Intravenous omega-3, a technique to prevent an excessive innate immune response to cardiac surgery in a rodent gut ischemia model

Objectives Neutrophil infiltration of tissues as part of the inflammatory response to cardiac surgery is one of the major mediators of postoperative multiple-organ dysfunction. Omega-3 fatty acids markedly attenuate endothelial cell inflammatory responses, including upregulation of neutrophil adhesi...

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Veröffentlicht in:The Journal of thoracic and cardiovascular surgery 2011-03, Vol.141 (3), p.803-807
Hauptverfasser: Byrne, John, MD, McGuinness, Jonathan, PhD, Chen, Gang, PhD, Hill, Arnold D.K., MD, Redmond, Mark J., MD
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container_issue 3
container_start_page 803
container_title The Journal of thoracic and cardiovascular surgery
container_volume 141
creator Byrne, John, MD
McGuinness, Jonathan, PhD
Chen, Gang, PhD
Hill, Arnold D.K., MD
Redmond, Mark J., MD
description Objectives Neutrophil infiltration of tissues as part of the inflammatory response to cardiac surgery is one of the major mediators of postoperative multiple-organ dysfunction. Omega-3 fatty acids markedly attenuate endothelial cell inflammatory responses, including upregulation of neutrophil adhesion molecules. The efficacy of a clinically safe form of omega-3 to produce this effect in vivo was examined. Methods Rat gut intravital microscopic analysis was used to visualize neutrophil transmigration from the microcirculation into the tissues of the gut. Inflammatory activation was in the form of 30 minutes of ischemia and 90 minutes of reperfusion. Sham, control (0.9% saline infusion over 4 hours), and omega-3 (Omegaven [Fresenius Kabi, Bad Homburg, Germany] infusion over 4 hours) pretreatments were compared. Results Ischemia–reperfusion resulted in a 4-fold increase in neutrophil adherence to the endothelium (baseline: 4.3 ± 0.2 vs control group: 19.2 ± 3.5 adherent neutrophils per 100 μm, P  
doi_str_mv 10.1016/j.jtcvs.2010.04.030
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Omega-3 fatty acids markedly attenuate endothelial cell inflammatory responses, including upregulation of neutrophil adhesion molecules. The efficacy of a clinically safe form of omega-3 to produce this effect in vivo was examined. Methods Rat gut intravital microscopic analysis was used to visualize neutrophil transmigration from the microcirculation into the tissues of the gut. Inflammatory activation was in the form of 30 minutes of ischemia and 90 minutes of reperfusion. Sham, control (0.9% saline infusion over 4 hours), and omega-3 (Omegaven [Fresenius Kabi, Bad Homburg, Germany] infusion over 4 hours) pretreatments were compared. Results Ischemia–reperfusion resulted in a 4-fold increase in neutrophil adherence to the endothelium (baseline: 4.3 ± 0.2 vs control group: 19.2 ± 3.5 adherent neutrophils per 100 μm, P  &lt; .01), which intravenous omega-3 suppressed (7.8 ± 1.7 adherent neutrophils per 100 μm, P  &lt; .01). Omega-3 pretreatment also reduced neutrophil transmigration into the tissues after reperfusion (sham group: 6.3 ± 0.8 vs control group: 13.2 ± 1.4 vs omega-3 group: 9.4 ± 0.9 neutrophils per field, P  = .037). Gut tissue levels of the neutrophil-released enzyme myeloperoxidase were similarly markedly reduced with omega-3 pretreatment (sham group: 10.5 ± 1.6 vs control group: 19.0 ± 3.3 vs omega-3 group: 10.1 ± 1.2 U/g, P  = .03). Conclusions Four hours' pretreatment with a relatively safe form of intravenous omega-3 suppressed neutrophil adherence and tissue infiltration, resulting in lower levels of the tissue-damaging enzyme myeloperoxidase. This suggests a possible strategy for diminishing postoperative multiple-organ dysfunction.