Efects of Irisin on muscle atrophy in denervated muscle flaps

Introduction and Objective: Flaps are commonly used in the repair of tissue defects, where the nutrition and adaptation of the flap play significant roles due to the defect area, the patient's coexisting diseases, and many pathophysiological changes related to the flap. Especially in muscle flaps, iatrogenically denervated flaps post-dissection undergo atrophy and fatty degeneration, leading to potential early and late postoperative complications such as wound dehiscence and exposure of underlying tissues or non-organic materials. This study investigated the preventive effect of irisin on atrophy and degeneration secondary to denervation in rat M.rectus femoris denervated muscle flaps. Light microscopy was used to evaluate degenerative changes and nucleus structure in muscle fibers, while immunohistochemical analysis was conducted using myosin heavy chain 2 antibodies for semi- quantitative evaluation based on staining intensities. Materials and Methods: 24 Wistar-Albino male rats, weights between 300 and 450 grams, were divided into three groups. The first group served as the control, undergoing only right inguinal femoral incision and preparation of the rectus femoris muscle flap through femoral nerve transection. The same procedure was applied to the irisin group, followed by intraperitoneal injections of 40ng/kg irisin three times a week for three weeks. The control and denervated muscle groups received volume- equivalent saline injections. At the end of three weeks, the animals were sacrificed, and the bilateral rectus femoris muscles were excised for evaluation of muscle weight and subsequent histopathological and immunohistochemical analysis for myofibril diameter, fatty degeneration, vacuolization, myofibril atrophy, and myosin heavy chain 2 protein quantity. Findings: Comparative analysis of histological, immunohistochemical examinations, and physical measurements statistically detected irisin's protective effect against atrophy in denervated M. rectus femoris muscle flaps by the end of week 3. Irisin application showed statistically significant protection in denervated muscle flaps against degenerative changes, heterochromatin staining, and nuclear picnotic changes (p<0.005). Moreover, immunohistochemical evaluation showed a significant increase in MYH2 expression in the irisin-treated group (p<0.005). Muscle weights of the irisin-treated group were significantly preserved compared to the untreated group, with no difference in inflammation across all groups. Conclusion: This study demonstrated irisin's protective effects against atrophy and degeneration in denervated muscle flaps. Irisin prevents degradation and increases the expression of MYH2 (Myosin Heavy Chain 2), playing a crucial role in muscle contraction. Additionally, irisin can be considered as a possible terapeutic agent in preventing atrophy and degeneration of muscle flaps that are deprived basal nerve stimulation secondary to tumor resection or trauma unrtil reinnervation surgery. It can also said to be possible therapeutic agent in preventing muscle loss due to aging and diseases.