardiovascular surgery; chronic lung disease; creatinine concentration; hemoglobin concentration; diabetes; hypertension; cerebrovascular disease; recent myocardial infarction; prior vascular surgery; number of arteries bypassed; and regular daily treatment with beta-blockers, aspirin within 5 days, calcium antagonists, angiotensin converting enzyme (ACE) inhibitors, digoxin, or warfarin. In-hospital mortality was 3.3%. The relative risk of in-hospital mortality (with 95% confidence intervals of the relative risk) associated with the following drug treatments was: nitrates 3.8 (1.5-9.6), beta-blockers 0.4 (0.2-0.8), aspirin within 5 days 1.0 (0.5-1.9), calcium antagonists 1.1 (0.6-2.1), ACE inhibitors 0.8 (0.4-1.5), digoxin 0.7 (0.2-1.8), and warfarin 0.3 (0.1-1.6). We conclude that in-hospital mortality is positively associated with preoperative nitrate therapy and negatively associated with beta-adrenergic blocker therapy. A significant association between in-hospital mortality and the preoperative use of calcium antagonists, ACE inhibitors, aspirin, digoxin, and warfarin was not confirmed.. We examined the association between common drug treatments for ischemic heart disease and short-term survival after cardiac surgery using a statistical method to adjust for patients' preoperative medical condition. Death after surgery was more likely after nitrate therapy and less likely after beta-blocker therapy.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Aspirin; Cardiotonic Agents; Cerebrovascular Disorders; Chronic Disease; Coronary Artery Bypass; Coronary Disease; Creatinine; Diabetes Complications; Digoxin; Female; Fibrinolytic Agents; Forecasting; Hemoglobins; Hospital Mortality; Humans; Hypertension; Logistic Models; Lung Diseases; Male; Middle Aged; Myocardial Infarction; Nitrates; Reoperation; Risk Factors; Sex Factors; Survival Rate; Ventricular Function, Left; Warfarin

This study was undertaken to identify gene(s) that may be associated with improved clinical outcome in patients with congestive heart failure (CHF). The adenosine monophosphate deaminase locus (AMPD1) was selected for study. We hypothesized that inheritance of the mutant AMPD1 allele is associated with increased probability of survival without cardiac transplantation in patients with CHF.. AMPD1 genotype was determined in 132 patients with advanced CHF and 91 control reference subjects by use of a polymerase chain reaction-based, allele-specific oligonucleotide detection assay. In patients with CHF, those heterozygous (n=20) or homozygous (n=1) for the mutant AMPD1 allele (AMPD1 +/- or -/-, respectively) experienced a significantly longer duration of heart failure symptoms before referral for transplantation evaluation than CHF patients homozygous for the wild-type allele (AMPD1 +/+; n=111; 7.6+/-6.5 versus 3.2+/-3.6 years; P<0.001). The OR of surviving without cardiac transplantation >/=5 years after initial hospitalization for CHF symptoms was 8.6 times greater (95% CI: 3.05, 23.87) in those patients carrying >/=1 mutant AMPD1 allele than in those carrying 2 wild-type AMPD1 +/+ alleles.. After the onset of CHF symptoms, the mutant AMPD1 allele is associated with prolonged probability of survival without cardiac transplantation. The mechanism by which the presence of the mutant AMPD1 allele may modify the clinical phenotype of heart failure remains to be determined.

Topics: Adenosine Monophosphate; Aged; Alleles; AMP Deaminase; Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathy, Dilated; Coronary Disease; Digoxin; Disease Progression; Diuretics; DNA Mutational Analysis; Energy Metabolism; Female; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Genotype; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardium; Oxygen Consumption; Phenotype; Proportional Hazards Models; Survival Analysis; Treatment Outcome

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Cardiomyopathy, Dilated; Cardiotonic Agents; Coronary Disease; Digoxin; Diuretics; Heart Defects, Congenital; Heart Failure; Hemodynamics; Humans; Hypertension; Myocardial Ischemia; Phosphodiesterase Inhibitors; Vasodilator Agents

We evaluated the clinical value of a new index combining deltaST/delta heart rate (HR) index and ST/HR slope for diagnosing coronary artery disease (CAD) in patients on digoxin therapy. Exercise treadmill tests were performed by 72 patients on digoxin therapy. Simple HR-adjusted indexes of ST-segment depression during exercise (deltaST/deltaHR index) and the decline calculated from the final 12 data points relating ST-segment depression to HR (ST/HR slope) were determined. A new index was obtained by subtracting the deltaST/deltaHR index from the ST/HR slope. On thallium scintigraphy, 37 of the 72 patients showed reversible perfusion defects related to the diseased coronary artery. The new index derived from this ST-HR relation was 4.1 +/- 3.6 microV/beats/min in the ischemic group and 1.3 +/- 1.0 microV/beats/min in the group of patients without ischemia (p <0.0001). An ST-HR relation > or = 1.5 was found in 33 of the 37 patients in the ischemic group, and in 7 of the 35 patients without ischemia (p <0.0001). The sensitivity of this criterion for prediction of myocardial ischemia was 89%, the specificity was 80%, and the predictive accuracy was 85%. Thus, this new ST-HR index is useful for detecting CAD in patients on digoxin therapy.

Topics: Aged; Anti-Arrhythmia Agents; Coronary Angiography; Coronary Disease; Digoxin; Electrocardiography; Exercise Test; Female; Heart Conduction System; Humans; Male; Middle Aged; Sensitivity and Specificity

Fluorescence polarization immunoassay was used to study the chronopharmacokinetics of digoxin in 10 patients with congestive heart failure (CHF) who also served as self-controls. Our results showed that the serum digoxin concentration reached peak value 1 h after taking digoxin at 7:00 a.m., but the serum digoxin concentration reached the peak value 2 h after taking digoxin at 4:00 p.m. The average serum digoxin concentration area under curve was greater and the best maintainable time of serum concentration within 24 h after taking digoxin at 4 p.m. longer than those at 7:00 a.m. The heart rates were obviously lower and the cardiac function was significantly improved in 4:00 p.m. group.

Topics: Adult; Aged; Chronotherapy; Coronary Disease; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Rheumatic Heart Disease

The presence of a higher concentration of digoxin-like immunoreactive substances (DLIS) in human serum have been reported in a number of pathophysiological conditions. DLIS can react with anti-digoxin antibodies when determination of serum digoxin was performed with immunoassay. It may falsely elevate the serum digoxin concentration and is troublesome in the therapeutic monitoring of digoxin. The apparent digoxin concentrations (DLIS) in serum were determined in 15 elder patients with cardiac insufficiency by fluorescence polarization immunoassay (FPIA). The lowest measurable concentration, defined as the concentration that could be distinguished from zero with 95% confidence, was 0.256 nmol.L-1. Steroids and drugs commonly administered with digoxin showed no significant cross-reactivity. In these patients, the positive ratio for determination of DLIS was 46.7% (7 in 15 cases), and its mean serum concentration was 0.55 +/- 0.44 nmol.L-1 (range 0.26-1.52 nmol.L-1). The results were well consistent with that obtained by Dasgupta et al. In conclusion, there are certain increased concentrations of DLIS in the sera of elder patients with cardiac insufficiency, suggesting that digoxin levels measured by immunoassay method must be interpreted carefully in these patients after treatment with digoxin or other digitalis preparations.

Topics: Aged; Aged, 80 and over; Cardenolides; Coronary Disease; Digoxin; Female; Fluorescence Polarization Immunoassay; Humans; Hypertension; Male; Middle Aged; Saponins

This prospective hospital-based, case-control study compares the outcome of unstable angina in non-insulin dependent diabetic patients and non-diabetic control subjects. One hundred and sixty-two diabetic patients and 162 non-diabetic control patients with unstable angina were entered into the study. The 3-month mortality was 8.6% (95% confidence interval, CI = 4.4-12.9%) in diabetic patients and 2.5% (CI = 0.1-4.9%) in control patients (p = 0.014). The 1-year mortality was 16.7% (CI = 10.9%-22.4%) in diabetic patients and 8.6% (CI = 4.4%-12.9%) in non-diabetic patients (p = 0.029). Diabetic patients received beta-blockade and underwent coronary angiography and angioplasty less frequently than controls; the frequency of unstable angina, of acute myocardial infarction, and coronary artery bypass grafting was similar in both groups at 1 year of follow-up. It is concluded that diabetic patients with unstable angina have a higher mortality than non-diabetic patients and that this difference is largely accounted for by early (first 3 months) mortality.

Topics: Adrenergic beta-Antagonists; Aged; Angina, Unstable; Angioplasty; Aspirin; Calcium Channel Blockers; Case-Control Studies; Confidence Intervals; Coronary Angiography; Coronary Artery Bypass; Coronary Disease; Diabetic Angiopathies; Digoxin; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Nitrates; Prospective Studies; Risk Factors; Time Factors

Review of the literature suggests that misdiagnosis of terminal illness is infrequent. In the first 6 months of the recently established Edmonton Regional Palliative Care Program, two of 330 referrals proved to be in the category of erroneous diagnosis of terminal disease. These two cases are reported, along with discussion of aspects of the time-honored usefulness of careful history and physical examination. This experience highlights the importance of assessment, investigation, and aggressive therapy, even in "terminal" patients, including those in the geriatric population.

Topics: Acute Kidney Injury; Adaptation, Psychological; Aged; Aged, 80 and over; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents, Tricyclic; Chest Pain; Coronary Disease; Depression; Diagnosis, Differential; Diagnostic Errors; Digoxin; Female; Geriatrics; Grief; Humans; Morphine; Neoplasms; Nortriptyline; Palliative Care; Stomach Ulcer; Terminally Ill; Weight Loss

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

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

To establish a method for the determination of free digoxin in serum for clinical use and to study the relationship between the free and total digoxin concentrations in chronic cardiac insufficiency patients receiving digoxin with different renal function.. The ultrafiltration with fluorescence polarization immunoassay was used to determine the concentration of free digoxin.. The concentrations of digoxin standards in serum were 0.96, 1.92, and 3.84 nmol.L-1. The relative standard deviation was < 7% for intra-day and < 6% for inter-day determinations. The average recovery was 99.95 +/- 2.18%. The ratio of free/total digoxin in chronic cardiac insufficiency patients with renal dysfunction was lower than that in patients with normal kidneys (63.5 +/- 4.7% vs 75.1 +/- 3.9%, P < 0.01).. The present method is simple and reliable. In these patients there is an over-measurement for total digoxin concentration, suggesting the presence of elevated endogenous digoxin-like immunoreactive substances.

Topics: Aged; Aged, 80 and over; Coronary Disease; Digoxin; Heart Failure; Humans; Male; Middle Aged; Renal Insufficiency

Topics: Adenosine; Aged; Atrial Fibrillation; Coronary Disease; Diagnosis, Differential; Digoxin; Electrocardiography; Humans; Male; Postoperative Complications; Tachycardia; Verapamil

To determine the relation between urinary digoxin-like immunoreactive substance (DLIS) and cardiac performance.. Cohort study.. Echocardiography laboratory of a university-affiliated teaching hospital.. Thirty-four individuals referred for echocardiographic studies who had never received cardiac glycosides or other substances known to cross-react with a digoxin radioimmunoassay and had no condition that has been associated with increased DLIS.. Cardiac dimensions and indices of cardiac performance derived from echocardiograms and cardiac Doppler flow studies and concentrations of urinary DLIS, creatinine, and electrolytes.. Urinary DLIS ranged from < 0.125 ng (digoxin equivalents) per milliliter (below the sensitivity of the assay) to 0.99 ng/ml, averaging 0.22 +/- 0.24 ng/ml. On bivariate analyses, UDLIS was found to correlate significantly with body weight, left ventricular (LV) end-diastolic dimension, LV fractional shortening, mitral transvalvular flow velocity following atrial systole, and urinary calcium. On multivariate analyses, the association between urinary DLIS (alone or adjusted for urinary creatinine) and LV fractional shortening emerged as the paramount independent relation.. Urinary DLIS can be related to cardiac performance under steady-state conditions. This suggests that DLIS may be a ligand for a cardiac glycoside receptor.

Topics: Adult; Blood Proteins; Cardenolides; Coronary Disease; Creatinine; Digoxin; Echocardiography, Doppler; Female; Heart; Humans; Male; Middle Aged; Multivariate Analysis; Radioimmunoassay; Regression Analysis; Saponins

This study tested the hypothesis that discriminant function analysis of clinical and exercise-test variables including computerized ST measurements could improve the prediction of severe coronary artery disease. Secondary objectives were to demonstrate the effect of digoxin and/or resting electrocardiographic (ECG) abnormalities, and to evaluate the relative importance of ST measurements made during the recovery phase and in the three lead group areas. The design was a retrospective analysis of data collected during exercise testing and coronary angiography. The ECG data were gathered and stored in digital format on optical discs and all ST measurements were made off-line using the authors' own software. Univariate and multivariate analytic methods were used to analyze all pretest characteristics as well as hemodynamic and computerized ECG responses to exercise. A 1,000-bed Veterans Affairs Medical Center served as the setting. The study included 446 male veterans who underwent a sign or symptom limited treadmill exercise test and coronary angiography. Analysis was also performed on a subset of this population formed by excluding patients receiving digoxin or with resting ECGs exhibiting left ventricular hypertrophy or ST depression (n = 328). In the total study population, the authors derived a treadmill score using discriminant function analysis. This score included: (1) the time-slope area in lead V5 during recovery; (2) delta heart rate; (3) angina pectoris during the exercise test; and (4) presence of diagnostic Q waves on the resting ECG. This score was effective in predicting triple vessel/left main disease and outperformed exercise-induced ST depression for predicting severe coronary artery disease. After exclusion of patients with ECGs exhibiting left ventricular hypertrophy or resting ST depression and patients receiving digoxin, discriminant function analysis chose: (1) the time-slope area in lead V5 during recovery and (2) delta heart rate. Exclusion of these patients resulted in a nonsignificant decrease in specificity of all ST criteria. ST-segment amplitude or slope in lead V5 at 3.5 minutes in recovery clearly outperformed the maximal exercise measurements in both groups. Summing the depressions or selecting the most depression in the three areas (ie, lateral-V5, inferior-II, anterior-V2) did not improve test performance. Leads other than V5 did not contain significant diagnostic information. A quantitative approach to exercise testing usi

Topics: Adult; Aged; Confounding Factors, Epidemiologic; Coronary Angiography; Coronary Disease; Digoxin; Discriminant Analysis; Electrocardiography; Exercise Test; Humans; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; ROC Curve; Signal Processing, Computer-Assisted

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

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

Topics: Coronary Disease; Diagnosis, Differential; Digoxin; Electrocardiography, Ambulatory; Humans

In 9 patients with atrial fibrillation the effect of zero, low and high levels of serum digoxin on exercise-induced hyperkalemia was assessed by bicycle exercise tests. Exercise at each level of serum digoxin was associated with a significant (up to 20%) rise in plasma potassium. At a work load of 75 W the highest level of serum digoxin was associated with a significantly higher maximum plasma potassium concentration as compared to the maximum valueatazero serum digoxin. The enhancement of exercise-induced hyperkalemia may add to the arrhythmogenic effect of digitalis.

