title: Local rh-VEGF administration enhances skin flap survival more than other types of rh-VEGF administration: a clinical, morphological and immunohistochemical study.
abstract: The aim of the present study was to evaluate experimentally whether administration of recombinant (rh) vascular endothelial growth factor (VEGF) can protect skin flaps from necrosis and to study the optimum mode of rh-VEGF administration. We used rats to study the effects of local or systemic administration of rh-VEGF on skin flap during surgery; we also tested preoperative systemic administration of rh-VEGF to assess whether it may prepare the tissue to respond to the hypoxic injury better than previously tested methods. The animals were 30 male Sprague-Dawley rats. Group I rats received multiple systemic injections of rh-VEGF in the tail artery prior to flap dissection. Group II rats were injected with rh-VEGF in the clamped left epigastric artery during flap dissection; in this group, the left flaps thus received rh-VEGF locally (via incubation for 10 min during hypoxia) and the right flaps systemically, after blood flow restoration. Group III received saline solution instead of VEGF in the same way as group II. Skin samples from the distal portion of the flaps were collected on day 7 for morphological and immunohistochemical analysis. The flaps exhibiting the least necrosis were those treated with local rh-VEGF, followed by those treated with systemic rh-VEGF. The flaps that received rh-VEGF locally showed a strong VEGF expression on keratinocytes and endothelial cells, the greatest amount of mature and newly formed vessels and strong survivin expression in endothelial cells. Local rh-VEGF administration should thus be considered as an effective therapeutic option to enhance the survival of a tissue at risk for perfusion.
authors.affiliation: Clinica di Chirurgia Plastica Ricostruttiva, Università Politecnica delle Marche, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Scalise
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Tucci
authors.forename: Guendalina
authors.initials: G
authors.lastname: Lucarini
authors.forename: Federica
authors.initials: F
authors.lastname: Giantomassi
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Orlando
authors.forename: Marina
authors.initials: M
authors.lastname: Pierangeli
authors.forename: Armanda
authors.initials: A
authors.lastname: Pugnaloni
authors.forename: Aldo
authors.initials: A
authors.lastname: Bertani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ricotti
authors.forename: Graziella
authors.initials: G
authors.lastname: Biagini
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D042783:Endothelial Cells / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D000860:Hypoxia; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D009336:Necrosis; D009363:Neoplasm Proteins; D018919:Neovascularization, Physiologic; D010477:Perfusion; D020033:Protein Isoforms; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects* / Q000473:pathology*; D016038:Skin Transplantation / Q000379:methods; D013524:Surgical Flaps; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D018952:Antigens, CD34; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D011994:Recombinant Proteins; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A; D005169:Factor VIII