digitoxin and Cardiac-Output--Low

National and international societies have issued guidelines on the management of heart failure: The European Society of Cardiology, WHO, ACC/AHA Task Force Report, US Department of Health and Human Services, German Society of Cardiology. The therapeutic approaches to heart failure have undergone considerable changes during the last few years. The guidelines have to be updated almost yearly due to new results from prospective randomized studies. Although an agreement could be reached with respect to general measures and drug treatment, no agreement on mechanical devices, pacemakers and surgical interventions has been reached. The basis for medical treatment of chronic heart failure depends on diuretics, digitalis, ACE inhibitors, and beta-blockers. Calcium antagonists and other positive inotropic drugs, other than digitalis, should be avoided as far as possible. Thiazides, loop diuretics and aldosterone antagonists are needed for acute and chronic treatment of heart failure, alone or in combination (diuretic resistant heart failure!). Digitalis glycosides are needed in patients with atrial fibrillation with a fast ventricular rate or atrial flutter and in patients with systolic dysfunction, large hearts and symptomatic failure class NYHA III and IV. However, digitalis does not convert atrial fibrillation to sinus rhythm. Today there is no question that ACE inhibitors improve the prognosis of all patients with heart failure in all stages, if ejection fraction is reduced. Therefore, most patients after myocardial infarction or after having experienced pump failure due to myocarditis or cardiomyopathy are treated with ACE inhibitors and diuretics. The beneficial effects of ACE inhibitors seem to be most pronounced the worse the situation is. Relative risk reductions (mortality!) between 10% and 40% have been published depending on the severity of symptomatic left ventricular dysfunction. Those patients with high absolute risk have more to gain than those with low risk for any given "risk reduction", of course. Recent studies also indicate that most high risk cardiac patients profit from ACE inhibitors even if pump function is normal (i.e., patients with coronary heart disease, diabetes mellitus, cerebral vascular disease, hypertension) (15). AT1 antagonists can substitute for ACE inhibitors, if the latter are not tolerated due to cough. Up to now, beta-blocking agents apart from diuretics seem to be the best investigated drugs in heart failure. Large controll

Topics: Adrenergic beta-Antagonists; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Cardiac Output, Low; Digitalis; Diuretics; Hormone Antagonists; Humans; Plants, Medicinal; Plants, Toxic

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

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

Topics: Animals; Cardiac Output, Low; Digitalis Glycosides; Digitoxin; Digoxin; Dose-Response Relationship, Drug; Heart Rate; Humans; Muscle Contraction; Ouabain

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: Atrial Fibrillation; Calcium Channel Blockers; Cardiac Output, Low; Case-Control Studies; Coronary Angiography; Coronary Artery Bypass; Coronary Disease; Digitalis; Diltiazem; Electrocardiography; Female; Hemodynamics; Humans; Logistic Models; Male; Middle Aged; Phytotherapy; Plants, Medicinal; Plants, Toxic; Postoperative Complications; Prospective Studies; Risk Factors

Topics: Cardiac Output, Low; Digitalis; Heart Septal Defects, Ventricular; Humans; Male; Medication Errors; Plants, Medicinal; Plants, Toxic

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

Cardiac beta-adrenoceptors and the positive inotropic effects of adenylate cyclase-dependent (dobutamine, histamine, forskolin) and adenylate cyclase-independent agents (isobutylmethylxanthine (IBMX), dibutyryl-cAMP (db-cAMP), digoxin, digitoxin and calcium were measured in papillary muscle strips from severely failing (NYHA IV), moderately failing (NYHA II-III) and non-failing (NYHA I) human hearts. The density of beta-adrenoceptors in three NYHA I patients were 40.0, 42.0 and 42.9 fmol mg-1 protein. The density of cardiac beta-adrenoceptors was significantly reduced in NYHA II-III to 18.0 +/- 1.1 fmol mg-1 protein (n = 16) and further reduced in NYHA IV to 9.5 +/- 1.6 fmol mg-1 protein (n = 7). The KD values did not differ between the groups. Correspondingly, the positive inotropic effect of dobutamine was significantly reduced in NYHA II-III and almost lost in NYHA IV. The positive inotropic effect of histamine was similar in non-failing and moderately failing myocardium but reduced in preparations from severely failing hearts (NYHA IV). The positive inotropic effect of IBMX was diminished in moderately and severely failing myocardium depending on the functional class of heart failure. In contrast, the effects of forskolin, db-cAMP, digoxin and digitoxin were not impaired in NYHA IV when compared with the maximal positive inotropic effect of calcium. It is concluded that in the failing human heart (a) the number of cardiac beta-adrenoceptors is reduced proportional to the severity of heart failure; (b) the receptor coupling of H2-receptors to adenylate cyclase may be impaired, but only in severe heart failure; (c) the basal cAMP formation may be diminished; and that (d) the catalytic subunit of the adenylate cyclase and the cAMP-dependent protein kinases may be promising targets for drugs to restore force of contraction in human heart failure.

Topics: 1-Methyl-3-isobutylxanthine; Adult; Bucladesine; Calcium; Cardiac Output, Low; Cardiotonic Agents; Colforsin; Digitoxin; Digoxin; Dobutamine; Histamine; Humans; In Vitro Techniques; Middle Aged; Myocardial Contraction; Myocardium; Receptors, Adrenergic, beta; Stimulation, Chemical