Investigation of the effect of topical nitroglycerin application on neoangiogenesis and flap autonomization (pedicle independent viability) process in rat back random skin flap model

Interpolation flaps are a common reconstruction option in plastic surgery. In flap transfers, the autonomization process, which allows the tissue to live independently of the pedicle in the new location, is critical to reduce postoperative complications. Physical and chemical methods have been investigated to accelerate vascularization in this process. Nitroglycerin shows angiogenetic, vasodilation and anti-inflammatory effects by releasing nitric oxide (NO). However, the effects of nitroglycerin on flap autonomization have not been discussed in detail in the literature. In this study, we investigated the effects of topical nitroglycerin application on flap autonomization and neoangiogenesis in dorsally raised random skin flaps in rats. In this study, a 3x3 cm caudal pedicled dorsal skin flap model was used in 60 female Wistar-Albino rats. The rats were divided into five groups following different application protocols. In the groups, a 3x3 cm skin flap was randomly removed from the back of the rat and returned to its place. Vaseline (Group 1) or topical nitroglycerin (Groups 2 and 3) was applied from the first postoperative day until the day of pedicle discontinuation (day 5) and/or for the following 7 days. In some groups (Groups 4 and 5), sacrification was performed on day 5 (the day of pedicle cutting) only to examine the microscopic effect of flap surgery and the effect of the drug on this process. In the groups in which clinical observation was performed, the necrotic areas of the flaps were determined before sacrification on day 12, and the ratio of the surviving flap tissue area was determined using the ImageJ program. In addition, the vascularization status of the tissues was examined immunohistochemically with VEGF, CD34 and CD105. The effect of topical nitroglycerin on the angiogenesis process was evaluated by statistically comparing the control group treated with vaseline alone and the groups treated with topical nitroglycerin for 5 days and 12 days. Our clinical findings showed that there was significantly more pedicle-independent flap viability (flap autonomization) in both the group in which nitroglycerin was applied for only 5 days until the pedicle was cut (Group 2) and in the group in which nitroglycerin continued to be applied for 7 more days after the pedicle was cut (Group 3) compared to the control group in which only vaseline was applied (Group 1). These clinical findings were confirmed immunohistochemically with higher vessel counts in the nitroglycerin groups. While the highest number of vessels was obtained in Group 3, it was observed that the increased vessel density with nitroglycerin for 5 days decreased to the values of the control group at the end of the 12th day after the cessation of nitroglycerin administration. This study shows that the use of nitroglycerin may be a promising agent to increase flap autonomization in reconstructive surgery, especially in cases where pedicle separation is required, such as interpolation flaps. However, it is important to reveal the pathophysiological processes of these findings with more extensive experimental studies in terms of the effects of nitroglycerin on neoangiogenesis processes and to confirm these findings with clinical studies.