Organ Care System Lung resulted in lower apoptosis and iNOS expression in donor lungs
Ischemia‐reperfusion (IR) injury after lung transplantation is still today an important complication in up to 25% of patients. The Organ Care System (OCS) Lung, an advanced normothermic ex vivo lung perfusion system, was found to be effective in reducing primary graft dysfunction compared to standar...
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Veröffentlicht in: | American journal of transplantation 2020-12, Vol.20 (12), p.3639-3648 |
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creator | Calabrese, Fiorella Schiavon, Marco Perissinotto, Egle Lunardi, Francesca Marulli, Giuseppe Di Gregorio, Guido Pezzuto, Federica Edith Vuljan, Stefania Forin, Edoardo Wiegmann, Bettina Jonigk, Danny Warnecke, Gregor Rea, Federico |
description | Ischemia‐reperfusion (IR) injury after lung transplantation is still today an important complication in up to 25% of patients. The Organ Care System (OCS) Lung, an advanced normothermic ex vivo lung perfusion system, was found to be effective in reducing primary graft dysfunction compared to standard organ care (SOC) but studies on tissue/molecular pathways that could explain these more effective clinical results are lacking. This observational longitudinal study aimed to investigate IR injury in 68 tissue specimens collected before and after reperfusion from 17 OCS and 17 SOC preserved donor lungs. Several tissue analyses including apoptosis evaluation and inducible nitric oxide synthase (iNOS) expression (by immunohistochemistry and real‐time reverse transcriptase‐polymerase chain reaction) were performed. Lower iNOS expression and apoptotic index were distinctive of OCS preserved tissues at pre‐ and post‐reperfusion times, independently from potential confounding factors. Moreover, OCS recipients had lower acute cellular rejection at the first 6‐month follow‐up. In conclusion, IR injury, in terms of apoptosis and iNOS expression, was less frequent in OCS‐ than in SOC‐preserved lungs, which could eventually explain a better clinical outcome. Further studies are needed to validate our data and determine the role of iNOS expression as a predictive biomarker of the complex IR injury mechanism.
Apoptosis and induced nitric oxide synthase expression, important morphological parameters associated with ischemia–reperfusion injury, are significantly lower in donor lungs preserved with ex vivo, normothermic perfusion than those preserved by cold static storage. |
doi_str_mv | 10.1111/ajt.16187 |
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Apoptosis and induced nitric oxide synthase expression, important morphological parameters associated with ischemia–reperfusion injury, are significantly lower in donor lungs preserved with ex vivo, normothermic perfusion than those preserved by cold static storage.</description><identifier>ISSN: 1600-6135</identifier><identifier>EISSN: 1600-6143</identifier><identifier>DOI: 10.1111/ajt.16187</identifier><identifier>PMID: 32652873</identifier><language>eng</language><publisher>United States: Elsevier Limited</publisher><subject>Apoptosis ; Cell death ; cell death: apoptosis ; clinical research/practice ; Graft rejection ; Humans ; Immunohistochemistry ; Ischemia ; ischemia‐reperfusion injury (IRI) ; Longitudinal Studies ; Lung ; Lung transplantation ; Lung Transplantation - adverse effects ; lung transplantation: living donor ; Lung transplants ; Lungs ; Nitric oxide ; Nitric Oxide Synthase Type II - genetics ; Nitric-oxide synthase ; organ perfusion and preservation ; pathology/histopathology ; Perfusion ; Polymerase chain reaction ; Reperfusion ; Reperfusion Injury ; RNA-directed DNA polymerase</subject><ispartof>American journal of transplantation, 2020-12, Vol.20 (12), p.3639-3648</ispartof><rights>2020 The American Society of Transplantation and the American Society of Transplant Surgeons</rights><rights>2020 The American Society of Transplantation and the American Society of Transplant Surgeons.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3887-bdc0ecd818dd3589fa0367c33f8081448365f1bfb393c9dcedd62dacb29583c53</citedby><cites>FETCH-LOGICAL-c3887-bdc0ecd818dd3589fa0367c33f8081448365f1bfb393c9dcedd62dacb29583c53</cites><orcidid>0000-0001-8780-2011 ; 0000-0001-5351-9226</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fajt.16187$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fajt.16187$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32652873$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Calabrese, Fiorella</creatorcontrib><creatorcontrib>Schiavon, Marco</creatorcontrib><creatorcontrib>Perissinotto, Egle</creatorcontrib><creatorcontrib>Lunardi, Francesca</creatorcontrib><creatorcontrib>Marulli, Giuseppe</creatorcontrib><creatorcontrib>Di Gregorio, Guido</creatorcontrib><creatorcontrib>Pezzuto, Federica</creatorcontrib><creatorcontrib>Edith Vuljan, Stefania</creatorcontrib><creatorcontrib>Forin, Edoardo</creatorcontrib><creatorcontrib>Wiegmann, Bettina</creatorcontrib><creatorcontrib>Jonigk, Danny</creatorcontrib><creatorcontrib>Warnecke, Gregor</creatorcontrib><creatorcontrib>Rea, Federico</creatorcontrib><title>Organ Care System Lung resulted in lower apoptosis and iNOS expression in donor lungs</title><title>American journal of transplantation</title><addtitle>Am J Transplant</addtitle><description>Ischemia‐reperfusion (IR) injury after lung transplantation is still today an important complication in up to 25% of patients. The Organ Care System (OCS) Lung, an advanced normothermic ex vivo lung perfusion system, was found to be effective in reducing primary graft dysfunction compared to standard organ care (SOC) but studies on tissue/molecular pathways that could explain these more effective clinical results are lacking. This observational longitudinal study aimed to investigate IR injury in 68 tissue specimens collected before and after reperfusion from 17 OCS and 17 SOC preserved donor lungs. Several tissue analyses including apoptosis evaluation and inducible nitric oxide synthase (iNOS) expression (by immunohistochemistry and real‐time reverse transcriptase‐polymerase chain reaction) were performed. Lower iNOS expression and apoptotic index were distinctive of OCS preserved tissues at pre‐ and post‐reperfusion times, independently from potential confounding factors. Moreover, OCS recipients had lower acute cellular rejection at the first 6‐month follow‐up. In conclusion, IR injury, in terms of apoptosis and iNOS expression, was less frequent in OCS‐ than in SOC‐preserved lungs, which could eventually explain a better clinical outcome. Further studies are needed to validate our data and determine the role of iNOS expression as a predictive biomarker of the complex IR injury mechanism.
