Prevention of free radical-induced myocardial reperfusion injury with allopurinol.
Prevention of free radical-induced myocardial reperfusion injury with allopurinol.
复制标题
用别嘌呤醇预防自由基引起的心肌再灌注损伤。
DOI：
10.1016/s0022-5223(19)38664-7
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
L. Greenfield
中科院分区：
文献类型：
--
作者：
J. Stewart;S. Crute;V. Loughlin;M. Hess;L. Greenfield
越来越多的证据支持氧自由基是心肌缺血再灌注损伤的重要原因。本研究旨在确定毒性氧代谢产物是否会加重复氧后的缺血性损伤。在一组接受间歇性、4° C、高渗、高钾（KCl 25 mEq/L）盐水心脏停搏液的7只犬中研究左心室功能。将该组与接受高钾（KCl 25 mEq/L）心脏停搏液的组（n = 7）进行比较，该心脏停搏液旨在消除超氧阴离子和羟基自由基：超氧化物歧化酶（3，000 U/ml）和甘露醇（325 mOsm/L）。第三组5只动物接受别嘌呤醇预处理（50 mg/kg/天）72小时和高钾盐水心脏停搏液。在缺血60分钟（10° ~ 15° C）和再灌注45分钟后，接受自由基清除剂和别嘌呤醇预处理的组的左心室机械功能优于仅接受高钾盐水心脏停搏液的组。自由基清除剂在低温全脑缺血和再灌注模型中保护了心肌功能。我们的数据支持这一概念，即损伤主要发生在再灌注过程中，通过次黄嘌呤-黄嘌呤氧化酶反应产生氧自由基。别嘌呤醇在预防再灌注损伤方面具有潜在的临床应用价值。
Growing evidence supports the concept that oxygen free radicals are an important cause of myocardial ischemic and reperfusion injury. This study was designed to determine if toxic oxygen metabolites may exacerbate ischemic injury upon reoxygenation. Left ventricular function was studied in a group of seven dogs receiving intermittent, 4° C, hyperosmolar, hyperkalemic (KCl 25 mEq/L) saline cardioplegic solution. This group was compared to a group (n = 7) receiving a hyperkalemic (KCl 25 mEq/L) cardioplegie solution designed to scavenge superoxide anion and hydroxyl radical: superoxide dismutase (3,000 U/ml) and mannitol (325 mOsm/L). A third group of five animals received allopurinol pretreatment (50 mg/kg/day) for 72 hours and hyperkalemic saline cardioplegic solution. After 60 minutes of ischemia (10° to 15° C) and 45 minutes of reperfusion, left ventricular mechanical function was better in the groups receiving free radical scavengers and allopurinol pretreatment than in the group receiving only hyperkalemic saline cardioplegic solution. Free radical scavengers preserved myocardial function in this model of hypothermic global ischemia and reperfusion. Our data support the concept that injury occurs primarily during reperfusion with the generation of oxygen free radicals via the hypoxanthine–xanthine oxidase reaction. Allopurinol has potential clinical application in the prevention of reperfusion injury.