EFFECT OF BAY-Y-5959 ON MYOCARDIAL-FUNCTION AND METABOLISM IN NORMAL AND FAILING HEARTS

BAY y 5959 is a dihydropyridine derivative with positive inotropic act ions mediated by a direct increase in intracellular calcium. We charac terized the direct myocardial actions of this new agent in hearts isol ated from seven normal dogs and from five dogs with repeated coronary microembolization-induced heart failure. Inotropic actions of BAY y 59 59 were accompanied by little effect on duration of contraction and by prolongation of the monophasic action potential (MAP); in contrast, i soproterenol decreased contraction and MAP durations. Whereas inotropi c responsiveness to isoproterenol was blunted in embolized hearts, the se actions of BAY y 5959 were relatively preserved in the heart failur e state. Isoproterenol increased heart rate, whereas BAY y 5959 had Li ttle effect. Changes in coronary vascular resistance also decreased si milarly for isoproterenol and BAY y 5959. Finally, for comparable inot ropy, increases in myocardial oxygen consumption were similar for isop roterenol and for BAY y 5959. In summary, preserved inotropic responsi veness and lack, of positive chronotropic actions are two clinically f avorable features of this type of inotropic agents compared with a typ ical beta-adrenergic agonist.