AJP - Heart and Circulatory Physiology, Vol 271, Issue 1 311-H319, Copyright © 1996 by American Physiological Society

ARTICLES

Differential effects of EMD-53998 on calcium-pressure relationship in normal and ischemic guinea pig heart

R. Ishisu, Y. Abe, K. Onishi, K. Sekioka and T. Nakano
First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan.

We investigated the effects of EMD-53998 and digoxin on Ca2+ transients and left ventricular (LV) function in indo 1-loaded Langendorff guinea pig hearts. EMD-53998 (10(-9) to 10(-5) M) and digoxin (10(-10) to 10(-6) M) increased +dP/dt and Ca2+ transients in normal hearts. The relative increase in Ca2+ transients by EMD-53998 was similar to digoxin. At 10(-5) M, EMD-53998 increased LV end-diastolic pressure. Low-flow ischemia decreased +dP/dt by 50%, while indo 1 ratio increased by 10-25%. EMD-53998 (10(-9) to 10(-6) M) effectively restored the depressed +dP/dt with little effect on indo 1 ratio, but at 10(-5) M, it markedly elevated LV end-diastolic pressure and the beneficial effect on contractile dysfunction disappeared. Digoxin (10(-10) to 10(-7) M) failed to improve LV function, but at 10(-6) M, it restored contractile dysfunction with a large increase in indo 1 ratio. The relation between indo 1 ratio and +dP/dt clearly showed that EMD-53998 restored contractile dysfunction by Ca2+ sensitization. These findings suggest that Ca2+ sensitization by EMD-53998 is an advantageous approach for ischemic contractile failure but impairs diastolic function.

This article has been cited by other articles:

				K. Onishi, K. Sekioka, R. Ishisu, Y. Abe, H. Tanaka, M. Nakamura, Y. Ueda, and T. Nakano MCI-154, a Ca2+ sensitizer, decreases the oxygen cost of contractility in isolated canine hearts Am J Physiol Heart Circ Physiol, October 1, 1997; 273(4): H1688 - H1695. [Abstract] [Full Text] [PDF]