title: Botulinum toxin A and B raise blood flow and increase survival of critically ischemic skin flaps.
abstract: 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.
authors: Department of Clinical Research, University of Bern, Bern, Switzerland.
authors: Dennis F
authors: DF
authors: Schweizer
authors: Riccardo
authors: R
authors: Schweizer
authors: Shengye
authors: S
authors: Zhang
authors: Pranitha
authors: P
authors: Kamat
authors: Claudio
authors: C
authors: Contaldo
authors: Robert
authors: R
authors: Rieben
authors: Daniel
authors: D
authors: Eberli
authors: Pietro
authors: P
authors: Giovanoli
authors: Dominique
authors: D
authors: Erni
authors: Jan A
authors: JA
authors: Plock
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001905:Botulinum Toxins / Q000494:pharmacology*; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D052250:Nitric Oxide Synthase Type III / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects*; D012867:Skin / Q000098:blood supply* / Q000473:pathology; D013524:Surgical Flaps / Q000098:blood supply*; D014022:Tissue Survival / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000502:physiology
chemical_list: C096323:rimabotulinumtoxinB; D052250:Nitric Oxide Synthase Type III; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A; D020742:rhoA GTP-Binding Protein
keywords: Botox; Endothelium; Microcirculation; Microhemodynamics; Preconditioning; Rho kinase; Smooth muscle cells; Vasodilation; eNOS