Metformin ameliorates blunted cardioprotective response of ischemic postconditioning in rats subjected to high fat diet

BACKGROUND: Cardioprotective response of ischaemic postconditioning (iPoCo) is blunted in conditions of vascular endothelial dysfunction (ED) associated with hypercholesterolaemia, diabetes, hypertension, etc. OBJECTIVE: The current study investigates the effect of metformin on the blunted cardioprotective response of iPoCo in rats subjected to high fat diet (HFD). METHODOLOGY: Wistar rats were subjected to HFD for 56 days. Myocardial ischaemia-reperfusion (I/R) injury was induced by subjecting the heart to global ischaemia of 30 min followed by reperfusion of 120 min after mounting on Langendorff Power Lab apparatus. iPoCo consisting of 6 alternative cycles of ischaemia and reperfusion of 10 sec each, was given after the global ischaemia at the onset of reperfusion. Metformin (25 µM and 50 µM) treatment was given after the global ischaemia just before reperfusion. Myocardial injury was assessed by estimation of infarct size, specific biomarkers of myocardial injury, oxidative stress, inflammation and hemodynamic index. RESULTS: HFD animal showed significant rise in serum total cholesterol and nitrate levels reflecting hypercholesterolaemia and ED. I/R produced significant myocardial damage indicated by an increase in infarct size, specific biomarkers (LDH, CK-MB, cTn I), oxidative stress- inflammatory parameters (heart Nrf-2, TBARS, TNF-α and decreased GSH and catalase levels) and altered hemodynamic index. iPoCo significantly alleviated I/R induced myocardial injury with respect to above parameters in normal rats but failed to produce such an effect in HFD rats. Treatment of metformin (25 µM and 50 µM) not only mimicked the cardioprotective effect of iPoCo in normal rats but also restored the lost effect of iPoCo in HFD rats.