proscillaridin and Heart-Failure

The task of this study was to examine the feasibility of applying echocardiography in determining alterations of left ventricular performance during administration of vasoactive drugs. Patients suffering from congestive heart failure were treated with Digitalis, other patients with normal hearts were subjected to infusion therapy of Isoproterenol, Propranolol, Verapamil and Calcium chloride. A new concept for interpretation of function curves relating the velocity of circumferential fiber shortening (VCF) and time was introduced to establish the inotropic, bathmotropic and chronotropic effects of vasoactive drugs to the myocardium. It can be concluded that echocardiography is a feasible tool in determining changes of left ventricular dynamics during administration of vasoactive drugs, in indicating the individual dosage of a vasoactive drug in each patient and the follow-up the course of the therapeutic success.

Topics: Digoxin; Echocardiography; Heart; Heart Failure; Heart Ventricles; Humans; Isoproterenol; Propranolol; Proscillaridin; Verapamil

Clinical open trials of beta-methyldigoxin were carried out in 15 institutions in order to examine the effect, usefulness and ease of its oral administration. In the case of oral digitalization with 0.2 mg, 3 times daily, an effect was obtained in all of 13 cases of congestive heart failure accompanied by atrial fibrillation or flutter. The average time and dose required for digitalization were about 50 hours and 1.27 mg respectively. In 9 of the 13 cases, the effect was achieved within 48 hours. The average maintenance does of beta-methyldigoxin in 102 cases of congestive heart failure with atrial fibrillation was 0.177 mg per day. About 75% of the cases were maintained with 0.15 to 0.2 mg. This range of dose of beta-methyldigoxin was much smaller than that of digoxin in our series. This can be ascribed to a higher absorption rate of beta-methyldigoxin from the digestive tract. Studies on the cases in which patients previously treated with other glycosides were switched over to beta-methyldigoxin revealed that 1 mg of beta-methyldigoxin is equivalent to 1.8 mg of digoxin or to 0.59 mg of digitoxin. The usefulness and ease of beta-methyldigoxin in maintenance was evaluated as being somewhat superior to other cardiac glycosides, according to the global judgement of the physicians. The observed side effects were similar to those of other glycosides in frequency and character.

Topics: Administration, Oral; Adult; Aged; Atrial Fibrillation; Clinical Trials as Topic; Digitoxin; Digoxin; Dose-Response Relationship, Drug; Female; Heart Failure; Humans; Lanatosides; Male; Middle Aged; Proscillaridin

We describe an elderly case of idiopathic dilatation of the right atrium in which right-sided heart failure was exacerbated by drug-induced bradyarrhythmia. An 84-year-old man, who had a 10-year history of episodic edema, was treated with proscillaridin and verapamil hydrochloride at another hospital. He had experienced a poor appetite and general malaise 2 months previously, and exertional dyspnea 10 days previously. On admission, he had jugular venous dilatation, systemic edema, and hepatomegaly. On auscultation, a third heart sound originating from the right ventricle and systolic murmur of tricuspid regurgitation were heard. An admission electrocardiogram showed an atrial standstill and junctional escape rhythm with a QRS rate of 31 beats/minute. Chest roentgenogram revealed a bilateral pleural effusion and cardiomegaly with a cardiothoracic ratio of 76%, but no pulmonary congestion. Echocardiogram disclosed idiopathic dilatation of the right atrium and secondary tricuspid regurgitation. He was given a diagnosis of right-sided heart failure due to idiopathic dilatation of the right atrium exacerbated by bradyarrhythmia, which was suspected to derive from the side effects of proscillaridin and verapamil hydrochloride. Thus, these agents were withheld. In addition, the patient reduced sodium intake and was treated with diuretics and beta-adrenergic agonist. Thereafter, right-sided heart failure markedly improved. At the time of the last follow-up 16 months after discharge, he felt well.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Bradycardia; Cardiomegaly; Cardiotonic Agents; Dilatation, Pathologic; Heart Atria; Heart Failure; Humans; Male; Proscillaridin; Verapamil

The hemodynamic effect of methylepoxyproscillaridin (3'-methyl-4'-5'-epoxy-proscillaridin) (P35) was studied according to the Swan Ganz thermodilution method in 6 patients with latent cardiac insufficiency. Both at rest and under ergometer exercise, the stroke volume and the systolic blood pressures increased under P35. Moreover, under physical exercise the heart rate decreased significantly, while cardiac output increased. The hemodynamic effect of P35 can therefore be regarded as typical of cardiac glycosides.

