digitoxin and Myocardial-Infarction

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

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

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

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

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

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

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

Topics: Animals; Digitalis; Digitalis Glycosides; Diuresis; Drug Interactions; Heart Failure; Hemodynamics; Humans; Kinetics; Myocardial Infarction; Plants, Medicinal; Plants, Toxic; Prognosis; Quinidine

Topics: Cardiac Output, Low; Cardiac Tamponade; Cardiotonic Agents; Catecholamines; Digitalis; Dobutamine; Dopamine; Glucagon; Humans; Isoproterenol; Metaraminol; Methoxamine; Myocardial Infarction; Norepinephrine; Phenylephrine; Plants, Medicinal; Plants, Toxic; Pulmonary Embolism; Shock, Cardiogenic

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

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

Topics: Action Potentials; Animals; Cell Membrane; Central Nervous System Diseases; Digitalis; Drug Interactions; Drug Resistance; Heart Conduction System; Heart Ventricles; Humans; Infusions, Parenteral; Injections, Intramuscular; Lidocaine; Liver Circulation; Microsomes, Liver; Myocardial Infarction; Plants, Medicinal; Plants, Toxic; Tachycardia; Time Factors; Ventricular Fibrillation

Topics: Cardiac Output; Catecholamines; Digitalis Glycosides; Digitoxin; Digoxin; Dopamine; Glucagon; Heart; Heart Failure; Humans; Isoproterenol; Myocardial Infarction; Norepinephrine

Topics: Adenylyl Cyclases; Adrenal Cortex Hormones; Catecholamines; Cyclic AMP; Depression, Chemical; Digitalis; Digitalis Glycosides; Fatty Acids, Nonesterified; Glucagon; Glucocorticoids; Growth Hormone; Humans; Insulin; Isoproterenol; Metaraminol; Methoxamine; Myocardial Infarction; Norepinephrine; Ouabain; Oxygen Consumption; Phosphoric Diester Hydrolases; Plants, Medicinal; Plants, Toxic; Shock, Cardiogenic; Stimulation, Chemical

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

Topics: Clinical Trials as Topic; Coronary Disease; Digitalis; Heart Failure; Humans; Myocardial Infarction; Plants, Medicinal; Plants, Toxic; Prognosis; Random Allocation; Statistics as Topic

Topics: Clinical Trials as Topic; Digitalis; Humans; Myocardial Infarction; Plants, Medicinal; Plants, Toxic; Random Allocation; Retrospective Studies

The influence of digitalis therapy on survivors of acute myocardial infarction was examined in the placebo-treated patients from the Beta-Blocker Heart Attack Trial (BHAT). Two hundred fifty (13%) of the 1,921 placebo-treated patients were receiving digitalis at the time of randomization. Patients receiving digitalis differed from those not receiving digitalis in such baseline characteristics as age, prior history of heart failure, prior myocardial infarction and angina pectoris. They also experienced a higher proportion of in-hospital complications including pulmonary edema, persistent hypotension, atrial fibrillation and heart failure in addition to a greater prevalence of complex ventricular premature beats. The total mortality rate over a mean 25 month follow-up period for digitalis-treated patients was 20.4% compared with 8.2% for patients not receiving digitalis; the odds ratio was 2.87 (p less than 0.05). When the mortality rates were adjusted for heart failure and ventricular premature beat complexity, patients receiving digitalis again demonstrated a higher mortality rate, although the adjusted odds ratio was now lower (1.70). When the patients receiving or not receiving digitalis were compared by a multiple logistic regression analysis adjusting for 17 independent variables predictive of mortality, the use of digitalis was no longer independently predictive of total mortality (adjusted odds ratio 1.07). These data indicate that patients receiving digitalis had more extensive cardiovascular disease and greater morbidity than patients not receiving digitalis. Their subsequent higher mortality rate was probably related to these factors rather than to digitalis therapy.

