PRECONDITIONING WITH ISCHEMIA - A DELAY OF LETHAL CELL INJURY IN ISCHEMIC MYOCARDIUM
PRECONDITIONING WITH ISCHEMIA - A DELAY OF LETHAL CELL INJURY IN ISCHEMIC MYOCARDIUM
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DOI：
10.1161/01.cir.74.5.1124
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发表时间：
1986-11-01
期刊：
影响因子：
37.8
通讯作者：
REIMER, KA
中科院分区：
文献类型：
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作者：
MURRY, CE;JENNINGS, RB;REIMER, KA
我们先前已经证明，短暂的缺血发作减缓了随后缺血发作期间ATP耗竭的速率。此外，间歇性再灌注可通过冲洗在缺血期间积累的钙离子而对心肌有益。因此，我们提出，多次短暂缺血发作实际上可能保护心脏免受随后的持续缺血性损伤。为了验证这一假设，进行了两组实验。在第一组中，一组狗（n = 7）预处理4个5分钟回旋支闭塞，每隔5分钟的再灌注，然后持续40分钟闭塞。对照组（n = 5）接受单次40 min闭塞。在第二项研究中，遵循相同的预处理方案，然后动物（n = 9）接受持续3小时的闭塞。对照动物（n = 7）接受单次3小时闭塞。此后允许动物再灌注4天。然后测量组织学梗死面积，并与梗死面积的主要基线预测因子相关，包括危险解剖区域和侧支血流。在40分钟的研究中，缺血预处理矛盾地将梗死面积限制在对照组的25%（p <0.001）。两组侧支循环血流量无显著差异。在3小时的研究中，预处理组和对照组的梗死面积没有差异。40 min研究中预处理的保护作用可能是由于持续闭塞期间ATP消耗减少和/或分解代谢物积累减少。这些结果表明，在人心肌梗死之前经常发生的多次心绞痛发作可能会延迟冠状动脉闭塞后的细胞死亡，从而通过再灌注治疗可以更好地挽救心肌。
We have previously shown that a brief episode of ischemia slows the rate of ATP depletion during subsequent ischemic episodes. Additionally, intermittent reperfusion may be beneficial to the myocardium by washing out catabolites that have accumulated during ischemia. Thus, we proposed that multiple brief ischemic episodes might actually protect the heart from a subsequent sustained ischemic insult. To test this hypothesis, two sets of experiments were performed. In the first set one group of dogs (n = 7) was preconditioned with four 5 min circumflex occlusion, each separated by 5 min of reperfusion, followed by a sustained 40 min occlusion. The control group (n = 5) received a single 40 min occlusion. In the second study, an identical preconditioning protocol was followed, and animals (n = 9) then received a sustained 3 hr occlusion. Control animals (n = 7) received a single 3 hr occlusion. Animals were allowed 4 days of reperfusion thereafter. Histologic infarct size then was measured and was related to the major baseline predictors of infarct size, including the anatomic area at risk and collateral blood flow. In the 40 min study, preconditioning with ischemia paradoxically limited infarct size to 25% of that seen in the control group (p < .001). Collateral blood flows were not significantly different in the two groups. In the 3 hr study, there was no difference between infarct size in the preconditioned and control groups. The protective effect of preconditioning in the 40 min study may have been due to reduced ATP depletion and/or to reduced catabolite accumulation during the sustained occlusion. These results suggest that the multiple anginal episodes that often precede myocardial infarction in man may delay cell death after coronary occlusion, and thereby allow for greater salvage of myocardium through reperfusion therapy.