Evaluation of the effect of antioxidant pretreatment timing on ischaemia-reperfusion injury in the rat inferior epigastric island flap model

Aim: Free flap surgeries represent significant advancements in reconstructive surgery. Despite surgical progress, ischemia-reperfusion injury (IRI) due to vascular complications remains a challenge, potentially leading to flap loss. Various strategies, including surgical methods and pharmacological treatments, have been explored to mitigate IRI. Among these, antioxidant treatments have garnered interest, but research on the optimal timing of antioxidant administration is lacking. This study addresses this gap by investigating the timing of antioxidant pretreatment. Material and Method: In this study, 40 male Wistar Albino rats were divided into five groups: a control group with no ischemia-reperfusion (IR), an IR group with saline injections, and three treatment groups pretreated with melatonin, vitamin C, and vitamin E (10 mg/kg, 200 mg/kg, and 40 mg/kg, respectively), starting 7 days preoperatively, 30 minutes before ischemia, and 30 minutes before reperfusion. A 6×3 cm2 epigastric island flap was elevated and subjected to 8 hours of ischemia. Blood samples were taken to assess total antioxidant capacity, flap photographs were taken to calculate necrosis rates, and tissue biopsies were collected for histopathological and biochemical analyses. Results: Results showed that the group receiving antioxidant pretreatment 7 days before surgery had the lowest necrosis rate (6.3%) among the IR groups. Histopathological and immunohistochemical evaluations (VEGF, caspase-3, eNOS, and IL-1 beta) favored this group. However, biochemical parameters did not show significant intergroup differences. Conclusion: Initiating antioxidant pretreatment 7 days prior to surgery significantly enhances flap viability, highlighting the importance of timing for optimal outcomes in elective free flap procedures.