Influence of peroxynitrite on energy metabolism and cardiac function in a rat ischemia-reperfusion model

Warren H. Lee, John S. Gounarides, Eric S. Roos, Michael S. Wolin
2003 American Journal of Physiology. Heart and Circulatory Physiology  
Lee, Warren H., John S. Gounarides, Eric S. Roos, and Michael S. Wolin. Influence of peroxynitrite on energy metabolism and cardiac function in a rat ischemiareperfusion model. reperfusion generates peroxynitrite (ONOO Ϫ ), which interacts with many of the systems altered by ischemia-reperfusion. This study examines the influence of endogenously produced ONOO Ϫ on cardiac metabolism and function. Nitro-L-arginine (an inhibitor of ONOO Ϫ biosynthesis) and urate (a scavenger of ONOO Ϫ ) were
more » ... ONOO Ϫ ) were utilized to investigate potential pathophysiological roles for ONOO Ϫ in a rat Langendorff heart model perfused with glucose-containing saline at constant pressure and exposed to 30 min of ischemia followed by 60 min of reperfusion. In this model, ischemia-reperfusion decreased contractile function (e.g., left ventricular developed pressure), cardiac work (rate-pressure product), efficiency of O2 utilization, membrane-bound creatine kinase activity, and NMR-detectable ATP and creatine phosphate without significantly altering the recovery of coronary flow, heart rate, lactate release, and muscle pH. Treatment with urate and nitro-L-arginine produced a substantial recovery of left ventricular developed pressure, rate-pressure product, efficiency of O 2 utilization, creatine kinase activity, and NMR-detectable creatine phosphate and a partial recovery of ATP. The pattern of effects observed in this study and in previously published work with similar models suggests that ONOO Ϫ may alter key steps in the efficiency of mitochondrial high-energy phosphate generation.
doi:10.1152/ajpheart.00808.2002 pmid:12816754 fatcat:lsftgmgajrflneyqjdqxhpgtza