The effect of carnosine and low molecular weight heparin on random pattern McFarlane flap viability and microbial metabolites in plasma fluid in rats

ABSTRACT THE EFFECT OF CARNOSINE AND LOW MOLECULAR WEIGHT HEPARIN ON RANDOM PATTERN MC FARLANE FLAP VIABILITY AND MICROBIAL METABOLITES IN PLASMA FLUID IN RATS The aim of this study is to evaluate the effects of Carnosine and DMAH on the viability of skin flaps in an experimental McFarlane skin flap model in rats and to assess their correlation with biochemical and pathological parameters. This study will include 40 female Sprague Dawley rats, aged between 0.5 and 1 year, all in the same reproductive cycle stage. The objective is to investigate the effects of Carnosine and DMAH on random skin flap viability and plasma microbial metabolites. For this purpose, the subjects will be divided into four groups: Group 1 (Control Group) (n=10): On day 0 of the study, a 3×9 cm caudally based random-pattern dorsal skin flap will be elevated and then repositioned. Daily wound care with povidone-iodine will be performed for 7 days. Group 2 (Carnosine Group) (n=10): The same procedures as in Group 1 will be applied, and in addition, Carnosine will be administered intraperitoneally at a dose of 100 mg/kg/day, starting from postoperative day 0. Group 3 (DMAH Group) (n=10): The same procedures as in Group 1 will be applied, and in addition, DMAH will be administered subcutaneously at a dose of 1 mg/kg/day, starting from postoperative day 0. Group 4 (Carnosine + DMAH Group) (n=10): The same procedures as in Group 1 will be applied, and both drugs will be administered in combination as described in Groups 2 and 3. After seven days of treatment, all animals' flaps will be photographed using a digital camera, and topographic measurements of the flap survival area relative to the total flap area will be performed. Under anesthesia, tissue sections will be taken from 5 cm distal to the flap base and from the necrotic boundary for histopathological examination. Afterward, the animals will be decapitated, and blood samples will be collected for biochemical parameter analysis to investigate microbial metabolites. The subjects will then be sacrificed. One of the biggest challenges in flap surgery is flap necrosis, which leads to increased morbidity, prolonged hospital stays, and the need for repeated surgeries, making it a major concern in plastic surgery. In commonly used random-pattern flaps, partial or complete flap necrosis frequently occurs. Although numerous studies and pharmacological treatments have been conducted on flap perfusion, the combined effect of Carnosine and DMAH on random-pattern flap survival and the biochemical parameters mentioned in this study has not been previously investigated. In this study, after establishing the ischemia-reperfusion model, Carnosine and DMAH were found to have a positive effect on flap viability. Additionally, when the biochemical parameters were compared with the control group, the highest values were observed in the group that received both DMAH and Carnosine. We believe that this increase could serve as an important biomarker in evaluating the efficacy of treatment once Carnosine and DMAH find their application in ischemia treatment. Histopathological evaluation revealed that necrosis, inflammation, and edema severity were lower in the Carnosine and combination therapy groups, suggesting that the drugs exerted anti-inflammatory and antioxidant effects. On postoperative day 7, flap viability assessment demonstrated that the surviving flap area was significantly higher in the Carnosine and DMAH-treated groups compared to the control group. Histopathological analysis also showed that the Carnosine and combination therapy groups had statistically significantly fewer inflammatory cells, less edema, and reduced necrosis per unit area than the controlgroup. Regarding biochemical parameters, the highest values were observed in the DMAH group, followed by the Carnosine group. This study demonstrates that the systemic administration of 100 mg/kg/day Carnosine and 1 mg/kg/day DMAH for 7 days postoperatively improves flap survival. It is believed that systemic administration of these drugs, either individually or in combination, after surgery in patients undergoing flap procedures may reduce complications, hospital stay duration, and the need for additional surgical interventions. Key words: Random patterned flap, Carnosine, Low molecular weight heparin, Microbial metabolite