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 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.
Ruixing
Yin
Y
Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China. yinruixing@yahoo.com.cn
Wenwu
Liang
L
Al-Ghazali
Rasheed
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D008315:Malondialdehyde / Q000097:blood; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D013482:Superoxide Dismutase / Q000097:blood; D014292:Trimetazidine / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D014292:Trimetazidine