Topics: Adult; Aged; Atrial Fibrillation; Coronary Disease; Digoxin; Exercise Test; Humans; Hyperkalemia; Male; Middle Aged; Potassium

This study was undertaken to assess the potential effects of drugs commonly used in the cardiac care unit (CCU) as well as other pharmacological interventions on the biodistribution of 99mTc-hexakis-2-methoxy-2-methylpropyl isonitrile, 99mTc-Sestamibi. 99mTc-Sestamibi was administered i.v. into pentobarbital anesthetized guinea pigs pretreated with either saline (control), verapamil (0.1 mg/kg), digoxin (0.2 mg/kg), propranalol (1 mg/kg), dipyridamole (1.2 mg/kg). The results showed that none of the above interventions decreased the myocardial biodistribution of 99mTc-Sestamibi. On the other hand, digoxin, propranalol and dipyridamole produced an increase in the myocardial uptake of 99mTc-Sestamibi. Furthermore, pretreatment with the ligand which is being used in the formulation of the kit, copper tetrakis-2-methoxy-2-methylpropyl isonitrile (Cu[MIBI]4) at doses ranging from 0.1 to 2.5 mg/kg did not interfere with the biodistribution of 99mTc-Sestamibi in guinea pig. An additional study was carried out in swine to determine the effect of dipyridamole (0.4 mg/kg) on the regional myocardial distribution of 99mTc-Sestamibi in relation to regional myocardial blood flow (microspheres-determined). This study clearly documented a direct relationship between regional myocardial blood flow and the myocardial distribution of 99mTc-Sestamibi (i.e. for each increase or decrease in blood flow there is a parallel increase or decrease in myocardial 99mTc-Sestamibi distribution). These studies indicated that any of the above drugs could be used in the CCU while imaging with 99mTc-Sestamibi.

Topics: Animals; Coronary Care Units; Coronary Disease; Digoxin; Dipyridamole; Drug Interactions; Guinea Pigs; Heart; Male; Myocardium; Organotechnetium Compounds; Swine; Swine, Miniature; Technetium Tc 99m Sestamibi; Verapamil

Heart rate and serum digoxin concentration in eight patients with atrial fibrillation were studied at rest and during exercise when initial serum digoxin concentrations were zero and at low and high therapeutic values. Eight patients with ischemic heart disease and in sinus rhythm were studied for comparison. Though the serum digoxin concentration decreased significantly during exercise, the absolute reduction in heart rate was the same at rest and during exercise in patients with atrial fibrillation. Compared with the control patients in sinus rhythm, the heart rate in patients with atrial fibrillation was not adequately controlled during exercise by any serum digoxin concentration tested despite a reduction in heart rate with increasing digoxin concentration. The effects of digoxin on heart rate regulation in atrial fibrillation are complex and include direct effects on the myocardium as well as indirect effects mediated by modulation of the autonomic nervous system; the present results indicate that the drug is not displaced from the target organs by decreasing serum concentrations during exercise. In atrial fibrillation, because the demands on the filter function of the atrioventricular node are highly unphysiological, the effect of digoxin on heart rate during exercise is not adequate.

Topics: Adult; Atrial Fibrillation; Coronary Disease; Digoxin; Heart Rate; Humans; Male; Middle Aged; Physical Exertion

1. In 24 patients who were undergoing coronary arteriography for the assessment of ischaemic heart disease, the relationship between the systemic and coronary vascular responses to acute intravenous digoxin administration (500 micrograms) and concurrent drug therapy with the calcium antagonist verapamil (group I) or a beta-adrenoceptor antagonist (group II) or neither of these agents (group III) was examined. 2. Systemic vascular resistance (SVR) tended to rise rapidly after digoxin injection in patients in groups II and III, and tended to decline initially in patients in group I; however, these differences were not statistically significant (variance ratio [VR] = 0.77). 3. No significant differences were observed in coronary vascular responses to acute digoxin administration between the three groups of patients (VR = 0.34). 4. For the entire group of 24 patients, no statistically significant digoxin-induced effects on resistance could be demonstrated in either the systemic or coronary circulations, although in individual patients vasoconstrictor effects were observed. 5. We conclude that acute intravenous administration of digoxin does not consistently cause systemic or coronary vasoconstriction in patients with ischaemic heart disease. Variability in vasomotor responses to digoxin is not clearly related to concurrent drug therapy with verapamil or a beta-adrenoceptor antagonist. The observation that systemic vascular resistance tends to increase in the first few minutes after digoxin injection should be addressed in future studies.

Topics: Adrenergic beta-Antagonists; Adult; Cardiac Catheterization; Coronary Disease; Coronary Vessels; Digoxin; Drug Therapy, Combination; Female; Hemodynamics; Humans; Male; Middle Aged; Vascular Resistance; Verapamil

Although exercise-induced ST segment depression is thought to be unreliable marker of myocardial ischemia in the presence of resting electrocardiographic changes, this conclusion is based on limited and disparate data from studies often lacking acceptable measures of ischemia. To determine the diagnostic accuracy of the ST segment response in a blinded prospective protocol, we compared ST deviation to thallium201 SPECT scintigraphy in 95 patients during exercise. Diagnostic accuracy was poor in the 95 patients with resting abnormalities: left bundle branch block (LBBB) = 70%, complete right bundle branch block (cRBBB) = 75%, incomplete right bundle branch block (incRBBB) = 79%, intraventricular conduction delay (IVCD) = 44%, left ventricular hypertrophy (LVH) = 59%, digitalis = 53%, compared with a diagnostic accuracy of 90% in 29 patients without resting changes. There were 20 false negative and 17 false positive ST segment responses. The extent and direction of resting ST deviation varied substantially and had no influence on diagnostic accuracy. The extent of change in ST deviation with exercise required for a positive response did not alter diagnostic accuracy: -1.0 mm = 61%, -1.5 mm = 63%, and -2.0 = 61%. While the location of regional ischemia did not influence the accuracy of ST segment analysis, a QRS duration less than 120 msec did improve diagnostic accuracy. Our data confirm that ST segment analysis with exercise testing is not reliable in patients with resting electrocardiographic abnormalities and demonstrates that accuracy is not improved by adjusting for either resting or exercise-induced ST segment changes or for location of the ischemic region.

Topics: Aged; Angiography; Bundle-Branch Block; Cardiomegaly; Coronary Angiography; Coronary Disease; Digoxin; Electrocardiography; Exercise Test; Female; Heart; Humans; Male; Middle Aged; Prognosis; Prospective Studies; Rest; Tomography, Emission-Computed, Single-Photon

Determination of serum endogenous digitalis-like factor (EDF) concentration was carried out in 52 patients with chronic congestive heart failure with radioimmunoassay. The results showed that concentration of serum EDF in patients with chronic congestive heart failure was significantly lower than that in normal subjects (P less than 0.001). The lowering of serum EDF concentration was significantly negatively correlated with the severity of heart failure, r = 0.6475, P less than 0.001. Age had no significant effect on serum EDF concentration (P greater than 0.05). Serum EDF concentration rose after the heart failure was treated, but was still lower than that in normal subjects (P less than 0.01). Serum EDF concentration in patients with coronary heart disease was the lowest and in patients with hypertension the highest.

Topics: Adult; Aged; Aged, 80 and over; Blood Proteins; Cardenolides; Coronary Disease; Digoxin; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Radioimmunoassay; Rheumatic Heart Disease; Saponins; Sodium-Potassium-Exchanging ATPase

Acute myocardial uptake of digoxin was measured at a constant paced heart rate (75 beats/min) for 30 min after an intravenous bolus injection of 500 micrograms of digoxin in 14 patients with ischemic heart disease. Myocardial digoxin content, determined by serial measurement of aortocoronary sinus digoxin concentration gradients and coronary sinus blood flow, was expressed relative to coronary sinus blood flow at rest and correlated with simultaneous hemodynamic and electrocardiographic changes. Myocardial digoxin uptake was extensive (4.1 +/- 0.7% of total injected dose at 30 min) and prolonged, with rapid initial uptake (75.3 +/- 6.6% of maximum at 3 min), followed by a variable phase of slower accumulation. Peak left ventricular positive first derivative of left ventricular pressure (dP/dt) increased progressively (p less than 0.01), with a similar time course to that of myocardial digoxin accumulation; maximal change was 18.5 +/- 4.7% at 27 min. The ratio of inotropic effect to myocardial digoxin content did not vary significantly over the period of the experiment. However, peak inotropic effects in individual patients were not significantly related to peak myocardial digoxin content. The spontaneous PR interval increased transiently, with a peak increase of 5.9 +/- 1.8% (p less than 0.05) 12 min after digoxin administration. It is concluded that after intravenous bolus administration, 1) peak effects of digoxin on atrioventricular (AV) conduction occur early, whereas positive inotropic effects increase progressively for greater than or equal to 27 min; and 2) digoxin accumulation in the human myocardium is prolonged and is a determinant of inotropic effects, but not of prolongation of AV node conduction.

Topics: Aged; Coronary Disease; Digoxin; Electrocardiography; Female; Heart Conduction System; Hemodynamics; Humans; Injections, Intravenous; Male; Middle Aged; Myocardium

The effect of empiric antiarrhythmic therapy with quinidine and procainamide on long-term mortality was examined in 209 patients with coronary artery disease resuscitated after out-of-hospital cardiac arrest. The antiarrhythmic agent used was determined by the patient's private physician without knowledge of the study ambulatory electrocardiogram. Of the 209 patients, procainamide was prescribed in 45 (22%), quinidine in 48 (23%) and no antiarrhythmic therapy in 116 (55%). Digoxin therapy was initiated in 101 patients. The 2-year total survival rate for the quinidine, procainamide and nontreated patients was 61, 57 and 71% (p less than 0.05), and for sudden death was 69, 69 and 89% (p less than 0.01), respectively. These observations suggest that empiric antiarrhythmic therapy in survivors of out-of-hospital cardiac arrest did not affect total mortality and was associated with an increased frequency of sudden death.

Topics: Aged; Anti-Arrhythmia Agents; Coronary Disease; Death, Sudden; Digoxin; Heart Arrest; Humans; Middle Aged; Procainamide; Quinidine; Resuscitation; Retrospective Studies

Topics: Animals; Anti-Arrhythmia Agents; Antibodies; Coronary Disease; Digoxin; Erythrocytes; In Vitro Techniques; Male; Rats; Rats, Inbred Strains; Sodium-Potassium-Exchanging ATPase

A treatment-related coronary arteriopathy has been observed in the dog following the oral or intravenous administration of 4 potent phosphodiesterase type III inhibiting inodilators at high multiples of their ED50 for periods from 1 day to 6 months. A fifth compound of a similar pharmacological class exhibited limiting toxicity at low multiples of its ED50 and this compound failed to induce coronary arterial lesions. The earliest treatment-related findings observed were medial hemorrhage and necrosis with focal breaks in the internal elastic lamina. Later changes, observed from day 9 onwards, included intimal thickening consisting of smooth muscle proliferation with a mucoid ground substance, variable and inconsistent inflammatory changes involving one or more arterial tunics and adventitial hemorrhage, fibrosis and neovascularization. The changes were restricted to the coronary arteries including the extramural and intramural branches. The distribution of lesions varied from widespread, multifocal involvement of both coronary arterial systems to focal lesions with no obvious site of predilection. Induction of this lesion may involve changes in coronary flow and pressure as a result of an exaggerated pharmacological response to this class of compound. The susceptibility of other species (rat, cynomolgus monkey, or pig) to this effect has been investigated with no treatment-related arteriopathy being observed.

Topics: Aminophylline; Animals; Coronary Disease; Coronary Vessels; Digoxin; Dogs; Electrocardiography; Female; Guanidines; Male; Myocardium; Phosphodiesterase Inhibitors; Pyrazines; Pyridazines; Pyridines

This study examines the relation between the change in clinical status and the change in plasma norepinephrine concentration in patients with congestive heart failure (CHF) receiving standard medical therapy. Hemodynamic measurements in 11 patients with CHF (ejection fraction 19 +/- 4%) were obtained before and immediately after the administration of digoxin and angiotensin-converting enzyme inhibitors. Patients were then followed for 1 year. Clinical status was determined using the Boston Clinical Heart Failure scoring system. Of the 11 patients, 6 demonstrated significant clinical improvement after therapy, based on the Boston score, over a 1-year period. Five patients did not respond to therapy: 4 died and the remaining patient had worsening CHF. There was no difference between responders and nonresponders in either baseline hemodynamics or acute response to the administration of digoxin and an angiotensin-converting enzyme inhibitor. In the patients who improved, plasma norepinephrine decreased from 706 +/- 235 to 545 +/- 223 pg/ml (p = 0.08) after 1 year of medical therapy. In patients whose CHF worsened or who died, plasma norepinephrine increased from 715 +/- 275 at baseline to 1,237 +/- 671 pg/ml at their last measurement (p = 0.06). Although at baseline the plasma norepinephrine levels were similar in both groups of patients, a significant difference between responders and nonresponders was observed at final follow-up (p less than 0.002). Change in plasma norepinephrine correlated with change in CHF score (r = 0.79, p less than 0.004). Thus, in patients with CHF, serial measurements of plasma norepinephrine correlate with changes in clinical status.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathy, Dilated; Coronary Disease; Digoxin; Diuretics; Drug Therapy, Combination; Heart Failure; Humans; Male; Norepinephrine; Prognosis; Stroke Volume

Topics: Adult; Aged; Ambulatory Care; Coronary Disease; Digoxin; Exercise Test; Female; Hemodynamics; Humans; Male; Middle Aged; Pacemaker, Artificial; Physical Exertion; Time Factors

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

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

It has been postulated that one or more plasma digitalis-like compounds may play an important role in body fluid regulation and in essential hypertension, although very little is known about their possible role in general haemodynamics. We therefore measured plasma inhibition of human kidney Na+,K+-ATPase and plasma cross-reactivity with digoxin antibodies in 11 normotensive cardiopathic subjects admitted to our clinic for heart catheterization. Possible correlations with haemodynamic parameters were studied. Plasma digoxin-like activity correlated directly with left atrial pressure and with pulmonary circulation data. The ability of the plasma to inhibit Na+,K+-ATPase showed an inverse correlation with cardiac output and cardiac index. No correlations were found with any of the other parameters measured, notably systemic resistance, blood pressure and natriuresis. These findings suggest the presence of more than one substance sharing chemical properties with digitalis: (1) a substance cross-reacting with digoxin antibodies and dependent on pulmonary vascular congestion; and (2) a substance capable of inhibiting the Na+-K+ pump and present in large amounts in heart diseases with a reduced cardiac index.

Topics: Adult; Aged; Blood Proteins; Cardenolides; Cardiac Catheterization; Coronary Disease; Digoxin; Heart Defects, Congenital; Hemodynamics; Humans; Middle Aged; Radioimmunoassay; Saponins; Sodium-Potassium-Exchanging ATPase

A survey of monitoring of digoxin treatment in five practices examined the indications for prescribing digoxin, its long term use, and how its use could be monitored. These data were used to generate a protocol for monitoring treatment with digoxin in general practice. The findings of the survey and the protocol were distributed to and discussed with all the partners in the practices participating in the study. One year later similar analysis showed that record keeping (recording of pulse rate and rhythm) had improved significantly in the group of principals carrying out the audit but not in other principals in these practices. Audit may change only the auditors.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Coronary Disease; Digoxin; Drug Prescriptions; Drug Utilization; England; Family Practice; Female; Humans; Infant; Infant, Newborn; Long-Term Care; Male; Medical Audit; Middle Aged

Information on drug consumption was collected in May 1987 within the framework of the 10 year follow-up survey of a coronary risk factor detection programme in the Tyrolean village of Oberperfuss. Data were obtained from the entire cohort born between 1913 and 1927. On average, men took 1.7 and women 2.8 different types of drugs. Blood pressure lowering substances, including diuretics, were the most frequently consumed drugs, followed by digitalis.

