Effects of intracoronary infusion of an inotropic agent, E-1020 (loprinone hydrochloride), on cardiac function: evaluation of left ventricular contractile performance using the end-systolic pressure-volume relationship

Abstract

The phosphodiesterase (PDE) III inhibitor, E-1020 (loprinone hydrochloride), has positive inotropic and vasodilating effects. This study evaluated the positive inotropic effect of intracoronary E-1020 in eight patients with coronary artery disease and hypertensive heart disease. A direct intracoronary infusion of the PDE III inhibitor minimizes its vasodilating effect. After baseline hemodynamic measurements and coronary arteriography, a micromanometer-tipped 8F conductance catheter was introduced into the left ventricle to determine the hemodynamic effects of E-1020. Saline and vehicle were infused into the left main coronary artery at a rate of 2 ml/min. The dose of intracoronary E-1020 increased from 2.5 to 5.0 and 7.5 μg/min. The inotropic effect of E-1020 was defined as the change in the slope of the end-systolic pressure-volume relationship (E max), which was independent of afterload and preload. E max significantly increased at infusion rates of 7.5 μg/min from control. Peak + dP dt increased at an infusion rate of 5.0 μg/min or higher, while left-ventricular end-diastolic pressure (LVEDP) decreased significantly at a rate of 5.0 and 7.5 μg/min. Intracoronary infusion of E-1020 at a rate of 2.5 μg/min produced a plasma concentration of 20 ng/ml, which was identical to the minimum effective plasma concentration seen in previous study by intra venous infusion. However, at a plasma concentration of 20 ng/ml, E-1020 has more vasodilating effects than inotropic effects. Clinically, E-1020 appears to have a positive inotropic effect that depends on the extent of myocardial perfusion.