Failure of the xanthine oxidase inhibitor allopurinol to limit infarct size after ischemia and reperfusion in dogs.
During the acute phase of myocardial ischemia, adenine nucleotides are degraded to nucleosides and bases, especially inosine and hypoxanthine. Simultaneously, xanthine dehydrogenase is converted to xanthine oxidase, an enzyme that converts hypoxanthine to xanthine, and xanthine to uric acid, producing a superoxide anion for each molecule of hypoxanthine or xanthine oxidized. To determine if free radicals via this enzymatic source contribute to cell death in myocardial ischemia, we determined whether allopurinol, an inhibitor of xanthine oxidase, could limit infarct size in a reperfusion preparation of myocardial infarction. The circumflex coronary artery of each of 34 dogs was occluded for 40 min, followed by reperfusion for 4 days. Infarct size then was measured by histologic methods and was related to major baseline predictors of infarct size, including anatomic area at risk and collateral blood flow. Infarct size was larger (NS) in the allopurinol (n = 8) than in the control (n = 11) group, a trend that was related to slightly higher (NS) collateral blood flow in the control group. We conclude that allopurinol has no beneficial effect in this preparation of experimental myocardial infarction. The results oppose the hypothesis that free radicals, produced via the xanthine oxidase reaction, are an important contributing factor in myocardial ischemic cell death.
D000493:Allopurinol / Q000627:therapeutic use*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D010477:Perfusion / Q000379:methods; D011184:Postoperative Period; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D000493:Allopurinol; D014969:Xanthine Oxidase