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

• Published in: American journal of physiology. Heart and circulatory physiology 1998-05, Vol.274 (5), p.H1560-H1568
• Main Authors: Todaka, Koji, Wang, Jie, Yi, Geng-Hua, Gu, Anguo, Zhu, Shu-Ming, Zhang, Hui, Burkhoff, Daniel
• Format: Article
• Language: English
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.1998.274.5.h1560

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