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  • Title: Trimetazidine inhibits cardiomyocyte apoptosis in a rabbit model of ischemia-reperfusion.
    Author: Ruixing Y, Wenwu L, Al-Ghazali R.
    Journal: Transl Res; 2007 Mar; 149(3):152-60. PubMed ID: 17320801.
    Abstract:
    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 micromol/, P < 0.01), and significantly lower serum superoxide dismuase (SOD) levels (66.40 +/- 7.92 vs 89.25 +/- 1.36 microU/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 micromol/L, P > 0.05 vs sham, P < 0.01 vs control), and increased SOD levels (88.81 +/- 2.81 microU/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.
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