P949Effect of dipeptidyl peptidase 4 inhibitor Sitagliptin against ischemia reperfusion injury in normolipidemic and hyperlipidemic rat models

Introduction: Hyperlipidemia has been associated with increased risk of myocardial infarction (MI). Inhibitors of dipeptidyl peptidase 4 (DPP-4) such as sitagliptin (Sitg) approved as a class of oral anti-diabetic drugs with pleiotropic secondary effects on cardiovascular parameters. However, this cardioprotective mechanism remains unknown in normal and hyperlipidemic conditions. Purpose: To investigate the cardioprotective effect of Sitg pre-treatment against heart ischemia- reperfusion (IR) injury originated from normal and hyperlipidaemic rats. Methods: Male wistar rats were fed with normal (N) rat chow or mixed with fats (High fat= HF) for 12 weeks to induce hyperlipidemia. At the end of last two weeks of feeding, animals were treated orally with Sitg of different doses (25mg, 50mg, 100mg, and 150 mg/kg/day), or its saline as a vehicle (control). Hearts were isolated to test infarct size (IS) and clarify the biochemical pathway of Sitg. Heart tissues were assigned to two different IR- injury protocols: 10 min perfusion, 45 min regional ischemia, and 120 min reperfusion for IS measurement or: 10 min reperfusion, 45 min regional ischemia and 10 min reperfusion, for biochemical analysis in both N and HF animals.