Lopaschuk G D, Saddik M
Cardiovascular Disease Research Group, Faculty of Medicine, University of Alberta, Edmonton, Canada.
Mol Cell Biochem. 1992 Oct 21;116(1-2):111-6. doi: 10.1007/BF01270577.
High levels of fatty acids decrease the extent of mechanical recovery of hearts reperfused following a transient period of severe ischemia. Glucose oxidation rates during reperfusion are low under these conditions, which can result in a decreased recovery of mechanical function. Stimulation of glucose oxidation with the carnitine palmitoyl transferase I inhibitor, Etomoxir, or by directly stimulating pyruvate dehydrogenase activity with dichloroacetate (DCA) results in an improvement in mechanical function during reperfusion of previously ischemic hearts. Addition of DCA (1 mM) to hearts perfused with 11 mM glucose and 1.2 mM palmitate results in an increase in contribution of glucose oxidation to overall ATP production from 6 to 23%, with a parallel decrease in that of fatty acid oxidation from 90 to 69%. In aerobic hearts, endogenous myocardial triglycerides are an important source of fatty acids for beta-oxidation. Using hearts in which the myocardial triglycerides were pre-labeled, the contribution of both endogenous and exogenous fatty acid oxidation to myocardial ATP production was determined in hearts perfused with 11 mM glucose, 1.2 mM palmitate and 500 microU/ml insulin. In hearts reperfused following a 30 min period of global no flow ischemia, 91.9% of ATP production was derived from endogenous and exogenous fatty acid oxidation, compared to 87.7% in aerobic hearts. This demonstrates that fatty acid oxidation quickly recovers following a transient period of severe ischemia. Furthermore, therapy aimed at overcoming fatty acid inhibition of glucose oxidation during reperfusion of ischemic hearts appears to be beneficial to recovery of mechanical function.
高水平脂肪酸会降低严重短暂缺血后再灌注心脏的机械功能恢复程度。在这些情况下，再灌注期间葡萄糖氧化速率较低，这可能导致机械功能恢复降低。用肉碱棕榈酰转移酶I抑制剂依托莫西或通过用二氯乙酸（DCA）直接刺激丙酮酸脱氢酶活性来刺激葡萄糖氧化，可使先前缺血心脏再灌注期间的机械功能得到改善。向灌注11 mM葡萄糖和1.2 mM棕榈酸的心脏中添加DCA（1 mM），会使葡萄糖氧化对总ATP产生的贡献从6%增加到23%，同时脂肪酸氧化的贡献从90%平行下降到69%。在有氧心脏中，内源性心肌甘油三酯是脂肪酸β氧化的重要来源。使用预先标记心肌甘油三酯的心脏，在灌注11 mM葡萄糖、1.2 mM棕榈酸和500微单位/毫升胰岛素的心脏中，测定内源性和外源性脂肪酸氧化对心肌ATP产生的贡献。在经历30分钟全心无血流缺血后再灌注的心脏中，91.9%的ATP产生来自内源性和外源性脂肪酸氧化，而有氧心脏中这一比例为87.7%。这表明在严重短暂缺血后，脂肪酸氧化能迅速恢复。此外，旨在克服缺血心脏再灌注期间脂肪酸对葡萄糖氧化抑制的治疗似乎有利于机械功能的恢复。
