Acute substantial benefit of inotropic therapy with amrinone on exercise hemodynamics and metabolism in severe congestive heart failure.

Abstract

SUMMARY The acute hemodynamic and metabolic effects of amrinone during exercise were studied in eight patients with severe congestive heart failure. The patients exercised to exhaustion on an upright bicycle ergometer at a fixed work load of 25 W. During the control period of exercise, exhaustion occurred at 3.16 + 1.39 minutes. Stroke volume increased from 29.5 ± 5.8 to 38.7 + 9.5 ml (p < 0.01), arteriovenous oxygen difference from 7.6 + 1.3 to 9.6 + 0.6 ml/100 ml (p < 0.001), oxygen consumption from 231 + 38 to 468 + 111 ml/min (p < 0.001) and arterial lactate concentration from 1.07 + 0.25 to 5.02 + 1.45 mmol/l (p < 0.01). During exercise after administration of amrinone, exhaustion occurred significantly later than during the control period: 6.28 ± 2.07 vs 3.16 ± 1.39 minutes (p < 0.05). At a time equal to the point of exhaustion during the control period, stroke volume was significantly greater after amrinone (46.7 + 9.8 vs 38.7 ± 9.5 ml, p < 0.05), arteriovenous oxygen difference and arterial lactate concentration were significantly lower (7.7 + 0.9 vs 9.6 ± 0.6 ml/100 ml [p < 0.05] and 2.96 t 1.01 vs 5.02 ± 1.45 mmol/l [p < 0.05], respectively) and oxygen consumption was similar.At the point of exhaustion during exercise after amrinone, there were further increases in stroke volume (to 54.0 ± 11.6 ml, p < 0.05), and oxygen consumption (to 674 ± 141 ml/min, p < 0.05), while arteriovenous oxygen difference and arterial lactate concentration reached values similar to those during control exercise. Thus, amrinone increased exercise capacity, improved exercise hemodynamics, and probably decreased anaerobic metabolism at a given duration of exercise.AMRINONE is a new synthetic cardiotonic agent that does not act through the mechanisms thought to mediate the action of digitalis glycosides or catecholamines.' Amrinone has been shown to improve left ventricular performance at rest in patients with severe congestive heart failure. This improvement occurs after either i.V.2' 8 or oral' administration of amrinone and is characterized by an increase in cardiac output (CO) and a reduction in left ventricular filling pressure without changes in mean arterial pressure (MAP) or heart rate (HR). Although preliminary data suggest that long-term therapy with amrinone can increase the exercise capacity of patients with severe chronic heart failure,517 the hemodynamic and metabolic responses to exercise after acute administration of the drug have not been evaluated.The major hemodynamic aims in the therapy of congestive heart failure are to control pulmonary and peripheral congestion and to improve exercise performance. Potent diuretics have helped to control the former problem, but do not acutely improve exercise performance. Short-term administration of vasodilators to patients with severe heart failure improves both resting and exercise hemodynamics, but does not increase exercise capacity.8 10 Accordingly, the effects of i.v. amrinone on the hemodynamic and metabolic response to upright exercise were evaluated in eight pat...

Is inotropic therapy appropriate for patients with chronic congestive heart failure? Or is the digitalis leaf withering?

“…Available data do not support this hypothesis. In a study by Weber et al (1981), amrinone did not produce an acute improvement in exercise time and peak oxygen consumption, whereas in a study by Siskind et al (1981) acute exercise performance was enhanced. Little data is presently available on acute exercise performance with other non-sympathomimetic investigational agents.…”

Relationships between Anaerobic Threshold and Exercise Hemodynamic Pattern in Patients with Previous Myocardial Infarction

“…Recently the anaerobic threshold has been proposed as a tool to evaluate the func tional status before and following aortic valve replacement [16] and for the study of the response to various pharmacologic inter ventions [12,[29][30][31][32][33][34][35][36] and training [37], The present study was designed to investigate whether in class I and II cardiac patients the anaerobic threshold was related to the hemo dynamic pattern during exercise.…”

The new inotropic phosphodiesterase inhibitors

“…In patients with severe congestive heart failure, intravenous and oral amrinone have been shown to substantially augment performance of the failing heart without producing an increase in heart rate or a fall in arterial pressure (BENOTTI et al, 1978;LEJEMTEL et al, 1979;WYNNE et al, 1980;SISKIND et al, 1981).…”