Effects Of Trimetazidine On Cardiomyocyte Apoptosis In Late Reperfusion After Acute Myocardial Infarction In Canine

OBJECTIVE Reperfusion of acute myocardial infarction(AMI) is the most effective method at present.It has already confirmed that earlier reperfusion of ischemia myocardium can decrease the infarct size,on the other hand the cardiocyte injury may be aggravated,such phenomenon is called ischemia reperfusion injury(IRI).It has confirmed that late reperfusion of ischemia myocardium also can delay myocardium remodeling and preserve heart function.But some recent research has proved the existence of late ischemia reperfusion injury in border region of infarcted myocardium. Trimetazidine,an antioxidant agent,has been extensively used in coronary artery disease and other cardiovascular disease.Also,it has been shown that trimetazidine can inhibit myocytes from ischemia reperfusion mediated apoptosis.But it is note clear wheather trimetazidine also inhibit myocytes apoptosis from late reperfusion.We investigated the cardiopro-tection effection and the possible mechanism of trimetazidine in the risk areas during late reperfusion after acute myocardial infarct in canine.Methods Twenty-four adult dogs were randomly divided into three groups:sham operation group(n=8),late reperfusion group(LR,n=8),and late reperfusion after trimetazidine treatment group(LR+TMZ,n=8).Physiological saline was orally given in the sham operation group and LR group and trimetazidine(2mg·kg^-1·d^-1) in the LR+TMZ group for fourteen days.Fourteen days later,all dogs were received chest operation and coronary artery was exposed.The late reperfusion of acute myocardial infarction model was made by ligating the coronary for 10 h,followed by reperfusion of 10h.Apoptotic index were detected by TUNEL.The Bcl-2,Bax,Cytochrome C and Apoptosis-inducing factor(AIF) proteins were detected by immunohistochemistry.Results Compared with LR group,myocardial apoptotic index and the expression of Bax,Cytochrome C and AIF proteins in LR+TMZ were decreased significantly(all P＜0.01),but the expression of Bcl-2 proteins were increased(P＜0.01).Comparing with shame operation group respectively,all indicators were significantly different(p＜0.001).Conclusion Trimetazidine can decrease cardiomyocyte apoptosis in the risk area during late reperfusion after acute myocardial infarction,which may be related to the increased expression level of Bcl-2 proteins and decreased expression level of Bax, Cytochrome C and AIF proteins.