The Study Of Cardiopretective Effect Of Trimetazidine On Ischemia-reperfusion Injury By Intervention Of Myocardial Metabolism

Objective:To study the cardioprotective effects of Trimetazidine on ischemia-reperfusion injure ,and explore its possible mechanisms and rational therapeutic pathway, thereby providing rationale for clinical application. Methods:The twenty rabbits were randomly assigned to A, B, C, D four groups. Group A is named control group, and the others are named experimental group. Using a Langendorff rabbit heart model with modified K-H buffer at 37℃,all groups were subjected to perfusion for 30 min,cold ischemia for an hour with St.Thomas II cardioplegia and reperfusion for 30 min .While, Experimental group B is using cardioplegia containing Trimetazidine, group C using K-H buffer containing Trimetazidine,and group D using both cardioplegia and K-H buffer containing Trimetazidine.The parameters of hemodynamics(HR CF LVDP ± dp/dtmax SV)and cardiac function(RPP), the incidence of arrhythmias,the levels of myocardial ATP and myocardial enzymes(LDH CK CK-MB) were measured before ischemia and during reperfusion. Meanwhile, myocardial water content and ultra structure were also examined. Results:The recovery of hemodynamics and cardiac function except HR in experimental group were significantly better than in control duringreperfusion, especially group D (P<0.01). Additional, in comparison withthe control group A, the incidence of arrhythmias became little(P<0.01),the myocardial ATP level was significantly higher (P<0.01),themyocardial enzymes leakage and water content was significantlydecreased (P<0.01)and the damage of myocardial ultra structure was littlein experimental group.Conclusion:Optimizing myocardial energy metabolism is benefit for alleviatingischemia-reperfusion injure. Trimetazidine have cardioprotective effectsagainst ischemia-reperfusion injure during ischemia or/and reperfusion.Itsmechanisms may be associated with intervening oxidative metabolism ofglucose and fatty acid , reducing intracellular acidosis and modulatingionic disturbance.