Apoptosis and induced nitric oxide synthase expression, important morphological parameters associated with ischemia–reperfusion injury, are significantly lower in donor lungs preserved with ex vivo, normothermic perfusion than those preserved by cold static storage.</description><subject>Apoptosis</subject><subject>Cell death</subject><subject>cell death: apoptosis</subject><subject>clinical research/practice</subject><subject>Graft rejection</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Ischemia</subject><subject>ischemia‐reperfusion injury (IRI)</subject><subject>Longitudinal Studies</subject><subject>Lung</subject><subject>Lung transplantation</subject><subject>Lung Transplantation - adverse effects</subject><subject>lung transplantation: living donor</subject><subject>Lung transplants</subject><subject>Lungs</subject><subject>Nitric oxide</subject><subject>Nitric Oxide Synthase Type II - genetics</subject><subject>Nitric-oxide synthase</subject><subject>organ perfusion and preservation</subject><subject>pathology/histopathology</subject><subject>Perfusion</subject><subject>Polymerase chain reaction</subject><subject>Reperfusion</subject><subject>Reperfusion Injury</subject><subject>RNA-directed DNA polymerase</subject><issn>1600-6135</issn><issn>1600-6143</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10E1LwzAYB_AgipvTg19AAl700C0vbZoex_CV4Q7bziVN0tHRNjVpmfv2ZnbuIJhLQvg9fx7-ANxiNMb-TMS2HWOGeXwGhpghFDAc0vPTm0YDcOXcFiEcE04uwYASFhEe0yFYL-xG1HAmrIbLvWt1BeddvYFWu65stYJFDUuz0xaKxjStcYWDovbfH4sl1F-Nd64w9YEpUxsLSz_trsFFLkqnb473CKyfn1az12C-eHmbTeeBpJzHQaYk0lJxzJWiEU9ygSiLJaU5RxyHIacsynGWZzShMlFSK8WIEjIjScSpjOgIPPS5jTWfnXZtWhVO6rIUtTadS0lIKGIJIgd6_4duTWdrv51XjKEQ4YR69dgraY1zVudpY4tK2H2KUXroOvVdpz9de3t3TOyySquT_C3Xg0kPdkWp9_8npdP3VR_5DY8nh6Y</recordid><startdate>202012</startdate><enddate>202012</enddate><creator>Calabrese, Fiorella</creator><creator>Schiavon, Marco</creator><creator>Perissinotto, Egle</creator><creator>Lunardi, Francesca</creator><creator>Marulli, Giuseppe</creator><creator>Di Gregorio, Guido</creator><creator>Pezzuto, Federica</creator><creator>Edith Vuljan, Stefania</creator><creator>Forin, Edoardo</creator><creator>Wiegmann, Bettina</creator><creator>Jonigk, Danny</creator><creator>Warnecke, Gregor</creator><creator>Rea, Federico</creator><general>Elsevier Limited</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>7QP</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8780-2011</orcidid><orcidid>https://orcid.org/0000-0001-5351-9226</orcidid></search><sort><creationdate>202012</creationdate><title>Organ Care System Lung resulted in lower apoptosis and iNOS expression in donor lungs</title><author>Calabrese, Fiorella ; Schiavon, Marco ; Perissinotto, Egle ; Lunardi, Francesca ; Marulli, Giuseppe ; Di Gregorio, Guido ; Pezzuto, Federica ; Edith Vuljan, Stefania ; Forin, Edoardo ; Wiegmann, Bettina ; Jonigk, Danny ; Warnecke, Gregor ; Rea, Federico</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3887-bdc0ecd818dd3589fa0367c33f8081448365f1bfb393c9dcedd62dacb29583c53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Apoptosis</topic><topic>Cell death</topic><topic>cell death: apoptosis</topic><topic>clinical research/practice</topic><topic>Graft rejection</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Ischemia</topic><topic>ischemia‐reperfusion injury (IRI)</topic><topic>Longitudinal Studies</topic><topic>Lung</topic><topic>Lung transplantation</topic><topic>Lung Transplantation - adverse effects</topic><topic>lung transplantation: living donor</topic><topic>Lung transplants</topic><topic>Lungs</topic><topic>Nitric oxide</topic><topic>Nitric Oxide Synthase Type II - genetics</topic><topic>Nitric-oxide synthase</topic><topic>organ perfusion and preservation</topic><topic>pathology/histopathology</topic><topic>Perfusion</topic><topic>Polymerase chain reaction</topic><topic>Reperfusion</topic><topic>Reperfusion Injury</topic><topic>RNA-directed DNA