Myocardial and vascular actions of milrinone

Abstract

Milrinone exerts potent positive inotropic and direct vasodilator properties in vitro. Several studies have been undertaken to elucidate the relative contributions of each of these actions to the overall haemodynamic effect of milrinone in patients with congestive heart failure. Intracoronary infusion of milrinone to patients with congestive heart failure results in a dose-related increase in left ventricular filling pressure, +dP/dt, indicating a positive inotropic effect due to direct myocardial stimulation. Infusion of milrinone into the brachial artery increases forearm blood flow and decreases forearm vascular resistance, indicating a direct vasodilator action in patients with congestive heart failure. The relative contribution of milrinone's positive inotropic and vasodilator actions has been assessed by two approaches. First, the haemodynamic effects of nitroprusside and milrinone were compared at doses that caused equal reductions in arterial pressure. Under this condition, the improvement in left ventricular pump function caused by milrinone exceeded that caused by nitroprusside, suggesting that a significant portion of milrinone's overall effect could not be attributed merely to vasodilatation. Second, the haemodynamic effects of intracoronary and intravenous milrinone administration were compared in the same subjects. Under these conditions, the haemodynamic effect of intracoronary drug infusion accounted for a substantial portion of the improvement in left ventricular pump function. The conclusion from these studies, taken together, is that the overall haemodynamic effect of milrinone is due to significant contributions from both its positive inotropic and its vasodilator actions. Consequently, milrinone differs significantly from pure vasodilators, such as nitroprusside, and relatively pure positive inotropic agents, such as dobutamine.