title: The coincidence of myocardial reperfusion injury and hydrogen peroxide production in the isolated rat heart.
abstract: To investigate the specific nature and timing of oxygen (O2) metabolite reperfusion injury, we used a rat-heart model (Langendorff's solution, 37 degrees C) and hydrogen peroxide (H2O2)-dependent aminotriazole inactivation of catalase as a measure of myocardial H2O2 before, during, and after ischemia. We found that after ischemia (20 minutes, global, 37 degrees C), ventricular functional loss--as assessed by measurement of developed pressure (DP), +dp/dt, and -dp/dt with a ventricular balloon--occurred at 10 minutes of reperfusion and that myocardial H2O2 production was maximal by this time. Furthermore, H2O2 production did not occur during ischemia, and inhibition of xanthine oxidase by tungsten feeding or infusing a permeable O2 metabolite scavenger during reperfusion (dimethylthiourea) prevented ventricular functional loss. We conclude that (1) reperfusion injury is in part mediated by toxic oxygen metabolites, (2) H2O2 is the central O2 metabolite responsible for reperfusion injury, and (3) the timing of H2O2 production coincides with the timing of ventricular functional loss.
authors.affiliation: Department of Surgery and Medicine, University of Colorado Health Sciences Center, Denver.
authors.forename: J M
authors.initials: JM
authors.lastname: Brown
authors.forename: M A
authors.initials: MA
authors.lastname: Grosso
authors.forename: G J
authors.initials: GJ
authors.lastname: Whitman
authors.forename: A
authors.initials: A
authors.lastname: Banerjee
authors.forename: L S
authors.initials: LS
authors.lastname: Terada
authors.forename: J E
authors.initials: JE
authors.lastname: Repine
authors.forename: A H
authors.initials: AH
authors.lastname: Harken
mesh_terms: D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000378:metabolism; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D006321:Heart / Q000503:physiopathology; D006352:Heart Ventricles; D006861:Hydrogen Peroxide / Q000096:biosynthesis*; D066298:In Vitro Techniques; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D006861:Hydrogen Peroxide; D002374:Catalase; D000640:Amitrole