(Circulation. 1997;96:2317-2324.)
© 1997 American Heart Association, Inc.
Articles |
Peroxynitrite Reduces Myocardial Infarct Size and Preserves Coronary Endothelium After Ischemia and Reperfusion in Cats
From the Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pa.
Correspondence to Dr Allan M. Lefer, Department of Physiology, Jefferson Medical College, 1020 Locust St, Philadelphia, PA 19107.
Background Peroxynitrite (ONOO-) is purported to exert cytotoxic effects at high doses. However, physiologically relevant concentrations of ONOO- inhibit polymorphonuclear neutrophil (PMN) adhesion to the endothelium and attenuate PMN-mediated contractile dysfunction in isolated perfused rat hearts. We are unaware of any reports in vivo showing effects of peroxynitrite in myocardial ischemia and reperfusion (MI/R). Thus, the purpose of this study was to examine the in vivo effects of a physiologically relevant concentration of ONOO- (1 µmol/L) in a feline model of MI/R injury.
Methods and Results ONOO- (1 µmol/L) or its vehicle (0.9% NaCl at pH 8.4) was infused intraventricularly, starting 10 minutes before reperfusion in cats subjected to 90 minutes of myocardial ischemia and 4.5 hours of reperfusion. ONOO--treated cats demonstrated marked attenuation of cardiac necrosis after MI/R compared with cats receiving only vehicle (P<.001). Moreover, vasorelaxation of ischemic-reperfused left anterior descending (LAD) coronary artery rings in response to the endothelium-dependent dilators acetylcholine and A23187 was greater in rings isolated from ONOO--treated MI/R cats compared with MI/R cats receiving only vehicle, indicating that postreperfusion coronary vascular endothelial function was preserved by ONOO-. ONOO- also significantly reduced adherence of neutrophils to the ischemic-reperfused LAD coronary endothelium. Immunohistochemical localization of P-selectin was also significantly attenuated in hearts from ONOO--infused MI/R cats.
Conclusions These data suggest that physiologically relevant concentrations of ONOO- exert significant cardioprotective and vasculoprotective effects in MI/R in cats, at least partially by attenuating PMN-endothelium interactions.
Key Words: neutrophils • vasorelaxation • leukocytes • endothelium • endothelium-derived factors • ischemia • reperfusion
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