title: Presurgical Botulinum Toxin A Treatment Increases Angiogenesis by Hypoxia-Inducible Factor-1α/Vascular Endothelial Growth Factor and Subsequent Superiorly Based Transverse Rectus Abdominis Myocutaneous Flap Survival in a Rat Model.
abstract: To date, there have been several experimental studies to assess tissue viability of transverse rectus abdominis myocutaneous (TRAM) flaps. Botulinum toxin A (BoTA) has gained popularity in many clinical fields, for a variety of therapeutic and aesthetic purposes. In addition, there have been reports regarding the positive effect of BoTA on flap survival by various mechanisms. In this study, we hypothesized that pretreatment with BoTA could augment the survival of TRAM flaps via increased hypoxia-inducible factor (HIF)1α/vascular endothelial growth factor (VEGF)-dependent angiogenesis.Twenty-four Sprague-Dawley rats were randomly divided into 2 groups: a control group and a BoTA group. Five days before superiorly based TRAM flap elevation, the BoTA group was pretreated with BoTA, whereas the control group was pretreated with normal saline. Gross flap survival rates were assessed, and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blotting were performed for the evaluation of angiogenesis-related factors (CD34, HIF-1α, and VEGF).In the BoTA group, the gross flap survival rate was significantly higher than that in the control group on both ipsilateral (92.78.3 ± 5.05% vs 86.8 ± 3.88%, P = 0.009) and contralateral (91.57 ± 5.79% vs 74.28 ± 11.83%, P < 0.001) sides.The relative mRNA expression of CD34 and VEGF was significantly higher in the BoTA group than that in the control group in every zone, whereas the relative mRNA expression of HIF-1α was significantly higher in the BoTA group than that in the control group on contralateral sides. The relative protein expression of CD34, VEGF, and HIF-1α was significantly higher in the BoTA group than that in the control group in every zone.In conclusion, we demonstrate that presurgical BoTA treatment might increase angiogenesis by HIF-1α/VEGF, subsequently increase superiorly based TRAM flap survival in a rat model.
authors.affiliation: From the *Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, College of Medicine, Yonsei University; †Department of Biochemistry, School of Medicine, Konkuk University, Research Institute of Medical Science, Konkuk University School of Medicine; and ‡Department of Radiology, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Korea.
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Park
authors.forename: Song Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Yun Joo
authors.initials: YJ
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: Sung Young
authors.initials: SY
authors.lastname: Kim
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D006085:Graft Survival / Q000187:drug effects* / Q000502:physiology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D064827:Myocutaneous Flap / Q000098:blood supply* / Q000637:transplantation; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D011300:Preoperative Care / Q000379:methods*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019651:Plastic Surgery Procedures / Q000379:methods; D017568:Rectus Abdominis / Q000098:blood supply* / Q000187:drug effects / Q000637:transplantation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D018952:Antigens, CD34; D015415:Biomarkers; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D019274:Botulinum Toxins, Type A