Effects of amrinone on isolated heart preparations: comparative study with other inotropic agents

We compared the effects of the phosphodiesterase inhibitor amrinone, the beta-adrenergic partial agonist xamoterol and the digitalis glycoside, ouabain, on isolated rabbit hearts perfused with the Langendorff technique. Heart rate, left ventricular pressure, as an index of myocardial contractility and coronary perfusion pressure, as an index of coronary resistances, were assessed before and after each drug. Perfusion with concentrations of each agent varying from 10(-9) to 10(-4) M induced a dose-dependent increase of left ventricular systolic pressure averaging 32.5 +/- 1.5% after amrinone (10(-5) M), 46.2 +/- 0.5% after xamoterol (10(-5) M) and 19.0 +/- 2.1% after ouabain (10(-4) M). Among the 3 agents, only amrinone was able to reduce basal coronary perfusion pressure (18.4 +/- 1.2% at the dose of 10(-5) M) and inhibit vasopressin-induced coronary spasm (86.8 +/- 2.5% inhibition at 10(-5) M); no significant change of coronary perfusion pressure was noted with either xamoterol or ouabain. Heart rate was not significantly modified by amrinone whereas, at the doses of 10(-5)-10(-4) M, xamoterol increased it by 21.6 +/- 0.7% and ouabain reduced it by 12.3 +/- 1.1%. Our results show that amrinone, in comparison with digitalis glycosides and beta-adrenergic agonists, presents the unique property to increase myocardial contractility with concomitant coronary vasodilation without significant changes of heart rate. Ouabain has a less potent positive inotropic activity and a slight negative chronotropic action, whereas xamoterol inotropic effect is accompanied by an increase of heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)