Trimetazidine of different concentrations prevents ischemia/reperfusion injury in isolated rat heart

  AIM  To demonstrate the protective effect of trimetazidine against rat isolated heart ischemia /reperfusion(I/R) injury and to search for the optimal drug concentration.

  METHODS  Male healthy SD rats weighing between 220g and 250 g were selected to feed adaptably for 1 week. The rats were rapidly intraperitoneally injected with chloral hydrate (100 mg/ml) and heparin (500 U/kg). After the normal perfusion of isolated heart, the rats were randomly divided into 5 groups: control group, I/R group, and respectively 5 μmol/L, 10 μmol/L and 20 μmol/L trimetazidine treatment with I/R group. The values of left ventricular pressure were recorded by Labchart software and left ventricular development pressure (LVDP) and left ventricular end-diastolic pressure (LVEDP) were used to evaluate the cardiac functions. The lactate dehydrogenase (LDH) content was detected, the myocardial infarction area was determined and the caspase-3 activity in the myocardial tissue of each group was detected. The protein levels of cytochrome c and cleaved caspase-3 were detected. These results were used as indicators to evaluate the degree of myocardial cell necrosis and apoptosis in each group.

  RESULTS  Compared with that in the I/R group, I/R treatment in 5 μmol/L TMZ group showed an increase in LVDP and a decrease in LVEDP, but there was no statistical difference. Both I/R treatment in 10 μmol/L TMZ group and in 20 μmol/L TMZ group significantly increased LVDP and significantly reduced LVEDP, but there was no statistical difference between the two groups. Compared with that in the I/R group, I/R treatment in 5 μmol/L TMZ group showed a tendency to reduce myocardial infarction area, LDH content in coronary outflow, caspase-3 activity and cytochrome c and cleaved caspase-3 protein expressions, but there was no statistical difference. Both I/R treatment in 10 μmol/L TMZ group and in 20 μmol/L TMZ group significantly reduced the myocardial infarction area, LDH content in coronary outflow, caspase-3 activity and cytochrome c and cleaved caspase-3 protein expressions, but there was no statistical difference between the two groups.

  CONCLUSION  This study confirms the protective effect of trimetazidine with 10 μmol/L and 20 μmol/L in isolated rat hearts I/R injury.