Topics: Aged; Antihypertensive Agents; Austria; Cardiovascular Agents; Coronary Disease; Digoxin; Drug Interactions; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Risk Factors

In 91 cases where the cause of death was heart disease, digoxin, Mg and K concentrations in serum and ventricular myocardium were measured post mortem. Forty per cent were positive for digoxin in both serum and myocardium. The mean serum level was 5.1 +/- 2.4 nmol/l and the mean myocardial level was 42.6 +/- 27.5 ng/g. Correlation could be established between serum and myocardial concentrations of digoxin. There were statistically significant differences in serum as well as in myocardial digoxin levels in persons on 0.13 mg and 0.25 mg per day, respectively. Myocardial levels of Mg and K were low as generally found in persons with ischemic heart disease. There was no correlation between these levels and myocardial digoxin concentrations. Caution must be exercised in the assessment of digoxin results from cadaver samples because of the postmortem rise of digoxin serum concentrations. Considering this fact, the results still indicate that the prevalence of toxic digoxin concentrations might be more common than previously thought.

Topics: Adult; Aged; Aged, 80 and over; Cause of Death; Coronary Disease; Death, Sudden; Digoxin; Female; Humans; Magnesium; Male; Middle Aged; Myocardium; Organ Size; Potassium

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

Digoxin toxicity developed in two patients awaiting cardiac transplantation upon the initiation of cyclosporine. Toxicity was associated with elevated digoxin concentrations (10.6 and 5.7 nmoles/L), gastrointestinal symptoms, and arrhythmias classic for digoxin toxicity (bidirectional ventricular tachycardia and AV nodal block with accelerated junctional rhythm respectively). A previously unreported drug interaction between cyclosporine and digoxin was suspected and digoxin pharmacokinetics were studied in two additional patients both before and after cyclosporine therapy prior to cardiac transplantation. The study confirmed a significant interaction between cyclosporine and digoxin; the apparent volume of distribution of digoxin decreased by 71% and its plasma clearance decreased by 53%. Until further information regarding the cyclosporine-digoxin interaction is available, this combination should be used with great caution.

Topics: Coronary Disease; Cyclosporins; Digoxin; Drug Interactions; Humans; Male; Middle Aged

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

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

Na, K-ATPase activity of the rat and guinea-pig myocardial sarcolemma and its sensitivity to digoxin (DG) and carbamylcholine (CCh) were investigated during experimental ischemia. Ischemia was induced by the incubation of hearts in the air at 37 degrees C. This 15-, 30- and 45-min treatment led to a decrease in enzymatic activity which was similar in both animal species. Dose-related dependence of DG effect (10(-8)-10(-2) M) on sarcolemmal Na, K-ATPase activity of guinea-pig ischemic hearts did not differ from the control, whereas the rat enzyme sensitivity to glycosides rose with the progress of ischemia. CCh (10(-7)-10(-3) M) produced an inhibition of Na, K-ATPase activity which had reached 40% both in the rat and guinea-pig myocardial preparations. This effect was blocked by atropine (10(-6) M). The magnitude of enzyme responses to CCh declined depending on the duration of ischemia, with it being greater in guinea-pig sarcolemma than in rat membrane. The increased sensitivity of the rat Na, K-ATPase to CCh was also observed.

Topics: Animals; Atropine; Carbachol; Coronary Disease; Digoxin; Dose-Response Relationship, Drug; Guinea Pigs; Heart; In Vitro Techniques; Myocardium; Rats; Sarcolemma; Sodium-Potassium-Exchanging ATPase; Time Factors

The influence of digoxin, digitoxin and g-strophanthin (ouabain) on the sinus node function (recovery time, sinoatrial conduction time, PP-interval) and on ventricular repolarisation (corrected QT interval and QT during permanent atrial stimulation) was studied in 101 patients (36 with sick sinus syndrome-SSS, 34 with ischaemic heart disease-IHD, and 31 control patients without cardiac disease). Digoxin caused marked prolongation of sinoatrial conduction time (in SSS and in control patients), digitoxin prolonged the PP interval (in IHD and SSS patients); digitoxin and ouabain shortened the QTcorr in SSS patients, ouabain shortened also QT during atrial pacing. The results do not point to specific indication of individual glycosides in sinus node function disturbances. Under certain clinical prerequisites, however, digitoxin can be recommended in ventricular ectopic contractions caused by prolonged or inhomogeneous repolarisation, and also the capacity of ouabain to shorten the repolarisation time deserves attention.

Topics: Cardiac Pacing, Artificial; Coronary Disease; Digitoxin; Digoxin; Electrocardiography; Electrophysiology; Female; Heart Conduction System; Humans; Male; Middle Aged; Myocardial Contraction; Ouabain; Sick Sinus Syndrome; Sinoatrial Node

Topics: Cardiomyopathy, Dilated; Coronary Disease; Digoxin; Heart Failure; Hemodynamics; Humans; Isosorbide Dinitrate; Middle Aged

The results of exercise electrocardiography were studied in a random sample of 317 subjects with clinical suspicion of coronary artery disease. In 278 patients with coronary artery disease the rate of false negative tests was 18% with and 12% without previous myocardial infarction. If ST elevation was considered a negative response, the corresponding values were 25% and 13%, respectively, p less than 0.01. The greatest prevalence of negative tests was seen after anterior myocardial infarction: 27% or 42% when ST elevation was not included into positive responses. The sensitivity of exercise-induced ST depression for the presence of multivessel disease was lower after anterior infarction (67%) than in other patients with previous infarction (86%), p less than 0.01. The corresponding specificities were 71% and 22%, respectively, p less than 0.005. If ST elevation was included into positive responses these differences were abolished. In subjects without myocardial infarction the sensitivity was 89% and specificity 43%. Digitalized patients had somewhat higher sensitivity in the exercise electrocardiogram than those without digoxin, 90% vs. 81% (p less than 0.05), but the difference was not seen with exclusion of ST elevation. The specificity was not influenced by digitalis. beta-blockade had no effect on the sensitivity or specificity, but the prevalence of postexercise ST evolution was lower with (11%) than without (30%) beta-blockade. The prevalence of slowly ascending ST depression was reduced by three factors: the presence of digitalis in patients without previous myocardial infarction, infarction itself, and the extent of coronary artery disease. We conclude that exercise electrocardiography has only a limited value in prediction of multivessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenergic beta-Antagonists; Chest Pain; Coronary Disease; Digoxin; Electrocardiography; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Infarction; Predictive Value of Tests; Time Factors

Topics: Animals; Antibodies; Antibodies, Monoclonal; Antibody Specificity; Cardiovascular Diseases; Coronary Disease; Digoxin; Humans; Immunization, Passive; Immunoglobulin Fragments; Myocardial Infarction; Myosins; Radionuclide Imaging; Receptors, Cell Surface; Receptors, Drug; Renin

Topics: Adult; Aged; Aminophylline; Coronary Disease; Digoxin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged

Topics: Adult; Coronary Disease; Digoxin; Drug Interactions; Drug Therapy, Combination; Humans; Kinetics; Middle Aged; Nifedipine

Topics: Adaptation, Physiological; Coronary Disease; Digoxin; Exercise Test; Hemodynamics; Humans; Male; Medigoxin; Middle Aged; Physical Exertion

The correlation between arterial blood pH and digoxin plasma levels was studied after digoxin (Eudigox) administration a) in a single p.o. dose, b) in a steady state p.o. regimen, or c) i.v. The clinical trial was carried out on 26 male hospitalized patients selected and divided into groups according to their arterial blood pH values, which ranged between 7.20 and 7.53. Arterial blood pH proved to be directly correlated with digoxin plasma levels and with the corresponding AUC and inversely with the total plasma clearance of the drug. The data may explain the strongly reduced activity shown by digoxin in patients suffering from respiratory acidosis in clinical practice.

Topics: Acidosis, Respiratory; Aged; Coronary Disease; Digoxin; Female; Humans; Hydrogen-Ion Concentration; Male; Middle Aged

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

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

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

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

Clinical and electrocardiographic manifestations of congestive cardiomyopathy are considered on the basis of observations of 25 patients with this pathology of the myocardium. No clinico-electrocardiographic signs specific for this disease were found. Most characteristic were cardiomegaly, congestive cardiac failure and various disturbances of rhythm and conductivity. Thromboembolic complications in the lung and kidney vessels are frequently found. Cardiac glycosides, saluretics and vasodilators were employed in the treatment of patients with congestive cardiomyopathy but the prognosis was usually poor.

Topics: Adolescent; Adult; Cardiomegaly; Cardiomyopathy, Dilated; Coronary Disease; Diagnosis, Differential; Digoxin; Drug Therapy, Combination; Female; Furosemide; Heart Failure; Humans; Male; Middle Aged; Nitroglycerin; Strophanthins

Acute myocardial ischemia reduces tolerance of the heart to arrhythmogenic actions of digitalis glycosides. Because both ischemia and the glycoside produce profound changes in activity of the autonomic nervous system and because sympathetic discharge or catecholamines enhance toxic actions of the cardiac glycosides, the possibility that alterations in digitalis sensitivity of ischemic heart involve changes in sympathetic nerve activity was examined using alpha-chloralose-anesthetized cats. Left anterior descending coronary artery (LAD) was completely occluded by ligation and, 40 min later, a slow i.v. infusion of digoxin was started at a rate of 1 microgram/kg/min. LAD ligation alone did not produce arrhythmias in that condition, but shortened the time to onset of digoxin-induced arrhythmias and thereby reduced the amount of digoxin required to produce the toxic manifestation. Concomitantly, digoxin concentration in plasma and nonischemic areas of the heart were lower in LAD-ligated cats at the onset of arrhythmias than those in sham-operated cats. Myocardial digoxin content in the ischemic area of the LAD-occluded heart was lower than that in nonischemic areas of the same heart. At the onset of digoxin-induced arrhythmias, Na,K-adenosine triphosphatase activity of ischemic myocardium was significantly higher than that in the nonischemic area, reflecting a lower digoxin occupancy of the glycoside binding sites on the sodium pump. Spinal cord (C1) transection or propranolol treatment prolonged the time to arrhythmias in both control and LAD-ligated cats, but failed to abolish the effect of LAD ligation to augment digoxin toxicity. Bilateral vagotomy also did not alter the enhancement of digoxin toxicity caused by ligation of LAD.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anesthesia; Animals; Catecholamines; Cats; Coronary Disease; Digoxin; Drug Tolerance; Female; Male; Myocardium; Sodium-Potassium-Exchanging ATPase; Sympathetic Nervous System; Vagotomy

Topics: Aged; Coronary Disease; Digoxin; Drug Interactions; Drug Therapy, Combination; Female; Heart Arrest; Humans; Male; Ventricular Fibrillation; Verapamil

Topics: Aged; Coronary Disease; Digoxin; Drug Therapy, Combination; Epilepsy, Tonic-Clonic; Female; Humans

Topics: Adult; Aged; Blood Circulation; Coronary Disease; Digoxin; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Contraction; Pulmonary Circulation

The hydrolytic cleavage of digoxin was studied after single oral doses of tritiated glycoside to four patients with gastric hyperacidity (GH-group) and to six patients during coronary care (CCU-group). Drug analysis was performed with a high-pressure liquid chromatographic method. Results in the two groups did not differ and were similar to results in a previous study in healthy volunteers. On the average 22% of the radioactivity was recovered in 24-h urine specimen. Of this 24.8 +/- 8.5% (GH-group, mean +/- SEM) and 19.3 +/- 6.6% (CCU-group) were cleavage products and unidentified, polar metabolites in equal amounts. This indicates that hydrolysis of digoxin is on average limited even in patients at risk for such metabolic cleavage.

Topics: Adult; Aged; Coronary Disease; Digoxin; Female; Gastric Acid; Humans; Male; Middle Aged

This brief review summarizes recent literature about plasma catecholamines as indices of sympathetic nervous and sympathoadrenomedullary activity in clinical cardiologic disease states. Many reports have described high plasma levels of norepinephrine, the neurotransmitter of the sympathetic nervous system, in acute myocardial infarction, congestive heart failure, the mitral valve prolapse syndrome, and early essential hypertension. Fewer studies have reported values for plasma epinephrine, which is the product of sympathoadrenomedullary secretion. The relationship between circulating catecholamine levels and activity of the sympathetic nervous system is obscured by ignorance about catecholamine removal mechanisms and regionalization of sympathetic outflow. Further, whether increased sympathetic outflow increases cardiovascular risk or reflects compensatory recruitment or a non-specific stress response is poorly understood.

Topics: Cardiovascular Diseases; Catecholamines; Coronary Disease; Digoxin; Epinephrine; Humans; Hypertension; Mitral Valve Prolapse; Myocardial Infarction; Norepinephrine

Following a 90-min coronary occlusion and 2 h reperfusion in 11 dogs, total tissue and subcellular distributions of [3H]digoxin in non-ischemic and various ischemic tissues were measured. In the non-ischemic tissue, [3H]digoxin in the crude homogenate, sediments obtained from 1000 X g, 10000 X g and 100000 X g centrifugations, and final supernatant fraction were 0.70 +/- 0.05, 0.79 +/- 0.05, 0.64 +/- 0.04, 3.87 +/- 0.34 and 0.19 +/- 0.02 ng/mg protein, respectively. As in studies with total tissue [3H]digoxin uptake, a reciprocal correlation was observed in reduction of digoxin binding in the crude homogenates and the 1000 X g sediments with increasing severity of ischemic injury estimated from the loss of nitro-blue-tetrazolium (NBT) stain. A 20% and 80% loss of NBT stain was associated with a 13.3% and 63.5% decrease in digoxin binding, respectively. In contrast, digoxin binding in the 10000 X g sediments increased progressively with the severity of ischemia. No significant change was observed in the final supernatant fraction. Digoxin binding in the 100000 X g sediments, which generally represent specific binding and which are associated with the pharmacologic effects, was not altered in tissues with a loss of NBT stain up to 50%. In fact, a loss of 80% NBT was associated with only a 33.9% decrease in digoxin binding. Thus, it appears that measurement of total tissue digoxin uptake does not provide an accurate measure of the effects of acute ischemia on specific digoxin binding. The ability of the peri- and moderately ischemic tissues (with less than 50% loss of NBT stain) to specifically bind digitalis was not altered after temporary myocardial ischemia.

