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Topical VEGF enhances healing of thoracic aortic anastomosis for coarctation in a rabbit model
Recurrent stenosis after extended end-to-end anastomosis for aortic coarctation is the primary indication for further interventions in children. Tension because of the extended resection and local arterial wall hypoxia are possible pathogenetic mechanisms. We hypothesized that (1) tension interferes...
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Published in: | Circulation (New York, N.Y.) N.Y.), 2003-09, Vol.108 (10), p.150-154 |
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creator | SEIPELT, Ralf G BACKER, Carl L MAVROUDIS, Constantine STELLMACH, Veronica SEIPELT, Ingrid M CORNWELL, Mona HERNANDEZ, Jose CRAWFORD, Susan E |
description | Recurrent stenosis after extended end-to-end anastomosis for aortic coarctation is the primary indication for further interventions in children. Tension because of the extended resection and local arterial wall hypoxia are possible pathogenetic mechanisms. We hypothesized that (1) tension interferes with healing and (2) that vascular endothelial growth factor (VEGF), a hypoxia sensitive angiogenic inducer, may enhance healing of the vascular anastomosis.
In a model of coarctation repair, rabbits underwent thoracic aortic end-to-end anastomosis after transection (no-tension; n=15), resection of an aortic ring (tension; n=14) or resection and topical VEGF treatment (0.75 microg VEGF165; tension+VEGF; n=14). Gross and histologic characteristics of the aortic wall were assessed at 1 week, 1 and 2 months. In the tension only group at 1 month, the severity of vascular remodeling was increased with fibrosis and calcification compared with controls. At 2 months, this group also revealed more luminal stenosis (29% versus 19%; P |
doi_str_mv | 10.1161/01.cir.0000087388.15066.1f |
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In a model of coarctation repair, rabbits underwent thoracic aortic end-to-end anastomosis after transection (no-tension; n=15), resection of an aortic ring (tension; n=14) or resection and topical VEGF treatment (0.75 microg VEGF165; tension+VEGF; n=14). Gross and histologic characteristics of the aortic wall were assessed at 1 week, 1 and 2 months. In the tension only group at 1 month, the severity of vascular remodeling was increased with fibrosis and calcification compared with controls. At 2 months, this group also revealed more luminal stenosis (29% versus 19%; P<0.001). Exogenous VEGF resulted in significantly less fibrosis, calcification and chondroid metaplasia at 1 month (P<0.05) and luminal area was only reduced 3% at 2 months (P<0.001 versus tension group).
In a rabbit model of coarctation repair, the addition of tension on the vascular anastomosis resulted in poor healing and luminal stenosis. Topical VEGF maintained luminal integrity by decreasing fibrosis and calcification. These findings suggest that topical VEGF may be a promising new strategy to enhance healing and improve the outcome of vascular anastomoses for coarctation of the aorta.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.cir.0000087388.15066.1f</identifier><identifier>PMID: 12970224</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Administration, Topical ; Anastomosis, Surgical ; Animals ; Aorta, Thoracic - surgery ; Aortic Coarctation - drug therapy ; Aortic Coarctation - pathology ; Aortic Coarctation - surgery ; Biological and medical sciences ; Combined Modality Therapy ; Constriction, Pathologic - prevention & control ; Endothelial Growth Factors - administration & dosage ; Endothelial Growth Factors - therapeutic use ; Intercellular Signaling Peptides and Proteins - administration & dosage ; Intercellular Signaling Peptides and Proteins - therapeutic use ; Lymphokines - administration & dosage ; Lymphokines - therapeutic use ; Male ; Medical sciences ; Rabbits ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Surgery of the heart ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; Wound Healing</subject><ispartof>Circulation (New York, N.Y.), 2003-09, Vol.108 (10), p.150-154</ispartof><rights>2004 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Sep 9 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c477t-21e962cb5fe651add2f6edc7e0685f7455d2fda96237e24713ec046bdf6e1bd33</citedby><cites>FETCH-LOGICAL-c477t-21e962cb5fe651add2f6edc7e0685f7455d2fda96237e24713ec046bdf6e1bd33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15160792$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12970224$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SEIPELT, Ralf G</creatorcontrib><creatorcontrib>BACKER, Carl L</creatorcontrib><creatorcontrib>MAVROUDIS, Constantine</creatorcontrib><creatorcontrib>STELLMACH, Veronica</creatorcontrib><creatorcontrib>SEIPELT, Ingrid M</creatorcontrib><creatorcontrib>CORNWELL, Mona</creatorcontrib><creatorcontrib>HERNANDEZ, Jose</creatorcontrib><creatorcontrib>CRAWFORD, Susan E</creatorcontrib><title>Topical VEGF enhances healing of thoracic aortic anastomosis for coarctation in a rabbit model</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Recurrent stenosis after extended end-to-end anastomosis for aortic coarctation is the primary indication for further interventions in children. Tension because of the extended resection and local arterial wall hypoxia are possible pathogenetic mechanisms. We hypothesized that (1) tension interferes with healing and (2) that vascular endothelial growth factor (VEGF), a hypoxia sensitive angiogenic inducer, may enhance healing of the vascular anastomosis.
