The coincidence of myocardial reperfusion injury and hydrogen perioxide production in the isolated rat heart

To investigate the specific nature and timing of oxygen (O₂) metabolite reperfusion injury, we used a rat-heart model (Langendorff's solution, 37° 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° 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.