Metabolism of preconditioned myocardium: Effect of loss and reinstatement of cardioprotection

Metabolism of preconditioned myocardium: Effect of loss and reinstatement of cardioprotection
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DOI:
10.1006/jmcc.2001.1425
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发表时间:
2001-09-01
影响因子:
5
通讯作者:
Reimer, KA
Reimer, KA
中科院分区:
医学2区
文献类型:
--
作者:
Jennings, RB;Sebbag, L;Reimer, KA

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缺血预适应与随后的缺血应激期间腺嘌呤核苷酸库的破坏速度减慢和无氧糖酵解速度减慢有关。这种关联是否存在因果关系尚不确定。本研究使用基线和 15 分钟缺血测试事件后发现的代谢水平,测试代谢特征的存在或不存在与预处理状态的存在或不存在之间的一致性或缺乏一致性。狗被分配到四组之一:非预处理对照组(C)、由 10 分钟缺血(I)+ 10 分钟再灌注引起的完全预处理(PC)(R)。由 10 分钟 I 和 180 分钟 R 引起的 PC 消散 (DPC),或恢复的 PC,其中 PC 通过另外 10 分钟 I 和 10 分钟 R 在 DPC 心脏中恢复。在基线时,PC 和 RPC 心脏的腺嘌呤核苷酸池 (Sigma Ad) 减少 25% 或更多,磷酸肌酸 (CP) 显着超调,组织葡萄糖 (G) 升高 4-6 倍。在这些变化中,Sigma Ad 的减少和 CP 超调在 DPC 期间持续存在,而只有 G 恢复到控制。因此,增加的 G 是唯一的基线特征,这与预处理状态一致。与 C 组或 DPC 组相比,PC 和 RPC 组织对缺血应激的反应包括乳酸产生较少,Sigma Ad 池降解为核苷和碱基的情况也少得多。因此,缺血期间 Sigma Ad 库破坏较慢和乳酸产生较慢也与 PC 状态一致。结果支持这样的假设:能量需求的减少是预调节心肌的心脏保护机制的重要组成部分。然而,缺血预处理导致较低能量需求的机制仍有待建立。 (C) 2001 年学术出版社。
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 (Sigma Ad), a substantial creatine phosphate (CP) overshoot, and a 4-6 times elevation in tissue glucose (G). Of these changes, the decreased Sigma Ad 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 Sigma Ad pool to nucleosides and bases than in the C or DPC groups. Thus, slower destruction of the Sigma Ad 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. (C) 2001 Academic Press.