beta-acetyldigoxin and Heart-Failure

Refracterin therapy of patients with chronic heart failure caused by coronary heart disease and postinfarction cardiosclerosis markedly promoted improvement in the pulmonary and systemic circulation in comparison with patients receiving traditional therapy. The mean functional class of chronic cardiac failure decreased by 43% under the effect of refracterin vs. 27% decrease in the group receiving traditional therapy. After 1-month refracterin course the end-systolic and end-diastolic sizes of the left ventricle decreased by 12 and 7%, respectively, ejection fraction increased by 7.2% in comparison with the initial level, total oxidant activity and MDA content in the plasma decreased significantly, while total antioxidant activity, catalase and SOD activities, cytochrome C, NADH, and NADPH levels increased. The prooxidant-antioxidant system was shifted towards antioxidants, which attests to activation of the defense and adaptive mechanisms after administration of refracterin, which is especially important in elderly patients with initially decreased reserve potentialities of the antioxidant defense system.

Topics: Acetyldigoxins; Aged; Aged, 80 and over; Antioxidants; Cardiotonic Agents; Cytochromes c; Drug Combinations; Heart Failure; Humans; Inosine; Myocardial Infarction; NAD; Oxidative Stress; Oxyfedrine; Sclerosis

Thirty-two patients with chronic heart failure were investigated with radionuclide ventriculography at rest and during exercise. The global ejection fraction (EF), ejection rate, ejection time, and filling rate were measured. The patients were subdivided into three subgroups: patients with extremely (< 25%), moderately (25-33%), and mildly decreased EF (33-40%). All patients were investigated by thallium-201 myocardial scintigraphy and the correlation between ejection parameters and infarct size was investigated. In a random protocol 17 patients (14 men, 3 women, mean age of 54.6 years) received beta-acetyldigoxin at a dose of 0.3 mg daily over 4 weeks, 15 patients (13 men, 2 women, mean age of 58.2 years) received nisoldipine at a dose of 20 mg daily. Patients on digitalis showed a further lowering of the extremely decreased EF (-1%), but in patients with moderately decreased EF, digoxin produced a marked increase in EF of +8% (p < 0.001). In mildly decreased EF, there was no significant change (+0.3%, n.s.). Nisoldipine produced an increase in pump function (+2%) in the group with extremely decreased EF up to 9% in some individual cases. A significant increase (+5%) was achieved in moderately decreased EF, while patients with mildly decreased EF did not respond. Thus, nisoldipine may be indicated in the treatment of heart failure after repeated myocardial infarctions, in particular in patients with severely decreased ejection fraction.

Topics: Acetyldigoxins; Female; Heart; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Nisoldipine; Radionuclide Ventriculography; Ventricular Function, Left

Topics: Acetyldigoxins; Aged; Clinical Trials as Topic; Digoxin; Dihydroergotoxine; Double-Blind Method; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Neurocognitive Disorders; Random Allocation

In a controlled double-blind trial in 80 patients with cerebrovascular and cardiac insufficiency the differentiated effect of a combination therapy with cardiac glycosides and Hydergin were studied both with regard to parameters of cerebral organic and cardiac performance. Two randomized collectives of patients with an average age of 63 years were compared with each other for this purpose. They received either acetyldigoxin (0.4 mg/day) alone or in combination with Hydergin (3 mg/day). Duration of treatment was 8 weeks altogether. The single treatment with the cardiac glycoside alone does not lead to a satisfactory improvement in the symptoms of cerebral attacks. The results presented of this study support the necessity in these patients of an internist basic therapy in combination with a preparation like Hydergin acting favorably on cerebral metabolism.

