The effect of Tadalafil on the healing process of the intestinal anastomosis with ischemia and reperfusion in rats

Anastomotic leakage still takes the first place among the factors responsible from morbidity and mortality in gastrointestinal surgery. Intestinal ischemia and reperfusion injury has been reported to have negative effect on anastomotic healing process. There is an interest among investigators for the investigations that can find a drug which can prevent the negative effects of small bowel ischemia-reperfusion injury or revert this process.In this study we aimed to investigate the effect of Tadalafil, a drug which is a vasodilatator agent on vascular smooth muscles and also repair the microcirculation by inhibiting the platelet aggregation, on the healing process of small bowel anastomosis in the intestinal ischemia-reperfusion model of rats.In this study forthy-eight male Sprague-Dawley rats (body weight 200-250 gr) were used. The rats are randomly divided into four groups. The first group has normal small bowel anastomosis, the second group has normal small bowel anastomosis and tadalafil treatment, the third group has intestinal ischemia-reperfusion and smal bowel anastomosis, and the fourth group has intestinal ischemia-reperfusion, small bowel anastomosis and Tadalafil treatment. In order to make intestinal ischemia and reperfusion the superior mesenteric artery and collateral vessels to the small bowel were clamped for 30 minutes and then released in groups III and IV. In groups II and IV tadalafil was given orally, started 2 hours prior to the operation and continued for 4 days at 10 mg/kg/day dosage. Four days after the operation the rats were sacrificed and their anastomotic bursting pressures were measured. Tissue samples for the histopathological evaluation and the measurement of hydroxyproline levels were collected in order to evaluate the healing of anastomosis. Hydroxyproline levels were measured with biochemical assay. For histopathologic evaluation, modified Ehrlich-Hunt scoring system is used. For the statistical analysis, SSPS 16.0 for Windows, with Anova and Tukey presets, is used and values p<0.05 are considered significant.Anostomotic bursting pressures in group II were found to be higher than in group I (p:0.041). This was also true for group IV against group III (p:0.000). Hydroxiproline levels of the perianastomotic tissue were found to be higher in group II than group I but with no statistical significance (p:0.081) but in group IV against group III it also posed a statistical significance (p:0.000).It has been shown that 30 minutes of intestinal ischemia and reperfusion has negatively affected the anastomotic healing shown by anastomotic bursting pressure and perianastomotic tissue levels of hydroxyproline matching with the literature. Tadalafil?s positive effects on the healing normal anastomosis was shown with anastomotic bursting pressure. In anastomosis with intestinal ischemia and reperfusion injury, Tadalafil?s positive effects on healing process was shown by both the anostomotic bursting pressure and perianastomotic tissue hydroxiproline levels.In conclusion: Tadalafil was shown to have positive effect on the healing process of anastomosis at dose of 10/mg/kg/day begining 2 hours prior to the operation and continued for 4 days.In future studies Tadalafil?s effect mechanisms, dosage and the borders of its effect on ischemia ? reperfusion injury will be further understood.