Topics: Adult; Aged; Blood Pressure; Digitalis; Electrocardiography; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Myocardial Infarction; Plants, Medicinal; Plants, Toxic; Random Allocation

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

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

Topics: Age Factors; Aged; Blood Pressure; Body Weight; Clinical Trials as Topic; Digitoxin; Female; Headache; Heart Diseases; Heart Rate; Heart Valve Diseases; Humans; Ischemia; Male; Middle Aged; Myocardial Infarction; Nausea; Pulmonary Heart Disease; Tachycardia, Paroxysmal

Topics: Adult; Digitoxin; Electrocardiography; Humans; Intestinal Absorption; Male; Middle Aged; Myocardial Infarction

Topics: Adult; Aged; Arteriosclerosis; Body Weight; Clinical Trials as Topic; Diet, Sodium-Restricted; Digitoxin; Diuresis; Electrocardiography; Heart Conduction System; Heart Failure; Humans; Hyperthyroidism; Injections, Intravenous; Middle Aged; Myocardial Infarction

The aim of the present study was to evaluate if the influence of digitalis on survival depends on the severity of cardiac dysfunction in heart failure (HF).. Doppler echocardiogram (DE) parameters were analyzed in 84 Wistar control (C) and 80 Wistar rats treated with 0.1mg/100g/day of digitoxin (D) five days after coronary occlusion. The DE variables correlated with the survival of the animals were: myocardial infarction size, left chamber dimensions, fractional area change and E/A ratio. The animals were observed for up to 280 days. Mortality was worsened in rats in the D group with a myocardial infarction (MI)<37% and with better DE predictors of survival. Digitoxin was found to prolong survival in rats with an MI ≥ 37% and worse DE predictors.. For the first time our study has shown experimentally that the action of digitalis glycosides can positively or negatively influence survival during treatment of HF. It prolongs survival of those in advanced state and compromises survival when there is less severity of the disease. In fact, the greater benefits occur when digitoxin was used in heightened ventricular dilatations and worse ventricular performance.

Topics: Animals; Digitalis; Digitoxin; Female; Heart Failure; Myocardial Infarction; Rats; Rats, Wistar; Severity of Illness Index; Survival Rate

We analyzed whether digitoxin affects the survival of rats with congestive heart failure.. The influence of digitoxin (0.1 mg.100 g.day, orally) on the survival of infarcted female rats (n=170) randomized as Control Infarcted (CI, n=85) or Digitoxin (D, n=85) was evaluated for 280 days. Mean survival was 235+/-7 days for CI and 255+/-5 days for D (log-rank test: P=.0602). Digitoxin did not affect survival in rats with congestive heart failure from myocardial infarction <40% of the left ventricle, but did prolong survival in rats with infarction >or=40%. The log-rank test defined higher mortality (P=.0161) in CI >40% (56%) than in D >40% (34%), with a hazard ratio of 2.03. Pulmonary water content and papillary muscle mechanics were analyzed in CI (n=7) and D (n=14) survivors. Significant differences were observed regarding pulmonary water content (CI: 82+/-0.3; D: 80+/-0.3%; P=.0014), developed tension (CI: 2.7+/-0.3; D: 3.8+/-0.3g/mm(2); P=.0286) and +dT/dt (CI: 24+/-3; D: 39+/-4 mg mm(2).s; P=.0109).. In conclusion, long-term digitoxin administration reduced cardiac impairment after myocardium infarction, attenuated myocardial dysfunction, reduced pulmonary congestion, and provided the first evidence regarding the efficiency of digitoxin in prolonging survival in experimental cardiac failure.

Topics: Animals; Digitoxin; Disease Models, Animal; Female; Heart Failure; Myocardial Infarction; Rats; Rats, Wistar; Survival Rate; Treatment Outcome

This study sought to examine the use of treatments at discharge in patients hospitalized for myocardial infarction in a French region.. Data from 2,102 patients discharged after myocardial infarction were prospectively collected at 48 university, community, and private hospitals in three departments in the Rh ne-Alpes region between September 1, 1993 and January 31, 1995. Beta-blockers were prescribed in 59% of the patients, calcium channel blockers in 22%, nitrates in 59%, antiplatelet agents in 82%, anticoagulants in 26%, angiotensin-converting enzyme inhibitors in 36%, diuretics in 33%. Beta-blockers were prescribed less often in older patients, and in patients with higher Killip classes or a history of pulmonary disease. Calcium channel blockers were prescribed more often in older patients, and in patients with a history of diabetes, pulmonary disease, or non-Q wave myocardial infarction. Nitrates were prescribed more often in older patients. Angiotensin-converting enzyme inhibitors were prescribed more often in patients with a history of diabetes, hypertension, or anterior myocardial infarction, and less often in patients with a history of renal failure. Diuretics were prescribed more often in older patients, and in patients with a history of renal failure, diabetes, hypertension, or higher Killip classes.. There is still underuse of beneficial treatments, particularly in elderly patients.

