Vuorinen K, Ylitalo K, Peuhkurinen K, Raatikainen P, Ala-Rämi A, Hassinen I E
Department of Medical Biochemistry, University of Oulu, Finland.
Circulation. 1995 Jun 1;91(11):2810-8. doi: 10.1161/01.cir.91.11.2810.
Adenosine has been proposed as one mediator for the preconditioning effect in the myocardium of some animals, but recent investigations have shown that this may not be the mechanism in the rat heart, although the effect itself is clearly demonstrable. The cellular energy state has been shown to be better in preconditioned hearts, and the role of ATP consumption has been discussed. The role of inhibition of mitochondrial F1F0-ATPase as a mechanism for the preservation of ATP in preconditioned hearts remains controversial.
Three-minute global ischemia followed by 9 minutes of reperfusion was used to precondition Langendorff-perfused rat hearts, and control hearts were perfused under normoxic conditions for the same time. The duration of sustained ischemia in both groups of hearts was 21 minutes, after which the hearts were reperfused for 15 minutes to evaluate their mechanical and metabolic recovery. Separate experiments were performed for tissue metabolite determinations, mitochondrial ATPase activity measurements, and 31P nuclear magnetic resonance studies. The recovery of the rate-pressure product was better in the preconditioned group. Three-minute preconditioning ischemia caused inhibition of the mitochondrial ATPase that persisted throughout the 9-minute intervening reperfusion so that at the early stages of sustained ischemia the enzyme activity was still more inhibited in preconditioned hearts. ATP was better preserved in preconditioned hearts than in control hearts during sustained ischemia. The accumulation of adenosine and its degradation products during sustained ischemia was greater in the control group. More lactate and H+ ions accumulated in this group, indicating higher anaerobic glycolysis. Also, inhibition of mitochondrial ATPase by oligomycin slowed ATP depletion during ischemia.
The results indicate that preconditioning causes inhibition of rat heart mitochondrial ATPase that persists during reperfusion so that the enzyme is inhibited from the very beginning of the sustained ischemia. This inhibition leads to sparing of high-energy phosphates and improves the time-averaged energy state during ischemia. Although a causal relationship is difficult to prove, this reversible inhibition may contribute to postischemic recovery of the heart.
腺苷被认为是某些动物心肌预处理效应的一种介质，但最近的研究表明，尽管预处理效应本身明显可证，但这可能不是大鼠心脏中的机制。已证明预处理心脏的细胞能量状态更好，并已讨论了ATP消耗的作用。抑制线粒体F1F0 - ATP酶作为预处理心脏中ATP保存机制的作用仍存在争议。
采用3分钟全心缺血继以9分钟再灌注对Langendorff灌注的大鼠心脏进行预处理，对照心脏在常氧条件下灌注相同时间。两组心脏的持续缺血时间均为21分钟，之后心脏再灌注15分钟以评估其机械和代谢恢复情况。分别进行组织代谢物测定、线粒体ATP酶活性测量和31P核磁共振研究的实验。预处理组的心率 - 血压乘积恢复情况更好。3分钟的预处理缺血导致线粒体ATP酶受到抑制，这种抑制在9分钟的中间再灌注过程中持续存在，因此在持续缺血的早期阶段，预处理心脏中的酶活性仍受到更大抑制。在持续缺血期间，预处理心脏中的ATP比对照心脏保存得更好。对照组在持续缺血期间腺苷及其降解产物的积累更多。该组中乳酸和H +离子积累更多，表明无氧糖酵解更高。此外，寡霉素对线粒体ATP酶的抑制减缓了缺血期间的ATP消耗。
结果表明，预处理导致大鼠心脏线粒体ATP酶受到抑制，这种抑制在再灌注期间持续存在，从而使该酶从持续缺血开始就受到抑制。这种抑制导致高能磷酸盐的节省，并改善缺血期间的时间平均能量状态。尽管因果关系难以证明，但这种可逆抑制可能有助于心脏缺血后的恢复。
