Akcal Arzu, Sevim K Zeynep, Yesilada Aysin, Kiyak Volkan, Sucu D Ozgur, Tatlidede H Soner, Sakiz Damlanur, Kaya Huseyin
Department of Plastic and Reconstructive Surgery, Sisli Etfal Research and Training Hospital, Acibadem Caddesi Is bankasi Bloklari A6/33, 34718 Acibadem Kadıko¨y, Istanbul, Turkey.
J Craniofac Surg. 2013 Jan;24(1):278-83. doi: 10.1097/SCS.0b013e318270fd5b.
Muscle flaps are known to be prone to local ischemia more than other flaps. The local and systemic injury that ensues after reperfusion of ischemic skeletal muscle is an important clinical problem in flap surgery. Flap delay may be applied chemically or sympathetically. Early use of botulinum toxin A (Btx-A) in muscle flap surgery relied on chemical denervation; however, in our study, we tried to emphasize a possible chemical delay mechanism of Btx-A, through the release of substance P and calcitonin gene-related peptide (CGRP) and vascular endothelial growth factor (VEGF).
Pretreatment with perivascular or intramuscular Btx-A was applied 1 week before the flap elevation, 3.5 units in 2 experimental groups each containing 8 Sprague-Dawley rats. The control groups (2 groups, each containing 8 rats) received 0.07 mL saline perivascularly and intramuscularly. The right gastrocnemius muscle flap was used as the experimental model. Ischemia-reperfusion cycle was applied to all groups. On the seventh day, the gastrocnemius flap was elevated, and perivascular tissues were observed macroscopically. Comparisons between perivascular Btx-A and intramuscular Btx-A groups were made, and the animals were killed. Muscle biopsies were taken. Damaged myocytes were counted using McCormack technique, and chemical delay was shown as angiogenesis, lymphocyte counts, and edema formation with VEGF3-R, CGRP, and substance P markers as immunohistochemical staining.
The amount of muscle necrosis was the highest in intramuscular Btx-A admitted groups. The intramuscular and perivascular Btx-A groups showed significant angiogenesis scored blindly by the senior pathologist.
Potential role of Btx-A in ischemic preconditioning of muscle flaps achieved through the release of substance P, CGRP, and VEGF was investigated. Chemical delay was shown objectively by Btx-applied groups.
已知肌皮瓣比其他皮瓣更容易发生局部缺血。缺血骨骼肌再灌注后随之发生的局部和全身损伤是皮瓣手术中的一个重要临床问题。皮瓣延迟可通过化学方法或交感神经方法实现。肉毒杆菌毒素A（Btx-A）在肌皮瓣手术中的早期应用依赖于化学去神经作用；然而，在我们的研究中，我们试图强调Btx-A可能的化学延迟机制，即通过P物质、降钙素基因相关肽（CGRP）和血管内皮生长因子（VEGF）的释放来实现。
在皮瓣掀起前1周，对每组8只Sprague-Dawley大鼠的2个实验组进行血管周围或肌肉内Btx-A预处理，剂量为3.5单位。对照组（2组，每组8只大鼠）在血管周围和肌肉内注射0.07 mL生理盐水。以右侧腓肠肌皮瓣作为实验模型。对所有组施加缺血-再灌注循环。在第7天，掀起腓肠肌皮瓣，肉眼观察血管周围组织。对血管周围Btx-A组和肌肉内Btx-A组进行比较，然后处死动物。取肌肉活检标本。使用麦科马克技术对受损肌细胞进行计数，并以VEGF3-R、CGRP和P物质标记物进行免疫组织化学染色，将化学延迟表现为血管生成、淋巴细胞计数和水肿形成。
肌肉内注射Btx-A组的肌肉坏死量最高。高级病理学家对血管周围和肌肉内Btx-A组的血管生成进行了盲法评分，显示差异有统计学意义。
研究了Btx-A通过释放P物质、CGRP和VEGF在肌皮瓣缺血预处理中的潜在作用。应用Btx-A的组客观地显示出化学延迟。
