Janz Brian A, Thomas Peter R, Fanua Sione P, Dunn Reginald E, Wilgis E F Shaw, Means Kenneth R
The Curtis National Hand Center, Union Memorial Hospital, 3333 North Calvert Street, #200, Baltimore, MD 21218, USA.
J Hand Surg Am. 2011 Oct;36(10):1585-91. doi: 10.1016/j.jhsa.2011.07.008. Epub 2011 Aug 19.
Revascularized or replanted digits may fail because of vessel thrombosis. Off-label use of botulinum toxin type A injected subcutaneously has been used successfully in limited case series to treat vasospastic disorders. Botulinum toxin type B (BTX-B) is thought to have an earlier onset of action than type A in certain settings. We used a rat model to determine the ability of BTX-B to decrease vasospasm and prevent thrombosis after acute vessel division and anastomotic repair.
We transected and immediately repaired the bilateral femoral arteries and veins of 25 rats via microscopic technique. We measured each vessel's diameter before transection. Each rat had 1 leg randomly assigned to receive BTX-B; the contralateral side received normal saline. We separated the animals into 5 groups. Each group underwent vasospastic stress at a different time point (12, 24, 48, 72, and 120 h) after the anastomoses and treatment with BTX-B or saline. Vasospastic stress included a lower extremity cold temperature challenge and systemic treatment with phenylephrine. After vasospastic stress, we reopened the wounds and recorded vessel thrombosis and diameter.
Vessel thrombosis rate was lower in the BTX-B-treated group of vessels compared with those receiving placebo. Thrombosis rate was 8% for BTX-B-treated arteries versus 68% for saline-treated arteries. Thrombosis rate was 20% for BTX-B-treated veins versus 76% for saline-treated veins. Overall vessel thrombosis rate was significantly lower for BTX-B at all time points except at 120 hours when no thrombotic events occurred for either group. Average increase in diameter for BTX-B-treated vessels was significantly greater than that for the controls regardless of patency.
BTX-B prevented or reduced the incidence of thrombosis after acute vessel anastomosis in this rat model at all time points less than 120 hours compared with placebo. The average final vessel diameter throughout the series of BTX-B-treated vessels was significantly larger than in the control group.
The use of BTX-B may improve the success rate of microvascular anastomoses by being protective against vasospastic stress and subsequent thrombosis.
再血管化或再植的手指可能会因血管血栓形成而失败。皮下注射A型肉毒杆菌毒素的非标签使用在有限的病例系列中已成功用于治疗血管痉挛性疾病。在某些情况下，B型肉毒杆菌毒素（BTX-B）被认为比A型起效更早。我们使用大鼠模型来确定BTX-B在急性血管离断和吻合修复后降低血管痉挛和预防血栓形成的能力。
我们通过显微技术横断并立即修复了25只大鼠的双侧股动脉和静脉。我们在横断前测量了每条血管的直径。每只大鼠的1条腿随机分配接受BTX-B；对侧接受生理盐水。我们将动物分为5组。每组在吻合和用BTX-B或生理盐水治疗后的不同时间点（12、24、48、72和120小时）接受血管痉挛应激。血管痉挛应激包括下肢低温刺激和用去氧肾上腺素进行全身治疗。在血管痉挛应激后，我们重新打开伤口并记录血管血栓形成情况和直径。
与接受安慰剂的血管相比，BTX-B治疗组的血管血栓形成率更低。BTX-B治疗的动脉血栓形成率为8%，而生理盐水治疗的动脉为68%。BTX-B治疗的静脉血栓形成率为20%，而生理盐水治疗的静脉为76%。除120小时时两组均未发生血栓形成事件外，在所有时间点BTX-B的总体血管血栓形成率均显著更低。无论通畅情况如何，BTX-B治疗的血管直径平均增加量均显著大于对照组。
与安慰剂相比，在该大鼠模型中，BTX-B在小于120小时的所有时间点均预防或降低了急性血管吻合后血栓形成的发生率。整个系列中BTX-B治疗的血管的平均最终血管直径显著大于对照组。
使用BTX-B可能通过预防血管痉挛应激和随后的血栓形成来提高微血管吻合的成功率。