Topics: Adrenergic beta-Antagonists; Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Anticoagulants; Calcium Channel Blockers; Chi-Square Distribution; Digitalis; Disease Management; Diuretics; Female; Humans; Logistic Models; Male; Middle Aged; Myocardial Infarction; Nitrates; Odds Ratio; Phytotherapy; Plants, Medicinal; Plants, Toxic; Platelet Aggregation Inhibitors; Prospective Studies

Traditionally, ST segment depression has been associated with acute coronary syndromes; this electrocardiographic pattern may also be found in patients with nonischemic events, such as left bundle branch block (LBBB), left ventricular hypertrophy (LVH), and those with therapeutic digitalis levels. Using the ECG as an adjunct in distinguishing those patients with acute coronary syndromes from those with more "benign," nonacute causes of STSD will obviously lead to divergent treatment and management plans. The following cases illustrate the use the ECG in patients presenting with chest pain and electrocardiographic ST segment depression attributable to an ACS, LVH, LBBB, or digitalis.

Topics: Bundle-Branch Block; Chest Pain; Diagnosis, Differential; Digitalis; Electrocardiography; Emergencies; Female; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Plants, Medicinal; Plants, Toxic

Topics: Adult; Bradycardia; Cardiotonic Agents; Chest Pain; Diagnosis, Differential; Digitoxin; Electrocardiography; Heart Block; Humans; Male; Myocardial Infarction; Poisoning; Suicide, Attempted

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

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

Topics: Aged; Aged, 80 and over; Aging; Cardiac Output; Coronary Vessels; Digitalis; Diuretics; Heart Failure; Heart Valves; Humans; Myocardial Infarction; Plants, Medicinal; Plants, Toxic; Recurrence; Vasodilator Agents; Ventricular Function, Left

The use of digitalis in patients who have sustained an acute myocardial infarction has been controversial. A number of reports have suggested that the use of the glucoside actually can increase mortality. In all previous reports, digoxin has been the glucoside in use. In 620 patients admitted to Hamar Hospital from January 1, 1982 to December 31, 1984 with an acute myocardial infarction, 159 were using digitoxin at entry. Their survival until January 1, 1985 was compared with the rest of the population, not using digitoxin. The patients on digitoxin had a significantly higher mortality than those who were not, with a relative risk ratio of 2.33. However, major differences in baseline risk factors existed, and a multivariate Cox regression analysis was employed to adjust for the inequalities in baseline covariates. Only variables available at the entry of the index infarction were used for adjustment. Serum sodium, serum creatinine, age and no smoking were identified in a backward selection procedure as independently influencing mortality. By adjusting for these variables the relative risk ratio was reduced to 1.41, but digitoxin still exerted a significant influence on mortality. It is concluded that the results obtained with the use of digitoxin during a myocardial infarction is similar to previous reports with digoxin. Most of the excess mortality in the digitoxin group can be accounted for by inequalities in baseline characteristics. However, the possibility that a small excess in mortality is due to the digitalis glucoside cannot be excluded.

Topics: Aged; Aged, 80 and over; Digitoxin; Female; Humans; Male; Middle Aged; Myocardial Infarction; Regression Analysis; Risk Factors; Survival Analysis; Survival Rate

In the framework of the secondary prevention after acute myocardial infarction the interaction between physical conditioning (pK) and medicamentous therapy was analysed and a retrospective evaluation of the therapy was performed during the rehabilitation phase III. During the physical conditioning (n = 110) in 31% of the patients changes of the medicamentous therapy rendered themselves necessary (15% increase of the dose, 16% reduction of the dose and withdrawal of a medicament, respectively). In the rehabilitation phase III (n = 277) 72% of the patients were given nitrates, 68% calcium antagonists and 55% beta-receptor blocking agents (43% double, 29% triple combinations) and 15% digitoxin. The aim of the medicamentous therapy is the treatment of the myocardial ischaemia and its sequels, taking into consideration the positive effects of the physical conditioning and the influence on the quality of life.

