Peroxynitrite aggravates myocardial reperfusion injury in the isolated perfused rat heart

Objective: This study examined the effects of peroxynitrite (ONOO-) on cardiac function and cellular injury following ischemia (30 min) and reperfusion (60 min) in isolated perfused rat hearts. Methods: 3-Morpholinosydnonimine (SIN-I, 0.1 mM), an ONOO- donor, was administered alone or combined with superoxide dismutase (SOD, 300 U/ml) or glutathione (GSH, 1 mM) at the time of reperfusion. Results: Administration of SIN-I alone significantly aggravated post-ischemic myocardial injury characterized by depressed cardiac function recovery (p < 0.05 vs. vehicle), increased lactic dehydrogenase (LDH) and creatine kinase (CK) release (p < 0.01 vs. Vehicle), and enlarged necrotic size (p < 0.01 vs. vehicle). The co-administration of either SOD to decrease the formation of ONOO-, or GSH to increase the detoxification of ONOO-, completely blocked the detrimental effects of SIN-1 and exerted significant cardioprotective effects against reperfusion injury. Conclusion: These results suggest that ONOO- may play a significant role in postischemic myocardial injury. (C) 1997 Elsevier Science B.V.