Incretin Mimetics Vildagliptin and exenatide improve pedicle skin flap survival in rats

Abstract

Hypoxia and tissue ischemia are the leading factors in the alteration of tissues in many pathological conditions. Prevention and reversion of the effects of local ischemia, which develops during various surgical interventions, is an actual problem of modern medicine. The aim of the present study was to investigate the effect of exenatide and vildagliptin on the survival rate of an isolated pedicle skin flap in sixty adults Wistar rats. Simulation of a pedicle skin graft was performed on the second day of the experiment. After anesthesia under aseptic conditions, a skin graft was cut out: isolated in a plastic bag, the edges of the skin were stitched with interrupted sutures (nylon 3/0). Rats were divided into six groups: control group, exenatide group (10 μg/kg/day subcutaneously for nine days after surgery), vildagliptin group (0.2 mg/kg/day intraperitoneally for nine days after surgery) and pentoxifylline group (100 mg/kg/day intravenously, two hours before the surgical intervention). In the other two groups, glibenclamide (5 mg/kg) were administered before injection of incretin mimetics. On the third, seventh and tenth day, area of the surviving tissue was measured. Subsequently, the survival rate of the skin graft was calculated. The area of the surviving tissue in exenatide and vildagliptin group was 1.5 and 1.7 times more compared to the control group, respectively. Preliminary blockade of ATP-dependent potassium channels by glibenclamide eliminated the protective effect of exenatide and vildagliptin. The increase in the survival of ischemic tissues using exenatide and vildagliptin has been experimentally proved. The current study confirmed the important role of ATP-dependent potassium channels in dermatoprotective properties of incretin mimetics.