Perivenous application of cyanoacrylate tissue sealants reduces intimal and medial thickening of the vein graft and inflammatory responses in a rabbit model of carotid artery bypass grafting

OBJECTIVES Effective therapies to prevent vein graft failure after coronary artery bypass grafting (CABG) are still lacking. α-Cyanoacrylate (α-CA, 99% n-octyl-α-cyanoacrylate + n-butyl-α-cyanoacrylate) has been increasingly used as a tissue sealant for wound closure because of its bacteriostatic, b...

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Veröffentlicht in:European journal of cardio-thoracic surgery 2016-02, Vol.49 (2), p.675-681
Hauptverfasser: Dai, Longsheng, Gao, Mingxin, Gu, Chengxiong, Zhang, Fan, Yu, Yang
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creator Dai, Longsheng
Gao, Mingxin
Gu, Chengxiong
Zhang, Fan
Yu, Yang
description OBJECTIVES Effective therapies to prevent vein graft failure after coronary artery bypass grafting (CABG) are still lacking. α-Cyanoacrylate (α-CA, 99% n-octyl-α-cyanoacrylate + n-butyl-α-cyanoacrylate) has been increasingly used as a tissue sealant for wound closure because of its bacteriostatic, biodegradable and haemostatic properties. As a strong tissue adhesive, α-CA might prevent an arterial circulation-induced mechanical stretch on vein graft to attenuate intimal hyperplasia. Here, we investigated the effects of perivenous application of α-CA on the vein graft in a rabbit model of carotid artery bypass grafting. METHODS Healthy New Zealand white rabbits were randomized into no graft, graft or graft + α-CA group (n = 10 per group). Rabbit carotid artery was bypassed with the jugular vein. α-CA sealants were sprayed on the entire jugular graft including both anastomotic sites after completion of anastomoses. Blood flow parameters and histological characteristics of the vein grafts including vessel wall thickness, number of medial elastic lamina and proliferation index were evaluated 4 weeks after the surgery. The mRNA or protein levels of proinflammatory factors, chemokine (C–C motif) ligand-2 (CCL-2) and tumour necrosis factor-α (TNF-α) were measured 4 weeks after the operation by quantitative reverse transcription polymerase chain reaction or enzyme-linked immunosorbent assay. RESULTS Compared with the untreated vein grafts at Week 4 after the operation, the α-CA spray significantly improved graft flow (39.4 ± 1.5 vs 27.8 ± 2.9 ml/min, P < 0.01), attenuated intimal and medial thickening (116.3 ± 1.0 vs 159.7 ± 0.9 μm, P < 0.01), reduced anti-proliferating cell nuclear antigen proliferation index of the vein grafts (15.0 ± 0.4 vs 23.6 ± 0.4%, P < 0.01), decreased the mRNA levels of plasminogen activator inhibitor-1 and CCL-2, and reduced the serum levels of TNF-α (92.9 ± 1.7 vs 102.7 ± 1.8 pg/ml, P < 0.01). CONCLUSION Perivenous application of α-CA sealants exerts short-term beneficial effects on the vein graft and reduces inflammatory responses in a rabbit model of carotid artery bypass grafting. Long-term effects of α-CA on vein graft remodelling and the clinical significance of α-CA in CABG remain to be determined in future studies.
