Jennings R B, Sebbag L, Schwartz L M, Crago M S, Reimer K A
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
J Mol Cell Cardiol. 2001 Sep;33(9):1571-88. doi: 10.1006/jmcc.2001.1425.
Ischemic preconditioning is associated with slower destruction of the adenine nucleotide pool and a slower rate of anaerobic glycolysis during subsequent ischemic stress. Whether this association is causal is uncertain. Using metabolite levels found at baseline and after a 15 min test episode of ischemia, this study tested for concordance, or lack thereof, between the presence or absence of metabolic features v the presence or absence of the preconditioned state. Dogs were assigned to one of four groups: non-preconditioned control (C), full preconditioning (PC) caused by 10 min ischemia (I)+10 min reperfusion (R), dissipated PC (DPC) caused by 10 min I and 180 min R, or reinstated PC in which PC was reinstated in DPC hearts by another 10 min I and 10 min R. At baseline, PC and RPC hearts had a 25% or more decrease in the adenine nucleotide pool (summation operatorAd), a substantial creatine phosphate (CP) overshoot, and a 4-6 times elevation in tissue glucose (G). Of these changes, the decreased summation operatorAd and the CP overshoot persisted during DPC, whereas only G returned to control. Thus, increased G was the only baseline feature, which was concordant with the preconditioned state. The response to ischemic stress in PC and RPC tissue included less lactate production and much less degradation of the summation operatorAd pool to nucleosides and bases than in the C or DPC groups. Thus, slower destruction of the summation operatorAd pool and slower lactate production during ischemia also were concordant with the PC state. The results support the hypothesis that a reduction in energy demand is an essential component of the mechanism of cardioprotection in preconditioned myocardium. However, the mechanism through which ischemic preconditioning results in lower energy demand remains to be established.
缺血预处理与腺嘌呤核苷酸池的破坏减缓以及随后缺血应激期间无氧糖酵解速率减慢有关。这种关联是否具有因果关系尚不确定。本研究利用基线时和15分钟缺血试验期后的代谢物水平，检测了代谢特征的存在与否与预处理状态的存在与否之间的一致性或不一致性。将犬分为四组之一：未预处理对照组（C）、由10分钟缺血（I）+10分钟再灌注（R）引起的完全预处理组（PC）、由10分钟I和180分钟R引起的消散预处理组（DPC），或恢复预处理组，其中在DPC心脏中通过另外10分钟I和10分钟R恢复PC。在基线时，PC和RPC心脏的腺嘌呤核苷酸池（总和运算符Ad）减少25%或更多，有大量磷酸肌酸（CP）超射，组织葡萄糖（G）升高4至6倍。在这些变化中，总和运算符Ad降低和CP超射在DPC期间持续存在，而只有G恢复到对照水平。因此，G升高是唯一与预处理状态一致的基线特征。PC和RPC组织对缺血应激的反应包括乳酸生成减少，以及与C组或DPC组相比，总和运算符Ad池降解为核苷和碱基的程度大大降低。因此，缺血期间总和运算符Ad池的破坏减缓以及乳酸生成减缓也与PC状态一致。结果支持以下假设，即能量需求降低是预处理心肌心脏保护机制的一个重要组成部分。然而，缺血预处理导致能量需求降低的机制仍有待确定。