</description><identifier>ISSN: 0022-5223</identifier><identifier>EISSN: 1097-685X</identifier><identifier>DOI: 10.1016/j.jtcvs.2010.04.030</identifier><identifier>PMID: 20708753</identifier><identifier>CODEN: JTCSAQ</identifier><language>eng</language><publisher>New York, NY: Mosby, Inc</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Anti-Inflammatory Agents - administration &amp; dosage ; Biological and medical sciences ; Cardiac Surgical Procedures - adverse effects ; Cardiology. Vascular system ; Cardiothoracic Surgery ; Cell Adhesion - drug effects ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - immunology ; Fatty Acids, Omega-3 - administration &amp; dosage ; Immunity, Innate - drug effects ; Infusions, Intravenous ; Intestines - blood supply ; Leukocyte Rolling - drug effects ; Male ; Medical sciences ; Microscopy, Video ; Neutrophil Activation - drug effects ; Neutrophil Infiltration - drug effects ; Neutrophils - drug effects ; Neutrophils - enzymology ; Neutrophils - immunology ; Peroxidase - metabolism ; Pneumology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury - etiology ; Reperfusion Injury - immunology ; Reperfusion Injury - prevention &amp; control ; Surgery (general aspects). Transplantations, organ and tissue grafts. 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Omega-3 fatty acids markedly attenuate endothelial cell inflammatory responses, including upregulation of neutrophil adhesion molecules. The efficacy of a clinically safe form of omega-3 to produce this effect in vivo was examined. Methods Rat gut intravital microscopic analysis was used to visualize neutrophil transmigration from the microcirculation into the tissues of the gut. Inflammatory activation was in the form of 30 minutes of ischemia and 90 minutes of reperfusion. Sham, control (0.9% saline infusion over 4 hours), and omega-3 (Omegaven [Fresenius Kabi, Bad Homburg, Germany] infusion over 4 hours) pretreatments were compared. Results Ischemia–reperfusion resulted in a 4-fold increase in neutrophil adherence to the endothelium (baseline: 4.3 ± 0.2 vs control group: 19.2 ± 3.5 adherent neutrophils per 100 μm, P  &lt; .01), which intravenous omega-3 suppressed (7.8 ± 1.7 adherent neutrophils per 100 μm, P  &lt; .01). Omega-3 pretreatment also reduced neutrophil transmigration into the tissues after reperfusion (sham group: 6.3 ± 0.8 vs control group: 13.2 ± 1.4 vs omega-3 group: 9.4 ± 0.9 neutrophils per field, P  = .037). Gut tissue levels of the neutrophil-released enzyme myeloperoxidase were similarly markedly reduced with omega-3 pretreatment (sham group: 10.5 ± 1.6 vs control group: 19.0 ± 3.3 vs omega-3 group: 10.1 ± 1.2 U/g, P  = .03). Conclusions Four hours' pretreatment with a relatively safe form of intravenous omega-3 suppressed neutrophil adherence and tissue infiltration, resulting in lower levels of the tissue-damaging enzyme myeloperoxidase. This suggests a possible strategy for diminishing postoperative multiple-organ dysfunction.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - administration &amp; dosage</subject><subject>Biological and medical sciences</subject><subject>Cardiac Surgical Procedures - adverse effects</subject><subject>Cardiology. Vascular system</subject><subject>Cardiothoracic Surgery</subject><subject>Cell Adhesion - drug effects</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - immunology</subject><subject>Fatty Acids, Omega-3 - administration &amp; dosage</subject><subject>Immunity, Innate - drug effects</subject><subject>Infusions, Intravenous</subject><subject>Intestines - blood supply</subject><subject>Leukocyte Rolling - drug effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microscopy, Video</subject><subject>Neutrophil Activation - drug effects</subject><subject>Neutrophil