Myocardial ischemia/reperfusion injury in NADPH oxidase-deficient mice

Previous studies have suggested that oxygen-derived free radicals are invol ved in the pathophysiology of myocardial ischemia/reperfusion (MI/R) injury . Specifically, neutrophils have been shown to mediate postischemic ventric ular arrhythmias and myocardial necrosis. We hypothesized that MI/R injury would be reduced in the absence (-/-) of NADPH oxidase. Heterozygous contro l mice (n=23) and NADPH oxidase(-/-) mice (n=24) were subjected to 30 minut es of coronary artery occlusion and 24 hours of reperfusion. Myocardial are a 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 m ice (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 significa ntly impaired (P<0.01) in NADPH oxidase(-/-) mice (n=6) compared with heter ozygous mice (n=7) (0.04+/-0.03 versus 2.2+/-0.08 nmol O-2-min(-1). 10(6) c ells(-1)). Intravital microscopy of the inflamed mesenteric microcirculatio n demonstrated that leukocyte rolling and adhesion were unaffected by the a bsence of NADPH oxidase. Oyster glycogen-stimulated neutrophil transmigrati on into the peritoneum was also similar in both the heterozygous control mi ce and NADPH oxidase(-/-) mice (P=not significant). These findings suggest Chat NADPH oxidase does not contribute to the development of myocardial inj ury and dysfunction after MI/R.