The effect of various pharmacological agents on wound healing in experimental skin flap

Aim: In Plastic and Reconstructive Surgery and General Surgery cases; especially in mastectomy and abdominal hernia repair, the formation of a skin flap is routinely performed. The deterioration in wound healing that may develop after the flap formation can cause infection, prolonged hospitalization time and antibiotic use and also a need for wound revision in patients. In this study, it was aimed to investigate the effect of cilostazol and pentoxifylline, common pharmacological agents for the treatment of peripheral arterial disease, and papaverine, a well-known local vasodilatator, on ischemia and vascularity in an experimental flap model. Materials and Methods: In this study, 40 Wistar-Albino, adult, male rats weighing 300-400 grams were used. The rats were randomly divided into 5 groups and groups were formed with 8 rats in each group. The rats in group 1 (control group) were sacrificed 7 days after the experimental skin flap was created. Rats in group 2 (Cilostazol group) were given 30 mg/kg of cilostazol 2 times a day by oral gavage for 7 days before and after the operation. Rats in group 3 (Cilostazol + Papaverine) were given 30 mg/kg of cilostazol 2 times a day by oral gavage for 7 days before and after the operation. In this group of rats, 50mg/2ml papaverine was given under the skin flap during the operation. After skin flap formation, 25 mg/kg of pentoxifylline was given intraperitoneally 1 time per day to rats in group 4 (Pentoxifylline group) for 7 days. Rats in Group 5 (Pentoxifylline + Papaverine group) were given 50mg/2ml of papaverine under the skin flap during the operation. After the formation of the skin flap, 25 mg/kg of pentoxifylline was given intraperitoneally 1 time per day for 7 days. During sacrification, all rats were given barium sulfate systemically as a radiopaque substance. Photographs of the flaps of all rats were taken before sacrification and the percentage of ischemia was calculated digitally. After excising the skin flaps, a direct graph was taken on the skin flaps and the percentage of vascularity was calculated digitally via X-ray images. Results: There were 8 (20.0%) rats in all 5 groups included in the study..Comparisons of the ischemia rate between the study groups were examined and a significant difference was found between the 5 groups in terms of ischemia rate (p=0.022). For the ischemia rate the averages belonging to the Group 1, Group 2, Group 3, Group 4 and Group 5 are respectively 45.70±5.45, 39.15±16.71, 30.94±14.86, 27.54±13.12, 27.06±10.69. When the binary groups that created the significant difference were examined, the difference between no binary groups was found to be significant (p>0.05). Comparisons of vascularization between the study groups were examined and a significant difference was found between the 5 groups in terms of vascularization (p=0.003). The highest average for vascularization was found in the Group 5, while the lowest average was found in the Group 3. When we looked at the binary groups that made the significant difference, the differences between the Group 1 – Group 5 and Group 5 – Group 3 were found to be significant (p=0.019 and p=0.004, respectively). When examined in all rats, a moderate, negative and statistically significant relationship was found between ischemia rate and vascularization (r=-0,401 and p=0.010). Conclusion: According to the results of our study, in which the effect of various pharmacological agents on the flap ischemia rate and vascularity percentage were investigated in the experimental skin flap model, it was observed that the administration of pentoxifylline+papaverine is the most effective method for preventing skin flap ischemia. It is thought that our results should be supported by prospective randomized clinical trials in order for the results of our study, which found that pentoxifylline is more effective than silostazole, to be reflected in clinical practice. Keywords: skin flap, ischemia, vascularity, wound healing, cilostazol, pentoxifylline, papaverine