doi_str_mv 10.1093/ejcts/ezv111
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As a strong tissue adhesive, α-CA might prevent an arterial circulation-induced mechanical stretch on vein graft to attenuate intimal hyperplasia. Here, we investigated the effects of perivenous application of α-CA on the vein graft in a rabbit model of carotid artery bypass grafting. METHODS Healthy New Zealand white rabbits were randomized into no graft, graft or graft + α-CA group (n = 10 per group). Rabbit carotid artery was bypassed with the jugular vein. α-CA sealants were sprayed on the entire jugular graft including both anastomotic sites after completion of anastomoses. Blood flow parameters and histological characteristics of the vein grafts including vessel wall thickness, number of medial elastic lamina and proliferation index were evaluated 4 weeks after the surgery. The mRNA or protein levels of proinflammatory factors, chemokine (C–C motif) ligand-2 (CCL-2) and tumour necrosis factor-α (TNF-α) were measured 4 weeks after the operation by quantitative reverse transcription polymerase chain reaction or enzyme-linked immunosorbent assay. RESULTS Compared with the untreated vein grafts at Week 4 after the operation, the α-CA spray significantly improved graft flow (39.4 ± 1.5 vs 27.8 ± 2.9 ml/min, P &lt; 0.01), attenuated intimal and medial thickening (116.3 ± 1.0 vs 159.7 ± 0.9 μm, P &lt; 0.01), reduced anti-proliferating cell nuclear antigen proliferation index of the vein grafts (15.0 ± 0.4 vs 23.6 ± 0.4%, P &lt; 0.01), decreased the mRNA levels of plasminogen activator inhibitor-1 and CCL-2, and reduced the serum levels of TNF-α (92.9 ± 1.7 vs 102.7 ± 1.8 pg/ml, P &lt; 0.01). CONCLUSION Perivenous application of α-CA sealants exerts short-term beneficial effects on the vein graft and reduces inflammatory responses in a rabbit model of carotid artery bypass grafting. Long-term effects of α-CA on vein graft remodelling and the clinical significance of α-CA in CABG remain to be determined in future studies.</description><identifier>ISSN: 1010-7940</identifier><identifier>EISSN: 1873-734X</identifier><identifier>DOI: 10.1093/ejcts/ezv111</identifier><identifier>PMID: 25838460</identifier><language>eng</language><publisher>Germany: Oxford University Press</publisher><subject>Animals ; Carotid Arteries - surgery ; Cyanoacrylates - pharmacology ; Cyanoacrylates - therapeutic use ; Female ; Graft Occlusion, Vascular - pathology ; Graft Occlusion, Vascular - prevention &amp; control ; Jugular Veins - drug effects ; Jugular Veins - pathology ; Jugular Veins - transplantation ; Male ; Rabbits ; Random Allocation ; Tissue Adhesives - pharmacology ; Tissue Adhesives - therapeutic use ; Treatment Outcome ; Tunica Intima - drug effects ; Tunica Intima - pathology ; Tunica Media - drug effects ; Tunica Media - pathology ; Vascular Grafting - methods</subject><ispartof>European journal of cardio-thoracic surgery, 2016-02, Vol.49 (2), p.675-681</ispartof><rights>The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved 2015</rights><rights>The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c361t-b2ba8639b7a737579095f32114d1115f1eafeaa94e5fa5f32567bd8ba77af8483</citedby><cites>FETCH-LOGICAL-c361t-b2ba8639b7a737579095f32114d1115f1eafeaa94e5fa5f32567bd8ba77af8483</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25838460$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dai, Longsheng</creatorcontrib><creatorcontrib>Gao, Mingxin</creatorcontrib><creatorcontrib>Gu, Chengxiong</creatorcontrib><creatorcontrib>Zhang, Fan</creatorcontrib><creatorcontrib>Yu, Yang</creatorcontrib><title>Perivenous application of cyanoacrylate tissue sealants reduces intimal and medial thickening of the vein graft and inflammatory responses in a rabbit model of carotid artery bypass grafting</title><title>European journal of cardio-thoracic surgery</title><addtitle>Eur J Cardiothorac Surg</addtitle><description>OBJECTIVES Effective therapies to prevent vein graft failure after coronary artery bypass grafting (CABG) are still lacking. α-Cyanoacrylate (α-CA, 99% n-octyl-α-cyanoacrylate + n-butyl-α-cyanoacrylate) has been increasingly used as a tissue sealant for wound closure because of its bacteriostatic, biodegradable and haemostatic properties. As a strong tissue adhesive, α-CA might prevent an arterial circulation-induced mechanical stretch on vein graft to attenuate intimal hyperplasia. Here, we investigated the effects of perivenous application of α-CA on the vein graft in a rabbit model of carotid artery bypass grafting. METHODS