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.

• Authors: Goltaj Bayrami, Pouran Karimi, Fariba Agha-Hosseini, Saeid Feyzizadeh, Reza Badalzadeh
• Journal: Journal of cardiovascular pharmacology and therapeutics (J Cardiovasc Pharmacol Ther) Vol. 23 Issue 2 Pg. 174-183 (03 2018) ISSN: 1940-4034 [Electronic] United States
• PMID: 28901167 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Dipeptidyl-Peptidase IV Inhibitors
• Il6 protein, rat
• Insulin
• Interleukin-6
• Lipids
• Troponin I
• 8-epi-prostaglandin F2alpha
• Dinoprost
• Vildagliptin

Topics

• Animals
• Blood Glucose (drug effects, metabolism)
• Diabetes Mellitus, Experimental (blood, complications, drug therapy)
• Diabetic Cardiomyopathies (etiology, pathology, physiopathology, prevention & control)
• Dinoprost (analogs & derivatives, 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, pathology, physiopathology, prevention & control)
• Myocardial Reperfusion Injury (etiology, pathology, physiopathology, prevention & control)
• Myocardium (metabolism, pathology)
• Rats, Wistar
• Troponin I (metabolism)
• Ventricular Function, Left (drug effects)
• Ventricular Pressure (drug effects)
• Vildagliptin (pharmacology)