Topics: Acute Disease; Adrenergic beta-Antagonists; Aged; Anti-Arrhythmia Agents; Antihypertensive Agents; Calcium Channel Blockers; Cardiovascular Agents; Digitoxin; Drug Therapy, Combination; Exercise Therapy; Female; Humans; Male; Middle Aged; Myocardial Infarction; Nitrates; Retrospective Studies

Topics: Clinical Trials as Topic; Digitalis; Digitalis Glycosides; Ethics, Medical; Humans; Myocardial Infarction; Plants, Medicinal; Plants, Toxic

In 105 patients at the age of 32-80 years after myocardial infarction the therapy with glycoside, diuretics and coronary pharmaca was analysed in dependence upon anamnesis, clinical treatment, ergometric and echocardiographic findings in the period from the discharge from the hospital to the first year. While glycosides, diuretics and nitrates were frequently prescribed unchanged, the intake of the beta-blockers increased from 19 to 28 per cent and that of the calcium antagonists from 21 to 39 per cent for the first year. In glycosides and diuretics the possible disadvantages of a withdrawal trial in clinically and paraclinically compensated patients were more taken into consideration than the side effects by uncritical administration. On the other hand, the advantages of the beta-receptor blockers and calcium antagonists were obviously not yet exhaustively used.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Calcium Channel Blockers; Digitoxin; Digoxin; Diuretics; Drug Therapy, Combination; Echocardiography; Exercise Test; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Pentaerythritol Tetranitrate

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

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

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

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

Early studies suggested that digitalis exacerbated ischemia (ST segment data); however, there are no studies assessing the effect of this agent on anatomic infarct size with the use of a risk zone technique. Therefore, the aim of this study was to assess quantitatively whether digitalis extends necrosis in a model of coronary artery occlusion. Anesthetized dogs were subjected to 6-hour occlusion and, 30 minutes after occlusion, were randomized to digoxin (250 micrograms bolus/5 min intravenously, n = 9) or saline (n = 9) groups. At 6 hours, in vivo area at risk was determined by monastral blue dye injection and area of necrosis was assessed by tetrazolium staining. Heart rate and blood pressure were not different between groups before treatment or at 6 hours after occlusion. Left ventricular dP/dt was similar in both groups before occlusion (2350 +/- 293 mm Hg/sec digoxin vs 1839 +/- 122 mm Hg/sec saline, p = NS), but after 6 hours of coronary occlusion, had increased in the digoxin group to 2583 +/- 340 mm Hg/sec while it decreased in the saline group to 1517 +/- 128 mm Hg/sec (p less than 0.05 between groups at 6 hours), suggesting that digoxin increased contractility. Area at risk was 17.7 +/- 1.3% of the left ventricle in the digoxin group and 20.9 +/- 2.0% of the left ventricle in the saline group (p = NS). Area of necrosis, expressed as a percentage of area at risk, was 90.0 +/- 3.5% in the digoxin group vs 88.6 +/- 2.1% in the saline group (p = NS). Therefore, during acute myocardial infarction, digitalis confers a moderate increase in contractility without extending necrotic damage.

Topics: Animals; Digitalis; Dogs; Hemodynamics; Myocardial Infarction; Necrosis; Plants, Medicinal; Plants, Toxic; Risk

