Protective Effect of Metformin on Cardiomyocytes Ischemia-Reperfusion (IR) Induced Apoptosis in Rats

The heart failures following infarctions is one of the most important causes of death throughout the world. This study was undertaken to investigate the protective effects of metformin on apoptotic cell death of cardiomyocytes during experimental cardiac Ischemia-Reperfusion (IR) in rats. The 25 male Wistar rats were randomly assigned into 5 groups of 5 animals each including; Sham/IR, IR, low dose metformin+IR, average dose metformin+IR and high dose metformin+LR.. Heart muscle ischemia was induced clamping the left descending coronary artery. After 30 min of ischemia, the clamps were taken off and the animals underwent 2 h reperfusion. Metformin (5, 10 and 20 pg/kg/min) was infused 15 min prior to reperfusion through jugular vein in treatment groups. At the end of experiment, the rats were euthanized and histological sections from left ventricles were prepared through Tunnel Staining method. Apoptotic cells were counted under light microscope. The data obtained were statistically analyzed using ANOVA. Differences were considered statistically significant at p<0.05. In group 2, ischemia-reperfusion caused occurrence of apoptotic cell death in cardiomyocytes. There was a significant increase in the incidence rate of apoptosis of cardiomyocytes in comparison with group 1 (p<0.001). In groups 3-5 metformin (5, 10 and 20)mu g/kg/min) caused significant decrease in the number of apoptotic cells in comparison with group 2 (p<0.05, p<0.01 and p<0.001, respectively). This study therefore, suggests that metformin may be a useful agent for the prevention of Ischemia-Reperfusion (IR) induced apoptotic cell death of cardiomyocytes in a dose dependent manner in the rats.