Topics: Acetyldigoxins; Cerebrovascular Disorders; Digoxin; Dihydroergotoxine; Double-Blind Method; Female; Heart Failure; Humans; Male; Middle Aged

The therapeutic action of adenocine during cardiac insufficiency (heart failure) caused by ischemic (stenosis) or reperfusion (removal of ligature) injury to the myocardium prevents depletion of ATP, the major energy source for myocytes in the right and left ventricles, and a drop in NAD/NADH ratio. The development of energy shortage during heart failure cannot be eliminated by β-acetyldigoxin, levosimendan, or milrinone: the content of ATP in the right and left ventricular myocardium remained below the normal level by 28 and 29%, 37 and 33%, 32 and 28%, respectively; the NAD/NADH ratio of the energy supply system in cardiomyocytes did not return to normal. Adenocine increased the content of NAD to the normal level in both the right and left ventricles, while it remained below the normal level after administration of β-acetyldigoxin (by 24 and 19.5%, respectively), levosimendan (by 27 and 29%), and milrinone (by 26 and 24%). In contrast to β-acetyldigoxin, levosimendan, and milrinone, adenocine inhibited activity of poly(ADP-ribose) polymerase in both ventricles. It is concluded that adenocine directly inhibits the key enzyme triggering apoptosis; we also hypothesized that this drug activates the regulatory and signal mechanisms arresting apoptotic alterations in the myocardium during heart failure.

Topics: Acetyldigoxins; Adenosine; Adenosine Triphosphate; Animals; Apoptosis; Cardiotonic Agents; Constriction, Pathologic; Female; Heart; Heart Failure; Heart Ventricles; Hydrazones; Male; Milrinone; Myocardium; Myocytes, Cardiac; NAD; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Pyridazines; Rabbits; Reperfusion; Simendan; Ventricular Function

Experiments were performed on the model of chronic heart failure. Functional capacity of myocardial structures under conditions of maximum pressure overload was within the upper limit of normal after treatment with Adenocin. The myocardial functional reserve and potential capacity index were shown to increase to normal under these conditions. Dobutamine, levosimendan, and milrinone increased functional capacity under conditions of maximum pressure overload. Treatment with adenocin restored diastolic function of the heart under conditions of maximum pressure overload. The end-diastolic pressure increased, but remained 1.7 times below the level observed in heart failure. After treatment with dobutamine and milrinone, the end-diastolic pressure (8th episode of ligation) did not differ from the level observed in heart failure, while after administration of levosimendan this parameter decreased by 31%. Contraction-relaxation coupling was completely restored under the influence of Adenocin in all episodes of ligation both before and after removal of the ligature. Nearly all animals with heart failure were resistant to 8 episodes of ligation after treatment with Adenocin (89 vs. 96% under normal conditions). Under these conditions, the survival rate of animals after administration of levosimendan, milrinone, and dobutamine was 65, 60, and 61%, respectively, (the mortality rate of animals with heart failure was 75%). Adenocin, a cardiotonic drug with cardioprotective properties, in contrast to other cardiotonic drugs, has a modulatory effect on the system of cell energy supply, restores myocardial reserves, and improves myocardial function under conditions of overload.

Topics: Acetyldigoxins; Animals; Cardiotonic Agents; Chronic Disease; Female; Heart Failure; Male; Rabbits

A 69 year old female with history of coronary heart disease, myocardial infarction and paroxysmal atrial fibrillation suffered from occipital apoplexy. Under treatment with amiodarone 600 mg daily and concomitant medication with beta-acetyldigoxine (0.1 mg daily) and bisoprolole (1.25 mg daily), significant QT-prolongation (max. 700 ms; QTc: 614 ms) could be documented. Out of normofrequent sinus rhythm but as well out of bradycardia, the patient developed repetitive short-lasting "torsade de pointes" tachycardias (320 bpm) which terminated spontaneously. Serum electrolytes, plasma levels of digoxine (1.76 ng/ml) and amiodarone (1.9 mcg/ml) were within therapeutic range. This case report is the first to describe induction of amiodarone-associated "torsade de pointes" tachycardia during concomitant beta-blocker and digitalis medication in a patient with atrial fibrillation and structural heart disease. This points towards an elevated risk for proarrhythmia under this triple therapy.