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

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

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

To determine whether treatment with digitalis is associated with decreased survival after acute myocardial infarction (AMI), data from 504 patients who were enrolled in a postinfarction natural history study were analyzed. At the time of discharge, 229 patients (45%) were taking digitalis. After 3 years of follow-up, the cumulative survival rate for patients discharged on a regimen of digitalis was 66%, compared with 87% for those not treated (p less than 0.001). Univariate analysis showed that statistically significant differences existed between the 2 groups with respect to age, previous AMI, left ventricular failure in the coronary care unit, atrial fibrillation in the coronary care unit, peak creatine kinase levels, enlarged heart and pulmonary vascular congestion on the discharge chest x-ray, ventricular arrhythmias and treatment with diuretic, antiarrhythmic and beta-blocking drugs. Survival analysis using Cox's regression model showed that the association between digitalis and decreased survival was of borderline significance after adjustment for atrial fibrillation and left ventricular failure. Serum digoxin concentration was measured in 83% of the patients who took digitalis. Survival was inversely and significantly related to serum digoxin, i.e., the higher the serum digoxin concentration, the lower the long-term survival rate. After adjusting for atrial fibrillation and left ventricular failure, serum digoxin was not significantly related to survival. Taken together with the results of 3 other large, nonrandomized studies of digitalis treatment after AMI, this study suggests that digitalis treatment may have adverse effects on survival during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Atrial Fibrillation; Digitalis; Digoxin; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Plants, Medicinal; Plants, Toxic; Risk

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

Topics: Adrenergic beta-Antagonists; Aged; Angina Pectoris; Anticoagulants; Aspirin; Calcium Channel Blockers; Coronary Disease; Digitalis; Diuretics; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Plants, Medicinal; Plants, Toxic; Platelet Aggregation; Time Factors; Vasodilator Agents

Specific binding sites have been demonstrated to exist in the heart for several drugs and hormones such as beta-blocking agents, cardiac glycosides, catecholamines, insulin, glucagon and acetylcholine. The specific binding sites for cardiac glycosides in the human heart have certain properties which make it likely that they are the pharmacological receptors for the therapeutic and toxic actions of digitalis glycosides: they are located in the cell membrane and bind cardioactive steroids reversibly with high affinity: half-maximal receptor binding occurs at approximately 2 nM (approximately 1.5 ng/ml) for digoxin; potassium decreases receptor affinity, calcium increases it; specific binding of ouabain, digoxin or digitoxin is related to inhibition of (Na+ + K+)-ATPase activity--which is supposed to be the receptor enzyme for cardiac glycosides. Human left ventricle contains approximately 1.5 x 10(14) binding sites/g wet weight, right ventricle approximately 0.9 x 10(14). In disease the number of receptors may decrease (hypothyroid states, myocardial infarction) or increase (hyperthyroidism, chronic hypokalaemia). Certain drugs (such as phenytoin) or different temperatures or pH changes cause a change in digitalis-receptor affinity. Thus, the number of receptors and possibly their properties are subject to regulation in clinically relevant situations. Further investigations will probably reveal those pathophysiological states, which allow the explanation of toxicity or digitalis refractoriness.

Topics: Animals; Binding Sites; Cats; Cell Membrane; Cells, Cultured; Digitoxin; Digoxin; Guinea Pigs; Humans; Hypokalemia; Myocardial Infarction; Myocardium; Ouabain; Receptors, Drug; Sodium-Potassium-Exchanging ATPase; Thyroid Diseases

Topics: Acute Disease; Digitalis; Drug Evaluation; Heart Failure; Hemodynamics; Humans; Myocardial Infarction; Plants, Medicinal; Plants, Toxic

Topics: Adult; Aged; Digitalis; Drug Utilization; Exercise Test; Exercise Therapy; Humans; Male; Middle Aged; Myocardial Infarction; Plants, Medicinal; Plants, Toxic

Topics: Digitalis; Drug Evaluation; Heart Failure; Hemodynamics; Humans; Models, Biological; Myocardial Contraction; Myocardial Infarction; Plants, Medicinal; Plants, Toxic; Vasodilator Agents

In 25 digitalized patients with ischaemic heart disease who had survived a myocardial infarction for 2 to 4 weeks, the systolic time intervals (STI) and changes of glycoside plasma level were measured before and up to 5 hrs after oral intake of a maintenance dose of digitoxin (n = 18) or of digoxin (n = 7). Between the changes of STI and the increase in digitoxon and digoxin plasma level no significant correlations were found. Therefore it is concluded that neither shortening of STI during the test period nor PEP/LVET are reliable criteria of individualizing and optimizing the therapy with cardioactive glycosides.

