Failure of the xanthine oxidase inhibitor allopurinol to limit infarct size after ischemia and reperfusion in dogs.
Failure of the xanthine oxidase inhibitor allopurinol to limit infarct size after ischemia and reperfusion in dogs.
复制标题
黄嘌呤氧化酶抑制剂别嘌呤醇未能限制狗缺血和再灌注后的梗塞面积。
DOI：
10.1161/01.cir.71.5.1069
复制
发表时间：
1985
期刊：
影响因子：
37.8
通讯作者：
Jennings,RB
中科院分区：
文献类型：
--
作者：
Reimer,KA;Jennings,RB
在心肌缺血的急性期，腺嘌呤核苷酸降解为核苷和碱基，特别是肌苷和次黄嘌呤。同时，黄嘌呤脱氢酶转化为黄嘌呤氧化酶，一种将次黄嘌呤转化为黄嘌呤，黄嘌呤转化为尿酸的酶，为每个次黄嘌呤或氧化的黄嘌呤分子产生超氧阴离子。为了确定自由基是否通过这种酶源导致心肌缺血中的细胞死亡，我们确定了黄嘌呤氧化酶抑制剂别嘌呤醇是否可以限制心肌梗死再灌注制剂中的梗死面积。34只犬结扎冠状动脉回旋支40 min，再灌注4 d。然后通过组织学方法测量脑梗死面积，并与梗死面积的主要基线预测因子相关，包括危险解剖区域和侧支血流。别嘌呤醇组（n = 8）的动脉大小（NS）大于对照组（n = 11），这一趋势与对照组侧支血流略高（NS）有关。我们的结论是，别嘌呤醇在这种制备实验性心肌梗死没有有益的影响。结果反对的假设，自由基，通过黄嘌呤氧化酶反应产生的，是心肌缺血细胞死亡的一个重要因素。
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.