ISCHEMIC PRECONDITIONING SLOWS ENERGY-METABOLISM AND DELAYS ULTRASTRUCTURAL DAMAGE DURING A SUSTAINED ISCHEMIC EPISODE
ISCHEMIC PRECONDITIONING SLOWS ENERGY-METABOLISM AND DELAYS ULTRASTRUCTURAL DAMAGE DURING A SUSTAINED ISCHEMIC EPISODE
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DOI：
10.1161/01.res.66.4.913
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发表时间：
1990-04-01
影响因子：
20.1
通讯作者：
JENNINGS, RB
中科院分区：
文献类型：
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作者：
MURRY, CE;RICHARD, VJ;JENNINGS, RB
我们以前已经表明，预处理心肌与4个5分钟的缺血和再灌注发作显着限制了梗死的大小所造成的随后40分钟的持续缺血发作。本研究旨在评估相同的预处理方案是否减缓了持续缺血发作期间高能磷酸盐的损失、有限的分解代谢物积累和/或延迟的超微结构损伤。比较了对照组和预处理组犬严重缺血心肌内膜下区的代谢产物和超微结构。在持续缺血0、5、10、20或40分钟后切除心脏（每组4 - 10个）。所有组的侧支血流量相当。预处理心脏的超微结构损伤比对照组慢;对照组在20分钟后观察到不可逆损伤的证据，但预处理心脏在40分钟后才观察到。此外，缺血40分钟后，不可逆损伤在对照组中是均匀的，但仅在预处理心肌中是局灶性的。预处理使ATP的起始水平降低了29%。然而，它也减缓了持续缺血发作期间ATP消耗的速率，因此在缺血10分钟后，预处理的心脏比对照组有更多的ATP。但40分钟后，ATP含量组间无显著差异。ATP的保存是由于ATP利用率的降低，而不是由于ATP产量的增加。嘌呤核苷和碱基（腺嘌呤核苷酸降解产物）的积累在预处理心肌中是有限的。由于糖原分解和无氧糖酵解的速率降低，预处理也显著减少了葡萄糖-1-磷酸、葡萄糖-6-磷酸和乳酸的积累。我们认为，预处理减少了心肌缺血时的能量需求，从而导致高能磷酸盐利用率降低和无氧糖酵解率降低。ATP的保存或分解代谢的细胞负荷的减少可能是延迟缺血性细胞死亡的原因。
We have shown previously that preconditioning myocardium with four 5-minute episodes of ischemia and reperfusion dramatically limited the size of infarcts caused by a subsequent 40-minute episode of sustained ischemia. The current study was undertaken to assess whether the same preconditioning protocol slowed the loss of high energy phosphates, limited catabolite accumulation, and/or delayed ultrastructural damage during a sustained ischemic episode. Myocardial metabolites and ultrastructure in the severely ischemic subendocardial regions were compared between control and preconditioned canine hearts. Hearts (four to 10 per group) were excised after 0, 5, 10, 20, or 40 minutes of sustained ischemia. All groups had comparable collateral blood flow. Preconditioned hearts developed ultrastructural injury more slowly than controls; evidence of irreversible injury was observed after 20 minutes in controls but not until 40 minutes in preconditioned hearts. Furthermore, after 40 minutes of ischemia, irreversible injury was homogeneous in controls but only focal in preconditioned myocardium. Preconditioning reduced starting levels of ATP by 29%. Nevertheless, it also slowed the rate of ATP depletion during the episode of sustained ischemia, so that after 10 minutes of ischemia, preconditioned hearts had more ATP than controls. However, after 40 minutes, ATP contents were not significantly different between groups. Preservation of ATP resulted from reduced ATP utilization and was not due to increased ATP production. Accumulation of purine nucleosides and bases (products of adenine nucleotide degradation) was limited in preconditioned myocardium. Accumulation of glucose-1-phosphate, glucose-6-phosphate, and lactate also was reduced markedly by preconditioning, due to reduced rates of glycogen breakdown and anaerobic glycolysis. We propose that preconditioning reduces myocardial energy demand during ischemia, which results in a reduced rate of high energy phosphate utilization and a reduced rate of anaerobic glycolysis. Either preservation of ATP or reduction of the cellular load of catabolities may be responsible for delaying ischemic cell death.