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 |
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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. Local rh‐VEGF administration should thus be considered as an effective therapeutic option to enhance the survival of a tissue at risk for perfusion.</description><identifier>ISSN: 0906-6705</identifier><identifier>EISSN: 1600-0625</identifier><identifier>DOI: 10.1111/j.0906-6705.2004.00220.x</identifier><identifier>PMID: 15500640</identifier><language>eng</language><publisher>Oxford, UK; Malden, USA: Munksgaard International Publishers</publisher><subject>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</subject><ispartof>Experimental dermatology, 2004-11, Vol.13 (11), p.682-690</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4320-207e5acd59b6f867d8a36fdcf717315035151628c51947e497839be0ed1e35c13</citedby><cites>FETCH-LOGICAL-c4320-207e5acd59b6f867d8a36fdcf717315035151628c51947e497839be0ed1e35c13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.0906-6705.2004.00220.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.0906-6705.2004.00220.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1413,27906,27907,45556,45557</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16209618$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15500640$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><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><title>Local rh-VEGF administration enhances skin flap survival more than other types of rh-VEGF administration: a clinical, morphological and immunohistochemical study</title><title>Experimental dermatology</title><addtitle>Exp Dermatol</addtitle><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.</description><subject>angiogenesis</subject><subject>Animals</subject><subject>Antigens, CD34 - biosynthesis</subject><subject>Biological and medical sciences</subject><subject>Dermatology</subject><subject>Endothelial Cells - metabolism</subject><subject>Factor VIII - metabolism</subject><subject>Hypoxia</subject><subject>Immunohistochemistry</subject><subject>Inhibitor of Apoptosis Proteins</subject><subject>ischaemic necrosis</subject><subject>Keratinocytes - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microtubule-Associated Proteins - biosynthesis</subject><subject>Necrosis</subject><subject>Neoplasm Proteins</subject><subject>Neovascularization, Physiologic</subject><subject>Perfusion</subject><subject>Protein Isoforms</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Recombinant Proteins - therapeutic use</subject><subject>rh-VEGF</subject><subject>Skin - drug effects</subject><subject>Skin - pathology</subject><subject>skin surgery</subject><subject>Skin Transplantation - methods</subject><subject>Surgical Flaps</subject><subject>survivin</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>Vascular Endothelial Growth Factor A - pharmacology</subject><issn>0906-6705</issn><issn>1600-0625</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkstu1DAUhiMEokPhFZA3sCLh2ImdBLGBMp0ijYAFl-4sj-MQT5M42Ek78zh9U046o3aFhDe-5Pt8-U-iiFBIKLa32wRKELHIgScMIEsAGINk9yhaUAEQg2D8cbS4h06iZyFsAWie5vxpdEI5BxAZLKLbtdOqJb6Jfy5X50RVne1tGL0areuJ6RvVaxNIuLI9qVs1kDD5a3uNSue8ISN-J25sjCfjfkDQ1f_Y6x1RRLe4gMe9meWhca37PU-J6itiu27qXYO8043p7tbDOFX759GTWrXBvDj2p9GP8-X3s4t4_XX1-ezDOtZZyiBmkBuudMXLjagLkVeFSkVd6TrHR1MOKaecClZoTsssN1mZF2m5MWAqalKuaXoavT7sO3j3ZzJhlJ0N2rSt6o2bgsQcMT8mECwOoPYuBG9qOXjbKb-XFORcHrmVc_KzweVcHnlXHrlD9eXxjGnTmepBPNYDgVdHQAVMoPYYvw0PnGBQClog9_7A3djW7P_7AnJ5-QkHqMcHHeM2u3td-St08BeRv76sJHy7zFNWXsiP6V-1srvN</recordid><startdate>200411</startdate><enddate>200411</enddate><creator>Alessandro, Scalise</creator><creator>Maria, Giovanna Tucci</creator><creator>Guendalina, Lucarini</creator><creator>Federica, Giantomassi</creator><creator>Fiorenza, Orlando</creator><creator>Marina, Pierangeli</creator><creator>Armanda, Pugnaloni</creator><creator>Aldo, Bertani</creator><creator>Giuseppe, Ricotti</creator><creator>Graziella, Biagini</creator><general>Munksgaard International Publishers</general><general>Blackwell</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200411</creationdate><title>Local rh-VEGF administration enhances skin flap survival more than other types of rh-VEGF administration: a clinical, morphological and immunohistochemical study</title><author>Alessandro, Scalise ; 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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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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