Evaluation of the effects of Theranekron on flap viability in the rat McFarlane skin flap model and comparison with the effects of pentoxifylline

Introduction and Objective: Flap perfusion and ischemia are among the fundamental research areas of reconstructive surgery. Ischemia occurring particularly in the distal parts of the flap, where blood supply is reduced after flap elevation, can lead to partial flap losses, and the resulting complications can disrupt the treatment process. Many methods are being tried today to increase flap survival. The surgical delay method performed by flap elevation and replacement, optimizing flap temperature to protect against vasoconstriction, and the use of therapeutic agents that increase flap survival can be given as examples of these methods. Tarantula Cubensis Alcoholic Extract (TCAE), known as Theranekron, is an injectable drug widely used in veterinary medicine, obtained by processing the entire Tarantula Cubensis, a dark brown hairy Cuban tarantula, in alcohol. Studies have revealed the drug's anti-inflammatory properties and its positive effects on wound healing. The aim of our study is to investigate the effects of Theranekron on skin flap viability and to compare these effects with pentoxifylline, which is known to have positive effects on flap viability. Material and Methods: A total of 18 female Wistar Albino rats, aged 8–10 weeks and weighing between 250–350 g, were divided into three groups. In all groups, a 3×9 cm random-pattern McFarlane skin flap was elevated on the dorsal region and resutured to its original position. Group 1 was the control group, and no drug was administered after flap elevation (n=6). In Group 2, 50 mg/kg pentoxifylline was administered intraperitoneal on postoperative days 0.,1.,2.,3.,4.,5. (n=6). In Group 3, 1 ml/kg Theranekron was administered subcutaneously on postoperative days 0.,3. and 5. (n=6). On the seventh postoperative day, the rats were photographed under anesthesia, and the necrotic area and percentage were calculated macroscopically using the ImageJ software. Tissue samples were obtained. The samples were evaluated by immunohistochemical examination (VEGF and eNOS expression) and electron microscopy. Results: The mean flap necrosis areas were found to be 11.24 ± 1.12 cm² (mean ± SD) (percentage 37.23 ± 3.71%) in the control group, 6.95 ± 0.87 cm² (percentage 23.04 ± 2.88%) in the pentoxifylline group, and 5.52 ± 1.03 cm² (percentage 18.28 ± 3.42%) in the Theranekron group. In both treatment groups, a significant reduction in the necrotic area ratio was observed compared to the control group (p=0.002). In addition, the necrotic area ratio in the Theranekron group was significantly lower than that in the pentoxifylline group (p=0.026). Immunohistochemical evaluation revealed increased VEGF and eNOS expression in both the pentoxifylline and Theranekron groups compared to the control group. Furthermore, VEGF and eNOS expression was higher in the Theranekron group than in the pentoxifylline group. Electron microscopic evaluation showed that endothelial cell integrity and mitochondrial structure were preserved and vacuolization was reduced in tissues treated with Theranekron. Conclusion: Both pentoxifylline and Theranekron demonstrated a positive effect on flap perfusion and survival in the random-pattern flap model. However, the percentage of necrotic area was lower and VEGF and eNOS expressions were higher in the Theranekron group. These findings suggest that Theranekron may be more effective than pentoxifylline in improving flap viability. Key words: eNOS, flap perfusion, ischemia, McFarlane flap, necrosis, Theranekron(TCAE), VEGF