Topics: Animals; Coronary Disease; Digoxin; Dogs; Hemodynamics; Male; Microsomes; Myocardium; Sodium-Potassium-Exchanging ATPase; Tritium

Digitalis sensitivity of the heart is increased in patients with ischemic heart disease. Whether this elevation of digitalis sensitivity occurs as the result of ischemia-induced changes in the cardiac tissue and whether changes in the sarcolemmal Na,K-adenosine triphosphatase (ATPase) or reserve capacity of the sodium pump are responsible for the increased digitalis sensitivity were examined using isolated heart preparations obtained from guinea pigs. Ligation of the left anterior descending coronary artery (LAD) in Langendorff preparations 40 min before perfusion with a toxic concentration (either 1.8 or 2.5 microM) of digoxin decreased the time to the onset of arrhythmias. LAD-ligation by itself did not cause arrhythmias. The time to the onset of arrhythmias during digoxin perfusion was slightly longer in preparations obtained from reserpine-treated animals; however, the reserpine pretreatment failed to alter the effect of LAD ligation on digitalis sensitivity, indicating that the release of catecholamines is not involved in the sensitization. The effects of ischemia on Na,K-ATPase and sodium pump activities, glycoside binding to the enzyme and reserve capacity of the sodium pump were examined in globally ischemic Langendorff preparations. The preparations were perfused with a Krebs-Henseleit bicarbonate buffer solution (pH 7.4) saturated with a 95% O2-5% CO2 gas mixture at a control flow rate of 2.5 ml/g of tissue per min or at 5 or 0% of the control flow rate. After 6 hr of zero perfusion, Na,K-ATPase activity and the number of specific ouabain binding sites were reduced in ventricular muscle homogenates. However, the remaining Na,K-ATPase was not altered in its sensitivity to dihydrodigoxin-induced inhibition or affinity of binding sites for ouabain, sodium or potassium. Similar results were observed after reperfusion following 2 or 5 hr of zero perfusion. A 5% perfusion for 2 or 6 hr, or zero perfusion for 2 hr failed to affect Na,K-ATPase activity in muscle homogenates. Sodium pump activity in ventricular slices, estimated from the ouabain-sensitive 86Rb+ uptake, was unchanged after 5% perfusion or zero perfusion for 2 hr, but was significantly reduced after a 20-min reperfusion following 2 hr of zero perfusion. Reserve capacity of the sodium pump, as estimated from the differences in 42K+ uptake by right ventricular strips under 1.5 and 7 Hz stimulation, was unaffected by 2 hr of 5% perfusion. These results indicate that coronary artery occlusion

Topics: Animals; Coronary Disease; Digitalis Glycosides; Digoxin; Female; Guinea Pigs; Heart; Male; Myocardium; Ouabain; Perfusion; Potassium; Rubidium; Sodium-Potassium-Exchanging ATPase

Vasodilator treatment with long-activity nitrate derivatives intensifies the effects of treatment with digitalis and diuretics in left ventricular insufficiency. The object of this study was to evaluate, in an open comparative trial, the clinical effects of a prolonged adjunctive treatment with Mycoril, which is composed of a sustained-release nitrate derivative (pentaerythrityl tetranitrate: PETN) and an antianoxic agent (piridoxilate). The study was conducted in 90 patients with cardiac insufficiency who were treated and followed-up for at least one year. Study patients were divided into two groups matched for age, sex and etiology. The control group (42 patients) received digitalis and diuretics; the treatment group (48 patients) was given digitalis, diuretics and Mycoril in a daily dose of 4 to 6 capsules. The results show a significant improvement of symptoms in patients with ischemic cardiac insufficiency treated with Mycoril (83%) compared with the control group (52%) (p less than 0,03). Diuretics were needed in lower doses or withdrawn in a significantly higher number of patients in the Mycoril group (67%) than in the control group (38%) (p less than 0,01). This study provides clinical confirmation of the value of adjunctive treatment with a product such as Mycoril in patients under digitalis and diuretic therapy.

Topics: Aged; Coronary Disease; Digoxin; Drug Combinations; Drug Therapy, Combination; Furosemide; Heart Failure; Humans; Pentaerythritol Tetranitrate; Pyridoxine

Topics: Adult; Amiodarone; Cardiotonic Agents; Coronary Disease; Digoxin; Drug Interactions; Humans; Male; Middle Aged; Molsidomine; Sydnones; Verapamil

To evaluate the importance of oral maintenance digoxin therapy in chronic congestive heart failure (CHF), 24 patients in sinus rhythm on maintenance digoxin for documented CHF were studied prospectively on and off the drug. The average duration of therapy was 39 months (range 2 to 180). All 24 patients had documented coronary artery disease (CAD): 22 were in New York Heart Association functional class III and 2 in class II. Twenty-one patients (88%) were receiving diuretic or vasodilator therapy, or both, before digoxin discontinuance. At 1 month off digoxin and with no increase in doses of other medications excepting minor increases in antianginal therapy in 2 patients, no difference was observed in the group as a whole in symptoms, resting heart rate, arterial blood pressure, physical findings, weight, cardiothoracic ratio, radiographic signs of pulmonary congestion, radionuclide left ventricular ejection fraction (LVEF), duration of symptom-limited treadmill exercise (14 patients), or CHF score, compared with evaluation during maintenance digoxin therapy. Similar results were obtained in a subgroup of 9 patients with a resting LVEF less than 0.35 (0.27 +/- 0.02; mean +/- standard error of the mean). Six patients had a decrease and 5 patients an increase in LVEF of greater than or equal to 0.05 units after cessation of digoxin. Off digoxin, the CHF score increased by only 1 point in 2 patients, but also decreased in 2 patients. Thus, in this study population comprised of patients with CAD with documented CHF, most of whom were receiving diuretics or vasodilators, or both, digoxin withdrawal had no adverse clinical or hemodynamic effects.

Topics: Adult; Aged; Coronary Disease; Digoxin; Diuretics; Heart; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Prospective Studies; Sinoatrial Node; Vasodilator Agents

Topics: Aged; Coronary Disease; Digoxin; Echocardiography; Female; Humans; Male; Medigoxin; Middle Aged; Myocardial Contraction; Myocardial Infarction; Stimulation, Chemical; Time Factors

Topics: Acute Kidney Injury; Adrenergic beta-Antagonists; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Coronary Disease; Digoxin; Female; Humans; Hypertension, Renal; Indomethacin; Male; Metoprolol; Middle Aged; Penicillamine

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

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

Topics: Aged; Coronary Disease; Digoxin; Electrocardiography; Female; Humans

Fifteen patients without sinoatrial (SA) or atrioventricular (AV) node dysfunction underwent electrophysiologic study (EPS) before and after intravenous diltiazem: 0.20 mg/kg bolus followed by 0.0007 mg/kg/min infusion (seven patients) or 0.25 mg/kg bolus followed by 0.0012 mg/kg/min infusion (eight patients). In six patients intravenous digoxin (0.018 mg/kg) was given and 45 minutes later EPS was repeated while the diltiazem infusion continued. Diltiazem prolonged sinus cycle length (+7%, p less than 0.01), lengthened AH conduction time (+22% in constant rate atrial paced rhythm, p less than 0.001), prolonged AV node functional and effective refractory periods (+6%, p less than 0.01 and +16%, p less than 0.05, respectively), lengthened AV node Wenckebach cycle length (+13%, p less than 0.001), shortened atrial functional refractory period (-3%, p less than 0.05), and reduced mean arterial pressure (-8%, p less than 0.005 in constant rate atrial paced rhythm). Subsequently, intravenous digoxin further prolonged sinus cycle length (+12%, p less than 0.05), AH conduction time (+17%, p less than 0.05), AV node Wenckebach cycle length (+9%, p less than 0.05), and AV node functional refractory period (+7%, p less than 0.05), shortened atrial effective refractory period (-7%, p less than 0.05) and ventricular effective refractory period (-6%, p less than 0.05), and increased systolic arterial pressure (+6%, p less than 0.05). Diltiazem and digoxin have additive depressant effects on SA and AV node function without significant adverse effects.

Topics: Adult; Atrioventricular Node; Benzazepines; Coronary Disease; Digoxin; Diltiazem; Drug Therapy, Combination; Electrocardiography; Female; Heart; Humans; Male; Middle Aged; Sinoatrial Node

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

To assess whether digitalis modifies or prevents the deterioration of the left ventricular ejection fraction and wall motion during acute ischemia, we performed gated blood pool radionuclide ventriculograms in 15 patients with angiographically documented coronary artery disease. All patients were studied in the resting state and during maximal supine bicycle exercise, both before and 1 hour after 1 mg intravenous digoxin. There was no significant difference, pre-digoxin vs post-digoxin, in exercise tolerance (415 +/- 84 vs 418 +/- 107 seconds), number of segments with abnormal resting wall motion (12 vs 11) or exercise wall motion (21 vs 19). Ten patients developed angina during the same exercise load, irrespective of digoxin administration. Twelve patients had subnormal left ventricular ejection fraction during exercise pre-digoxin, vs 13 patients post-digoxin (P = ns). In the resting state, the left ventricular ejection fraction was higher after digoxin (53 +/- 14% pre vs 58 +/- 14% post, P less than 0.05). During exercise, however, the left ventricular ejection fraction was not significantly improved after digoxin (50 +/- 16% pre vs 53 +/- 17% post, P = ns). These data indicate that although acute administration of digoxin improves the resting left ventricular function, it does not improve exercise tolerance to angina. Furthermore, intravenous digoxin does not appear to prevent the deterioration of left ventricular wall motion and ejection fraction during exercise induced ischemia.

Topics: Blood Pressure; Cardiac Output; Coronary Disease; Digoxin; Exercise Test; Heart; Heart Function Tests; Heart Rate; Heart Ventricles; Humans; Male; Middle Aged; Stroke Volume

Topics: Coronary Disease; Digoxin; Heart Failure; Heart Ventricles; Humans

Topics: Angina Pectoris; Coronary Circulation; Coronary Disease; Digoxin; Hemodynamics; Humans; Middle Aged; Myocardial Infarction

Topics: Age Factors; Aged; Coronary Disease; Digoxin; Humans; Kinetics; Male

Topics: Adult; Arthritis; Aspirin; Coronary Disease; Digoxin; Drug Interactions; Humans; Indomethacin; Male; Middle Aged; Neuritis; Nifedipine; Phenylbutazone; Pyridines

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

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

Our own experience with the production of digoxin-specific antibody preparations from the sheep and the results of the experimental and clinical use are briefly reviewed. Advantages, risks and unsolved problems of therapy with glycoside-specific antibodies are discussed.

Topics: Animals; Antibodies, Heterophile; Coronary Disease; Digitalis Glycosides; Digoxin; Heart Failure; Humans; Lanatosides; Rabbits; Sheep

The effect exerted on the partially ischaemic heart when administering 0.9 mg/kg L-3-(beta-hydroxy-alpha-methylphenethylamino)-3'-methoxypropiophenone (oxyfedrine, ildamen) approx. 10 min after i.v. application of 0.05 mg/kg digoxin was tested on 20 dogs previously anaesthetized with propiomazine-pentobarbital. The following parameters were studied and subsequently compound with the results of former trials of ours' without digoxin premedication: aortic pressure (ASP, ADP), left-ventricular pressure (LVSP, LVEDP), heart rate (HR), cardiac output (HMV), stroke volume (SV), dp/dtmax, dp/dtmax/IP, t-dp/dtmax, blood flow in the normal and partially ischaemic myocardium, the latter being measured with heat conductance probes and labelled microspheres. ASP and ADP show the same reduction--as compared with the control value--both after the administration of oxyfedrine with and without digoxin premedication. After digoxin premedication oxyfedrine led to a somewhat less marked reduction of LVSP; on premedication with digoxin LVEDP was slightly increased whereas it was reduced after additional administration of oxyfedrine as was also the case without digoxin pretreatment. The increase in HR after oxyfedrine is almost the same as without digoxin pretreatment. Also the increase in HMV and the SV lowering are not influenced by digoxin. By administration of oxyfedrine dp/dtmax is always increased by the same amount, starting from the already increased value after digoxin premedication, which is probably an additive effect. The same applies to the quotient dp/dtmax/IP. After oxyfedrine the time t-dp/dtmax is lowered by the same amount, irrespective of a digoxin premedication. Oxyfedrine does not produce a further increase in the heat conductance values after previous application of digoxin; when measuring the blood flow with labelled microspheres the same result was found, which means that by previous administration of digoxin the circulatory effect of oxyfedrine is obviously inhibited. Summing up one can say that by combining the active principles digoxin and oxyfedrine the function parameters of the heart can be influenced only positively.

Topics: Anesthesia; Animals; Coronary Circulation; Coronary Disease; Digoxin; Dogs; Female; Hemodynamics; Male; Myocardial Contraction; Oxyfedrine; Propiophenones; Time Factors

This study was undertaken to investigate the hemodynamic effect of prophylactic digitalization before major surgical procedures. Sixteen patients, all admitted for an elective vascular operation for arteriosclerotic disease and all with impaired left ventricular function, were investigated. In half of the patients, digitalis was given before the operation, the other half of the patients served as the control study. The measured parameters were pulmonary artery mean pressure, pulmonary capillary wedge pressure, central venous pressure, mean arterial blood pressure, heart rate, cardiac output, blood volume and arterial, as well as venous, oxygen content. Preoperatively, before digitalization, no significant differences were noted between the two groups at rest and during exercise. Before anesthesia and postoperatively, those given digitalis had improved cardiac function. Those in both groups, however, had a normal hemodynamic response to the surgical trauma. In this study, a definite answer is not provided concerning the usefulness of prophylactic digitalization but an increase in the ability of the digitalized heart to withstand the imposition of a pressure load postoperatively is suggested.

Topics: Aged; Arteriosclerosis; Blood Pressure; Blood Volume; Cardiac Output; Coronary Disease; Digitalis; Digoxin; Female; Heart Rate; Humans; Male; Middle Aged; Oxygen Consumption; Plants, Medicinal; Plants, Toxic; Preoperative Care; Vascular Surgical Procedures

The results of this study with 102 patients, suffering from cardiac insufficiency and coronary heart disease are that a fixed combination of digoxin with nitrate-compositions is not convenient. In 45 cases the digoxin dose had to be altered, partly even several times, whilst only in 23 patients an alteration of the dosage of the nitrate compositions had to be done, independently from the digoxin dose.

Topics: Coronary Disease; Digoxin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Heart Failure; Humans; Nitrates

With ever increasing frequency potentially dangerous interactions are reported between Cardiac Glycosides and other drugs, particularly the antiarrhythmic one. The AA, carried out this work with the intent of studying the possible modifications produced by Q and A on the SDL. First of all the AA. retrospectively studied the SDL of patients treated with the associations Q-D and A-D and this SDL was compared with the SDL of patients treated with D alone. Then 10 subjects treated sequentially, at first with D alone and after with the Q-D (5 p.) and A-D (5 p.) association, were studied. The results obtained confirm the data of other AA. regarding the Q-D interaction; in fact, in the presence of this antiarrhythmic drug, the SDL increase significantly following the concomitant pharmacological effects of the Cardiac Glycosides. The SDL on the contrary seem not be influenced by the A-D association. The AA. then reviewed the literature about the mechanism of the Q-D interaction. The majority of the AA. agree outlining a reduction of the Volume of Distribution and of D Clearance, in consequence of the concomitant administration of Q, which would explain the high SDL obtained. In conclusion the AA. suggest, when the Q-D association is mandatory, a 50% reduction of the D maintenance dose and to check periodically the ECG and SDL.

