Parmley L F, Mufti A G, Downey J M
Department of Medicine, College of Medicine, University of South Alabama, Mobile 36617.
Can J Cardiol. 1992 Apr;8(3):280-6.
Free radicals produced by the hypoxanthine-xanthine oxidase reaction in ischemia/reperfusion experiments have been proposed as contributing to myocardial cell necrosis in acute myocardial infarction. In this study, the hypothesis was tested that a commonly observed late phase of necrosis, infarct extension, could be prevented by allopurinol, an inhibitor of xanthine oxidase.
Allopurinol, a xanthine oxidase inhibitor, was used with placebo in a double-blind randomized therapy study in 140 patients with ischemic heart disease admitted to the authors' hospital. Eighty-four had acute myocardial infarction and the remaining 56 had unstable angina. Of the 84 patients with infarction, 39 received allopurinol treatment. If xanthine oxidase production of cytotoxic free radical plays a major role in the pathogenesis of infarct extension, blockade of the reaction with allopurinol should decrease the occurrence of extension.
Nineteen infarct extensions were observed; five (11%) in the placebo group and 14 (36%) in the allopurinol.
The increased incidence of extension (P less than 0.007) in the treatment group does not support the hypothesis that xanthine oxidase contributes to infarct extension, which is consistent with recent reports that xanthine oxidase is not a significant component of the human myocardium. These findings indicate that allopurinol may actually be contraindicated in patients with ischemic heart disease.
在缺血/再灌注实验中，次黄嘌呤-黄嘌呤氧化酶反应产生的自由基被认为与急性心肌梗死时的心肌细胞坏死有关。在本研究中，对黄嘌呤氧化酶抑制剂别嘌呤醇能否预防常见的坏死后期即梗死扩展这一假说进行了验证。
在作者所在医院收治的140例缺血性心脏病患者中，将黄嘌呤氧化酶抑制剂别嘌呤醇与安慰剂用于一项双盲随机治疗研究。其中84例为急性心肌梗死患者，其余56例为不稳定型心绞痛患者。在84例梗死患者中，39例接受别嘌呤醇治疗。如果黄嘌呤氧化酶产生的细胞毒性自由基在梗死扩展的发病机制中起主要作用，那么用别嘌呤醇阻断该反应应能减少扩展的发生。
观察到19例梗死扩展；安慰剂组5例（11%），别嘌呤醇组14例（36%）。
治疗组中扩展发生率的增加（P<0.007）不支持黄嘌呤氧化酶导致梗死扩展这一假说，这与最近关于黄嘌呤氧化酶不是人类心肌重要组成部分的报道一致。这些发现表明，缺血性心脏病患者实际上可能禁忌使用别嘌呤醇。