Topics: Aged; Blood Pressure; Bufanolides; Cardiac Glycosides; Heart Failure; Hemodynamics; Humans; Middle Aged; Proscillaridin; Stroke Volume

Topics: Cardiac Glycosides; Digitoxin; Digoxin; Half-Life; Heart Failure; Humans; Kidney; Myocardial Contraction; Proscillaridin; Strophanthins

Topics: Digitoxin; Digoxin; Dose-Response Relationship, Drug; Glycosides; Heart Failure; Humans; Kidney Failure, Chronic; Metabolic Clearance Rate; Proscillaridin; Strophanthins; Uremia

Topics: Adult; Aged; Bufanolides; Computers; Digitoxin; Female; Heart Failure; Humans; Male; Mathematics; Middle Aged; Monitoring, Physiologic; Proscillaridin

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

Topics: Adult; Aged; Bufanolides; Digitoxin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug Tolerance; Female; Heart Failure; Humans; Lanatosides; Male; Middle Aged; Proscillaridin

Meproscillarin is a glycoside with a high bioavailability (about 70%) and an elimination independent of the renal function. It was to be investigated whether a good cardiac effectiveness can be demonstrated during oral long-term application of meproscillarin to patients with renal failure. 29 patients with renal failure of varying degree and concomitant heart failure were daily given an oral dose of 0.75 mg of meproscillarin over 14 days. The effectiveness of the glycoside was measured as change of the electromechanical systole (QS2c) and the quotient of the diameter of heart and thorax (C/T) from the 1st--15th day. The plasma levels of the glycoside were determined on the 1st, 8th, and 15th day. There was a significant shortening of QS2c (by mean = 27 ms, P less than 0.005) and a marked decrease in the size of the heart (P less than 0.0025); heart rate and PQ-interval were only insignificantly influenced. Plasma levels of 0.95 ng/ml were found after 8 days of treatment compared to 1.25 ng/ml after 15 days. As the pharmacokinetics of the glycoside is practically not influenced by the renal function, meproscillarin represents an alternative in the treatment of patients with heart failure and impaired renal function.

Topics: Adult; Aged; Bufanolides; Cardiac Volume; Drug Evaluation; Female; Heart Failure; Heart Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Proscillaridin

Topics: Biological Availability; Bufanolides; Circadian Rhythm; Half-Life; Heart Failure; Humans; Injections, Intravenous; Proscillaridin

After multiple oral doses, the disposition rate constant (beta) of proscillaridin was studied in 4 young healthy volunteers and 33 elderly patients with congestive heart failure. Glycoside activity in plasma was assayed by the 86Rb-technique. In the volunteers the beta averaged 0.0299 corresponding to a half-life (t 1/2) of 23 h. beta could be determined in 24 patients and was 0.0139 +/- 0.0077 (mean +/- SD). The SD of beta due to biological factors was estimated to be 0.0072. The total variation of beta was 10fold. The mean beta corresponded to a t 1/2 of 49 h with a range from 19 to 209 h. It is concluded that the great variation of beta means difficulty in obtaining adequate plasma levels of proscillaridin and that a rapid elimination of the glycoside cannot be presumed.

Topics: Administration, Oral; Adult; Age Factors; Aged; Bufanolides; Female; Half-Life; Heart Failure; Humans; Kinetics; Male; Proscillaridin

The effect of an association of proscillaridin A, thioridazine and Cori ester in ambulatory management of certain heart diseases, particularly in aged subjects, was assessed. Satisfactory results were observed in 58.3% of cases, with significant improvement of cardiac erethism, psychomotor instability and sleep disturbances, as well as cardiac frequency and signs of myocardial insufficiency. It is felt that the association is of assistance in the treatment of certain heart diseases unaccompanied by frank signs of insufficiency, especially in aged subjects.

Topics: Aged; Bufanolides; Coronary Disease; Drug Combinations; Female; Glucosephosphates; Heart Diseases; Heart Failure; Heart Valve Diseases; Humans; Hypertension; Male; Middle Aged; Proscillaridin; Pulmonary Heart Disease; Thioridazine

20 cardiac patients with the clinical and radiological signs of heart failure were treated alternately intravenously and orally with proscillaridin-4'-methyl ether in a 2-period change-over procedure. With medium rate full saturation a steady state was maintained under observation of electrocardiographic parameters. The maintenance dose was determined to be 1.00 mg intravenously and 1.71 mg orally. Thus, relative enteral availability was 60%. In 70% of patients cardiac recompensation could be reached only by treatment with proscillaridin-4'-methyl ether. In 9 of 20 patients undesirable side effects consisted of laxative effects.

Topics: Administration, Oral; Adult; Aged; Biological Availability; Bufanolides; Female; Heart Failure; Heart Rate; Humans; Injections, Intravenous; Intestinal Absorption; Male; Middle Aged; Proscillaridin

Topics: Angina Pectoris; Arteriosclerosis; Asthma; Cardiac Glycosides; Drug Therapy; Electrocardiography; Geriatrics; Heart Failure; Hypertension; Proscillaridin