Trimetazidine inhibits cardiomyocyte apoptosis in a rabbit model of ischemia-reperfusion

The effects of trimetazidine on cardiomyocyte apoptosis and hemodynamics in a rabbit model of ischemia-reperfusion were determined. Thirty male New Zealand white rabbits were randomly divided into sham, control, and treated groups (n = 10). Trimetazidine (2 mg/kg−1/day−1) was fed for 2 weeks to treated animals before the procedure. Control and treated groups were subjected to a 30-min coronary occlusion followed by a 2-h reperfusion. Mean arterial pressure, left ventricular systolic pressure, and maximum rate of left ventricular pressure rise were significantly higher in the treated group than in the controls (P < 0.01, < 0.01, and < 0.05, respectively), whereas left ventricular end-diastolic pressure was significantly lower in the treated group than in the controls (P < 0.01). As compared with the sham group, controls had a significantly higher apoptotic index (22.10% ± 2.85% vs 0.51% ± 0.31%, P < 0.01) and malondialdehyde (MDA) concentration (18.52 ± 1.51 vs 5.75 ± 0.95 μmol/, P < 0.01), and significantly lower serum superoxide dismuase (SOD) levels (66.40 ± 7.92 vs 89.25 ± 1.36 μU/L, P < 0.01). Trimetazidine pretreatment apparently decreased apoptotic index (11.37% ± 2.53%, P < 0.01 vs the sham or control) and MDA concentration (5.49 ± 0.74 μmol/L, P > 0.05 vs sham, P < 0.01 vs control), and increased SOD levels (88.81 ± 2.81 μU/L, P > 0.05 vs sham, P < 0.01 vs control). The caspase-3 activation and mitochondrial cytochrome c release were also higher in controls than in the treated group (P < 0.01). The apoptotic indices were negatively correlated with SOD and positively correlated with MDA in the groups, suggesting that trimetazidine may be a useful drug in preventing cardiomyocyte apoptosis and ischemia-reperfusion injury.