Positive Inotropic and Vasodilating Effects of Amrinone and Milrinone in Isolated Canine Heart

The question has been raised whether the in vivo positive inotropic effect of amrinone and milrinone is a primary effect or secondary to vasodilation. The effects of each drug on isolated trabeculae and resistance vessels obtained from the same dog hearts were determined separately. The positive inotropic and vasodilatory effects coincided over the same concentration range for amrinone. The active isometric force of trabeculae and resistance vessels was increased, and respectively decreased by 20% at comparable concentrations of amrinone--20% ED (effective dose) ranging between 9.5 and 18 microM. By contrast, the vasodilatory properties of milrinone (20% ED, 15-34 microM) appeared only at concentrations at which milrinone had already evoked a maximal positive inotropic response in trabecular muscle (20% ED, 0.36-0.38 microM). Based on the present experiments and their limitations, it would thus appear that, in the intact heart and at therapeutic doses, positive inotropic and vasodilatory effects may be equally present for amrinone, whereas, for milrinone, the positive inotropic effect would largely predominate the vasodilatory effect.