AJP - Heart and Circulatory Physiology, Vol 272, Issue 3 1212-H1219, Copyright © 1997 by American Physiological Society

ARTICLES

Peroxynitrite impairs cardiac contractile function by decreasing cardiac efficiency

R. Schulz, K. L. Dodge, G. D. Lopaschuk and A. S. Clanachan
Department of Pediatrics, University of Alberta, Edmonton, Canada. richard.schulz@ualberta.ca

Peroxynitrite (ONOO-) inhibits energy metabolism in isolated cells and mitochondria and may be involved in the depression of cardiac mechanical function during pathophysiological states. We determined the actions of ONOO- on cardiac function and energy metabolism in isolated working rat hearts and compared them with the NO donor S-nitroso-DL-acetylpenicillamine (SNAP). After a 15-min baseline aerobic perfusion, ONOO- (4 or 40 microM), SNAP (40 microM), or their vehicles were infused over a 60-min period. ONOO- or SNAP (40 microM each) caused a rapid and sustained rise in coronary flow. Infusion of 40 microM (but not 4 microM) ONOO- caused a marked depression in cardiac work with a delayed onset but no change in O2 consumption, resulting in a marked loss of cardiac efficiency. Cardiac work, O2 consumption, and cardiac efficiency remained constant in vehicle- and SNAP-treated hearts. ONOO- (40 microM) enhanced glycolysis and glucose oxidation but did not change pyruvate oxidation compared with its vehicle control, whereas SNAP was without effect. ONOO(-)-mediated depression in cardiac efficiency may be due to reduced coupling between ATP production and mechanical work.

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