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

Am J Physiol. 1998 May;274(5):H1560-8. doi: 10.1152/ajpheart.1998.274.5.H1560.

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.

MeSH terms

  • Animals
  • Cardiotonic Agents / pharmacology*
  • Dihydropyridines / pharmacology*
  • Dogs
  • Heart / drug effects*
  • Heart / physiology*
  • Heart Failure / metabolism*
  • Heart Failure / physiopathology*
  • Heart Rate / drug effects
  • Hemodynamics / drug effects
  • Myocardial Contraction / drug effects
  • Myocardium / metabolism*

Substances

  • BAY y 5959
  • Cardiotonic Agents
  • Dihydropyridines