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 actions mediated by a direct increase in intracellular calcium. We characterized the direct myocardial actions of this new agent in hearts isolated from seven normal dogs and from five dogs with repeated coronary microembolization-induced heart failure. Inotropic actions of BAY y 5959 were accompanied by little effect on duration of contraction and by prolongation of the monophasic action potential (MAP); in contrast, isoproterenol decreased contraction and MAP durations. Whereas inotropic responsiveness to isoproterenol was blunted in embolized hearts, these actions of BAY y 5959 were relatively preserved in the heart failure state. Isoproterenol increased heart rate, whereas BAY y 5959 had little effect. Changes in coronary vascular resistance also decreased similarly for isoproterenol and BAY y 5959. Finally, for comparable inotropy, increases in myocardial oxygen consumption were similar for isoproterenol and for BAY y 5959. In summary, preserved inotropic responsiveness and lack of positive chronotropic actions are two clinically favorable features of this type of inotropic agents compared with a typical beta-adrenergic agonist.
Todaka
K
K
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Wang
J
J
Yi
G H
GH
Gu
A
A
Zhu
S M
SM
Zhang
H
H
Burkhoff
D
D
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*
C109289:BAY y 5959; D002316:Cardiotonic Agents; D004095:Dihydropyridines