Protectıve effects of vascular endothelıal growth factor and adrenomedullın on ıschemıa reperfusıon ınjury ın skeletal muscle ın rats

Aim: The aim of this study is to investigate the effects of vascular endothelial growth factor (VEGF) and adrenomedullin (ADM) in the model of lower extremity skeletal muscle ischemia reperfusion injury.Method: Thirty-six Wistar rats were randomized into six groups (n=6). Laparotomy was performed in all groups under general anesthesia. Nothing else was done in Group S (Sham). Ischemia reperfusion group (Group IR) underwent ischemia and reperfusion performed by Clamping and declamping of the infrarenal abdominal aorta for 120 minutes, respectively. Group VGEF and Group ADM received intravenous infusion of VEGF (0,8 ?g/kg ) or ADM (12 ?g /kg) respectively, without ischemia and reperfusion. Group IR+VEGF and Group IR+ADM received intravenous infusion of VEGF (0,8 ?g/kg ) or ADM (12 ?g /kg) respectively immediately after 2 hours period of ischemia. At the end of reperfusion period, skeletal muscle samples of lower extremity were taken from all groups for biochemical and histopathologic examinations.Results: Tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO) and hypoxia inducible factor 1 alpha (HIF 1 alpha) were found to be significantly higher in Group IR than the levels in Group S (p < 0.05). Tissue levels of MDA, SOD, NO and HIF 1 alpha were significantly lower in Group IR+ADM when compared with the levels in Group IR (p < 0.05). In Group IR+VEGF, tissue levels of MDA and NO were significantly lower than the levels in Group IR (p < 0.05). No statistically significant difference was found in the tisue levels of catalase among the groups. In histopathologic examination, central muscular necrosis was found to be larger than the peripheral necrosis, red blood cells were found in the lumens of capillary vessels and atrophy and elliptical or round shape in muscle fibers in Group IR. In groups IR+ADM and IR+VEGF, statistically significant decreases were detected in these changes.Conclusion: These results indicate that ADM ve VEGF have protective effects on ischemia reperfusion injury in skeletal muscle in rats.