Sako E Y, Kingsley-Hickman P B, From A H, Foker J E, Ugurbil K
Department of Biochemistry, University of Minnesota, Navarre 55392.
J Biol Chem. 1988 Aug 5;263(22):10600-7.
The effects of ischemia on mitochondrial function and the unidirectional rate of ATP synthesis (Pi----ATP rate) were studied using a Langendorff-perfused heart preparation and 31P NMR spectroscopy. There was significant postischemic depression of mechanical function assessed as the heart rate pressure product, and the myocardial oxygen consumption rate at a given rate pressure product was elevated. Experiments performed on glucose- and pyruvate-perfused hearts demonstrated the presence of a large contribution to the unidirectional Pi----ATP rate catalyzed by glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase. This rate was much greater than the maximal glucose utilization rate in the myocardium, demonstrating that the glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase reactions are near equilibrium both before and after ischemia. In the pyruvate-perfused postischemic hearts, the glycolytic contribution was eliminated and the net rate of ATP synthesis by oxidative phosphorylation was measurable. Despite the reduced mechanical function and increased myocardial oxygen consumption rate, the ratio of the net rate of ATP synthesis by oxidative phosphorylation to oxygen consumption rate (the P:O ratio) was not altered subsequent to ischemia (2.34 +/- 0.12 and 2.36 +/- 0.09 in normal and postischemic hearts, respectively). Therefore, mitochondrial uncoupling cannot be the cause of postischemic depression in mechanical function; instead, the data suggest the existence of ischemia-induced inefficiency in ATP utilization.
利用Langendorff灌流心脏标本和31P核磁共振波谱技术，研究了缺血对线粒体功能和ATP合成单向速率（Pi→ATP速率）的影响。以心率压力乘积评估，缺血后机械功能出现显著下降，且在给定的心率压力乘积下心肌耗氧率升高。在葡萄糖和丙酮酸灌流心脏上进行的实验表明，甘油醛-3-磷酸脱氢酶和磷酸甘油酸激酶催化的单向Pi→ATP速率有很大贡献。该速率远大于心肌中最大葡萄糖利用率，表明甘油醛-3-磷酸脱氢酶/磷酸甘油酸激酶反应在缺血前后均接近平衡。在丙酮酸灌流的缺血后心脏中，糖酵解贡献被消除，通过氧化磷酸化的ATP合成净速率可被测量。尽管机械功能下降且心肌耗氧率增加，但缺血后氧化磷酸化的ATP合成净速率与耗氧率之比（P:O比）并未改变（正常心脏和缺血后心脏分别为2.34±0.12和2.36±0.09）。因此，线粒体解偶联不可能是缺血后机械功能下降的原因；相反，数据表明存在缺血诱导的ATP利用效率低下。