Topics: Adult; Aged; Digitalis Glycosides; Digitoxin; Digoxin; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Myocardial Contraction; Myocardial Infarction

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

26 mongrel dogs were given a single dose of 0.03mg/kg tritium-labelled digoxin, beta-methyldigoxin, digitoxin or ouabain 2 hrs or 95 hrs following experimental coronary occlusion. Examination of the epicardial ECG was performed by moving from intact to ischemic or necrotic zones. 60 min after glycoside administration the animals were sacrificed and tissue samples from the marked heart muscles areas and from the skeletal muscle were analysed for glycoside content. The early glycoside uptake in acute ischemic or necrotic myocardium was diminished independently of the physicochemical properties of the glycoside. Significantly higher glycoside concentrations (ng/g wet weight) were measured in the injured myocardium 3 hrs after coronary occlusion than 96 hrs afterward (p less than 0.005). The values in acute ischemic myocardium varied considerably. This nonhomogeneity of glycoside uptake in the acute ischemic heart muscle may partly explain the increased sensitivity to glycosides in myocardial infarction. The decline of glycoside concentration correlates with the alterations in the epicardial ECG. The cardiac effects of cardenolides 60 min after intravenous administration was caused by the unchanged glycoside. In contrast to the myocardium, glycoside accumulation could not be found in the skeletal muscle. The concentrations of digoxin, beta-methyldigoxin and digitoxin in the skeletal muscle were significantly higher than the concentration of ouabain, which was rapidly eliminated via the urine.

Topics: Animals; Cardiac Glycosides; Chromatography, Thin Layer; Coronary Vessels; Digitoxin; Digoxin; Dogs; Electrocardiography; Ligation; Muscles; Myocardial Infarction; Myocardium; Ouabain; Time Factors; Tritium

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

Topics: Age Factors; Aged; Atrial Fibrillation; Cardiac Complexes, Premature; Cardiomegaly; Digitalis; Electrocardiography; Female; Heart Block; Heart Conduction System; Heart Rate; Humans; Male; Myocardial Infarction; Plants, Medicinal; Plants, Toxic

Topics: Aged; Autopsy; Bundle-Branch Block; Chronic Disease; Digitalis; Diuretics; Female; Follow-Up Studies; Heart Block; Hospitalization; Humans; Isoproterenol; Long-Term Care; Male; Middle Aged; Myocardial Infarction; Myocardium; Pacemaker, Artificial; Phytotherapy; Plants, Medicinal; Plants, Toxic

Topics: Aged; Assisted Circulation; Blood Pressure; Cardiac Catheterization; Chlorpromazine; Digitalis; Evaluation Studies as Topic; Female; Humans; Hydrogen-Ion Concentration; Lactates; Male; Methods; Methylprednisolone; Middle Aged; Myocardial Infarction; Plants, Medicinal; Plants, Toxic; Prognosis; Pulmonary Edema; Shock, Cardiogenic; Time Factors; Vasoconstrictor Agents; Vasodilator Agents

Topics: Acute Disease; Blood Pressure; Cardiac Output; Coronary Circulation; Depression, Chemical; Digitalis; Digitalis Glycosides; Furosemide; Heart; Heart Rate; Humans; Myocardial Infarction; Norepinephrine; Oxygen Consumption; Phentolamine; Plants, Medicinal; Plants, Toxic; Propranolol; Stimulation, Chemical; Vascular Resistance

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Digitalis; Digoxin; Electric Countershock; Heart Block; Heart Ventricles; Humans; Lidocaine; Myocardial Infarction; Pacemaker, Artificial; Phenytoin; Phytotherapy; Plants, Medicinal; Plants, Toxic; Procainamide; Propranolol; Quinidine; Tachycardia; Tachycardia, Paroxysmal; Ventricular Fibrillation

Topics: Ampicillin; Blood; Chemical and Drug Induced Liver Injury; Digitalis; Drug Hypersensitivity; Female; Fever; Furosemide; Humans; Lidocaine; Middle Aged; Myocardial Infarction; Phytotherapy; Plants, Medicinal; Plants, Toxic; Procainamide; Quinidine; Urine; Vomiting

Topics: Adult; Aged; Arterial Occlusive Diseases; Coronary Disease; Digitalis; Electrocardiography; Ethylamines; Female; Furans; Humans; Injections, Intravenous; Male; Middle Aged; Myocardial Infarction; Naphthalenes; Pacemaker, Artificial; Phytotherapy; Plants, Medicinal; Plants, Toxic; Propionates; Vasodilator Agents

