oxyfedrine and Heart-Failure

Topics: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Administration, Oral; Aminopyridines; Amrinone; Cardiotonic Agents; Coenzymes; Enoximone; Heart; Heart Failure; Hemodynamics; Humans; Imidazoles; Injections, Intravenous; Milrinone; Nifedipine; Oxyfedrine; Phosphodiesterase Inhibitors; Pyridazines; Pyridones; Quinazolines; Ubiquinone

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

In 34 patients with chronic cor pulmonale, the drugs from a group of beta-adrenostimulants, nonachlazinum and oxyphedrinum, were tested for effects on their hemodynamics, pulmonary ventilation function, blood gas composition and acid-base balance. In patients with circulatory failure due to lung diseases, nonachlazinum and oxyphedrinum were found to exert a pronounced positive intropic action, to contribute to an increase in cardiac output. The agents may be included into the multimodality therapy of patients with decompensated chronic cor pulmonale.

Topics: Adolescent; Adult; Aged; Bronchitis; Chronic Disease; Clinical Trials as Topic; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Nonachlazine; Oxyfedrine; Phenothiazines; Propiophenones; Respiration; Tuberculosis, Pulmonary

The haemodynamic effects of single oral doses of alifedrine 40 mg, 50 mg, 60 mg and placebo were compared in 30 patients with mild to moderate heart failure. Individual patients received either alifedrine 60 mg and placebo (15 patients) or alifedrine 40 mg and 50 mg (15 patients). All doses of alifedrine produced qualitatively similar haemodynamic responses, with maximum changes between 90 and 180 min after drug administration. The cardiac index was increased by +39%, +57%, and +50% by 40 mg, 50 mg and 60 mg, respectively. The increases were due to rises in stroke volume index (SVI) and in heart rate of +15%, +20% and +23%. Mean arterial blood pressure fell in a dose-related fashion, with a maximum fall of 11% by 120 min after 60 mg. The systemic vascular resistance index (SVRI) fell by 28%, 39% and 41%, and pulmonary vascular resistance index (PVRI) by 32%, 44% and 32% after 40 mg, 50 mg and 60 mg, respectively. The optimum dose appears to be 40 mg, which caused very little fall in blood pressure or increase in heart rate, yet significantly improved cardiac output. Alifedrine may have a place in the treatment of heart failure as an oral by active, positive inotropic agent.

Topics: Aged; Cardiac Output; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Oxyfedrine; Propiophenones; Pulmonary Circulation; Stroke Volume; Vascular Resistance

A randomized, double-blind, double-crossover, placebo-controlled haemodynamic study was undertaken in patients with Grade II/III (NYHA) cardiac failure to examine the acute effects of intravenous alifedrine, 20 mg and 40 mg (17 patients), and oral 40 mg alifedrine (8 of these patients). Patients received single doses of alifedrine and placebo on separate days, with invasive monitoring. Alifedrine resulted in a significant (p less than 0.001), dose-dependent increase in cardiac output. The peak effect (+23% with 20 mg i.v., +42% with 40 mg i.v. and +29% with 40 mg orally) was seen approximately 1 hour after intravenous administration (with about half of these increases still apparent at 3 hours) but developed progressively over 3 hours after oral administration. There were significant reductions (p less than 0.001) in peripheral resistance (peak mean changes -21% with 20 mg i.v., -31% with 40 mg i.v. and -23% with 40 mg orally), but little (less than +/- 6%) observed change in arterial pressure. With intravenous alifedrine, there were significant increases in stroke volume (+19% with 20 mg, +35% with 40 mg, p less than 0.001) with little (5%) change in heart rate (+3% and +7%, respectively, N.S.). With the 40 mg oral dose, there was a small increase in heart rate (+12%, p less than 0.005) associated with a 19% (N.S.) increase in stroke volume. Peak haemodynamic responses to 40 mg alifedrine orally were 50% to 75% of those seen after administration of the same dose intravenously. When assessed 3 hours after administration, responses to the two routes of administration were similar. There were no clinically or statistically significant changes in arterial (non-invasive), pulmonary artery, pulmonary capillary or right atrial pressures with any dose of alifedrine. No significant arrhythmias were noted clinically with the doses studied. Alifedrine, therefore, is an interesting agent, available both orally and intravenously, which is well tolerated and appears to produce marked acute increases in cardiac output with little change in heart rate or blood pressure. Further studies should determine whether these effects are maintained during longer-term therapy and clarify the relative contributions of positive inotropic and peripheral vasodilator activity to the effects observed.

Topics: Administration, Oral; Adult; Aged; Double-Blind Method; Female; Heart Failure; Hemodynamics; Humans; Injections, Intravenous; Male; Middle Aged; Oxyfedrine; Propiophenones; Random Allocation

Topics: Adolescent; Adrenergic beta-Agonists; Adult; Aged; Biopsy; Cardiomyopathies; Chronic Disease; Cytochrome c Group; Drug Combinations; Female; Heart Failure; Humans; Inosine; Male; Middle Aged; NAD; Oxyfedrine; Treatment Outcome

Acute ischemic left ventricular failure was induced in dogs by coronary embolization with plastic microspheres, resulting in reduced cardiac output (CO), increased left ventricular end-diastolic pressure (LVEDP), pulmonary capillary pressure (PCP), and total peripheral resistance (TPR). Intravenous (i.v.) administration of alifedrine, a beta-adrenergic partial agonist (0.3 mg/kg as bolus and 0.3 mg/kg/h as infusion), significantly improved performance of the failing heart. Left ventricular contractility was increased up to 50%, heart rate (HR) up to 28%, and CO up to 30%. LVEDP, PCP, and TPR were markedly decreased. Myocardial oxygen consumption was increased only to a minor degree despite the positive inotropic effect; coronary flow was augmented up to 26%. Thus, alifedrine in this model markedly improved left ventricular function by balanced stimulation of the myocardium and reduction of pre- and afterload.

Topics: Acute Disease; Adrenergic beta-Antagonists; Anesthesia; Animals; Blood Pressure; Coronary Disease; Dogs; Female; Heart; Heart Failure; Heart Rate; Hemodynamics; Male; Microspheres; Oxyfedrine; Propiophenones

The newly synthesized cardiotonic agent alifedrine (1-cyclohexyl-3-[(1S, 2R)-2-hydroxy-methyl-2-phenylethylamino]-propan-1-one) was shown to have vasodilating and positive inotropic effects in experimental animals. The effectiveness was tested in 8 patients with congestive heart failure already receiving digitalis and diuretics. After the intravenous administration of 40 mg alifedrine, cardiac output and stroke volume index increased and systemic vascular resistance and left ventricular filling pressure decreased. Left ventricular ejection fraction improved and there were no significant changes in heart rate and mean aortic pressure. Alifedrine, therefore, improves left ventricular performance in patients with congestive heart failure treated with digitalis and diuretic agents.

Topics: Adult; Blood Pressure; Cardiac Output; Cardiotonic Agents; Coronary Circulation; Heart Failure; Heart Rate; Hemodynamics; Humans; Male; Middle Aged; Oxyfedrine; Propiophenones; Stroke Volume; Vascular Resistance

Topics: Adult; Aged; Coronary Disease; Heart Failure; Humans; Middle Aged; Myocardial Contraction; Myocardial Infarction; Myocardium; Oxyfedrine; Propiophenones