Topics: Acetyldigoxins; Adrenergic beta-Antagonists; Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Bisoprolol; Drug Interactions; Drug Therapy, Combination; Electrocardiography; Female; Heart Failure; Humans; Torsades de Pointes

Color discrimination ability of 100 in-patients suffering from congestive heart failure and treated with digitoxin (D), pengitoxin (P), or digoxin (Dg) was determined with the Farnsworth-Munsell 100 Hue test (FM 100) and compared with the color discrimination of 72 in-patients who were not treated with digitalis glycosides (control group C). Parallel to the performance of the FM 100, the glycoside plasma level was measured by radioimmunoassay. The total error score (TES) of the FM 100 was correlated with the glycoside plasma level and the patient's age. In the C as well as in the D or P groups up to 172 errors and in the Dg group up to 586 errors were observed. With the exception of Dg, no differences were observed between the regression lines indicating an age-dependent increase in TES even under D or P treatment. In contrast to the two glycosides, Dg enhances the TES in therapeutically relevant plasma concentrations. The differences between the glycosides are due to differences in their volume of distribution and their plasma protein binding.

Topics: Acetyldigoxins; Adolescent; Adult; Aged; Aged, 80 and over; Color Perception; Digitoxin; Digoxin; Discrimination, Psychological; Female; Heart Failure; Humans; Male; Middle Aged

In a therapeutic study, 120 inpatients suffering from congestive heart failure were treated with a daily maintenance dose of 0.3 mg pengitoxin (penta-acetyl-gitoxin) over several weeks or months. The plasma level and the glycoside concentration in urine were measured by radioimmunoassay. The therapeutic effects were evaluated considering clinical signs and criteria following the functional capacity according to the New York Heart Association (NYHA). In 27 patients both plasma and urine concentration were measured during 2 weeks after the beginning of the pengitoxin therapy. On the 3rd day of the pengitoxin dosage schedule, a mean plasma level of 18.1 ng.ml-1 (SD 5.1 ng.ml-1) was measured. During this day 26.6% of the daily administered glycoside dose was excreted in urine. In 26 of the 120 patients the mean steady state plasma level was between 7.6 and 22.5 ng.ml-1. A maximum of frequency was found in the 17.6 to 22.5 ng-subclass. In 118 patients the mean urinary excretion of 16-acetyl-gitoxin reached 24.7% (SD 11.8%) of the administered dose. The creatinine clearance and the 16-acetyl-gitoxin plasma level did not correlate, while between the renal clearance values of creatinine and the glycoside a correlation was found, however, it was of no significance for dosage schedules in patients with impaired renal function. After treatment, the NYHA classes III and II were reached in 57 patients; in 3 patients suffering from renal diseases, the NYHA class I remained unchanged. In 90 patients the clinical signs improved and in 27 patients the clinical situation remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acetyldigoxins; Adolescent; Adult; Aged; Aged, 80 and over; Biological Availability; Digoxin; Electrocardiography; Female; Glycosides; Heart Failure; Humans; Male; Middle Aged

In 1063 patients (greater than or equal to 60 years, 531 men, 532 women) the plasma concentration during digitalis maintenance therapy (metildigoxin, n = 356, beta-acetyldigoxin, n = 359, and digitoxin, n = 348) was determined and related to sex, age, body weight, serum potassium, renal function and the prescribed daily maintenance dose. Classification of treatment groups according to renal function (Crea less than or equal to 1.3 mg/dl parallel greater than 1.3 mg/dl) did not show any difference of the mean maintenance doses. In multiple linear regression analyses only a weak relationship between plasma digitalis concentration and the studied variables was found, which could be equally attributed to dose, creatinine and serum potassium in the digoxin derivative groups, whereas for digitoxin only body weight had a significant effect on the plasma concentration. During a maintenance dose of 0.07 or 0.1 mg/die which was given to 87% of patients in the digitoxin group, 70% were found to have plasma levels within the therapeutic range.

