title: Angiogenic effects of injected VEGF165 and sVEGFR-1 (sFLT-1) in a rat flap model.
abstract: BACKGROUND
  Injections of single-dose vascular endothelial growth factor (VEGF)(165) have been advocated as a therapeutic tool for angiogenesis in ischemic flaps. We challenged this thesis by employing both VEGF(165) and vascular endothelial growth factor receptor-1 (VEGFR-1) (for competitive inhibition of VEGF signal transduction) in different experimental settings of an ischemic rat flap model.
  
  
  METHODS
  80 isogenic rats were divided in two groups of 40 animals (groups 1A-1D and 2A-2D). The ischemic target was a 7 x 7-cm epigastric island flap, based on the right inferior epigastric pedicle. Group 1 received flap treatment 1 week prior to flap elevation by test substance injection into its flap panniculus carnosus: 1 ml NaCl 0.9% (1A), 1 ml Dulbecco's modified Eagle's medium (1B), 1.0 microg VEGF(165) (1C), and 10 microg sFLT-1 with 1.0 microg VEGF(165) (1D). sFLT-1 is a soluble receptor for VEGF and is able to prevent VEGF signaling through the cell surface receptor. Group 2 had the same flap treatment at the day of flap elevation.
  
  
  RESULTS
  In group 1C we found the most vital flap tissue, without reaching significance. Compared with group 1D, however, significantly more flap tissue maintained vital. In groups 2A-2D, no significant results were found with respect to flap survival.
  
  
  CONCLUSIONS
  Local application of single-dose VEGF(165) 1 week prior to ischemia dose not have significant clinical angiogenic effects. In this experimental setting, VEGF(165)-induced angiogenic effects can be significantly inhibited by adding sFLT1 in vivo. A single-dose of VEGF(165) under ischemic conditions causes no significantly better flap survival in this model.
authors.affiliation: Clinic for Plastic, Hand and Reconstructive Surgery, Lübeck University Clinics, Lübeck, Germany. Machens@medinf.mu-luebeck.de
authors.forename: Hans-Günther
authors.initials: HG
authors.lastname: Machens
authors.forename: Jila
authors.initials: J
authors.lastname: Salehi
authors.forename: Herbert
authors.initials: H
authors.lastname: Weich
authors.forename: Susanne
authors.initials: S
authors.lastname: Münch
authors.forename: Frank
authors.initials: F
authors.lastname: Siemers
authors.forename: Björn D
authors.initials: BD
authors.lastname: Krapohl
authors.forename: Kay-Henryk
authors.initials: KH
authors.lastname: Herter
authors.forename: Stefan
authors.initials: S
authors.lastname: Krüger
authors.forename: Bert
authors.initials: B
authors.lastname: Reichert
authors.forename: Alfred
authors.initials: A
authors.lastname: Berger
authors.forename: Peter
authors.initials: P
authors.lastname: Vogt
authors.forename: Peter
authors.initials: P
authors.lastname: Mailänder
mesh_terms: D000818:Animals; D004247:DNA / Q000096:biosynthesis; D016228:Endothelial Growth Factors / Q000008:administration & dosage* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D007267:Injections; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000378:metabolism; D019194:Ischemic Preconditioning; D008222:Lymphokines / Q000008:administration & dosage* / Q000378:metabolism; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew; D012995:Solubility; D013524:Surgical Flaps; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000008:administration & dosage* / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D004247:DNA; D040281:Vascular Endothelial Growth Factor Receptor-1