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: Acute Disease; Bundle-Branch Block; Computers; Coronary Vessels; Diagnosis, Computer-Assisted; Diagnosis, Differential; Diaphragm; Digitalis; Electrocardiography; Heart Block; Heart Diseases; Heart Rate; Heart Ventricles; Humans; Hypertrophy; Infarction; Ischemia; Mathematics; Mitral Valve; Myocardial Infarction; Pericarditis; Plants, Medicinal; Plants, Toxic; Potassium

Topics: Adult; Aged; Aortic Valve Insufficiency; Arrhythmia, Sinus; Atrial Fibrillation; Cardiac Volume; Digitalis; Electric Countershock; Electrocardiography; Female; Humans; Hypertension; Male; Middle Aged; Mitral Valve Stenosis; Myocardial Infarction; Plants, Medicinal; Plants, Toxic

Topics: Aged; Bundle-Branch Block; Cardiac Catheterization; Coronary Disease; Digitalis; Electrocardiography; Female; Heart Block; Heart Conduction System; Heart Diseases; Humans; Male; Middle Aged; Minor Surgical Procedures; Myocardial Infarction; Pacemaker, Artificial; Phytotherapy; Plants, Medicinal; Plants, Toxic; Postoperative Complications; Procainamide; Quinidine; Surgical Procedures, Operative; Time Factors

Topics: Aged; Atrial Fibrillation; Bronchopneumonia; Cardiovascular Diseases; Digitalis; Diuretics; Electrocardiography; Endocarditis, Subacute Bacterial; Female; Heart Block; Heart Failure; Heart Septal Defects; Humans; Myocardial Infarction; Phytotherapy; Plants, Medicinal; Plants, Toxic; Potassium; Pulmonary Heart Disease; Radiography

Topics: Cardiac Output; Digitoxin; Digoxin; Heart; Heart Failure; Heart Rate; Humans; Myocardial Infarction; Potassium Chloride; Shock, Cardiogenic

Topics: Digitalis Glycosides; Digitoxin; Digoxin; Heart Diseases; Humans; Myocardial Infarction; Myocardium

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: Digitalis Glycosides; Digitoxin; Humans; Myocardial Infarction

Topics: Animals; Cardiomyopathies; Desoxycorticosterone; Digitoxin; Disease Models, Animal; Ethylestrenol; Female; Fludrocortisone; Myocardial Infarction; Necrosis; Norsteroids; Oxandrolone; Perchlorates; Prednisolone; Progesterone; Rats; Sodium; Spironolactone; Steroids; Triamcinolone

Topics: Aged; Blood Pressure Determination; Blood Volume; Central Venous Pressure; Digitalis; Diuretics; Humans; Isoproterenol; Myocardial Infarction; Plants, Medicinal; Plants, Toxic; Pulmonary Edema; Shock; Vasoconstrictor Agents

Topics: Animals; Cardiomyopathies; Digitoxin; Drug Synergism; Enzyme Induction; Female; Heart; Injections, Subcutaneous; Liver; Myocardial Infarction; Myocardium; Necrosis; Phosphates; Rats; Spironolactone; Triamterene

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

Topics: Angina Pectoris; Anticoagulants; Coronary Disease; Digitoxin; Hemodynamics; Humans; Myocardial Infarction; Oxygen Inhalation Therapy

Topics: Adams-Stokes Syndrome; Bradycardia; Digitalis; Digoxin; Electrocardiography; Heart Arrest; Heart Rate; Humans; Myocardial Infarction; Plants, Medicinal; Plants, Toxic; Procainamide; Propranolol; Quinidine; Sympathomimetics

Topics: Acute Disease; Assisted Circulation; Digitalis; Hemodynamics; Humans; Isoproterenol; Myocardial Infarction; Plants, Medicinal; Plants, Toxic; Plasma Substitutes; Shock; Vasoconstrictor Agents; Vasodilator Agents

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

Topics: Anesthesia; Digitalis; Gastrointestinal Diseases; Humans; Kidney; Liver; Myocardial Infarction; Nutritional Physiological Phenomena; Obesity; Plants, Medicinal; Plants, Toxic; Preoperative Care; Water-Electrolyte Balance; Wounds and Injuries

