Acute effects of intravenous milrinone in heart failure

Milrinone exerts positive inotropic and dose-dependent vasodilatory effects that promote haemodynamic improvement after intravenous administration to patients with heart failure. Bolus doses of 12.5-75 micrograms kg-1 markedly increase cardiac output and cause a substantial reduction in cardiac filling pressure and in systemic vascular and pulmonary vascular resistance. There is no evidence of tolerance to these effects which are maintained during continuous infusion for up to 48 h. In contrast, there are minimal effects on heart rate or systemic blood pressure, except at very high doses. At lower filling pressures, milrinone increases cardiac output more markedly than equally hypotensive doses of pure vasodilators. This response is accompanied by an increased left ventricular dP/dtmax and a shift in the left ventricular performance is associated with a lower myocardial energy requirement. Despite a fall in mean arterial pressure and transcoronary driving pressure, coronary venous flow is increased and there is a reduction in the arterio-coronary venous oxygen difference. This reflects a global improvement in left ventricular diastolic function, characterized by accelerated early relaxation and greater chamber distensibility. Improved performance of the right ventricle is due primarily to reduced right ventricular afterload as milrinone produces minimal inotropic effects on the right ventricle.