Evaluation of the vasodilator vs inotropic effect of milrinone using an animal model of left ventricular failure: reversal of disopyramide depression of the myocardium with milrinone.

Milrinone (M) has been shown to improve left ventricular (LV) performance in animal and human studies. M has strong vasodilator action, and whether increased LV performance is due primarily to vasodilation or to a direct positive inotropic effect is unclear. Ten mongrel dogs were studied. Disopyramide caused a significant and sustained decrease in LV function and was a good model for myocardial depression. At equal reduction in systemic vascular resistance (SVR), M reversed this LV depression to a significantly greater degree than nitroprusside (NP) did. At equal levels of vasodilation, M produced significantly greater improvement in indices of LV function than NP did in our model of disopyramide-induced LV failure. This suggest that its effect on LV function is not due entirely to afterload reduction, or to reflex sympathetic stimulation, but has a substantial component of direct inotropic stimulation. This study also demonstrated a reversal of disopyramide-induced LV dysfunction by M, which may be clinically useful since, as in many antiarrhythmics, myocardial depression may be a limiting factor in its use.