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

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

Topics: Aneurysm, False; Anticoagulants; Cardiomegaly; Digitoxin; Heart Aneurysm; Heart Failure; Heart Ventricles; Humans; Infarction; Myocardial Infarction; Pathology; Pericardium; Quinidine

Topics: Adrenal Cortex Hormones; Digitoxin; Electrocardiography; Myocardial Infarction; Myocardium; Pharmacology; Prednisone; Procainamide; Quinidine; Tachycardia; Tachycardia, Supraventricular

Topics: Blood Transfusion; Death; Death, Sudden; Digitalis; Digitalis Glycosides; Hyperkalemia; Myocardial Infarction; Surgical Procedures, Operative; Toxicology

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

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

Topics: Adrenergic Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Digitalis; Digoxin; Electrocardiography; Ethanolamines; Geriatrics; Heart Block; Heart Failure; Hypotension; Myocardial Infarction; Nausea; Paresthesia; Sympatholytics; Toxicology; Vertigo; Vomiting

Topics: Aged; Anticoagulants; Digitalis; Digitalis Glycosides; Drug Therapy; Geriatrics; Heart Diseases; Humans; Hypertension; Myocardial Infarction; Norepinephrine

Topics: Angina Pectoris; Aortic Valve Stenosis; Digitalis; Digitalis Glycosides; Drug Therapy; Electrocardiography; Exercise Test; Heart Septal Defects; Heart Septal Defects, Atrial; Hematocrit; Humans; Hypertension; Mitral Valve Insufficiency; Myocardial Infarction; Polycythemia Vera; Postoperative Care; Potassium; Tachycardia; Tachycardia, Paroxysmal; Water-Electrolyte Balance

Topics: Adenosine Triphosphate; Animals; Calcium; Coenzymes; Digitalis; Digitalis Glycosides; Diuresis; Drug Therapy; Guinea Pigs; Heart Failure; Humans; Hypertension; Metabolism; Myocardial Infarction; Myocardium; Pharmacology

Topics: Cardiac Glycosides; Cats; Coronary Circulation; Coronary Vessels; Digitoxin; Electrocardiography; Heart; Metabolism; Myocardial Infarction; Myocardium; Oxygen; Pharmacology; Research; Strophanthins

Topics: Angiotensins; Blood Pressure; Blood Volume; Cardiovascular Diseases; Digitalis; Digitalis Glycosides; Heart Failure; Humans; Myocardial Infarction; Nikethamide; Norepinephrine; Pentylenetetrazole; Sympathomimetics; Vasodilator Agents

Topics: Digitalis; Digitalis Glycosides; Diuretics; Electrocardiography; Heart Diseases; Heart Failure; Heart Septum; Humans; Morphine; Myocardial Infarction; Norepinephrine; Vasodilator Agents

Topics: Atrial Fibrillation; Atrial Flutter; Cardiotonic Agents; Digitalis; Digitalis Glycosides; Electrocardiography; Heart Failure; Humans; Myocardial Infarction; Pulmonary Edema; Tachycardia; Tachycardia, Paroxysmal

Topics: Cardiovascular Diseases; Digitalis; Heart Failure; Humans; Myocardial Infarction; Plant Extracts

Topics: Angina Pectoris; Cardiovascular Diseases; Chest Pain; Digitalis; Humans; Myocardial Infarction

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

Topics: Acute Disease; Cardiovascular Diseases; Digitalis; Digitalis Glycosides; Humans; Myocardial Infarction

Topics: Digitalis; Digitalis Glycosides; Digitoxin; Humans; Myocardial Infarction; Tachycardia; Tachycardia, Ventricular

Topics: Digitoxin; Humans; Infarction; Myocardial Infarction; Ventricular Flutter

Topics: Cardiovascular Diseases; Digitalis; Digitalis Glycosides; Myocardial Infarction

Topics: Digitalis; Digitalis Glycosides; Heart; Humans; Infarction; Myocardial Infarction

Topics: Adrenal Glands; Digitalis; Digitalis Glycosides; Epinephrine; Heart; Infarction; Myocardial Infarction; Tissue Extracts; Water