EFFECTS OF EXOGENOUS FREE-RADICALS ON ELECTROMECHANICAL FUNCTION AND METABOLISM IN ISOLATED RABBIT AND GUINEA-PIG VENTRICLE - IMPLICATIONS FOR ISCHEMIA AND REPERFUSION INJURY
EFFECTS OF EXOGENOUS FREE-RADICALS ON ELECTROMECHANICAL FUNCTION AND METABOLISM IN ISOLATED RABBIT AND GUINEA-PIG VENTRICLE - IMPLICATIONS FOR ISCHEMIA AND REPERFUSION INJURY
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DOI：
10.1172/jci114085
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发表时间：
1989-06-01
影响因子：
15.9
通讯作者：
WEISS, JN
中科院分区：
文献类型：
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作者：
GOLDHABER, JI;JI, S;WEISS, JN
氧衍生自由基与缺血期间心脏功能障碍、缺血后心肌“震颤”和再灌注损伤的发病机制有关。我们研究了氧自由基对完整离体兔心脏和单个豚鼠心室肌细胞心脏功能的影响。在完整的兔心室中，暴露于自由基生成系统会导致细胞 K+ 流出增加、动作电位持续时间缩短、张力变化以及高能磷酸盐的消耗，类似于缺血和代谢抑制。在膜片钳单心室肌细胞中，自由基生成系统激活 ATP 敏感的 K+ 通道，降低钙电流，并通过不可逆地抑制糖酵解和氧化代谢而导致细胞缩短。结果表明，缺血和再灌注过程中产生的自由基可能通过抑制糖酵解和氧化磷酸化而导致电生理异常和收缩功能障碍。自由基对代谢的抑制可能是在重建有效血流后限制缺血性损伤功能恢复的重要因素。
Oxygen-derived free radicals have been implicated in the pathogenesis of cardiac dysfunction during ischemia, postischemic myocardial "stunning" and reperfusion injury. We investigated the effects of oxygen-derived free radicals on cardiac function in intact isolated rabbit hearts and single guinea pig ventricular myocytes. In the intact rabbit ventricle, exposure to free radical-generating systems caused increased cellular K+ efflux, shortening of the action potential duration, changes in tension, and depletion of high energy phosphates similar to ischemia and metabolic inhibition. In patch-clamped single ventricular myocytes, free radical-generating systems activated ATP-sensitive K+ channels, decreased the calcium current, and caused cell shortening by irreversibly inhibiting glycolytic and oxidative metabolism. The results suggest that free radicals generated during ischemia and reperfusion may contribute to electrophysiologic abnormalities and contractile dysfunction by inhibiting glycolysis and oxidative phosphorylation. Inhibition of metabolism by free radicals may be an important factor limiting functional recovery from an ischemic insult after reestablishment of effective blood flow.