title: Myocardial ischemia/reperfusion injury in NADPH oxidase-deficient mice.
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 O(2).min(-1).10(6) 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.
authors.affiliation: Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, LA, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Hoffmeyer
authors.forename: S P
authors.initials: SP
authors.lastname: Jones
authors.forename: C R
authors.initials: CR
authors.lastname: Ross
authors.forename: B
authors.initials: B
authors.lastname: Sharp
authors.forename: M B
authors.initials: MB
authors.lastname: Grisham
authors.forename: F S
authors.initials: FS
authors.lastname: Laroux
authors.forename: T J
authors.initials: TJ
authors.lastname: Stalker
authors.forename: R
authors.initials: R
authors.lastname: Scalia
authors.forename: D J
authors.initials: DJ
authors.lastname: Lefer
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D004562:Electrocardiography; D007958:Leukocyte Count; D051379:Mice; D008833:Microcirculation / Q000473:pathology; D017202:Myocardial Ischemia / Q000201:enzymology* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000473:pathology; D009206:Myocardium / Q000276:immunology / Q000473:pathology*; D019255:NADPH Oxidases / Q000172:deficiency*; D009504:Neutrophils / Q000276:immunology; D010976:Platelet Count; D013481:Superoxides / Q000378:metabolism; D016277:Ventricular Function, Left
chemical_list: D013481:Superoxides; D019255:NADPH Oxidases