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Effect of BAY y 5959 on myocardial function and metabolism in normal and failing hearts.

Abstract
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.
AuthorsK Todaka, J Wang, G H Yi, A Gu, S M Zhu, H Zhang, D Burkhoff
JournalThe American journal of physiology (Am J Physiol) Vol. 274 Issue 5 Pg. H1560-8 (05 1998) ISSN: 0002-9513 [Print] United States
PMID9612364 (Publication Type: Journal Article)
Chemical References
  • BAY y 5959
  • Cardiotonic Agents
  • Dihydropyridines
Topics
  • Animals
  • Cardiotonic Agents (pharmacology)
  • Dihydropyridines (pharmacology)
  • Dogs
  • Heart (drug effects, physiology)
  • Heart Failure (metabolism, physiopathology)
  • Heart Rate (drug effects)
  • Hemodynamics (drug effects)
  • Myocardial Contraction (drug effects)
  • Myocardium (metabolism)

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