Brown J M, Grosso M A, Whitman G J, Banerjee A, Terada L S, Repine J E, Harken A H
Department of Surgery and Medicine, University of Colorado Health Sciences Center, Denver.
Surgery. 1989 Apr;105(4):496-501.
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.
为了研究氧（O₂）代谢产物再灌注损伤的具体性质和时间，我们使用了大鼠心脏模型（Langendorff溶液，37℃），并通过过氧化氢（H₂O₂）依赖性的氨基三唑使过氧化氢酶失活，以此来测量缺血前、缺血期间和缺血后的心肌H₂O₂。我们发现，缺血（20分钟，全心，37℃）后，通过心室球囊测量的舒张期压力（DP）、+dp/dt和 -dp/dt来评估，心室功能丧失在再灌注10分钟时出现，此时心肌H₂O₂生成达到最大值。此外，缺血期间未出现H₂O₂生成，在再灌注期间通过钨喂养抑制黄嘌呤氧化酶或注入可渗透的氧代谢产物清除剂（二甲基硫脲）可防止心室功能丧失。我们得出结论：（1）再灌注损伤部分由有毒的氧代谢产物介导；（2）H₂O₂是导致再灌注损伤的主要氧代谢产物；（3）H₂O₂生成的时间与心室功能丧失的时间一致。