Infiltration - drug effects</subject><subject>Neutrophils - drug effects</subject><subject>Neutrophils - enzymology</subject><subject>Neutrophils - immunology</subject><subject>Peroxidase - metabolism</subject><subject>Pneumology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reperfusion Injury - etiology</subject><subject>Reperfusion Injury - immunology</subject><subject>Reperfusion Injury - prevention &amp; control</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgery of the heart</subject><subject>Time Factors</subject><issn>0022-5223</issn><issn>1097-685X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk2LFDEQhoMo7uzqLxAkF_GyPeaju9N9cEEWPxYWPKjgLVTS1bMZu9Njkh6co__c9M6o4MVTheKpN1UvLyHPOFtzxutX2_U22X1cC5Y7rFwzyR6QFWetKuqm-vqQrBgToqiEkGfkPMYtY0wx3j4mZyI_GlXJFfl541OAPfppjnQacQOFvKRAE9o7777PSNNEdwEzkSh4ij8sxuj2SJ33kHIZx9kjDRh3k4_3uIXQObA0zmGD4ZDJLBimbpHYzIm6aO9wdEDH3BuekEc9DBGfnuoF-fLu7efrD8Xtx_c3129uC1s2TSqMAVWbHk3bW6hZVyqhDOcGW1PxumyUqUrVdWhL0_IGABWHDoWUtjWWi0pekJdH3V2Y8l0x6TEvgsMAHvPxuqmkEBUTTSblkbRhijFgr3fBjRAOmjO9WK-3-t56vVivWamz9Xnq-Ul_NiN2f2Z-e52BFycAooWhD-Cti3852XLFa56510cOsxt7h0FH69Bb7FxAm3Q3uf8scvXPvB2cd_nLb3jAuJ3m4LPRmusoNNOflpQsIeE5H6WsG_kLZnq6cQ</recordid><startdate>20110301</startdate><enddate>20110301</enddate><creator>Byrne, John, MD</creator><creator>McGuinness, Jonathan, PhD</creator><creator>Chen, Gang, PhD</creator><creator>Hill, Arnold D.K., MD</creator><creator>Redmond, Mark J., MD</creator><general>Mosby, Inc</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</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>20110301</creationdate><title>Intravenous omega-3, a technique to prevent an excessive innate immune response to cardiac surgery in a rodent gut ischemia model</title><author>Byrne, John, MD ; McGuinness, Jonathan, PhD ; Chen, Gang, PhD ; Hill, Arnold D.K., MD ; Redmond, Mark J., MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c488t-bba76bfeb9fca60d4727b11be9b516487b547ddec4b918aae71ade233c9bc1253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - administration &amp; dosage</topic><topic>Biological and medical sciences</topic><topic>Cardiac Surgical Procedures - adverse effects</topic><topic>Cardiology. Vascular system</topic><topic>Cardiothoracic Surgery</topic><topic>Cell Adhesion - drug effects</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - immunology</topic><topic>Fatty Acids, Omega-3 - administration &amp; dosage</topic><topic>Immunity, Innate - drug effects</topic><topic>Infusions, Intravenous</topic><topic>Intestines - blood supply</topic><topic>Leukocyte Rolling - drug effects</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microscopy, Video</topic><topic>Neutrophil Activation - drug effects</topic><topic>Neutrophil Infiltration - drug effects</topic><topic>Neutrophils - drug effects</topic><topic>Neutrophils - enzymology</topic><topic>Neutrophils - immunology</topic><topic>Peroxidase - metabolism</topic><topic>Pneumology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reperfusion Injury - etiology</topic><topic>Reperfusion Injury - immunology</topic><topic>Reperfusion Injury - prevention &amp; control</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Surgery of the heart</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Byrne, John, MD</creatorcontrib><creatorcontrib>McGuinness, Jonathan, PhD</creatorcontrib><creatorcontrib>Chen, Gang, PhD</creatorcontrib><creatorcontrib>Hill, Arnold D.K., MD</creatorcontrib><creatorcontrib>Redmond, Mark J., MD</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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>The Journal of thoracic and cardiovascular surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Byrne, John, MD</au><au>McGuinness, Jonathan, PhD</au><au>Chen, Gang, PhD</au><au>Hill, Arnold