Topics: Adult; Aged; Amiodarone; Benzofurans; Coronary Disease; Digoxin; Drug Interactions; Female; Heart Diseases; Humans; Hypertension; Male; Middle Aged; Quinidine; Rheumatic Heart Disease

In order to prove the efficacy of the long-term nitrate pentaerythrityltetranitrate (PETN; Pentalong) in latent and stress heart insufficiency (causes ischaemic heart disease and/or hypertension) we examined 18 patients with this vasodilator with monotherapy as well as with digoxin combinations. Under PETN the symptoms of the clinical degree of severity could be clearly improved. Before and after stress the tension index showed a significant increase in the region of sufficiency. The sums of stress and recreation pulse and the mean arterial pressure proved a trend to decrease. The load tolerance on the bicycle ergometer was improved. Under the additional therapy with the fully effective dose of digoxin (dilanacin) with regard to the symptoms, load tolerance and partly also to pulse sums a deterioration of the parameters could be recognized in comparison to the PETN-monotherapy; only the combination with the half digoxin saturation does yielded more favourable results of the pulse sums. Apparently the treatment of patients with latent and stress heart insufficiency with long-term nitrates is an alternative to the therapy with glycosides and is even possibly superior to this.

Topics: Adult; Coronary Disease; Digoxin; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Pentaerythritol Tetranitrate; Physical Exertion; Pulse

Topics: Cimetidine; Coronary Disease; Digoxin; Drug Interactions; Gastric Acid; Guanidines; Humans

To determine whether a single dose of quinidine sulfate might alter serum digoxin levels, patients receiving maintenance digoxin therapy who required quinidine had their serum digoxin levels measured after oral administration of digoxin, quinidine, or both. In group 1, digoxin and quinidine were administered orally together; in group 2, digoxin was administered orally alone; and in group 3, quinidine was administered orally, 24 hours after the last dose of digoxin. In group 1, serum digoxin level increased by 2.0+/-0.4 ng/mL (from 1.0+/-0.1 ng/mL), but in group 2, serum digoxin level increased by only 1.0+/-0.1 ng/mL (from 1.0+/-0.1 ng/mL). Group 3 showed no change in serum digoxin concentration. Time of maximum digoxin concentration also occurred earlier when digoxin and quinidine were administered together. Thus, a single dose of quinidine will increase the peak digoxin level when administered together with oral digoxin.

Topics: Administration, Oral; Aged; Cardiac Complexes, Premature; Coronary Disease; Digoxin; Drug Interactions; Female; Humans; Male; Middle Aged; Quinidine; Time Factors

Topics: Aged; Coronary Disease; Digoxin; Drug Interactions; Drug Therapy, Combination; Humans; Male; Middle Aged; Quinidine

Topics: Acid-Base Equilibrium; Cardiac Output; Coronary Disease; Digitalis Glycosides; Digoxin; Diuretics; Dose-Response Relationship, Drug; Drug Therapy; Drug Tolerance; Heart Failure; Humans; Risk; Tissue Distribution

Topics: Adult; Aged; Cardiac Output; Coronary Disease; Diastole; Digoxin; Exercise Test; Female; Heart Ventricles; Humans; Male; Middle Aged; Radionuclide Imaging; Rest; Stroke Volume; Systole

Topics: Acute Disease; Coronary Disease; Digoxin; Humans; Lidocaine; Tachycardia; Ventricular Fibrillation

Topics: Aged; Anti-Arrhythmia Agents; Cardiac Glycosides; Coronary Disease; Digoxin; Drug Interactions; Humans; Male; Quinidine; Tachycardia

The bioaccessibility of Soviet produced digoxin tablets in elderly patients with cardiac insufficiency was studied. It is shown that in absolute bioaccessibility (62%) and other biopharmaceutic indices digoxin tablets made in the Soviet Union are equivalent to lanoxin tablets of the Burroughs Wellcome firm which are accepted by the USA FDA as the bioaccessibility standard. Equations fitted within a two-part mathematical model satisfactorily describe the changes in blood serum digoxin concentration in oral medication and in intravenous administration.

Topics: Aged; Biological Availability; Coronary Disease; Digoxin; Heart Failure; Humans; Male; Rheumatic Heart Disease; Tablets; Therapeutic Equivalency; Time Factors

In a prospective symptom-oriented study, patients with (n = 81) or without (n = 206) digoxin toxicity were not discernible on their serum digoxin concentration (SDC) because of a large overlap between toxic and non-toxic groups. There was, however, a significant difference between the mean values of the groups (p < 0,01). Serum creatinine, the presence or absence of ischemic heart disease, and/or chronic pulmonary heart disease were significantly different (both p < 0,025) between toxic and non-toxic groups. It is concluded that a decision on digitalis toxicity should be made by a synopsis of the influencing factors in the individual case. Dosage, serum creatinine and cardiac status seem to be the most important factors to be taken into account. Lack of agreement between SDC and digoxin effects could be demonstrated in differences in "T 1/2" between SDC and the normalisation of prolonged PQ-time after digoxin withdrawal. The inability of the SDC to describe all alterations important for digitalis effects and side effects seems to be that it does neither mirror the glycoside concentration at the receptor site, nor the changes of receptor affinity, nor the changes of (Na+ + K+)-ATPase activity.

Topics: Aged; Coronary Disease; Creatinine; Digitalis Glycosides; Digoxin; Electrocardiography; Humans; Middle Aged; Prospective Studies; Pulmonary Heart Disease

Topics: Acetyldigoxins; Adult; Aged; Coronary Disease; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged

Topics: Aged; Coronary Disease; Digitalis Glycosides; Digoxin; Dose-Response Relationship, Drug; Humans; Middle Aged; Myocardial Contraction

Haemodynamic incidence of induction of anaesthesia was evaluated in four groups of 10 patients in general surgery: patients without heart disease (gr. I), patients with ischaemic myocardiopathy (gr. II, gr. IV), patients with ischaemic heart disease who were digitalized before anaesthesis (gr. III). An anaesthetic technique comprising a combination of phenoperidine, thiopentone, suxamethonium, pancuronium, N2O/O2 was used in groups I, II, III and patients of group IV were anaesthetized with a protocol of narconeuroleptanalgesia (phenoperidine, droperidol, thiopentone, pancuronium, N2O/O2). Induction of anaesthesia in patient with ischaemic myocardiopathy leads to haemodynamic changes with a predominant decrease of mean arterial pressure. But the haemodynamic changes are less important with neuroleptanalgesia than with balanced anaesthesia. With neuroleptanalgesia decrease of mean arterial pressure is rather less important than with balanced anaesthesia and it is not coupled with a significant decrease of cardiac index but only with a decrease of total peripheral resistances. On contrary with balanced anaesthesia decrease of mean arterial pressure is connected with a significant decrease of cardiac index related to a decrease of systolic index. Pre-operative digitalization do not attenuate cardiac and haemodynamic changes occurring after induction and balanced anaesthesia. Though neuroleptanalgesia appears to be a safe technique in patients with ischaemic heart disease.

Topics: Abdomen; Acid-Base Equilibrium; Aged; Anesthesia, General; Coronary Disease; Digoxin; Hemodynamics; Humans; Middle Aged; Neuroleptanalgesia; Oxygen

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

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

Topics: Coronary Disease; Digoxin; Heart Failure; Humans; Sinoatrial Node

The influence of therapeutic digitalisation on ST depression due to myocardial ischemia was investigated in 11 patients, average age 53.6 years, with coronary heart disease, compared with the effectiveness of nitroglycerine. Therapeutic digitalis led to an average increase of ischaemic ST depression from -0.53 to -0.73 mV. The mean pulmonary arterial and pulmonary capillary pressure decreased slightly, the frequency of pectanginous attacks increased. Independent of the digitalis effect nitroglycerine had an opposing action on these parameters. In decompensated patients with coronary heart disease (n = 4) both digitalis and nitroglycerine produced a shift of the left ventricular function curve as an expression of improved cardiac action. This could not be observed in patients with compensated ventricular function (n = 7). In sufficient ventricular function digitalis led to a further increase of myocardial ischaemic ST depression. In ventricular insufficiency no uniform behaviour was apparent. ST depression induced by digitalis could be reversibly influenced by nitroglycerine.

Topics: Adult; Aged; Cardiac Output; Cardiac Volume; Coronary Disease; Digoxin; Drug Interactions; Electric Stimulation; Electrocardiography; Female; Heart Atria; Humans; Male; Middle Aged; Nitroglycerin

Two hundred consecutive catheterized patients with unstable angina pectoris were reviewed to find clinical and noninvasive indicators of left main coronary artery disease (greater than or equal to 50% lesion). Thirty-five patients (17.5% of total) had left main coronary artery disease. There were no differences between patients with and without left main coronary artery disease in age, sex, results of resting electrocardiogram, congestive heart failure, dyspnea during pain, duration of longest pain, arrhythmias, response to medical therapy, or other risk factors. Crescendo angina pectoris (worsening of pre-existing angina), transient ST-segment depression with pain, simultaneous anterior and inferior ST changes during pain, and fluoroscopic calcification of the left main coronary artery were all significantly more common in patients with left main coronary artery disease. However, low sensitivity or low predictive value, or both, limit the usefulness of these clinical predictors. Left main coronary artery disease cannot be reliably predicted in patients with unstable angina pectoris before coronary arteriography.

Topics: Angina Pectoris; Angiography; Anticoagulants; Calcinosis; Cardiac Catheterization; Cardiomegaly; Collateral Circulation; Coronary Angiography; Coronary Circulation; Coronary Disease; Digoxin; Electrocardiography; Female; Heart Conduction System; Heart Failure; Humans; Male; Middle Aged; Nitrates; Propranolol; Risk

Topics: Adenine Nucleotides; Animals; Coronary Disease; Digoxin; Drug Evaluation, Preclinical; Electron Transport Complex IV; Myocardium; Rats

To study the effects of digoxin on regional left ventricular performance, continuous ventricular dynamics were assessed in nine patients with stable coronary disease. Computer-assisted analysis of the fluoroscopic motion of surgically implanted mid wall myocardial markers was used. The markers define six minor ventricular radii and outline the left ventricle. One and one-half hours after administration of 1 mg of intravenous digoxin, mean velocity of circumferential fiber shortening for all segments increased 19 percent, from 0.67 +/- 0.06 to 0.78 +/- 0.06 circumference/sec (P less than 0.01) and ejection fraction increased 4.5 percent, from 0.50 +/- 0.03 to 0.53 +/- 0.03 (P less than 0.05). Segmental velocity of circumferential fiber shortening, total segmental shortening and early segmental systolic shrtening increased in 83 percent to 91 percent of normal segments, depending on which index was used. Only 45 to 55 percent of initially abnormal segments benefited from digoxin. In general, segmental dyssynergy increased even when net ventricular function was enhanced. These results suggest that in pateints with chronic left ventricular contraction abnormalities due to coronary disease, deterioration of performance in abnormal regions after administration of digoxin may result from increased stress imposed by increased afterload and by improved segmental dynamics in more normal areas.

Topics: Adult; Analog-Digital Conversion; Coronary Disease; Digoxin; Fluoroscopy; Heart; Humans; Infusions, Parenteral; Middle Aged; Myocardial Contraction; Systole

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

Topics: Animals; Coronary Disease; Digoxin; Dogs; Myocardium

Topics: Ambulatory Care; Coronary Disease; Digoxin; Drug Therapy, Combination; Humans; Pentaerythritol Tetranitrate

Topics: Aged; Coronary Disease; Digoxin; Drug Interactions; Female; Humans; Lung Diseases, Obstructive; Male; Pulmonary Heart Disease; Quinidine

Topics: Action Potentials; Adolescent; Adult; Aged; Ajmaline; Bunaftine; Coronary Disease; Diabetes Mellitus; Digoxin; Electrocardiography; Female; Heart; Heart Diseases; Heart Ventricles; Humans; Hypertension; Male; Middle Aged; Ventricular Function

A 72-year-old man with coronary heart disease and renal failure required hospitalization because of digoxin intoxication with severe arrhythmias and generalised heart failure. The intoxication was successfully treated and sinus rhythm rapidly restored after administration of heterologous digoxin-specific F(ab')2 antibody fragments. There were no side-effects and the heart failure improved after treatment.

Topics: Aged; Animals; Antibodies; Coronary Disease; Digoxin; Heart Failure; Humans; Kidney Failure, Chronic; Male; Sheep

The activity of the beta-receptor blocker pindolol (0.4 mg i.v.) was investigated alone and in combination with digitalis (moderately fast loading) in 12 patients with coronary heart disease and without manifest signs of cardiac insufficiency. These patients showed pathological increase of left ventricular filling pressure during exercise testing. The exercise-induced rise of the mean pulmonary arterial and capillary pressures were increased by pindolol. Concurrently the increase of cardiac frequency was clearly diminished during ergometry (from 107/min without pindolol to 96/min, P less than 0.005). Digoxin given orally for an average of 5 days prevented the pressure increase in the pulmonary circulation induced by pindolol during exercise testing and at rest. The frequency reducing effect of pindolol was potentiated by digitalis. Use of digitalis alone did not influence mean exercise-induced pressure increase of the pulmonary circulation. In fact in some cases deterioration of these parameters was observed.

Topics: Acetyldigoxins; Aged; Blood Pressure; Capillaries; Coronary Disease; Digoxin; Drug Interactions; Female; Humans; Lung; Male; Middle Aged; Pindolol; Pulmonary Artery

Topics: Aged; Coronary Disease; Creatinine; Digitalis Glycosides; Digoxin; Electrocardiography; Female; Heart Diseases; Humans; Male; Middle Aged; Potassium

Topics: Adult; Biological Availability; Capsules; Coronary Disease; Digoxin; Female; Heart Diseases; Humans; Male; Middle Aged; Myocardial Contraction; Tablets

The effects of moderately rapid oral digitalization and sublingual nitroglycerine were studied in 13 patients with coronary heart disease without signs of manifest heart failure but definite rise in pulmonary artery pressure on ergometric exercise. Digitalis had no effect on exercise-induced rise in pulmonary pressure. In the individual case there may be a clear-cut deterioration in exercise response. This possible unfavourable digitalis effect cannot be predicted in a given case from the clinical state and thus one must critically assess digitalis treatment in coronary heart disease without manifest heart failure. On the other hand, the favourable effect of nitroglycerine in lowering pulmonary arterial pressure at rest and preventing an abnormal pressure rise on exercise underlines its value in the treatment of both compensated and uncompensated coronary heart disease.

Topics: Aged; Blood Pressure; Coronary Disease; Digoxin; Female; Humans; Male; Middle Aged; Nitroglycerin; Physical Exertion; Pulmonary Artery

Topics: Adult; Aged; Angina Pectoris; Coronary Disease; Digoxin; Electrocardiography; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Myocardial Contraction

Topics: Adult; Aged; Chronic Disease; Coronary Disease; Digoxin; Drug Therapy, Combination; Female; Humans; Hypertension; Middle Aged; Propranolol; Rheumatic Heart Disease

Topics: Administration, Oral; Adult; Cardiac Output; Coronary Disease; Digoxin; Drug Evaluation; Heart Failure; Humans; Infusions, Parenteral; Middle Aged; Myocardial Contraction; Time Factors

Topics: Adult; Aged; Ambulatory Care; Coronary Disease; Digoxin; Female; Humans; Male; Middle Aged; Rheumatic Heart Disease; Time Factors

Topics: Adult; Aged; Blood Flow Velocity; Cardiac Pacing, Artificial; Chronic Disease; Coronary Circulation; Coronary Disease; Digoxin; Drug Evaluation; Hemodynamics; Humans; Injections, Intravenous; Lactates; Male; Middle Aged; Myocardium; Oxygen Consumption; Vascular Resistance

Topics: Cardiac Glycosides; Chronic Disease; Coronary Disease; Digoxin; Humans; Mitral Valve Insufficiency; Pulmonary Heart Disease; Rheumatic Heart Disease; Risk

The 83-year-old woman in this case report developed paranoid delusions and auditory hallucinations in association with toxic serum levels of digoxin, while remaining alert, unagitated, and coherent in thinking. No cardiovascular or metabolic abnormalities were discovered to account for her psychiatric symptoms. Her mental status rapidly returned to normal as serum digoxin declined to therapeutic levels.

