- 作者：Dennis F. Schweizer ; Riccardo Schweizer ; Shengye Zhang ; Pranitha Kamat ; Claudio Contaldo ; Robert Rieben ; Daniel Eberli ; Pietro Giovanoli ; Dominique Erni ; Jan A. Plock
- 关键词：Botox ; Endothelium ; eNOS ; Microcirculation ; Microhemodynamics ; Preconditioning ; Rho kinase ; Smooth muscle cells ; Vasodilation
- 刊名：Journal of Surgical Research
- 出版年：2013
- 出版时间：October, 2013
- 年：2013
- 卷：184
- 期：2
- 页码：1205-1213
- 全文大小：2206 K
Background
Botulinum toxin (BTX) A and B are commonly used for aesthetic indications and in neuromuscular disorders. New concepts seek to prove efficacy of BTX for critical tissue perfusion. Our aim was to evaluate BTX A and B in a mouse model of critical flap ischemia for preoperative and intraoperative application.Methods
BTX A and B were applied on the vascular pedicle of an axial pattern flap in mice preoperatively or intraoperatively. Blood flow, tissue oxygenation, tissue metabolism, flap necrosis rate, apoptosis assay, and RhoA and eNOS expression were endpoints.
Results
Blood-flow measurements 1 d after the flap operation revealed a significant reduction to 53 % in the control group, while flow was maintained or increased in all BTX groups (103 % -129 % ). Over 5 d all BTX groups showed significant increase in blood flow to 166-187 % (P?<?0.01). Microdialysis revealed an increase of glucose and reduced lactate/pyruvate ratio and glycerol levels in the flap tissue of all BTX groups. This resulted in significantly improved tissue survival in all BTX groups compared with the control group (62 % ¡À 10 % ; all P < 0.01): BTX A preconditioning (84 % ¡À 5 % ), BTX A application intraoperatively (88 % ¡À 4 % ), BTX B preconditioning (91 % ¡À 4 % ), and intraoperative BTX B treatment (92 % ¡À 5 % ). This was confirmed by TUNEL assay. Immunofluorescence demonstrated RhoA and eNOS expression in BTX groups. All BTX applications were similarly effective, despite pharmacologic dissimilarities and different timing.
Conclusions
In conclusion, we were able to show on a vascular, tissue, cell, and molecular level that BTX injection to the feeding arteries supports flap survival through ameliorated blood flow and oxygen delivery.