title: The Protective Effects of Botulinum Toxin A Against Flap Necrosis After Perforator Twisting and Its Underlying Molecular Mechanism in a Rat Model.
abstract: OBJECTIVE
  The purpose of this study was to examine our hypotheses that botulinum toxin A (BoTA) protect necrosis of perforator flap from perforator twisting.
  
  
  METHODS
  Twenty-four rats were randomly divided into 2 groups. Twelve International Units of BoTA versus 1.2 mL normal saline was injected subdermally 3 days before flap elevation. In each group, bilateral before deep inferior epigastric perforator (DIEP) flaps, 5 × 3 cm in size, were created. The right and left (180 and 360 degrees of perforator twisting) DIEP flaps were separated. At 1 and 3 days postoperatively, skin above the perforator of the DIEP flaps was harvested to examine the degrees of gene expressions. Final survival percentage of flap and histology were assessed at postoperative day 5.
  
  
  RESULTS
  The survival percentage of flap was significantly higher in the BoTA group than in the control group at both DIEP flaps after 180 and 360 degrees of perforator twisting at postoperative day 5 (95.23 ± 2.85% vs 91.00 ± 3.77%; P = 0.021 and 91.59 ± 2.87% vs 30.03 ± 6.91%; P < 0.001, respectively).Higher fibroblast density, enhanced epithelial necrosis, and inflammation were noted in the control group than in the BoTA group. In 180 degrees of perforator twisting group, BoTA may augment angiogenesis possibly via nuclear factor-κB-induced destabilization and the nuclear factor-κB/hypoxia-inducible factor 1-α/vascular endothelial growth factor pathway, whereas in the 360 degrees of perforator twisting group, the mechanistic target of rapamycin/hypoxia-inducible factor 1-α/vascular endothelial growth factor pathway may participate in BoTA-induced effective angiogenesis.
  
  
  CONCLUSIONS
  We demonstrated that pretreatment with BoTA protects perforator flap caused by perforator at the pathological and molecular level using an experimental rat model.
authors.affiliation: From the *Department of Biochemistry, School of Medicine, Konkuk University; †Department of Pathology, Samsung Medical Center; ‡Department of Radiology, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine; §Department of Plastic and Reconstructive Surgery, Kangbuk Samsung Hospital, College of Medicine, Sungkyunkwan University; and ∥Institute for Human Tissue Restoration, Department of Plastic and Reconstructive Surgery, College of Medicine, Yonsei University, Seoul, Korea.
authors.forename: Sung Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Song Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Boram
authors.initials: B
authors.lastname: Lee
authors.forename: Yun Joo
authors.initials: YJ
authors.lastname: Park
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Park
authors.forename: Young Seok
authors.initials: YS
authors.lastname: Lee
authors.forename: Dong Kyun
authors.initials: DK
authors.lastname: Rah
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Park
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019274:Botulinum Toxins, Type A / Q000627:therapeutic use*; D019074:Epigastric Arteries / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008297:Male; D009336:Necrosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D061525:Perforator Flap / Q000098:blood supply* / Q000473:pathology* / Q000502:physiology; D011183:Postoperative Complications / Q000378:metabolism / Q000517:prevention & control*; D020011:Protective Agents / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019651:Plastic Surgery Procedures
chemical_list: D015415:Biomarkers; D020011:Protective Agents; D019274:Botulinum Toxins, Type A