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Division of Circulatory Physiology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032
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
-adrenergic agonist.
heart failure; inotropic agents; calcium; oxygen consumption; heart rate; coronary vascular resistance; action potential
This article has been cited by other articles:
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G.-H. Yi, D. Burkhoff, H. Zhang, S.-M. Zhu, D. Zwas, and J. Wang Hemodynamic Effects of a Calcium Channel Promoter, BAY y 5959, are Preserved after Chronic Administration in Ischemic Heart Failure in Conscious Dogs J. Pharmacol. Exp. Ther., August 1, 1998; 286(2): 760 - 766. [Abstract] [Full Text] |
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