Healthy New Zealand white rabbits were randomized into no graft, graft or graft + α-CA group (n = 10 per group). Rabbit carotid artery was bypassed with the jugular vein. α-CA sealants were sprayed on the entire jugular graft including both anastomotic sites after completion of anastomoses. Blood flow parameters and histological characteristics of the vein grafts including vessel wall thickness, number of medial elastic lamina and proliferation index were evaluated 4 weeks after the surgery. The mRNA or protein levels of proinflammatory factors, chemokine (C–C motif) ligand-2 (CCL-2) and tumour necrosis factor-α (TNF-α) were measured 4 weeks after the operation by quantitative reverse transcription polymerase chain reaction or enzyme-linked immunosorbent assay. RESULTS Compared with the untreated vein grafts at Week 4 after the operation, the α-CA spray significantly improved graft flow (39.4 ± 1.5 vs 27.8 ± 2.9 ml/min, P &lt; 0.01), attenuated intimal and medial thickening (116.3 ± 1.0 vs 159.7 ± 0.9 μm, P &lt; 0.01), reduced anti-proliferating cell nuclear antigen proliferation index of the vein grafts (15.0 ± 0.4 vs 23.6 ± 0.4%, P &lt; 0.01), decreased the mRNA levels of plasminogen activator inhibitor-1 and CCL-2, and reduced the serum levels of TNF-α (92.9 ± 1.7 vs 102.7 ± 1.8 pg/ml, P &lt; 0.01). CONCLUSION Perivenous application of α-CA sealants exerts short-term beneficial effects on the vein graft and reduces inflammatory responses in a rabbit model of carotid artery bypass grafting. Long-term effects of α-CA on vein graft remodelling and the clinical significance of α-CA in CABG remain to be determined in future studies.</description><subject>Animals</subject><subject>Carotid Arteries - surgery</subject><subject>Cyanoacrylates - pharmacology</subject><subject>Cyanoacrylates - therapeutic use</subject><subject>Female</subject><subject>Graft Occlusion, Vascular - pathology</subject><subject>Graft Occlusion, Vascular - prevention &amp; control</subject><subject>Jugular Veins - drug effects</subject><subject>Jugular Veins - pathology</subject><subject>Jugular Veins - transplantation</subject><subject>Male</subject><subject>Rabbits</subject><subject>Random Allocation</subject><subject>Tissue Adhesives - pharmacology</subject><subject>Tissue Adhesives - therapeutic use</subject><subject>Treatment Outcome</subject><subject>Tunica Intima - drug effects</subject><subject>Tunica Intima - pathology</subject><subject>Tunica Media - drug effects</subject><subject>Tunica Media - pathology</subject><subject>Vascular Grafting - methods</subject><issn>1010-7940</issn><issn>1873-734X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1TAQRi0EoqWwY428gwWhdpzEyRJV_EmVYAESu2icjFuXxA4e50rh4Xg2fG8KS1YeyUdnRt_H2HMp3kjRqUu8GxJd4q-DlPIBO5etVoVW1feHeRZSFLqrxBl7QnQnhGhUqR-zs7JuVVs14pz9_oLRHdCHlTgsy-QGSC54HiwfNvABhrhNkJAnR7QiJ4QJfCIecVwHJO58cjNMHPzIZxxdHtOtG36gd_7mqEm3yA_oPL-JYNOJc95OMM-QQtyyiJbg6aTiwCMY4xKfw4jT6QqIIbmRQ0yYabMtQLS78oKn7JGFifDZ_XvBvr1_9_XqY3H9-cOnq7fXxaAamQpTGmgb1RkNWulad6KrrSqlrMacWm0lgkWArsLawvGnbrQZWwNag22rVl2wV7t3ieHnipT62dGAU84Cc3S91I1odVXLMqOvd3SIgSii7ZeYE4pbL0V_bKw_NdbvjWX8xb15NTm_f_DfijLwcgfCuvxf9QfI7qbQ</recordid><startdate>201602</startdate><enddate>201602</enddate><creator>Dai, Longsheng</creator><creator>Gao, Mingxin</creator><creator>Gu, Chengxiong</creator><creator>Zhang, Fan</creator><creator>Yu, Yang</creator><general>Oxford University Press</general><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>201602</creationdate><title>Perivenous application of cyanoacrylate tissue sealants reduces intimal and medial thickening of the vein graft and inflammatory responses in a rabbit model of carotid artery bypass grafting</title><author>Dai, Longsheng ; Gao, Mingxin ; Gu, Chengxiong ; Zhang, Fan ; Yu, Yang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c361t-b2ba8639b7a737579095f32114d1115f1eafeaa94e5fa5f32567bd8ba77af8483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Carotid Arteries - surgery</topic><topic>Cyanoacrylates - pharmacology</topic><topic>Cyanoacrylates - therapeutic use</topic><topic>Female</topic><topic>Graft Occlusion, Vascular - pathology</topic><topic>Graft Occlusion, Vascular - prevention &amp; control</topic><topic>Jugular Veins - drug effects</topic><topic>Jugular Veins - pathology</topic><topic>Jugular Veins - transplantation</topic><topic>Male</topic><topic>Rabbits</topic><topic>Random Allocation</topic><topic>Tissue Adhesives - pharmacology</topic><topic>Tissue Adhesives - therapeutic use</topic><topic>Treatment Outcome</topic><topic>Tunica Intima - drug effects</topic><topic>Tunica Intima - pathology</topic><topic>Tunica Media - drug effects</topic><topic>Tunica Media - pathology</topic><topic>Vascular Grafting - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dai, Longsheng</creatorcontrib><creatorcontrib>Gao, Mingxin</creatorcontrib><creatorcontrib>Gu, Chengxiong</creatorcontrib><creatorcontrib>Zhang, Fan</creatorcontrib><creatorcontrib>Yu, Yang</creatorcontrib><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>European journal of cardio-thoracic surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dai, Longsheng</au><au>Gao, Mingxin</au><au>Gu, Chengxiong</au><au>Zhang, Fan</au><au>Yu, Yang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Perivenous application of cyanoacrylate tissue sealants reduces intimal and medial thickening of the vein graft and inflammatory responses in a rabbit model of carotid artery bypass grafting</atitle><jtitle>European journal of cardio-thoracic surgery</jtitle><addtitle>Eur J Cardiothorac Surg</addtitle><date>2016-02</date><risdate>2016</risdate><volume>49</volume><issue>2</issue><spage>675</spage><epage>681</epage><pages>675-681</pages><issn>1010-7940</issn><eissn>1873-734X</eissn><abstract>OBJECTIVES Effective therapies to prevent vein graft failure after coronary artery bypass grafting (CABG) are still lacking. α-Cyanoacrylate (α-CA, 99% n-octyl-α-cyanoacrylate + n-butyl-α-cyanoacrylate) has been increasingly used as a tissue sealant for wound closure because of its bacteriostatic, biodegradable and haemostatic properties. As a strong tissue adhesive, α-CA might prevent an arterial circulation-induced mechanical stretch on vein graft to attenuate intimal hyperplasia. Here, we investigated the effects of perivenous application of α-CA on the vein graft in a rabbit model of carotid artery bypass grafting. METHODS Healthy New Zealand white rabbits were randomized into no graft, graft or graft + α-CA group (n = 10 per group). Rabbit carotid artery was bypassed with the jugular vein. α-CA sealants were sprayed on the entire jugular graft including both anastomotic sites after completion of anastomoses. Blood flow parameters and histological characteristics of the vein grafts including vessel wall thickness, number of medial elastic lamina and proliferation index were evaluated 4 weeks after the surgery. The mRNA or protein levels of proinflammatory factors, chemokine (C–C motif) ligand-2 (CCL-2) and tumour necrosis factor-α (TNF-α) were measured 4 weeks after the operation by quantitative reverse transcription polymerase chain reaction or enzyme-linked immunosorbent assay. RESULTS Compared with the untreated vein grafts at Week 4 after the operation, the α-CA spray significantly improved graft flow (39.4 ± 1.5 vs 27.8 ± 2.9 ml/min, P &lt; 0.01), attenuated intimal and medial thickening (116.3 ± 1.0 vs 159.7 ± 0.9 μm, P &lt; 0.01), reduced anti-proliferating cell nuclear antigen proliferation index of the vein grafts (15.0 ± 0.4 vs 23.6 ± 0.4%, P &lt; 0.01), decreased the mRNA levels of plasminogen activator inhibitor-1 and CCL-2, and reduced the serum levels of TNF-α (92.9 ± 1.7 vs 102.7 ± 1.8 pg/ml, P &lt; 0.01). CONCLUSION Perivenous application of α-CA sealants exerts short-term beneficial effects on the vein graft and reduces inflammatory responses in a rabbit model of carotid artery bypass grafting. Long-term effects of α-CA on vein graft remodelling and the clinical significance of α-CA in CABG remain to be determined in future studies.</abstract><cop>Germany</cop><pub>Oxford University Press</pub><pmid>25838460</pmid><doi>10.1093/ejcts/ezv111</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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source Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
subjects Animals
Carotid Arteries - surgery
Cyanoacrylates - pharmacology
Cyanoacrylates - therapeutic use
Female
Graft Occlusion, Vascular - pathology
Graft Occlusion, Vascular - prevention & control
Jugular Veins - drug effects
Jugular Veins - pathology
Jugular Veins - transplantation
Male
Rabbits
Random Allocation
Tissue Adhesives - pharmacology
Tissue Adhesives - therapeutic use
Treatment Outcome
Tunica Intima - drug effects
Tunica Intima - pathology
Tunica Media - drug effects
Tunica Media - pathology
Vascular Grafting - methods
title Perivenous application of cyanoacrylate tissue sealants reduces intimal and medial thickening of the vein graft and inflammatory responses in a rabbit model of carotid artery bypass grafting
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