MYOCARDIAL GLUTATHIONE DEPLETION IMPAIRS RECOVERY AFTER SHORT PERIODS OF ISCHEMIA
MYOCARDIAL GLUTATHIONE DEPLETION IMPAIRS RECOVERY AFTER SHORT PERIODS OF ISCHEMIA
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DOI：
10.1161/01.cir.80.5.1449
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发表时间：
1989-11-01
期刊：
影响因子：
37.8
通讯作者：
FANBURG, BL
中科院分区：
文献类型：
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作者：
BLAUSTEIN, A;DENEKE, SM;FANBURG, BL
离体等容大鼠心脏，灌注Krebs-Henseleit缓冲液在恒定的冠状动脉流速，用于探讨假设内源性心脏谷胱甘肽提供保护，对心肌功能障碍与短期缺血。通过腹腔注射马来酸二乙酯（DEM）使实验动物的心脏谷胱甘肽耗尽至对照水平的35%。左心室压力，冠状动脉灌注压，谷胱甘肽水平进行了测量，在对照组和实验组的心脏后60分钟的氧合灌注和20分钟后的全球，无流量缺血和30分钟的再灌注。对于每个方案，对照和谷胱甘肽耗尽的心脏接受标准缓冲液或补充有2 mM谷胱甘肽的缓冲液。与对照组相比，缺血-再灌注后DEM治疗心脏的收缩功能恢复受损。此外，与对照组相比，DEM治疗心脏的灌注压和心室僵硬度的升高也更大。当再灌注液中补充谷胱甘肽时，谷胱甘肽耗竭心脏的恢复得到改善。此外，补充的再灌注液防止了谷胱甘肽耗竭心脏的顺应性降低和冠状动脉灌注压升高。单独缺血再灌注与心肌谷胱甘肽水平的显著变化无关。补充谷胱甘肽的缓冲液再灌注后，洗脱前心肌谷胱甘肽水平升高，但在短暂的洗脱期后降至基线水平。这些研究表明，内源性谷胱甘肽在缺血再灌注后保护心肌免受损伤中是重要的，可能是通过改变活性氧中间体的水平。GSH给药后左心室压力和冠状动脉阻力的较小变化可能反映了细胞外机制，因为再灌注后很快就可以看到益处。
Isolated, isovolumic rat hearts, perfused by Krebs-Henseleit buffer at constant coronary flow rate, were used to explore the hypothesis that endogenous cardiac glutathione provides protection against myocardial dysfunction associated with short periods of ischemia. Experimental animals were depleted of cardiac glutathione to 35% of control levels by intraperitoneal injections of diethylmaleate (DEM). Left ventricular pressure, coronary perfusion pressure, and glutathione levels were measured in control and experimental hearts after 60 minutes of oxygenated perfusion and after 20 minutes of global, no-flow ischemia and 30 minutes of reperfusion. With each protocol, both control and glutathione-depleted hearts received either standard buffer or one supplemented with 2 mM glutathione. Recovery of systolic function after ischemia-reperfusion was impaired in DEM-treated hearts compared with controls. In addition, the rise in perfusion pressure and chamber stiffness was also greater in DEM-treated hearts compared with controls. Recovery in glutathione-depleted hearts was improved when the reperfusate was supplemented with glutathione. In addition, the supplemented reperfusate prevented the decrease in compliance and the increase in coronary perfusion pressure in the glutathione-depleted hearts. Ischemia-reperfusion alone were not associated with a significant alteration in myocardial glutathione levels. Prewashout myocardial levels of glutathione were elevated after reperfusion with glutatione-supplemented buffer but fell to baseline levels after a short washout period. These studies demonstrate that endogenous glutathione is important in protection of myocardium from injury after ischemia-reperfusion, presumably by modifying levels of active oxygen intermediates. The smaller changes in left ventricular pressure and coronary resistance after administration of GSH probably reflects an extracellular mechanism because benefit is seen soon after reperfusion.