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.