Finegan B A, Gandhi M, Lopaschuk G D, Clanachan A S
Department of Anaesthesia, Faculty of Medicine, University of Alberta, Edmonton, Canada.
Am J Physiol. 1996 Nov;271(5 Pt 2):H2116-25. doi: 10.1152/ajpheart.1996.271.5.H2116.
This study compared the effects of adenosine (Ado) on the coupling of glycolysis and glucose oxidation and on mechanical function in normal hearts and in hearts subjected to transient ischemia. Isolated working rat hearts were perfused with Krebs containing 1.2 mM palmitate and 100 microU/ml insulin. After 15 min of aerobic perfusion, hearts underwent either two cycles of 10 min of ischemia and 5 min of reperfusion (stressed) or 30 min of aerobic perfusion (control). After 45 min, hearts underwent either aerobic perfusion for 35 min (series A) or 30 min of ischemia and 30 min of reperfusion (series B). In series A, left ventricular minute work (LV work) was similar in control and stressed hearts and was not affected by Ado (500 microM) or N6-cyclohexyladenosine (CHA 0.5 microM). Ado reduced glycolysis by 49% in control hearts but increased glycolysis by 74% in stressed hearts. CHA inhibited glycolysis in both groups by 50 and 62%, respectively. In series B, LV work during reperfusion recovered to a similar extent in untreated control and stressed hearts. In control hearts, Ado reduced glycolysis by 50% while enhancing LV work to 81% of preischemic values. In stressed hearts, Ado increased glycolysis by 34% and depressed LV work to 9%, whereas CHA inhibited glycolysis by 53% and LV work to 91%. These data indicate that coupling of glycolysis to glucose oxidation is a key determinant of mechanical function of the postischemic myocardium. They also show that the metabolic and protective effects of Ado depend on the status of the heart before sustained ischemia.
本研究比较了腺苷（Ado）对正常心脏以及经历短暂缺血的心脏中糖酵解与葡萄糖氧化偶联和机械功能的影响。将离体工作的大鼠心脏用含1.2 mM棕榈酸酯和100微单位/毫升胰岛素的 Krebs 溶液灌注。有氧灌注15分钟后，心脏经历两个10分钟缺血和5分钟再灌注的周期（应激组）或30分钟有氧灌注（对照组）。45分钟后，心脏进行35分钟有氧灌注（A组）或30分钟缺血和30分钟再灌注（B组）。在A组中，对照组和应激组的左心室每分钟功（LV功）相似，且不受Ado（500 microM）或N6 - 环己基腺苷（CHA 0.5 microM）影响。Ado使对照组心脏的糖酵解降低49%，但使应激组心脏的糖酵解增加74%。CHA在两组中分别抑制糖酵解50%和62%。在B组中，再灌注期间未处理的对照组和应激组心脏的LV功恢复程度相似。在对照组心脏中，Ado使糖酵解降低50%，同时将LV功提高到缺血前值的81%。在应激组心脏中，Ado使糖酵解增加34%，并使LV功降低至9%，而CHA抑制糖酵解53%，使LV功降低至91%。这些数据表明，糖酵解与葡萄糖氧化的偶联是缺血后心肌机械功能的关键决定因素。它们还表明，Ado的代谢和保护作用取决于心脏在持续缺血前的状态。
