Effect of Ischemic Postconditioning on Myocardial Function and Infarct Size Following Reperfusion Injury in Diabetic Rats Pretreated With Vildagliptin

Abstract

Background: Cardioprotective actions of ischemic postconditioning (IPostC) against ischemia/reperfusion (I/R) injury are abolished in diabetic hearts. This study has investigated the combined effects of IPostC and vildagliptin (Vilda) on myocardial function and infarct size (IS) against I/R injury in diabetic myocardium.

Methods: Diabetes was induced by a high-fat diet/low dose of streptozotocin (35 mg/kg; intraperitoneally) in Wistar rats (200-250 g) and lasted for 12 weeks. Vilda (6 mg/kg/d) was orally administered for 5 weeks in diabetic groups after seventh week of diabetes. At the end of the 12-week period, the hearts of rats were removed and subjected to 35-minute regional ischemia (through left anterior descending ligation) followed by 60-minute reperfusion, on Langendorff apparatus. Ischemic postconditioning was induced by 6 repetitive cycles of 10-second ischemia and 10-second reperfusion, immediately at the onset of the reperfusion. Myocardial hemodynamic was measured throughout the experiment. The IS was assessed by triphenyltetrazolium chloride staining method. The myocardial contents of troponin-I (cTnI), interleukin-6 (IL-6), and 8-isoprostane were measured in the homogenate from ischemic zone of left ventricles by enzyme-linked immunosorbent assay kit.

Results: Pretreatment of the diabetic rats with Vilda significantly recovered the diabetes-induced reduction in left ventricular developed pressures and contractility at the baseline ( P < .05 to P < .01). After I/R injury, IPostC could not significantly improve the myocardial function, cTnI content, and IS of the diabetic hearts. However, in Vilda-treated hearts, concomitant application of IPostC significantly recovered the heart functions, returned cTnI content as well as myocardial IL-6 and 8-isoprostane levels back to the control values ( P < .01 to P < .001), and reduced IS more effectively (by 45%) in comparison to the diabetic group ( P < .001).

Conclusion: Besides its glycemic and lipid profile controlling effects, Vilda has a protective effect on heart function and tends to restore cardioprotective effects of IPostC on diabetic hearts.

Keywords: cardioprotection; diabetes; infarct size; ischemic postconditioning; reperfusion injury.