El Banani H, Bernard M, Cozzone P, James F, Feuvray D
Laboratoire de Physiologie Cellulaire, Université Paris XI, Orsay, France.
Am J Cardiol. 1998 Sep 3;82(5A):25K-29K. doi: 10.1016/s0002-9149(98)00534-7.
This study examined the influence of metabolic substrates on the effects of trimetazidine on functional and metabolic aspects of the ischemic reperfused heart. Isovolumic rat hearts were submitted to a 30-minute period of global mild ischemia (coronary flow decreased by an average of 70%) and then reperfused at constant preischemic coronary flow rate. Either glucose (11 mM) or glucose and palmitic acid (0.1 mM) were used as metabolic substrates. Trimetazidine (6 x 10(-7)M) markedly reduced the increase in diastolic pressure that occurred on reperfusion after the ischemic episode, whatever the exogenous substrate used. However, in those hearts that received fatty acid, the postischemic increase in diastolic pressure was abolished. Ischemia-induced increase in acyl carnitine levels-determined as indicators of fatty acid utilization by myocardial cells-was significantly decreased by trimetazidine in those hearts receiving fatty acid. Also, similar effects to those of trimetazidine on the postischemic increase in diastolic pressure and on tissue levels of acyl carnitine were obtained in the presence of dichloroacetate. Moreover, the presence of trimetazidine was associated with a reduction in the intracellular pH decrease during ischemia in those hearts receiving fatty acid. Combined with previous studies, these results suggest that an improved metabolic balance by trimetazidine may well consequently decrease the ionic imbalance after a transient period of ischemia.
本研究考察了代谢底物对曲美他嗪作用于缺血再灌注心脏功能及代谢方面的影响。将大鼠等容心脏进行30分钟的整体轻度缺血（冠脉血流量平均减少70%），然后以缺血前恒定的冠脉血流量进行再灌注。分别使用葡萄糖（11 mM）或葡萄糖与棕榈酸（0.1 mM）作为代谢底物。无论使用何种外源性底物，曲美他嗪（6×10⁻⁷M）均能显著降低缺血发作后再灌注时出现的舒张压升高。然而，在接受脂肪酸的心脏中，缺血后舒张压的升高被消除。在接受脂肪酸的心脏中，曲美他嗪可使作为心肌细胞脂肪酸利用指标的缺血诱导的酰基肉碱水平升高显著降低。此外，在二氯乙酸存在的情况下，也获得了与曲美他嗪对缺血后舒张压升高及组织酰基肉碱水平类似的作用效果。而且，在接受脂肪酸的心脏中，曲美他嗪的存在与缺血期间细胞内pH值下降的减少有关。结合先前的研究，这些结果表明，曲美他嗪改善代谢平衡很可能会因此减少短暂缺血后的离子失衡。
