Observations on the intracoronary administration of milrinone and dobutamine to patients with congestive heart failure.

A direct intracoronary infusion technique was used to characterize the mechanisms of action of milrinone, a new phosphodiesterase inhibitor. Because of the small quantity of drug infused, it is possible to achieve a therapeutic concentration of drug in the heart with little or no systemic accumulation. Because loading conditions are largely unaffected during intracoronary drug infusion, it is possible to use left ventricular +dP/dt as a convenient measure of changes in contractility. Intracoronary milrinone infusion caused a dose-related increase in +dP/dt associated with a substantial improvement in left ventricular pump function. In addition, there is a small decrease in heart rate, which appeared to be secondary to reflex withdrawal of sympathetic tone, since it was associated with a decrease in plasma norepinephrine. Measurement of forearm vascular resistance and forearm venous capacitance by plethysmography indicated that although there was no significant decrease in forearm vascular resistance during intracoronary drug infusion, there was a small increase in venous capacitance. Subsequent intravenous administration of milrinone caused a substantial further improvement in left ventricular pump function, associated with a substantial decrease in left- and right-sided cardiac filling pressures and forearm vascular resistance, and an increase in forearm venous capacitance. These findings suggest that reflex sympathetic withdrawal may contribute to the venous dilation that occurs with milrinone, but that the major effects of milrinone on vascular tone are due to a direct vascular action of the drug. Intracoronary infusion of dobutamine has also demonstrated a substantial decrease in the inotropic response to beta-adrenergic stimulation in patients with congestive heart failure, presumably because of down-regulation of beta-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)