CARDIAC REPERFUSION DAMAGE PREVENTED BY A NITROXIDE FREE-RADICAL
CARDIAC REPERFUSION DAMAGE PREVENTED BY A NITROXIDE FREE-RADICAL
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DOI：
10.1073/pnas.88.11.4680
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发表时间：
1991-06-01
影响因子：
11.1
通讯作者：
POWELL, SR
中科院分区：
文献类型：
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作者：
GELVAN, D;SALTMAN, P;POWELL, SR
实验证据表明，直接链接缺血/再灌注损伤的氧衍生的自由基的形成。 2，2，6，6-四甲基哌啶-N-氧基（克里思）-一种稳定的氮氧自由基，可抑制超氧自由基并氧化OH所需的还原金属离子。在经受局部缺血的离体大鼠心脏中测试其防止再灌注损伤的能力。 严重的再灌注心律失常-室颤和室性心动过速-在对照心脏中是突出的，并且它们的持续时间通过0.4或1 mM克里思的存在而显著减少。 克里思还抑制了缺血后乳酸脱氢酶和OH的释放。阵 克里思减慢心率，但代偿性起搏并没有改变氮氧化物对再灌注心律失常的显著影响。 克里思是部分保护时，引入在缺血结束，但没有效果时，加入1分钟再灌注。 结果表明，再灌注心律失常和细胞损伤与再灌注关键的第一分钟发生的氧化损伤直接相关。 克里思通过阻止OH的形成而对再灌注损伤有很强的保护作用。而不是通过降低心率或直接抑制心律失常。
Experimental evidence is presented that directly links ischemia/reperfusion injury to the formation of oxygen-derived free radicals. 2,2,6,6-Tetramethylpiperidine-N-oxyl (TEMPO)-a stable nitroxide radical that disproportionates superoxide radicals and oxidizes reduced metal ions required for OH. formation - was tested for its ability to prevent reperfusion damage in the isolated rat heart subjected to regional ischemia. Severe reperfusion arrhythmia - ventricular fibrillation and ventricular tachycardia - were prominent in control hearts, and their duration was significantly reduced by the presence of 0.4 or 1 mM TEMPO. TEMPO also repressed both postischemic release of lactate dehydrogenase and OH. formation. TEMPO slowed the heart rate, but compensatory pacing did not alter the dramatic effect of the nitroxide on reperfusion arrhythmia. TEMPO was partially protective when introduced at the end of ischemia but had no effect when added 1 min into reperfusion. It was concluded that both reperfusion arrhythmia and cell damage were directly related to oxidative damage incurred during the critical first minute of reperfusion. TEMPO strongly protected against reperfusion injury by preventing the formation of OH. and not by decreasing heart rate or by direct suppression of arrhythmia.