Topics: Acetyldigoxins; Aged; Body Weight; Digitoxin; Digoxin; Dose-Response Relationship, Drug; Heart Failure; Humans; Kidney Function Tests; Medigoxin

To determine whether nifedipine or diltiazem affect digoxin kinetics, glycoside plasma concentrations and renal excretion were measured before and during dosing in 23 patients with cardiac insufficiency achieving steady-state conditions. Mean (+/- SD) digoxin plasma concentration was 0.64 +/- 0.22 before and 0.61 +/- 0.21 ng/ml during nifedipine dosing in 11 subjects over a period of 10 to 14 days. Renal digoxin clearance was not influenced by nifedipine, whereas total body clearance and extrarenal clearance of digoxin increased slightly. In contrast, diltiazem resulted in a 24% to 70% (means = 46%) increase in plasma digoxin concentrations in eight of 12 subjects. Renal digoxin clearance was not influenced by diltiazem, whereas total body clearance and extrarenal clearance of digoxin were reduced 28% and 44% in five of the eight subjects in whom renal digoxin excretion was measured. From these data it was concluded that nifedipine has no significant effects on digoxin kinetics, but that digoxin plasma concentrations should be controlled in subjects receiving digoxin with diltiazem until new steady-state digoxin concentrations are established, and that the digoxin dose be reduced if there is evidence of toxicity.

Topics: Acetyldigoxins; Aged; Benzazepines; Digoxin; Diltiazem; Drug Therapy, Combination; Female; Heart Failure; Humans; Kinetics; Male; Middle Aged; Nifedipine

The effect of diltiazem (D) on the pharmacokinetics and pharmacodynamics of beta-acetyldigoxin (AD; n = 12) and digitoxin (DGT; n = 10) was studied in 22 patients with cardiac insufficiency stages II-III by the New York Heart Association. Glycoside plasma concentration and renal excretion as well as electrocardiogram [heart rate, atrioventricular transconduction time (PQ), duration of electrical systole corrected for heart rate (QTc), mean amplitude of T-waves in leads V2 to V6 (TV2-6)] and systole time intervals [total electromechanical systole index (QS21), left ventricular ejection time index (LVETI), pre-ejection period index (PEPI), PEP/LVET ratio] were recorded repeatedly before and during co-administration of 180 mg/day D. In eight patients digoxin plasma levels increased continuously during additional D administration. After reaching a new steady state at 0.93 +/- 0.35 ng/ml digoxin concentrations were at an average 43% higher than before D administration (0.65 +/- 0.27 ng/ml) with a simultaneous increase in renal glycoside excretion. The other four patients showed neither changes in digoxin concentrations in plasma nor in renal glycoside excretion. Only half the patients treated with DGT and D revealed an increase in DGT plasma levels of 21.4%. Daily renal glycoside excretion was not altered by D administration. In accordance to the increasing AD plasma concentration, PQ-interval was prolonged and T-wave flattening was intensified, whereas the systolic time intervals after concomitant treatment of AD and D did not differ from those after AD alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acetyldigoxins; Aged; Benzazepines; Blood Pressure; Digitoxin; Digoxin; Diltiazem; Drug Therapy, Combination; Electrocardiography; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Pulse

Cardiac frequency could not be lowered in a 62-year-old patient with atrial flutter and 2:1 conduction. Using an electrode catheter positioned in the His bundle area an electric current of 80 Ws was effected. A third-degree atrioventricular block developed which regressed after 6 hours. The electrophysiologic assessment after one week showed a marked diminution of AV node conduction capacity.

Topics: Acetyldigoxins; Atrial Flutter; Bundle of His; Diltiazem; Electric Countershock; Electrocardiography; Electrodes, Implanted; Heart Block; Heart Failure; Humans; Male

Topics: Acetyldigoxins; Adult; Aged; Bufanolides; Computers; Digoxin; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Mathematics; Middle Aged; Monitoring, Physiologic; Proscillaridin

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

Topics: Acetyldigoxins; Biomedical Research; Digitoxin; Heart Failure; Humans