Peroxynitrite impairs cardiac contractile function by decreasing
cardiac efficiency.
Schulz, Richard, Karen L. Dodge, Gary D. Lopaschuk, and Alexander S.
Clanachan.
Departments of Pediatrics and Pharmacology, Cardiovascular Disease
Research Group, 413 Heritage Medical Research Centre, University of
Alberta, Edmonton, Alberta T6G 2S2 Canada
APStracts 3:0421H, 1996.
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-D,L-acetylpenicillamine (SNAP). After a 15 min baseline
aerobic perfusion, ONOO- (4 or 40 [mu]M), SNAP (40 [mu]M) or their
vehicles were infused over a 60 min period. ONOO- or SNAP (40 [mu]M
each) caused a rapid and sustained rise in coronary flow. Infusion of
40 [mu]M ONOO- (but not 4 [mu]M), caused a marked depression in
cardiac work with a delayed onset, but no change in oxygen
consumption, resulting in a marked loss of cardiac efficiency.
Cardiac work, oxygen consumption and cardiac efficiency remained
constant in vehicle and SNAP-treated hearts. ONOO- (40 [mu]M)
enhanced glycolysis and glucose oxidation but did not change pyruvate
oxidation compared to 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.
Received 5 June 1996; accepted in final form 12 September 1996.
APS Manuscript Number H505-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996