Botulinum toxin A and B raise blood flow and increase survival of critically ischemic skin flaps

Schweizer, Dennis F.; Schweizer, Riccardo; Zhang, Shengye; Kamat, Pranitha; Contaldo, Claudio; Rieben, Robert; Eberli, Daniel; Giovanoli, Pietro; Erni, Dominique; Plock, Jan A. (2013). Botulinum toxin A and B raise blood flow and increase survival of critically ischemic skin flaps. Journal of surgical research, 184(2), pp. 1205-1213. Elsevier 10.1016/j.jss.2013.04.004

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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% ± 10%; all P < 0.01): BTX A preconditioning (84% ± 5%), BTX A application intraoperatively (88% ± 4%), BTX B preconditioning (91% ± 4%), and intraoperative BTX B treatment (92% ± 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Herz und Gefässe
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Plastic and Hand Surgery > Plastic, Reconstructive and Aesthetic Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Plastische Chirurgie

UniBE Contributor:

Schweizer, Riccardo; Zhang, Shengye; Jayadev Kamat, Pranitha; Rieben, Robert; Erni, Dominique and Plock, Jan Alexander

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0022-4804

Publisher:

Elsevier

Language:

English

Submitter:

Verena de Serra Frazao-Bill

Date Deposited:

05 May 2014 14:25

Last Modified:

02 Nov 2015 11:02

Publisher DOI:

10.1016/j.jss.2013.04.004

PubMed ID:

23651811

Uncontrolled Keywords:

Botox, Endothelium, Microcirculation, Microhemodynamics, Preconditioning, Rho kinase, Smooth muscle cells, Vasodilation, eNOS

BORIS DOI:

10.7892/boris.46031

URI:

https://boris.unibe.ch/id/eprint/46031

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