Pirolo J S, Allen D G
Cardiovasc Res. 1986 Nov;20(11):837-44. doi: 10.1093/cvr/20.11.837.
Studies of myocardial function during ischaemic or anoxia would be assisted if it were possible to inhibit glycolysis completely and reversibly. Three methods of preventing glycolysis in isolated perfused ferret hearts were studied: (a) the removal of glucose from the perfusate followed by manoeuvres designed to deplete glycogen stores, (b) the use of 2-deoxyglucose, and (c) the use of iodoacetate. The rate of glycolysis before and after applying the three methods was assessed by measuring lactate production during short periods of anoxia. Metabolic changes associated with each method were investigated with phosphorus nuclear magnetic resonance, and other side effects associated with each method were assessed by measuring developed pressure. The results show that removal of glucose followed by glycogen depletion reduced the rate of glycolysis to any chosen extent and that the method was reversible. 2-Deoxyglucose treatment did not lead to complete inhibition of glycolysis, was not reversible, and reduced the concentrations of phosphocreatinine and adenosine triphosphate in the heart. Iodoacetate treatment completely blocked glycolysis, but it was not reversible and subsequent periods of anoxia lead to a rapid fall in adenosine triphosphate owing to the accumulation of phosphorylated glycolytic intermediates.
如果能够完全且可逆地抑制糖酵解,那么对于缺血或缺氧期间心肌功能的研究将有所助益。本研究了在离体灌注雪貂心脏中防止糖酵解的三种方法:(a) 从灌注液中去除葡萄糖,随后采取措施耗尽糖原储备;(b) 使用2-脱氧葡萄糖;(c) 使用碘乙酸盐。通过测量短时间缺氧期间乳酸的产生来评估应用这三种方法前后的糖酵解速率。利用磷核磁共振研究了与每种方法相关的代谢变化,并通过测量心脏发育压力评估了与每种方法相关的其他副作用。结果表明,去除葡萄糖并耗尽糖原储备可将糖酵解速率降低至任何选定程度,且该方法是可逆的。2-脱氧葡萄糖处理并未导致糖酵解完全抑制,不可逆,且降低了心脏中磷酸肌酸和三磷酸腺苷的浓度。碘乙酸盐处理完全阻断了糖酵解,但不可逆,且随后的缺氧期会由于磷酸化糖酵解中间产物的积累导致三磷酸腺苷迅速下降。