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© 2000 American Heart Association, Inc.
Integrative Physiology |
Myocardial Ischemia/Reperfusion Injury in NADPH Oxidase–Deficient Mice
From the Department of Molecular and Cellular Physiology (M.R.H., S.P.J., B.S., M.B.G., F.S.L., D.J.L.), LSU Health Sciences Center, Shreveport, La; Department of Anatomy & Physiology, College of Veterinary Medicine (C.R.R.), Kansas State University, Manhattan, Kans; and Department of Physiology (T.J.S., R.S.), Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pa.
Correspondence to David J. Lefer, PhD, Department of Molecular and Cellular Physiology, LSU Health Sciences Center, 1501 Kings Hwy, Shreveport, LA 71130. E-mail dlefer{at}lsuhsc.edu\\ © 2000 American Heart Association, Inc.
Abstract—Previous studies have suggested that oxygen-derived free radicals are involved in the pathophysiology of myocardial ischemia/reperfusion (MI/R) injury. Specifically, neutrophils have been shown to mediate postischemic ventricular arrhythmias and myocardial necrosis. We hypothesized that MI/R injury would be reduced in the absence (-/-) of NADPH oxidase. Heterozygous control mice (n=23) and NADPH oxidase–/– mice (n=24) were subjected to 30 minutes of coronary artery occlusion and 24 hours of reperfusion. Myocardial area at risk per left ventricle was similar in heterozygous control hearts (55±3%) and NADPH oxidase–/– hearts (61±4%). Contrary to our hypothesis, the size of infarct area at risk was similar in the heterozygous control mice (42±4%) and NADPH oxidase–/– mice (34±5%) (P=not significant). In addition, echocardiographic examination of both groups revealed that left ventricle fractional shortening was similar in NADPH oxidase–/– mice (n=8; 27±2.5%) and heterozygous control mice (n=10; 23.3±3.3%) after MI/R. Superoxide production, as detected by cytochrome c reduction, was significantly impaired (P<0.01) in NADPH oxidase–/– mice (n=6) compared with heterozygous mice (n=7) (0.04±0.03 versus 2.2±0.08 nmol O2·min–1·106 cells–1). Intravital microscopy of the inflamed mesenteric microcirculation demonstrated that leukocyte rolling and adhesion were unaffected by the absence of NADPH oxidase. Oyster glycogen-stimulated neutrophil transmigration into the peritoneum was also similar in both the heterozygous control mice and NADPH oxidase–/– mice (P=not significant). These findings suggest that NADPH oxidase does not contribute to the development of myocardial injury and dysfunction after MI/R.
Key Words: murine • infarct • oxygen free radicals • neutrophils • echocardiography
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