de Groot M J, Coumans W A, van der Vusse G J
Department of Physiology, Cardiovascular Research Institute Maastricht, University of Limburg, The Netherlands.
Mol Cell Biochem. 1992 Dec 2;118(1):1-14. doi: 10.1007/BF00249689.
It was examined whether lactate influences postischaemic hemodynamic recovery as a function of the duration of ischaemia and whether changes in high-energy phosphate metabolism under ischaemic and reperfused conditions could be held responsible for impairment of cardiac function. To this end, isolated working rat hearts were perfused with either glucose (11 mM), glucose (11 mM) plus lactate (5 mM) or glucose (11 mM) plus pyruvate (5 mM). The extent of ischaemic injury was varied by changing the intervals of ischaemia, i.e. 15, 30 and 45 min. Perfusion by lactate evoked marked depression of functional recovery after 30 min of ischaemia. Perfusion by pyruvate resulted in marked decline of cardiac function after 45 min of ischaemia, while in glucose perfused hearts hemodynamic performance was still recovered to some extent after 45 min of ischaemia. Hence, lactate accelerates postischaemic hemodynamic impairment compared to glucose and pyruvate. The marked decline in functional recovery of the lactate perfused hearts cannot be ascribed to the extent of degradation of high-energy phosphates during ischaemia as compared to glucose and pyruvate perfused hearts. Glycolytic ATP formation (evaluated by the rate of lactate production) can neither be responsible for loss of cardiac function in the lactate perfused hearts. Moreover, failure of reenergization during reperfusion, the amount of nucleosides and oxypurines lost or the level of high-energy phosphates at the end of reperfusion cannot explain lactate-induced impairment. Alternatively, the accumulation of endogenous lactate may have contributed to ischaemic damage in the lactate perfused hearts after 30 min of ischaemia as it was higher in the lactate than in the glucose or pyruvate perfused hearts. It cannot be excluded that possible beneficial effects of the elevated glycolytic ATP formation during 15 to 30 min of ischaemia in the lactate perfused hearts are counterbalanced by the detrimental effects of lactate accumulation.
研究了乳酸是否作为缺血持续时间的函数影响缺血后血流动力学恢复，以及缺血和再灌注条件下高能磷酸代谢的变化是否可能是心脏功能受损的原因。为此，用葡萄糖（11 mM）、葡萄糖（11 mM）加乳酸（5 mM）或葡萄糖（11 mM）加丙酮酸（5 mM）灌注离体工作大鼠心脏。通过改变缺血间隔时间（即15、30和45分钟）来改变缺血损伤的程度。缺血30分钟后，乳酸灌注引起功能恢复的明显抑制。丙酮酸灌注导致缺血45分钟后心脏功能明显下降，而在葡萄糖灌注的心脏中，缺血45分钟后血流动力学性能仍有一定程度的恢复。因此，与葡萄糖和丙酮酸相比，乳酸加速了缺血后血流动力学损伤。与葡萄糖和丙酮酸灌注的心脏相比，乳酸灌注的心脏功能恢复的明显下降不能归因于缺血期间高能磷酸盐的降解程度。糖酵解ATP生成（通过乳酸生成速率评估）也不能解释乳酸灌注心脏中心脏功能的丧失。此外，再灌注期间的再能量化失败、核苷和氧嘌呤的丢失量或再灌注结束时的高能磷酸盐水平都不能解释乳酸诱导的损伤。另外，内源性乳酸的积累可能在缺血30分钟后导致了乳酸灌注心脏的缺血损伤，因为乳酸灌注心脏中的内源性乳酸积累高于葡萄糖或丙酮酸灌注的心脏。不能排除在乳酸灌注心脏中，缺血15至30分钟期间糖酵解ATP生成增加可能带来的有益作用被乳酸积累的有害作用所抵消。
