Intravenous prenalterol in acute and chronic heart failure

Abstract

The new inotropic agent prenalterol was administered intravenously in a canine model of acute ischemic heart failure and in patients with severe chronic heart failure. Experimental heart failure in anesthetized dogs was induced by two vessel coronary artery constriction and intravenous prenalterol (0.005–15 Μg/kg/min) was compared to dobutamine (0.001–30 Μg/kg/min) and saline. Significant dose–dependent increases in left ventricular dP/dt max ′ cardiac output and non–ischemic zone contractile force and significant reductions in systemic vascular resistance were present during infusions of both inotropic agents. High dose dobutamlne caused greater increases in mean arterial pressure and pressure rate product with a trend toward greater increases in heart rate. However, neither inotropic agent significantly improved ischemic zone contractile force. Prenalterol possessed a markedly longer hemodynamic half–life than dobutamlne (3.0 hours compared to 1.7 minutes). Nine patients with severe chronic heart failure (left ventricular ejection fraction mean ± SD 17 ± 5%, cardiac index 1.7±0.4 1/min/m 2 ) responded to intravenous prenalterol (1, 4, and 8 mg) with significant increases in cardiac index, left ventricular ejection fraction and left ventricular stroke work index. Left ventricular filling pressure, mean right atrial pressure and pulmonary arteriolar resistance were significantly reduced. No significant differences were present among peak responses to the three doses employed. An inverse correlation between basal heart rate and increase in left ventricular ejection fraction following prenalterol was noted. The mechanisms by which prenalterol causes hemodynamic improvement appear to include a direct inotropic effect, a reduction in left ventricular outflow resistance and a reduction in left and right ventricular filling pressure (venodilating effect). The net result is an upward and leftward shift of the depressed ventricular function curve. Both prenalterol and dobutamine were associated with sustained ventricular tachyarrhythmias in the experimental acute low output state and two digitalized patients with ischemic cardiomyopathy developed transient ventricular tachycardia after prenalterol administration. These findings indicated that adrenergic stimulants should be administered in severe ischemic states with careful monitoring.