Local rh-VEGF administration enhances skin flap survival more than other types of rh-VEGF administration: a clinical, morphological and immunohistochemical study

:  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 adm...

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Veröffentlicht in:Experimental dermatology 2004-11, Vol.13 (11), p.682-690
Hauptverfasser: Alessandro, Scalise, Maria, Giovanna Tucci, Guendalina, Lucarini, Federica, Giantomassi, Fiorenza, Orlando, Marina, Pierangeli, Armanda, Pugnaloni, Aldo, Bertani, Giuseppe, Ricotti, Graziella, Biagini
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container_end_page 690
container_issue 11
container_start_page 682
container_title Experimental dermatology
container_volume 13
creator Alessandro, Scalise
Maria, Giovanna Tucci
Guendalina, Lucarini
Federica, Giantomassi
Fiorenza, Orlando
Marina, Pierangeli
Armanda, Pugnaloni
Aldo, Bertani
Giuseppe, Ricotti
Graziella, Biagini
description :  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.
doi_str_mv 10.1111/j.0906-6705.2004.00220.x
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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. 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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. 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Maria, Giovanna Tucci ; Guendalina, Lucarini ; Federica, Giantomassi ; Fiorenza, Orlando ; Marina, Pierangeli ; Armanda, Pugnaloni ; Aldo, Bertani ; Giuseppe, Ricotti ; Graziella, Biagini</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4320-207e5acd59b6f867d8a36fdcf717315035151628c51947e497839be0ed1e35c13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>angiogenesis</topic><topic>Animals</topic><topic>Antigens, CD34 - biosynthesis</topic><topic>Biological and medical sciences</topic><topic>Dermatology</topic><topic>Endothelial Cells - metabolism</topic><topic>Factor VIII - metabolism</topic><topic>Hypoxia</topic><topic>Immunohistochemistry</topic><topic>Inhibitor of Apoptosis Proteins</topic><topic>ischaemic necrosis</topic><topic>Keratinocytes - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microtubule-Associated Proteins - biosynthesis</topic><topic>Necrosis</topic><topic>Neoplasm Proteins</topic><topic>Neovascularization, Physiologic</topic><topic>Perfusion</topic><topic>Protein Isoforms</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Recombinant Proteins - therapeutic use</topic><topic>rh-VEGF</topic><topic>Skin - drug effects</topic><topic>Skin - pathology</topic><topic>skin surgery</topic><topic>Skin Transplantation - methods</topic><topic>Surgical Flaps</topic><topic>survivin</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><topic>Vascular Endothelial Growth Factor A - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alessandro, Scalise</creatorcontrib><creatorcontrib>Maria, Giovanna Tucci</creatorcontrib><creatorcontrib>Guendalina, Lucarini</creatorcontrib><creatorcontrib>Federica, Giantomassi</creatorcontrib><creatorcontrib>Fiorenza, Orlando</creatorcontrib><creatorcontrib>Marina, Pierangeli</creatorcontrib><creatorcontrib>Armanda, Pugnaloni</creatorcontrib><creatorcontrib>Aldo, Bertani</creatorcontrib><creatorcontrib>Giuseppe, Ricotti</creatorcontrib><creatorcontrib>Graziella, Biagini</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental dermatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alessandro, Scalise</au><au>Maria, Giovanna Tucci</au><au>Guendalina, Lucarini</au><au>Federica, Giantomassi</au><au>Fiorenza, Orlando</au><au>Marina, Pierangeli</au><au>Armanda, Pugnaloni</au><au>Aldo, Bertani</au><au>Giuseppe, Ricotti</au><au>Graziella, Biagini</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Local rh-VEGF administration enhances skin flap survival more than other types of rh-VEGF administration: a clinical, morphological and immunohistochemical study</atitle><jtitle>Experimental dermatology</jtitle><addtitle>Exp Dermatol</addtitle><date>2004-11</date><risdate>2004</risdate><volume>13</volume><issue>11</issue><spage>682</spage><epage>690</epage><pages>682-690</pages><issn>0906-6705</issn><eissn>1600-0625</eissn><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.</abstract><cop>Oxford, UK; Malden, USA</cop><pub>Munksgaard International Publishers</pub><pmid>15500640</pmid><doi>10.1111/j.0906-6705.2004.00220.x</doi><tpages>9</tpages></addata></record>
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ispartof Experimental dermatology, 2004-11, Vol.13 (11), p.682-690
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source MEDLINE; Wiley Online Library Journals Frontfile Complete
subjects angiogenesis
Animals
Antigens, CD34 - biosynthesis
Biological and medical sciences
Dermatology
Endothelial Cells - metabolism
Factor VIII - metabolism
Hypoxia
Immunohistochemistry
Inhibitor of Apoptosis Proteins
ischaemic necrosis
Keratinocytes - metabolism
Male
Medical sciences
Microtubule-Associated Proteins - biosynthesis
Necrosis
Neoplasm Proteins
Neovascularization, Physiologic
Perfusion
Protein Isoforms
Rats
Rats, Sprague-Dawley
Recombinant Proteins - therapeutic use
rh-VEGF
Skin - drug effects
Skin - pathology
skin surgery
Skin Transplantation - methods
Surgical Flaps
survivin
Vascular Endothelial Growth Factor A - metabolism
Vascular Endothelial Growth Factor A - pharmacology
title Local rh-VEGF administration enhances skin flap survival more than other types of rh-VEGF administration: a clinical, morphological and immunohistochemical study
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