Topics: Aged; Auditory Perception; Coronary Disease; Delusions; Digoxin; Female; Hallucinations; Humans; Paranoid Disorders; Substance Withdrawal Syndrome

The serum-digoxin level was measured by radio-immunoassay (Immutope) on 245 patients in a coronary care unit. Cardiac arrhythmias were assumed to be digoxin-induced if they disappeared after the drug had been stopped. Patients who had received digitoxin or spironolactone were excluded. The results indicated a normal digoxin range of 1.52 +/- 0.2 ng/ml and a toxic one of 2.78 +/- 0.38 ng/ml. First degree A-V block, atrial ectopic beats and ventricular ectopics with variable coupling intervals were frequently associated with serum-digoxin levels of 1.5-2.5 ng/ml, while higher grade A-V block, atrial tachycardia, bigeminy and atrial tachycardia with block were more frequent with higher serum-digoxin levels (greater than 3.0 ng/ml). Atrial arrhythmias were especially frequent with serum levels above 3.0 ng/ml. This suggests different sensitivities of atrial and ventricular myocardium. Atrial arrhythmias thus in general indicate a higher degree of toxicity at high serum levels, while ventricular ectopic beats occur both with high serum levels and also with increased digoxin sensitivity of the ventricles.

Topics: Arrhythmias, Cardiac; Cardiac Complexes, Premature; Coronary Disease; Digoxin; Heart Block; Humans; Radioimmunoassay; Reference Values; Tachycardia

Topics: Aged; Angina Pectoris; Blood Glucose; Cardiac Pacing, Artificial; Coronary Disease; Digoxin; Electrolytes; Fatty Acids, Nonesterified; Female; Glucose; Hemodynamics; Humans; Lactates; Male; Medigoxin; Middle Aged; Nitroglycerin; Pyruvates

Recently direct myocardial effects of antikaliuretic diuretics with respect to contractility parameters and prevention of digitalis-induced arrhythmias were published. In order to test the value of these reports we measured the effect of potassium-canrenoate and triamterene on cardiac output and on digitalis-induced arrhythmias in patients during diagnostic and the therapeutic flow directed right heart catheterization (Swan-Ganz) in our intensive care unit. In addition the influence of these drugs on (Na+ + K+)-ATPase and on (3H)g-strophanthin binding to human cardiac cell membranes was investigated to gain information on the mechanism of their action. Triamterene (100-200 mg p.o.) was without any effect on cardiac output, the same was found true for potassium-canrenoate given in a single dose (200-1000 mg intravenously). However, when applied in two doses (200 mg i.v. and 60 min later 400 mg i.v.), potassium-canrenoate increased cardiac output by 11 percent (p less than 0.05). Only in 2 out of 14 patients potassium-canrenoate (200-400 mg i.v.) suppressed digitalis-induced ventricular ectopic beats. Canrenone, the active metabolite of potassium-canrenoate displaces [(3H)]g-strophanthin from its binding sites in human cardiac cell membranes and inhibits (Na+ + K+)-ATPase activity. These in vitro effects were measured at the same concentrations as found in vivo after "therapeutical" doses. The effects of triamterene in this respect were found only in extremely high concentrations. Our results imply that canrenone has cardiac glycoside-like effects in human cardiac cell membranes.

Topics: Adenosine Triphosphatases; Adult; Aged; Arrhythmias, Cardiac; Canrenoic Acid; Cardiac Output; Cell Membrane; Coronary Disease; Digoxin; Diuretics; Dose-Response Relationship, Drug; Drug Interactions; Female; Heart; Humans; In Vitro Techniques; Male; Middle Aged; Myocardium; Ouabain; Potassium; Receptors, Drug; Sodium; Triamterene

The rapid i.v. administration of digitalis has recently been shown to cause a substantial increase in coronary vascular resistance in the normal heart. This neurogenically mediated decrease in coronary blood flow would be potentially detrimental if it occurred during ischemia. The present study evaluates the effects of i.v. acetylstrophanthidin and digoxin on coronary vascular resistance during acute global ischemia in 29 dogs anesthetized with chloralose and urethane. Under these conditions, 0.5 mg of i.v. acetylstrophanthidin in 15 dogs resulted in erratic increases in coronary vascular resistance. The peak rise was 12+/-5% above control (P less than 0.01). In 7 of the 15 dogs, the initial erratic rise in coronary vascular resistance culminated in a steep rise associated with acute elevation in left ventricular end-diastolic pressure, which in four dogs terminated in ventricular fibrillation. During the nonischemic control periods, the peak rise in coronary vascular resistance with acetylstrophanthidin was 16+/-1% above control (P less than 0.01). In five dogs, prior alpha adrenergic receptor blockade with phenoxybenzamine prevented the rise in coronary vascular resistance with acetylstrophanthidin during ischemia. Similar erratic increases in coronary vascular resistance were observed with i.v. digoxin (1 mg) during ischemia in three dogs. In two of these dogs, there was a progressive rise in coronary vascular resistance associated with elevation of left ventricular end-diastolic pressure and ventricular fibrillation. The increase in coronary vascular resistance with digoxin during ischemia was abolished with phenoxybenzamine in two additional dogs. Thus, i.v. digitalis in the ischemic heart results in potentially detrimental increases in coronary vascular resistance mediated through alpha adrenergic receptor stimulation.

Topics: Animals; Coronary Circulation; Coronary Disease; Coronary Vessels; Digoxin; Dogs; Phenoxybenzamine; Receptors, Adrenergic; Receptors, Adrenergic, alpha; Stimulation, Chemical; Strophanthins; Vascular Resistance; Ventricular Fibrillation

Therapeutic doses of digitalis may give rise to depressions and abnormities of the ST segment. In coronary patients this is occasionally also associated with anginal complaints. In 7 patients the ST segment was investigated at rest and under increasing stress by atrial frequency without and with digitalis at increasing therapeutic dosage. In all patients a glycoside-induced, linearly intensifying depression of the ST segment was demonstrated as a regular and dose-dependent pattern the onset of which was already recognizable at an average effective level of 0,59 mg digoxin. The opinion is held that glycoside-induced ST depressions in the ECG are not in general of insignificant nature but may be the reflection of myocardial ischemia.

Topics: Aged; Angina Pectoris; Coronary Disease; Digoxin; Dose-Response Relationship, Drug; Electric Stimulation; Electrocardiography; Female; Heart; Heart Rate; Humans; Male; Middle Aged; Oxygen Consumption

Topics: Adult; Cardiac Pacing, Artificial; Coronary Disease; Digoxin; Female; Heart Atria; Humans; Male; Medigoxin; Middle Aged; Myocardial Contraction; Systole

Topics: Adult; Aged; Biological Availability; Coronary Disease; Digoxin; Drug Labeling; Humans; Israel; Legislation, Drug; Male; Medication Errors; Middle Aged; Pulmonary Heart Disease; Rheumatic Heart Disease

Topics: Adult; Aged; Arrhythmias, Cardiac; Coronary Disease; Digoxin; Female; Heart Diseases; Heart Failure; Humans; Male; Middle Aged

Topics: Administration, Oral; Blood Pressure; Cardiac Output; Coronary Disease; Digitalis Glycosides; Digoxin; Heart Rate; Heart Ventricles; Hemodynamics; Humans; Infusions, Parenteral; Male; Middle Aged; Ouabain; Time Factors

Topics: Acute Disease; Child; Child, Preschool; Chronic Disease; Coronary Disease; Digoxin; Humans; Infant; Infant, Newborn; Myocarditis; Pneumonia; Strophanthins

Digitalis has been shown to improve the impaired ventricular function associated with coronary artery disease as well as to increase myocardial oxygen consumption and produce coronary vasoconstriction. To elucidate the net result of these contrasting effects, six patients with coronary artery disease and left ventricular ejection fractions less than 0.50 had 1.0 mCi thallium-201 injected intravenously at rest and during three minutes of 33% of maximal handgrip, off and on 0.25 mg daily maintenance digoxin. Thallium-201 scintigram images were taken 30 minutes later and were computer processed with orthogonal linearly interpolated background subtraction and maximal count density equalization. Processed images were visually graded on a 0, 1, or 2 scale for 18 sectors--nine from the AP projections and nine from the 40 degrees left anterior oblique projections. A score resulting from the summation of the 18 sector grades was made for each study, the maximum score being 36. Off digitalis, patients performing handgrip exercise decreased their scintigram scores from 25.7 +/- 1.5 (mean +/- SEM) to 23.0 +/- 1.0, P less than 0.05. When patients were on maintenance digoxin, scores did not change significantly during handgrip exercise. Post exercise scores were significantly higher on digoxin than off (P less than 0.05), whereas, resting scores were unaffected by digoxin. These data suggest that myocardial perfusion, as measured by thallium-201 uptake, is improved in patients on digitalis who have coronary artery disease and left ventricular dysfunction.

Topics: Blood Pressure; Coronary Disease; Digoxin; Heart Rate; Heart Ventricles; Humans; Isometric Contraction; Male; Middle Aged; Myocardium; Oxygen Consumption; Physical Exertion; Radioisotopes; Radionuclide Imaging; Rest; Thallium

The structure of cardiac rhythm was studied with the help of specialized computers during digitalization in 60 patients with atrial fibrillation of different etiology. The reduction of the heart contractions rate under digitalization is accompanied by certain changes in the structure of cardiac rhythm: the arrhythmic pattern of the ventricular contractions increases with a predominant growth of the number of long R--R intervals, the transitions from short intervals to longer ones become sharper, and portions of a relatively stable ventricular rhythm appear. Three main types of dynamics of the rhythm structure were distinguished on the basis of the changes in the interval R--R histogram. The described changes in the structure of cardiac rhythm are not specific, but when Digitalis drugs are used alone they can be used as additional criteria for digitalization.

Topics: Adult; Aged; Atrial Fibrillation; Atrioventricular Node; Coronary Disease; Digoxin; Electrocardiography; Heart Conduction System; Humans; Hyperthyroidism; Middle Aged; Rheumatic Heart Disease

Topics: Adult; Aged; Biopharmaceutics; Chronic Disease; Coronary Disease; Digitalis Glycosides; Digoxin; Dose-Response Relationship, Drug; Drug Evaluation; Female; Heart Failure; Humans; Male; Middle Aged; Rheumatic Heart Disease

Therapeutically effective doses of beta-acetyldigoxin in healthy subjects produced no or only minor S-T depression both at rest and under maximal cycle-ergometry, in individual instances the S-T segment never being depressed by more than 0.1 mV. On the other hand, similar exercise in patients with latent coronary insufficiency produced marked, significantly and dose-dependent S-T segment depressions under increasing digitalisation within the therapeutic range, and in some of the patients there was also decreased exercise tolerance before anginal symptoms. It is concluded that the so-called digitalis effect is definitely of diagnostic significance in the recognition of latent coronary insufficiency, contrary to previously held belief.

Topics: Adult; Coronary Disease; Digitalis Glycosides; Digoxin; Electrocardiography; Female; Humans; Male; Middle Aged; Physical Exertion

Controversy continues regarding the effects of administration of digitalis upon the exercise electrocardiogram. Thus, maximal treadmill exercise tests were performed before and two weeks after administration of 0.25 mg of digoxin daily in 15 normal subjects (documented by cardiac catheterization and coronary arteriographic studies). Administration of digitalis induced abnormal findings on exercise tests in all 14 subjects with serum levels of digoxin greater than or equal to 0.5 ng/ml; however, at workloads greater than 75 to 90 percent of maximal predicted heart rate, the changes in the ST segment reverted to a normal configuration in all subjects, thereby providing differentiation of digitalis-induced ST-segment alterations from those due to myocardial ischemia at maximal treadmill stress.

Topics: Adult; Aged; Coronary Disease; Diagnosis, Differential; Digitalis Glycosides; Digoxin; Electrocardiography; Exercise Test; Female; Heart; Hemodynamics; Humans; Male; Middle Aged; Myocardium; Oxygen Consumption; Radioimmunoassay

Topics: Adult; Aged; Biological Availability; Coronary Disease; Digoxin; Drug Tolerance; Female; Humans; Middle Aged

In patients of a cardiological practice, 121 digoxin serum concentrations were determined by radioimmunoassay (RIA). Some drugs were suspected of interfering with the RIA or with the pharmacokinetics of digoxin. Patients having such additional drugs or patients with elevated serum creatinine were not included. The daily maintenance dose of digoxin was roughly adjusted to body weight. Patients with 0.5 mg digoxin daily showed unexpectedly low serum digoxin levels not fully explained by the relatively high body weight. This dose group was not included in the following correlations. At a maintenance dose of 0.25 and 0.375 mg digoxin and in the age groups 40-69 years (n = 66) there was an approximately inverse proportionality between serum digoxin concentration (per 0.25 mg digoxin daily) and body weight. When all age classes from 20 to 89 years were included (n = 96), a week positive correlation between serum digoxin concentration (per 0.25 mg digoxin daily and per 69.28 kg body weight) and age was found. A similar positive correlation resulted between serum digoxin concentration (per 0.25 mg digoxin daily) and the reciprocal of the nomographically determined creatinine clearance, always within the normal serum creatinine range. Based on these correlations, two simplified formulas are presented to predict the serum concentration and therapeutic maintenance dose of digoxin. The formulas are valid for the normal serum creatinine range and for digoxin tablets of optimal bioavailability.

Topics: Adult; Age Factors; Aged; Body Weight; Coronary Disease; Creatinine; Digoxin; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Radioimmunoassay

Topics: Adrenergic beta-Antagonists; Aged; Aging; Antihypertensive Agents; Biological Availability; Coronary Disease; Digoxin; Diuretics; Dose-Response Relationship, Drug; Drug Interactions; Female; Heart Diseases; Humans; Hypertension; Hypokalemia; Male; Potassium; Risk

Topics: Coronary Disease; Digoxin; Estrogens; Female; Humans; Male

Using Indium-113m and the Gamma Retina V (Fucks-Knipping Camera), the minimal cardiac transit times (MTTs) were measured radiocardiographically from the right auricle to the aortic root. This analysis served to determine the relation between stroke volume and the segment volume of the part of circulation between the right auricle and the aortic root. In 39 patients with myocardial insufficiency of different clinical degree the effectiveness of digitalization was, up to a period of 5 years, measured by means of the volume relation mentioned above. The following conclusions can be drawn from the results: digitalization of patients with myocardial insufficiency leads to an improvement of the impaired relation of central volumes. In patients with diminished cardiac reserve the improvement is drastic and often results in a nearly complete normalization. The data remain constant during therapy even for an observation period of 5 years. Digitalization of patients with congestive heart failure only leads to a partial improvement. In contrast to patients with diminished cardiac reserve this effect is temporary. The different behaviour of the relation between stroke volume and segment volume in patients with diminished cardiac reserve and congestive heart failure under prolonged administration of digitalis points to the necessity of treatment with digitalis in the early stage of myocardial disease.

