title: Trimetazidine pretreatment inhibits myocardial apoptosis and improves cardiac function in a Swine model of coronary microembolization.
abstract: OBJECTIVE
  Trimetazidine (TMZ) is a well-known anti-ischemic agent; however, its efficacy and mechanism of cardioprotection on coronary microembolization (CME) are largely unknown. The present study was undertaken to determine whether TMZ pretreatment could attenuate myocardial apoptosis and improve cardiac function in a swine model of CME.
  
  
  METHODS
  Fifteen swine were randomly and equally divided into a sham-operated (control) group, CME group and CME plus TMZ (TMZ) group. CME was induced by injecting inert plastic microspheres (42 μm in diameter) into the left anterior descending artery. For the control group, the same dose of normal saline was substituted for the microspheres, and the TMZ group was pretreated with TMZ 30 min before microsphere injection. Cardiac function was assessed by echocardiography, myocardial apoptosis was detected by TUNEL staining, and the expression levels of cleaved caspase-9/3 were measured by Western blot 12 h after operation.
  
  
  RESULTS
  Compared to the control group, cardiac function in the CME group was significantly decreased (p < 0.05); however, TMZ pretreatment showed significantly improved cardiac function as compared to the CME group (p < 0.05). The myocardial apoptotic rate and the expression levels of cleaved caspase-9/3 increased remarkably in CME group as compared with the control group (p < 0.001). Again, TMZ pretreatment significantly reduced the apoptotic rate and also the expression levels of cleaved caspase-9/3 (p < 0.001).
  
  
  CONCLUSIONS
  The present study demonstrated that TMZ pretreatment could significantly inhibit CME-induced myocardial apoptosis and improve cardiac function, and that the cardioprotective effect appeared to be mediated by the blockade of the mitochondrial apoptotic pathway. These results emphasize the importance of TMZ pretreatment in the therapy of CME-induced myocardial injury.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, PR China.
authors.forename: Yang-Chun
authors.initials: YC
authors.lastname: Liu
authors.forename: Lang
authors.initials: L
authors.lastname: Li
authors.forename: Qiang
authors.initials: Q
authors.lastname: Su
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Zhong-li
authors.initials: ZL
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D003331:Coronary Vessels; D004195:Disease Models, Animal; D004452:Echocardiography; D004617:Embolism / Q000188:drug therapy*; D005260:Female; D006334:Heart Function Tests; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D013552:Swine; D014292:Trimetazidine / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D014665:Vasodilator Agents; D053148:Caspase 3; D053453:Caspase 9; D014292:Trimetazidine