D.K., MD</au><au>Redmond, Mark J., MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intravenous omega-3, a technique to prevent an excessive innate immune response to cardiac surgery in a rodent gut ischemia model</atitle><jtitle>The Journal of thoracic and cardiovascular surgery</jtitle><addtitle>J Thorac Cardiovasc Surg</addtitle><date>2011-03-01</date><risdate>2011</risdate><volume>141</volume><issue>3</issue><spage>803</spage><epage>807</epage><pages>803-807</pages><issn>0022-5223</issn><eissn>1097-685X</eissn><coden>JTCSAQ</coden><abstract>Objectives Neutrophil infiltration of tissues as part of the inflammatory response to cardiac surgery is one of the major mediators of postoperative multiple-organ dysfunction. Omega-3 fatty acids markedly attenuate endothelial cell inflammatory responses, including upregulation of neutrophil adhesion molecules. The efficacy of a clinically safe form of omega-3 to produce this effect in vivo was examined. Methods Rat gut intravital microscopic analysis was used to visualize neutrophil transmigration from the microcirculation into the tissues of the gut. Inflammatory activation was in the form of 30 minutes of ischemia and 90 minutes of reperfusion. Sham, control (0.9% saline infusion over 4 hours), and omega-3 (Omegaven [Fresenius Kabi, Bad Homburg, Germany] infusion over 4 hours) pretreatments were compared. Results Ischemia–reperfusion resulted in a 4-fold increase in neutrophil adherence to the endothelium (baseline: 4.3 ± 0.2 vs control group: 19.2 ± 3.5 adherent neutrophils per 100 μm, P  &lt; .01), which intravenous omega-3 suppressed (7.8 ± 1.7 adherent neutrophils per 100 μm, P  &lt; .01). Omega-3 pretreatment also reduced neutrophil transmigration into the tissues after reperfusion (sham group: 6.3 ± 0.8 vs control group: 13.2 ± 1.4 vs omega-3 group: 9.4 ± 0.9 neutrophils per field, P  = .037). Gut tissue levels of the neutrophil-released enzyme myeloperoxidase were similarly markedly reduced with omega-3 pretreatment (sham group: 10.5 ± 1.6 vs control group: 19.0 ± 3.3 vs omega-3 group: 10.1 ± 1.2 U/g, P  = .03). Conclusions Four hours' pretreatment with a relatively safe form of intravenous omega-3 suppressed neutrophil adherence and tissue infiltration, resulting in lower levels of the tissue-damaging enzyme myeloperoxidase. This suggests a possible strategy for diminishing postoperative multiple-organ dysfunction.</abstract><cop>New York, NY</cop><pub>Mosby, Inc</pub><pmid>20708753</pmid><doi>10.1016/j.jtcvs.2010.04.030</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record>
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subjects Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Anti-Inflammatory Agents - administration & dosage
Biological and medical sciences
Cardiac Surgical Procedures - adverse effects
Cardiology. Vascular system
Cardiothoracic Surgery
Cell Adhesion - drug effects
Endothelium, Vascular - drug effects
Endothelium, Vascular - immunology
Fatty Acids, Omega-3 - administration & dosage
Immunity, Innate - drug effects
Infusions, Intravenous
Intestines - blood supply
Leukocyte Rolling - drug effects
Male
Medical sciences
Microscopy, Video
Neutrophil Activation - drug effects
Neutrophil Infiltration - drug effects
Neutrophils - drug effects
Neutrophils - enzymology
Neutrophils - immunology
Peroxidase - metabolism
Pneumology
Rats
Rats, Sprague-Dawley
Reperfusion Injury - etiology
Reperfusion Injury - immunology
Reperfusion Injury - prevention & control
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Surgery of the heart
Time Factors
title Intravenous omega-3, a technique to prevent an excessive innate immune response to cardiac surgery in a rodent gut ischemia model
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