Topics: Adult; Aged; Cardiac Output; Cardiac Volume; Coronary Disease; Digoxin; Heart Failure; Humans; Middle Aged; Radioisotope Dilution Technique; Time Factors

Cardiac glycosides may cause in the exercise ECG of healthy persons S-T segment depressions, which imitate a coronary insufficiency. If this method of examination is to be carried out in diagnosing coronary heart disease, it is - therefore - recommended in many cases to discontinue, at all events, an eventual digitals therapy before the examination in order to avoid falsely positive results. 23 healthy men (average age 30.2 years) were applied digoxin of medially quick saturation over seven days. Exertion electrocardiograms at the bicycle ergometer were registered before and after digoxin application. In five further cases, plasma glycoside concentrations were evaluated by 86Rb erythrocyte assay; upon the degree of saturation used, these concentrations - on the sixth and seventh day - amounted to x = 1.03 ng/ml. The following items manifested after digoxin administration, under stress and after resting: Retardation of heart rate, declination of T amplitude, and individually to a very different extent - depression of the S-T segment. After application of digoxin, only 8 of the 23 test persons demonstrated S-T depressions that would have corresponded entirely to the conditions of a "coronary insufficiency". Thus, it appears to be justified to carry out - first of all and in order to exclude the possibility of a coronary insufficiency - an exertion electrocardiogram, without interruption of the glycoside therapy, also in patients who are undergoing a digitalis therapy. The reason for this measure is the fact that in healthy persons only one third of the cases must be expected to show a falsely positive result. If, however, significant S-T depressions occur, the examination has to be repeated after a sufficiently long-lasting glycoside-free interval.

Topics: Adult; Coronary Disease; Digoxin; Dose-Response Relationship, Drug; Electrocardiography; Exercise Test; False Positive Reactions; Heart; Heart Rate; Humans; Male

Blood concentrations of Digoxin were determined by radioimmuno-assay in 80 patients with different stages of circulatory insufficiency receiving maintenance therapy with Digoxin, 0.25-0.75 mg/day. The range of Digoxin concentration fluctuations is very wide--from 0.25 to 2.4 ng/ml. Some elevation of Digoxin concentration in blood was observed when the dose of the drug was increased, both in different groups of patients, and in the same patients when the maintenance dose was altered. Studies conducted during digitalis intoxication in 4 patients demonstrated different levels of Digoxin concentration in blood--from 0.8 to 2.6 ng/ml. The obtained results permitted to conclude that the concentration of Digoxin in blood has no significance in choosing the optimum therapeutic dose, unless the clinical data are taken into account.

Topics: Adult; Aged; Biopharmaceutics; Coronary Disease; Digoxin; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Radioimmunoassay; Rheumatic Heart Disease

ST-segmental depression below the isoelectric line in the ECG occurring under a therapy of sub-therapeutical and therapeutical digitalising doses, very often involves an increase of pre-existent stress stenocardia with cardiovascularily compensated patients having a coronary heart disease. For this purpose, 13 patients of both sexes with latent coronary insufficiency were examined. The patients were treated with beta-Acetyldigoxin i.v. and were controlled under bicycle ergometric test-conditions before as well as during the different saturation phases with digitalis (0.66 +/- 0.03 mg, 1.20 +/- 0.07 mg and 1.54 +/- 0.10 mg beta-Acetyldigoxin) in a miximum of 4 functional tests alltogether. Dose-depent depression of the ST-segment accurred regularly accompanied by a reduction of the T-wave amplitude. A comparative valuation of myocardischemic and glycoside conditioned repolarisation disorders in the ECG demonstrated formalanalytically no differences concerning differential diagnosis. With the appearance of digitalis conditioned ST-T-changes an increase of angina pectoris could be proved. There were hints that the so-called adhesive signs of digitalis are an expression of myocardial ischemia and therefore principally of diagnostic value.

Topics: Aged; Coronary Disease; Digoxin; Electrocardiography; Female; Humans; Male; Middle Aged; Physical Exertion

Topics: Coronary Disease; Digoxin; Electrocardiography; Exercise Test; Hemodynamics; Humans

Topics: Aged; Coronary Disease; Digoxin; Exercise Therapy; Female; Humans; Male; Middle Aged; Myocardial Infarction; Oxyfedrine

The results of a single intravenous injections of strophanthin or digoxin and of a course-wise medication with cardiac glycosides in acute and chronic ischemic heart disease are contrasted. Investigations were carried out in 64 patients under cardiomonitoring with an automatic extrasystoles count. In the absence of extrasystoles or infrequent ones the cardiac glycosides provoked frequent extrasystoles in 10 per cent of the patients. The antiarrhythmic effect was recorded in 1/3 of the patients with infrequent extrasystoles. In cases of frequent extra systoles the positive result of the glycoside test justifies anticipating a beneficial influence of digitalization on the heart rate. In all the cases the results of the glycoside test determine in a large measure the individual prognosis.

Topics: Administration, Oral; Cardiac Complexes, Premature; Cardiac Glycosides; Coronary Disease; Digoxin; Humans; Injections, Intravenous; Prognosis; Strophanthins; Tablets

Eight patients with chronic congestive heart failure (four with cardiomyopathy and four with ischemic heart disease) underwent hemodynamic studies during acute administration of digoxin, given intravenously in two 0-5 mg doses 2 hours apart. Observations were made before administration of digitalis (control period) and serially therafter for 4 hours after the first dose. Resting mean cardiac index and pulmonary arterial wedge pressure were as follows: 2.0 liters/min per m2 and 23 mm Hg (control period); 2.1 and 24 (at 1 hour); 2.0 and 23 (at 2 hours); 2.7 and 19 (at 3 hours); and 2.3 and 20 (at 4 hours). Exercise responses of mean cardiac index and pulmonary arterial wedge pressure in five patients were: 3.1 liters/min per m2 and 36 mm Hg (control period); 3.2 and 33 (at 1 hour); 3.2 and 28 (at 2 hours); 3.1 and 27 (at.3 hours); and 3.4 and 31 (at 4 hours). The pulmonary arterial wedge pressure remained elevated during exercise in all cases. Arrhythmias were seen in five patients after administration of 0.5 mg of digoxin. Hemodynamic improvement at 4 hours involving both reduced filling pressure and increased blood flow was observed in only two patients at rest and in one additional patient during exercise. Acute deterioration of cardiac function (elevated pulmonary arterial wedge pressure of decreased cardiac index) occurred 30 minutes after administration of digoxin in four patients, concomitantly with increased systemic resistance. In six patients, a peak hemodynamic effect appeared 1 to 1 1/2 hours after administration of digoxin, with partial or total loss of initial benefit by 2 and 4 hours. In previously performed studies observations have seldom exceeded 1 hour; the results of this 4 hour study suggest that, in patients with cardiomyopathy or coronary artery disease and chronic congestive heart failure, acute digitalization does not necessarily lead to consistent, marked or lasting hemodynamic improvement. Thus, current concepts of the use of digitalis is such patients may require revision.

Topics: Adult; Blood Pressure; Cardiac Catheterization; Cardiac Output; Cardiomyopathies; Coronary Disease; Digoxin; Heart Failure; Hemodynamics; Humans; Injections, Intravenous; Middle Aged; Pulmonary Circulation; Time Factors; Vascular Resistance

A dose-response relation between cardiac glycosides and systolic time intervals has previously been established in short-term studies in which the glycoside was administered intravenously in these studies there was uncertainty regarding the steady state kinetics, and maintenance of the early serum levels would have resulted in toxicity. Accordingly, we studied the effect on systolic time intervals of small increments of serum digoxin within the therapeutic range. Serum digoxin concentration and systolic time intervals were measured in 21 patients receiving 0.25 mg of the glycoside daily. The daily dose was increased to 0.5 mg and measurements were repeated 5 to 7 days later. Serum digoxin concentration with the smaller dose was 0.56 plus or minus (standard error) 0.06 ng/ml and increased to 1.18 plus or minus 0.11 ng/ml with the larger dose. Associated with the increased serum digoxin was a mean decrease in duration of total electromechanical events of 6.3 plus or minus 2.9 msec (P smaller than 0.025), which resulted from a mean shortening of left ventricular ejection time of 5.6 plus or minus 3.0 msec (P smaller than 0.05). The mean decrease in preejection phase of 1.1 plus or minus 2.1 msec was insignificant (P larger than 0.2). Repeated measurements in control patients showed no change in serum digoxin concentration or systolic time intervals. In nine patients the digoxin dose was randomly varied between 0 and 0.75 mg and measurements were made 4 to 5 days after drug administration at each dose level. The correlation coefficient between changes in serum digoxin and changes in left ventricular ejection time was minus 0.55 (P smaller than 0.01) the data indicated that increasing the maintenance dose of digoxin while keeping the serum level within therapeutic range will result in improved ventricular function as assessed by determination of systolic time intervals.

Topics: Adult; Aged; Carotid Arteries; Coronary Disease; Digoxin; Dose-Response Relationship, Drug; Electrocardiography; Heart; Heart Failure; Heart Ventricles; Humans; Hypertension; Injections, Intravenous; Middle Aged; Myocardial Infarction; Phonocardiography; Pulse; Radioimmunoassay

Physiologic concepts relating to reperfusion of ischemic areas of myocardium may be applied both to acute coronary insuficiency, manifested by angina pectoris, and to restoration of coronary blood flow by coronary bypass procedures, currently employed both in acute myocardial infarction and in chronic myocardial ischemia for relief of angina pectoris. Of the information currently available from experimental studies, much may be applicable to the clinical situation. After acutr transient coronary occlusion mechanical and electrical properties of the ischemic area rapidly return to normal, but there is prolongation of tension development and occurrence of ventricular arrhythmias; implications of these phenomena for clinical coronary ischemia deserve exploration. Following more prolonged coronary ischemia, results of experimental reperfusion appear to be variable and, although restoration of function following several hours of ischemia is possible, certain deleterious effects are often observed in the form of myocardial edema and hemorrhage. Clinical use of bypass procedures in acute myocardial infarction suggests that results may be good, but that deleterious effects are occasionally observed; occurrence of the later requires definition and explanation. Restoration of myocardial blood flow in the presence of normal left ventricular function in chronic coronary artery disease, and failure to reverse functional abnormalities when left ventricular damage has already ensued in the clinical situation, appears to be well established; however, better methods to assess the potential for recovery of function following revascularization are needed in both acute and chronic coronary artery diseases. It is anticipated that more careful exploration of pathophysiology both in the catheterization laboratory and in the operating room may aid this process.

Topics: Acute Disease; Animals; Cardiac Catheterization; Coronary Circulation; Coronary Disease; Digoxin; Electrocardiography; Heart; Heart Conduction System; Humans; Myocardial Infarction; Myocardial Revascularization; Myocardium; Oxygen Consumption

This study examines the effect of 2 hours of reperfusion on transiently ischemic myocardium in pigs. Indexes of myocardial viability measured were mitochondrial function, oxygen extraction, epicardial S-T segment change and distribution of tritiated digoxin. Results were as follows: (1) Mitochondrial function was markedly impaired in the reperfused area after 60 minutes or more of coronary occlusion. The defect would seem to be a block in electron flow near site I, which can be partially bypassed with succinate. (2) An apparent inability of the reperfused myocardium to extract oxygen did not improve with 2 hours of reperfusion. (3) Epicardial S-T segment mapping suggested that necrosis occurred during reperfusion. (4) There was an altered distribution of tritiated digoxin in the reperfused area. The results show that reperfusion for 2 hours did not improve myocardial viability after 60 minutes or more of ischemia.

Topics: Adenosine Triphosphate; Animals; Coronary Circulation; Coronary Disease; Digoxin; Dogs; Electrocardiography; Female; Heart Conduction System; Male; Mitochondria, Muscle; Myocardial Contraction; Myocardium; Oxidative Phosphorylation; Oxygen Consumption; Swine

Topics: Aged; Anesthesia; Anesthesia, Conduction; Anesthesia, General; Anesthetics; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Coronary Disease; Digoxin; Emergencies; Geriatrics; Homeostasis; Humans; Kidney; Liver; Metabolism; Nerve Block; Postoperative Care; Postoperative Complications; Preoperative Care; Respiratory Physiological Phenomena; Respiratory Therapy; Respiratory Tract Diseases; Surgical Procedures, Operative; Thromboembolism

Topics: Adult; Aged; Azepines; Coronary Disease; Digoxin; Dilazep; Drug Combinations; Drug Evaluation; Female; Humans; Male; Middle Aged

Topics: Coronary Disease; Digoxin; Drug Combinations; Heart Failure; Humans; Prenylamine

Topics: Cardiomyopathies; Coronary Disease; Digoxin; Heart Valve Diseases; Humans

The effects of coronary reperfusion on the uptake of digoxin by ischemic myocardium were studied in 17 open chest dogs undergoing anterior wall infarction produced by snaring confluent branches of the left coronary arterial system. Epicardial electrograms delineated ischemic, border and nonischemic zones. The hearts were reperfused by snare release after 1, 2 and 6 hours of occlusion. After 15 minutes of reperfusion, 1.0 mg of tritiated digoxin (3H-digoxin) was given intravenously, and 2 hours later the hearts were excised and endocardial and epicardial samples from each zone were analyzed for 3H-digoxin concentration. In another group of eight dogs regional myocardial blood flow was assessed utilizing 15 mu of radio-labeled microspheres administered during occlusion and reperfusion. In five dogs with 1 hour of coronary occlusion and subsequent reperfusion, 3H-digoxin uptake was comparable in endocardial and epicardial layers of all three zones. In six dogs undergoing reperfusion after 2 hours of occlusion, mean 3H-digoxin concentration was significantly (P less than 0.001) reduced from the mean nonischemic concentration, by 54 percent in endocardial and 35 percent in epicardial layers of the ischemic zone. Border zone endocardial and epicardial 3H-digoxin uptake was reduced by 21 percent and 16 percent, respectively (P less than 0.05). In six dogs undergoing reperfusion after 6 hours of occlusion, 3H-digoxin uptake in the ischemic zone was significantly (P less than 0.001) reduced by 85 percent in endocardial and 60 percent in epicardial layers from the concentration in the nonischemic zone. Border zone uptake was decreased by 54 percent in endocardial and 36 percent in epicardial regions (P less than 0.01). These alterations of in vivo digoxin binding could not be explained by impaired reflow of blood to ischemic myocardium. We conclude that coronary reperfusion after 2 to 6 hours of occlusion is associated with a marked reduction in myocardial digoxin uptake, which is more pronounced in subendocardial than in subepicardial regions of ischemic tissue.

Topics: Animals; Coronary Circulation; Coronary Disease; Digoxin; Disease Models, Animal; Dogs; Myocardium

The radioisotope method with Rb86 was used for determining in vitro the serum concentration of Digoxin. The study was conducted in 57 patients with cardiac insufficiency in the acute period of myocardial infarction and with post infarction cardiosclerosis. The mean values of Digoxin concentration depending on the daily maintenance dose were obtained. The direct correlation between the amount of the drug taken and the content of the drug in the blood serum was proved. Digoxin intoxication was found to develop in cases of its content exceeding the mean level for the given dosage (4 patients), however, in 2 patients signs of intoxication developed with a low concentration of Digoxin. The causes favouring the development of intoxication are discussed.