In a model of coarctation repair, rabbits underwent thoracic aortic end-to-end anastomosis after transection (no-tension; n=15), resection of an aortic ring (tension; n=14) or resection and topical VEGF treatment (0.75 microg VEGF165; tension+VEGF; n=14). Gross and histologic characteristics of the aortic wall were assessed at 1 week, 1 and 2 months. In the tension only group at 1 month, the severity of vascular remodeling was increased with fibrosis and calcification compared with controls. At 2 months, this group also revealed more luminal stenosis (29% versus 19%; P<0.001). Exogenous VEGF resulted in significantly less fibrosis, calcification and chondroid metaplasia at 1 month (P<0.05) and luminal area was only reduced 3% at 2 months (P<0.001 versus tension group).
In a rabbit model of coarctation repair, the addition of tension on the vascular anastomosis resulted in poor healing and luminal stenosis. Topical VEGF maintained luminal integrity by decreasing fibrosis and calcification. These findings suggest that topical VEGF may be a promising new strategy to enhance healing and improve the outcome of vascular anastomoses for coarctation of the aorta.</description><subject>Administration, Topical</subject><subject>Anastomosis, Surgical</subject><subject>Animals</subject><subject>Aorta, Thoracic - surgery</subject><subject>Aortic Coarctation - drug therapy</subject><subject>Aortic Coarctation - pathology</subject><subject>Aortic Coarctation - surgery</subject><subject>Biological and medical sciences</subject><subject>Combined Modality Therapy</subject><subject>Constriction, Pathologic - prevention & control</subject><subject>Endothelial Growth Factors - administration & dosage</subject><subject>Endothelial Growth Factors - therapeutic use</subject><subject>Intercellular Signaling Peptides and Proteins - administration & dosage</subject><subject>Intercellular Signaling Peptides and Proteins - therapeutic use</subject><subject>Lymphokines - administration & dosage</subject><subject>Lymphokines - therapeutic use</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Rabbits</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgery of the heart</subject><subject>Vascular Endothelial Growth Factor A</subject><subject>Vascular Endothelial Growth Factors</subject><subject>Wound Healing</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNpdkUtPAyEUhYnRaH38BUOa6G5GLgzQcWdMfSRN3KhLCcOApZkZKkwX_nupNmkimxO4373cnIPQFEgJIOCGQGl8LMn2zCSbzUrgRIgS3AGaAKdVUXFWH6JJrteFZJSeoNOUVvkqmOTH6ARoLQml1QR9vIa1N7rD7_PHB2yHpR6MTXhpdeeHTxwcHpchauMN1iGOWxl0GkMfkk_YhYhN0NGMevRhwH7AGkfdNH7EfWhtd46OnO6SvdjpGXp7mL_ePxWLl8fn-7tFYSopx4KCrQU1DXdWcNBtS52wrZGWiBl3suI8v7Q6M0xaWklg1pBKNG3GoGkZO0PXf3PXMXxtbBpV75OxXacHGzZJSSZYzanI4PQfuAqbOOTdFAUqqQBRZ-j2DzIxpBStU-voex2_FRC1jUARUDkCtY9A_UagwOXmy90Pm6a37b5153kGrnaATtl5F7PlPu05DoLImrIfTFKQNw</recordid><startdate>20030909</startdate><enddate>20030909</enddate><creator>SEIPELT, Ralf G</creator><creator>BACKER, Carl L</creator><creator>MAVROUDIS, Constantine</creator><creator>STELLMACH, Veronica</creator><creator>SEIPELT, Ingrid M</creator><creator>CORNWELL, Mona</creator><creator>HERNANDEZ, Jose</creator><creator>CRAWFORD, Susan E</creator><general>Lippincott Williams & Wilkins</general><general>American Heart Association, Inc</general><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>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope></search><sort><creationdate>20030909</creationdate><title>Topical VEGF enhances healing of thoracic aortic anastomosis for coarctation in a rabbit model</title><author>SEIPELT, Ralf G ; BACKER, Carl L ; MAVROUDIS, Constantine ; STELLMACH, Veronica ; SEIPELT, Ingrid M ; CORNWELL, Mona ; HERNANDEZ, Jose ; CRAWFORD, Susan E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c477t-21e962cb5fe651add2f6edc7e0685f7455d2fda96237e24713ec046bdf6e1bd33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Administration, Topical</topic><topic>Anastomosis, Surgical</topic><topic>Animals</topic><topic>Aorta, Thoracic - surgery</topic><topic>Aortic Coarctation - drug therapy</topic><topic>Aortic Coarctation - pathology</topic><topic>Aortic Coarctation - surgery</topic><topic>Biological and medical sciences</topic><topic>Combined Modality Therapy</topic><topic>Constriction, Pathologic - prevention & control</topic><topic>Endothelial Growth Factors - administration & dosage</topic><topic>Endothelial Growth Factors - therapeutic use</topic><topic>Intercellular Signaling Peptides and Proteins - administration & dosage</topic><topic>Intercellular Signaling Peptides and Proteins - therapeutic use</topic><topic>Lymphokines - administration & dosage</topic><topic>Lymphokines - therapeutic use</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Rabbits</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Surgery of the heart</topic><topic>Vascular Endothelial Growth Factor A</topic><topic>Vascular Endothelial Growth Factors</topic><topic>Wound Healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SEIPELT, Ralf G</creatorcontrib><creatorcontrib>BACKER, Carl L</creatorcontrib><creatorcontrib>MAVROUDIS, Constantine</creatorcontrib><creatorcontrib>STELLMACH, Veronica</creatorcontrib><creatorcontrib>SEIPELT, Ingrid M</creatorcontrib><creatorcontrib>CORNWELL, Mona</creatorcontrib><creatorcontrib>HERNANDEZ, Jose</creatorcontrib><creatorcontrib>CRAWFORD, Susan E</creatorcontrib><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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SEIPELT, Ralf G</au><au>BACKER, Carl L</au><au>MAVROUDIS, Constantine</au><au>STELLMACH, Veronica</au><au>SEIPELT, Ingrid M</au><au>CORNWELL, Mona</au><au>HERNANDEZ, Jose</au><au>CRAWFORD, Susan E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Topical VEGF enhances healing of thoracic aortic anastomosis for coarctation in a rabbit model</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2003-09-09</date><risdate>2003</risdate><volume>108</volume><issue>10</issue><spage>150</spage><epage>154</epage><pages>150-154</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Recurrent stenosis after extended end-to-end anastomosis for aortic coarctation is the primary indication for further interventions in children. Tension because of the extended resection and local arterial wall hypoxia are possible pathogenetic mechanisms. We hypothesized that (1) tension interferes with healing and (2) that vascular endothelial growth factor (VEGF), a hypoxia sensitive angiogenic inducer, may enhance healing of the vascular anastomosis.
In a model of coarctation repair, rabbits underwent thoracic aortic end-to-end anastomosis after transection (no-tension; n=15), resection of an aortic ring (tension; n=14) or resection and topical VEGF treatment (0.75 microg VEGF165; tension+VEGF; n=14). Gross and histologic characteristics of the aortic wall were assessed at 1 week, 1 and 2 months. In the tension only group at 1 month, the severity of vascular remodeling was increased with fibrosis and calcification compared with controls. At 2 months, this group also revealed more luminal stenosis (29% versus 19%; P<0.001). Exogenous VEGF resulted in significantly less fibrosis, calcification and chondroid metaplasia at 1 month (P<0.05) and luminal area was only reduced 3% at 2 months (P<0.001 versus tension group).
In a rabbit model of coarctation repair, the addition of tension on the vascular anastomosis resulted in poor healing and luminal stenosis. Topical VEGF maintained luminal integrity by decreasing fibrosis and calcification. These findings suggest that topical VEGF may be a promising new strategy to enhance healing and improve the outcome of vascular anastomoses for coarctation of the aorta.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>12970224</pmid><doi>10.1161/01.cir.0000087388.15066.1f</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Administration, Topical Anastomosis, Surgical Animals Aorta, Thoracic - surgery Aortic Coarctation - drug therapy Aortic Coarctation - pathology Aortic Coarctation - surgery Biological and medical sciences Combined Modality Therapy Constriction, Pathologic - prevention & control Endothelial Growth Factors - administration & dosage Endothelial Growth Factors - therapeutic use Intercellular Signaling Peptides and Proteins - administration & dosage Intercellular Signaling Peptides and Proteins - therapeutic use Lymphokines - administration & dosage Lymphokines - therapeutic use Male Medical sciences Rabbits Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the heart Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Wound Healing |
title | Topical VEGF enhances healing of thoracic aortic anastomosis for coarctation in a rabbit model |
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