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

• Published in: Journal of cardiovascular pharmacology and therapeutics Vol. 23; no. 2; pp. 174 - 183
• Main Authors: Bayrami, Goltaj, Karimi, Pouran, Agha-Hosseini, Fariba, Feyzizadeh, Saeid, Badalzadeh, Reza
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.03.2018
• Subjects: Animals; Blood Glucose - drug effects; Blood Glucose - metabolism; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - drug therapy; Diabetic Cardiomyopathies - etiology; Diabetic Cardiomyopathies - pathology; Diabetic Cardiomyopathies - physiopathology; Diabetic Cardiomyopathies - prevention & control; Dinoprost - analogs & derivatives; Dinoprost - metabolism; Dipeptidyl-Peptidase IV Inhibitors - pharmacology; Insulin - blood; Interleukin-6 - metabolism; Ischemic Postconditioning; Isolated Heart Preparation; Lipids - blood; Male; Myocardial Contraction - drug effects; Myocardial Infarction - etiology; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardial Infarction - prevention & control; Myocardial Reperfusion Injury - etiology; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - physiopathology; Myocardial Reperfusion Injury - prevention & control; Myocardium - metabolism; Myocardium - pathology; Rats, Wistar; Troponin I - metabolism; Ventricular Function, Left - drug effects; Ventricular Pressure - drug effects; Vildagliptin - pharmacology; cardioprotection; ischemic postconditioning; infarct size; reperfusion injury; diabetes
• ISSN: 1074-2484; 1940-4034
• DOI: 10.1177/1074248417729881

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.