Topics: Adult; Aged; Coronary Disease; Digoxin; Dose-Response Relationship, Drug; Drug Tolerance; Humans; In Vitro Techniques; Male; Middle Aged; Radioisotopes; Rubidium

Topics: Adult; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Chronic Disease; Coronary Disease; Digoxin; Female; Humans; Male; Middle Aged; Strophanthins

Topics: Coronary Disease; Digoxin; Female; Humans; Male; Middle Aged; Myocardium

This study examines indices of respiratory function in mitochondria prepared from transiently ischemic myocardium that had been reperfused in order to evaluate the validity of performing early surgical revascularization procedures. Experiments were performed in pigs with temporary ligation (15-80 min) of an anterior descending coronary artery followed by a 2-hr reperfusion period. Mitochondria preparations were studied simultaneously from normal and reperfused mitochondria in malate and glutamate substrates using the polarographic method. Results revealed a marked decrease of oxygen consumption of mitochondria from reperfused myocardium with relative preservation of oxidative phosphorylation (near normal ADP/O ratio). These results are compatible with a block in electron transport, a theory which was further supported by the data obtained using dinitrophenol as an uncoupler. Additional studies suggested the block was located at site I in the electron transport chain since mitochondrial oxygen consumption, including ATP-linked oxygen consumption, was enhanced by the use of succinate in combination with glutamate. The abnormal mitochondrial function observed is probably due to ischemia persisting despite reperfusion.

Topics: Acute Disease; Adenosine Diphosphate; Animals; Coronary Disease; Coronary Vessels; Digoxin; Glutamates; Malates; Mitochondria, Muscle; Myocardium; Oxygen Consumption; Perfusion; Succinates; Swine

Topics: Cardiac Output; Coronary Disease; Digoxin; Exercise Test; Heart; Heart Rate; Humans

Topics: Blood Pressure; Coronary Disease; Digoxin; Heart Rate; Humans; Isometric Contraction; Physical Exertion

Topics: Animals; Cardanolides; Chromatography, Thin Layer; Coronary Disease; Digoxin; Dogs; Electrocardiography; Myocardial Infarction; Myocardium; Tritium

Using the recipient's human heart removed at cardiac transplantation, the distribution of digoxin at both the cellular and subcellular level has been studied. In the presence of diffuse histological myocardial abnormalities tissue digoxin is decreased, but the subcellular distribution, presumably reflecting binding to a possible receptor site, is uniform. When the histological abnormality is focal then digoxin distribution is uniform.These results suggest that in the presence of myocardial ischaemia plasma digoxin concentrations may not reflect total myocardial levels accurately.

Topics: Adenosine Triphosphatases; Adult; Blood Urea Nitrogen; Cardiomyopathy, Hypertrophic; Coronary Disease; Digoxin; Female; Heart Atria; Heart Transplantation; Heart Ventricles; Humans; Magnesium; Male; Microsomes; Middle Aged; Myocardium; Potassium; Radioimmunoassay; Sodium; Transplantation, Homologous

Topics: Animals; Arteriosclerosis; Biopsy; Coronary Disease; Digoxin; Female; Heart Atria; Heart Valve Diseases; Humans; Myocardium; Oxidation-Reduction; Radioimmunoassay; Rats; Tritium

Topics: Arrhythmia, Sinus; Arrhythmias, Cardiac; Coronary Disease; Digoxin; Diuretics; Electroconvulsive Therapy; Endocarditis, Bacterial; Heart Aneurysm; Heart Failure; Heart Valve Diseases; Heart Ventricles; Humans; Lidocaine; Myocardial Infarction; Pacemaker, Artificial; Pericarditis, Constrictive; Potassium Deficiency; Rupture; Spironolactone; Tachycardia; Ventricular Fibrillation; Wolff-Parkinson-White Syndrome

Topics: Acetyldigoxins; Adult; Aged; Blood Pressure; Coronary Disease; Digoxin; Drug Combinations; Female; Heart Rate; Humans; Male; Middle Aged; Oxyfedrine; Propiophenones; Time Factors

Topics: Aged; Animals; Atropine; Bradycardia; Coronary Disease; Digoxin; Female; Heart Block; Heart Failure; Humans; Injections, Intravenous; Lidocaine; Male; Myocardial Infarction; Rabbits

Topics: Age Factors; Aged; Aortic Diseases; Arrhythmias, Cardiac; Cardanolides; Coronary Disease; Digoxin; Female; Gastrointestinal Diseases; Heart Block; Heart Failure; Heart Valve Diseases; Humans; Lung Diseases; Male; Middle Aged; Mitral Valve Insufficiency; Rheumatic Heart Disease; Tachycardia

Topics: Adult; Angina Pectoris; Coronary Disease; Digoxin; Drug Combinations; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Prenylamine

Topics: Administration, Oral; Coronary Disease; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Myocardial Infarction; Phenytoin; Tachycardia

Topics: Coronary Disease; Digoxin; Drug Combinations; Heart Failure; Humans

Topics: Arrhythmias, Cardiac; Carbon Dioxide; Cardiac Complexes, Premature; Cardiomegaly; Coronary Disease; Digoxin; Heart Failure; Heart Rate; Humans; Hypertension, Pulmonary; Male; Oxygen; Potassium; Pulmonary Heart Disease

Topics: Aortic Valve Stenosis; Arrhythmias, Cardiac; Cardiac Complexes, Premature; Cardiomyopathies; Coronary Disease; Digoxin; Electrocardiography; Heart; Heart Ventricles; Humans; Hypertension; Middle Aged; Mitral Valve Stenosis; Myocardial Infarction; Pulmonary Heart Disease; Time Factors

Topics: Aged; Ambulatory Care; Arteriosclerosis; Aspartate Aminotransferases; Blood Pressure; Coronary Disease; Digoxin; Female; Humans; Male; Methods; Middle Aged; Myocardial Infarction; Radioisotopes; Rubidium; Sex Factors

Topics: Aged; Blood Urea Nitrogen; Calcium; Coronary Disease; Creatinine; Digitalis Glycosides; Digitoxin; Digoxin; Electrocardiography; Evaluation Studies as Topic; Heart Failure; Heart Valve Diseases; Humans; Kidney Failure, Chronic; Middle Aged; Myocardial Infarction; Photometry; Potassium; Radioimmunoassay; Saliva; Specimen Handling; Spectrophotometry, Atomic

Topics: Animals; Coronary Disease; Digoxin; Dogs; Heart Ventricles; Myocardium; Time Factors; Tritium

Topics: Aged; Blood Pressure; Body Surface Area; Cardiac Output; Coronary Disease; Digoxin; Electrocardiography; Female; Heart Failure; Heart Rate; Heart Ventricles; Hemodynamics; Humans; Injections, Intravenous; Male; Middle Aged; Myocardial Infarction; Potassium; Pulmonary Artery; Tachycardia; Vascular Resistance

Topics: Aged; Aminosalicylic Acids; Arrhythmias, Cardiac; Arteriosclerosis; Cerebrovascular Disorders; Coronary Disease; Digoxin; Electrocardiography; Furosemide; Heart Conduction System; Humans; Hypertension; Isoniazid; Kidney Failure, Chronic; Lung Diseases, Obstructive; Middle Aged; Myocardial Infarction; Phenytoin

Topics: Adult; Aged; Coronary Disease; Digoxin; Drug Combinations; Female; Humans; Male; Middle Aged; Pentaerythritol Tetranitrate; Tranquilizing Agents

Topics: Aged; Arteriosclerosis; Coronary Disease; Creatinine; Diabetes Complications; Digoxin; Gout; Half-Life; Humans; Kidney Failure, Chronic; Kinetics; Male; Time Factors

Topics: Age Factors; Aged; Angina Pectoris; Blood Pressure; Chronic Disease; Coronary Disease; Digoxin; Drug Synergism; Drug Therapy, Combination; Electrocardiography; Female; Geriatrics; Heart Failure; Heart Rate; Humans; Male; Nitro Compounds; Pentaerythritol Tetranitrate

Topics: Adrenergic beta-Antagonists; Coronary Disease; Digoxin; Humans; Nitrites; Physical Therapy Modalities; Vasodilator Agents

Topics: Angiocardiography; Carotid Arteries; Coronary Artery Bypass; Coronary Disease; Coronary Vessels; Digoxin; Electrocardiography; Female; Heart Rate; Heart Ventricles; Humans; Male; Myocardial Infarction; Phonocardiography; Pulse

Topics: Coronary Disease; Digoxin; Heart Diseases; Heart Failure; Hemodynamics; Humans; Hypertension; Indicator Dilution Techniques; Indium; Radioisotopes

Topics: Adolescent; Adult; Aged; Coronary Disease; Digoxin; Female; Heart Diseases; Humans; Male; Middle Aged; Tablets

Topics: Arrhythmias, Cardiac; Benzoates; Coronary Disease; Digoxin; Drug Combinations; Heart Diseases; Heart Failure; Humans; Morpholines; Tranquilizing Agents; Verapamil

Topics: Arrhythmias, Cardiac; Arteriosclerosis; Cardiac Output; Coronary Disease; Digoxin; Heart Rate; Humans; Intestinal Absorption; Rheumatic Heart Disease

Topics: Angiocardiography; Cardiac Catheterization; Coronary Circulation; Coronary Disease; Coronary Vessels; Cyanosis; Digoxin; Electrocardiography; Heart Failure; Heart Ventricles; Humans; Infant, Newborn; Infant, Newborn, Diseases; Oxygen Inhalation Therapy; Pulmonary Circulation; Respiratory Distress Syndrome, Newborn

Topics: Accidents; Adolescent; Adult; Aged; Cardiac Complexes, Premature; Child, Preschool; Coronary Disease; Digoxin; Female; Half-Life; Humans; Male; Middle Aged; Poisoning; Radioimmunoassay; Suicide; Tachycardia, Paroxysmal; Ventricular Fibrillation

Topics: Adult; Aged; Angina Pectoris; Arrhythmias, Cardiac; Blood Pressure; Cardiac Complexes, Premature; Coronary Disease; Digoxin; Geriatrics; Heart Diseases; Heart Failure; Humans; Hypertension; Middle Aged; Morpholines; Myocardial Infarction; Phenethylamines; Pulmonary Heart Disease; Pulse; Tachycardia

Topics: Acute Disease; Aged; Arrhythmias, Cardiac; Coronary Disease; Digitalis Glycosides; Digitoxin; Digoxin; Electrocardiography; Female; Humans; Lung Diseases; Male; Myocardial Infarction; Poisoning; Prognosis; Prospective Studies; Radioimmunoassay

Topics: Administration, Oral; Adult; Age Factors; Aged; Arrhythmias, Cardiac; Coronary Disease; Digoxin; Electrocardiography; Female; Humans; Hypothyroidism; Male; Middle Aged; Nausea; Potassium; Radioimmunoassay; Rheumatic Heart Disease; Urea; Vomiting

Topics: Aspartic Acid; Coronary Disease; Digoxin; Humans; Magnesium; Magnesium Deficiency; Potassium

Topics: Administration, Oral; Animals; Cardiac Catheterization; Cardiac Output; Cardiomyopathies; Chagas Disease; Coronary Disease; Digitalis Glycosides; Digoxin; Dogs; Electrocardiography; Heart Diseases; Hemodynamics; Humans; Hypertension; Male; Mitral Valve Insufficiency; Ouabain; Oxygen Consumption; Phonocardiography

Topics: Aged; Arrhythmias, Cardiac; Bradycardia; Coronary Disease; Digoxin; Electrocardiography; Heart Block; Humans; Hypertension; Ischemic Attack, Transient; Middle Aged; Rheumatic Heart Disease; Syncope; Tachycardia

Topics: Angina Pectoris; Coronary Disease; Digitalis Glycosides; Digoxin; Drug Synergism; Electrocardiography; Female; Humans; Male; Middle Aged; Pentaerythritol Tetranitrate

Topics: Arrhythmias, Cardiac; Coronary Disease; Digoxin; Heart Diseases; Humans

Topics: Chronic Disease; Coronary Disease; Digoxin; Drug Synergism; Electrocardiography; Female; Heart Failure; Humans; Male; Pentaerythritol Tetranitrate

Topics: Adult; Aged; Arteriosclerosis; Coronary Disease; Digoxin; Female; Heart Diseases; Humans; Male; Middle Aged

Topics: Angina Pectoris; Collateral Circulation; Coronary Disease; Digoxin; Humans; Male; Middle Aged; Myocardium; Oxygen; Time Factors

Topics: Adult; Coronary Disease; Digoxin; Electrocardiography; Exercise Test; Humans; Middle Aged; Rest

Topics: Aged; Coronary Disease; Digoxin; Heart Diseases; Humans; Middle Aged

Topics: Aged; Coronary Disease; Digoxin; Electrocardiography; Female; Heart; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Phytotherapy; Plants, Medicinal; Tablets

Topics: Adult; Aged; Coronary Disease; Digoxin; Diuresis; Female; Heart Failure; Heart Valve Diseases; Humans; Hypertension; Male; Middle Aged; Pulmonary Heart Disease; Radiography

Topics: Aged; Arrhythmias, Cardiac; Aspartate Aminotransferases; Biophysical Phenomena; Biophysics; Blood Flow Velocity; Blood Pressure; Cardiac Output; Coronary Disease; Digoxin; Electrocardiography; Heart; Heart Failure; Humans; Hydrocortisone; Hypotension; Isoproterenol; Lidocaine; Male; Methyldopa; Middle Aged; Models, Biological; Propranolol; Stress, Psychological; Veins

Topics: Aged; Coronary Disease; Digoxin; Female; Humans; Lanatosides; Male; Middle Aged

Topics: Adult; Aged; Coronary Disease; Digoxin; Electrocardiography; Female; Humans; Male; Methods; Middle Aged

Topics: Cardiomyopathies; Child; Child, Preschool; Coronary Disease; Diagnosis, Differential; Digoxin; Humans; Hypertension; Infarction; Mitral Valve Insufficiency; Pericarditis, Constrictive; Prognosis

Topics: Adult; Aged; Arrhythmias, Cardiac; Coronary Disease; Digoxin; Female; Humans; Male; Middle Aged; Rheumatic Heart Disease

Topics: Coronary Disease; Digoxin; Female; Humans; Male; Vasodilator Agents

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Child; Coronary Disease; Digoxin; Female; Heart Defects, Congenital; Heart Diseases; Heart Valve Diseases; Humans; Male; Middle Aged; Pulmonary Heart Disease; Rheumatic Heart Disease; Tachycardia, Paroxysmal

Topics: Blood Pressure; Coronary Disease; Digoxin; Heart Diseases; Heart Rate; Humans; Hypertension; Intestinal Absorption; Pulmonary Heart Disease; Pulse; Tablets; Tachycardia, Paroxysmal

Topics: Coronary Disease; Digitalis Glycosides; Digoxin; Electrocardiography; Heart Failure; Humans; Vasodilator Agents

Topics: Angina Pectoris; Coronary Disease; Digoxin; Electrocardiography; Hydrochlorothiazide; Hypercholesterolemia; Hypertension; Metaraminol; Nitroglycerin; Shock; Shock, Cardiogenic; Vasopressins; Warfarin

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