Evaluation of the role of xanthine oxidase in myocardial reperfusion injury.
Evaluation of the role of xanthine oxidase in myocardial reperfusion injury.
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DOI：
10.1016/s0021-9258(19)39200-2
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发表时间：
1990-04
期刊：
影响因子：
--
通讯作者：
S. Thompson-Gorman;J. Zweier
中科院分区：
文献类型：
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作者：
S. Thompson-Gorman;J. Zweier
据推测，产生自由基的酶黄嘌呤氧化酶是缺血后组织损伤的核心机制。然而，其重要性仍然存在争议。许多注意力集中在这种酶在心肌再灌注损伤中的作用。虽然在缺血组织匀浆中观察到黄嘌呤氧化酶，但在完整组织中该酶产生自由基的存在和重要性尚不清楚。因此，我们进行了电子顺磁共振、核磁共振和血流动力学研究，以测量离体大鼠心脏中黄嘌呤氧化酶介导的自由基生成的存在和意义。当离体灌注大鼠心脏在整体缺血 30 分钟后进行再灌注时，在有效的黄嘌呤氧化酶阻滞剂奥嘌呤醇的存在下，心肌功能和冠状动脉血流显着改善。通过使用 5,5'-二甲基-1-吡咯啉-N-氧化物自旋捕获测量的自由基浓度，奥嘌呤醇显着降低，并且心脏的能量状态得到改善，这反映在磷酸肌酸的恢复增加和更高的磷酸肌酸/Pi 比率上。然而，ATP 恢复并没有改变，这表明心脏功能和代谢状态的改善并不是由于 ATP 挽救。该酶的分光光度测定显示，缺血后黄嘌呤氧化酶的量相对于脱氢酶有所增加，大鼠心脏中可用的黄嘌呤氧化酶库总量约为 150 毫单位/克蛋白质。因此，黄嘌呤氧化酶是缺血大鼠心脏再灌注时发生的氧化损伤的重要来源。
The free radical-generating enzyme xanthine oxidase has been hypothesized to be a central mechanism of the injury which occurs in postischemic tissues; however, its importance remains controversial. Much attention has focused on the role of this enzyme in myocardial reperfusion injury. While xanthine oxidase has been observed in ischemic tissue homogenates, the presence and importance of radical generation by the enzyme in intact tissues are unknown. Therefore, we performed electron paramagnetic resonance, nuclear magnetic resonance and hemodynamic studies to measure the presence and significance of xanthine oxidase-mediated free radical generation in the isolated rat heart. When isolated perfused rat hearts were reperfused after 30 min of global ischemia, myocardial function and coronary flow were significantly improved in the presence of the definitive xanthine oxidase blocker oxypurinol. Free radical concentrations measured by spin-trapping with 5,5'-dimethyl-1-pyrroline-N-oxide were significantly decreased by oxypurinol and the energetic state of the heart was improved as reflected by an increased recovery of phosphocreatine and a higher phosphocreatine/Pi ratio. ATP recovery, however, was not altered, indicating that the improved functional and metabolic state of the heart was not due to ATP salvage. Spectrophotometric assays for the enzyme showed an increase in the amount of xanthine oxidase relative to dehydrogenase following ischemia, and a total available xanthine oxidase pool in the rat heart of approximately 150 milliunits/g of protein. Thus, xanthine oxidase is a significant source of the oxidative injury which occurs upon reperfusion of the ischemic rat heart.