PRECONDITIONING MYOCARDIUM WITH ISCHEMIA
PRECONDITIONING MYOCARDIUM WITH ISCHEMIA
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DOI：
10.1007/bf00053555
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发表时间：
1991-10-01
影响因子：
3.4
通讯作者：
REIMER, KA
中科院分区：
文献类型：
--
作者：
JENNINGS, RB;MURRY, CE;REIMER, KA
预处理和击晕是短暂的可逆性缺血随后动脉再灌注引起的心肌的主要适应性变化。在狗的心脏中，两者共存至少 20 分钟的再灌注期，但在 120 分钟的回流后，预处理大大减弱，而击晕仍然完全发展。预调节、击晕的心肌与对照“原始”心肌的不同之处在于，腺嘌呤核苷酸含量减少至对照的约50-70%，而磷酸肌酸(CP)大大超过正常值——所谓的CP超调。当预处理的心肌遭受持续缺血时，ATP利用和无氧糖酵解发生的速率比在原始心肌中观察到的速率慢得多。由于代谢率的早期差异，预处理组织的 ATP 和乳酸需要较长时间的缺血才能达到与不可逆损伤相关的水平。与这种变化相关的是心肌细胞死亡的延迟。导致缺血代谢减慢以及预调节、震惊组织对新的缺血发作的相关耐受性的分子事件尚不清楚。在可能导致能量代谢减少的反应中，由于在缺血的初始阶段试图收缩的震惊心肌，大约减少了 P 消耗。然而，体内和体外实验的结果表明，虽然击晕可能是预适应发生所必需的，但仅靠击晕不足以引起预适应。或者，代谢变化可以通过持续缺血期间线粒体 ATP 酶活性降低来解释。然而，到目前为止，还没有直接的实验证据支持这一假设。
Preconditioning and stunning are the chief adaptive changes induced in myocardium by a brief episode of reversible ischemia followed by arterial reperfusion. In the dog heart, both coexist for a period of at least 20 minutes of reperfusion, but after 120 minutes of reflow, preconditioning is much diminished, while stunning remains fully developed. Preconditioned, stunned, myocardium differs from control "virgin" myocardium in that adenine nucleotide content is reduced to about 50-70% of control, whereas creatine phosphate (CP) greatly exceeds normal - the so-called CP overshoot. When preconditioned myocardium is subjected to sustained ischemia, ATP utilization and anaerobic glycolysis occur at much slower rates than those observed in virgin myocardium. As a result of the early difference in metabolic rate, a longer period of ischemia is required for the ATP and lactate of the preconditioned tissue to reach the levels associated with irreversible injury. Associated with this change is a delay in myocyte death.The molecular events responsible for slower ischemic metabolism and associated tolerance of preconditioned, stunned tissue to a new ischemic episode are not known. Among the reactions that could cause a reduction in energy metabolism is reduced approximately P expenditure by stunned myocardium attempting to contract during the initial phase of ischemia. However, results from in vivo and in vitro experiments suggest that although stunning maybe necessary for preconditioning to develop, it alone is not sufficient to cause preconditioning. Alternatively, metabolic changes may be explained by depressed activity of the mitochondrial ATPase during the episode of sustained ischemia. However, no direct experimental evidence supporting this hypothesis is available up to the present time.