polymerase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Calabrese, Fiorella</creatorcontrib><creatorcontrib>Schiavon, Marco</creatorcontrib><creatorcontrib>Perissinotto, Egle</creatorcontrib><creatorcontrib>Lunardi, Francesca</creatorcontrib><creatorcontrib>Marulli, Giuseppe</creatorcontrib><creatorcontrib>Di Gregorio, Guido</creatorcontrib><creatorcontrib>Pezzuto, Federica</creatorcontrib><creatorcontrib>Edith Vuljan, Stefania</creatorcontrib><creatorcontrib>Forin, Edoardo</creatorcontrib><creatorcontrib>Wiegmann, Bettina</creatorcontrib><creatorcontrib>Jonigk, Danny</creatorcontrib><creatorcontrib>Warnecke, Gregor</creatorcontrib><creatorcontrib>Rea, Federico</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Calabrese, Fiorella</au><au>Schiavon, Marco</au><au>Perissinotto, Egle</au><au>Lunardi, Francesca</au><au>Marulli, Giuseppe</au><au>Di Gregorio, Guido</au><au>Pezzuto, Federica</au><au>Edith Vuljan, Stefania</au><au>Forin, Edoardo</au><au>Wiegmann, Bettina</au><au>Jonigk, Danny</au><au>Warnecke, Gregor</au><au>Rea, Federico</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Organ Care System Lung resulted in lower apoptosis and iNOS expression in donor lungs</atitle><jtitle>American journal of transplantation</jtitle><addtitle>Am J Transplant</addtitle><date>2020-12</date><risdate>2020</risdate><volume>20</volume><issue>12</issue><spage>3639</spage><epage>3648</epage><pages>3639-3648</pages><issn>1600-6135</issn><eissn>1600-6143</eissn><abstract>Ischemia‐reperfusion (IR) injury after lung transplantation is still today an important complication in up to 25% of patients. The Organ Care System (OCS) Lung, an advanced normothermic ex vivo lung perfusion system, was found to be effective in reducing primary graft dysfunction compared to standard organ care (SOC) but studies on tissue/molecular pathways that could explain these more effective clinical results are lacking. This observational longitudinal study aimed to investigate IR injury in 68 tissue specimens collected before and after reperfusion from 17 OCS and 17 SOC preserved donor lungs. Several tissue analyses including apoptosis evaluation and inducible nitric oxide synthase (iNOS) expression (by immunohistochemistry and real‐time reverse transcriptase‐polymerase chain reaction) were performed. Lower iNOS expression and apoptotic index were distinctive of OCS preserved tissues at pre‐ and post‐reperfusion times, independently from potential confounding factors. Moreover, OCS recipients had lower acute cellular rejection at the first 6‐month follow‐up. In conclusion, IR injury, in terms of apoptosis and iNOS expression, was less frequent in OCS‐ than in SOC‐preserved lungs, which could eventually explain a better clinical outcome. Further studies are needed to validate our data and determine the role of iNOS expression as a predictive biomarker of the complex IR injury mechanism.
Apoptosis and induced nitric oxide synthase expression, important morphological parameters associated with ischemia–reperfusion injury, are significantly lower in donor lungs preserved with ex vivo, normothermic perfusion than those preserved by cold static storage.</abstract><cop>United States</cop><pub>Elsevier Limited</pub><pmid>32652873</pmid><doi>10.1111/ajt.16187</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-8780-2011</orcidid><orcidid>https://orcid.org/0000-0001-5351-9226</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Apoptosis Cell death cell death: apoptosis clinical research/practice Graft rejection Humans Immunohistochemistry Ischemia ischemia‐reperfusion injury (IRI) Longitudinal Studies Lung Lung transplantation Lung Transplantation - adverse effects lung transplantation: living donor Lung transplants Lungs Nitric oxide Nitric Oxide Synthase Type II - genetics Nitric-oxide synthase organ perfusion and preservation pathology/histopathology Perfusion Polymerase chain reaction Reperfusion Reperfusion Injury RNA-directed DNA polymerase |
title | Organ Care System Lung resulted in lower apoptosis and iNOS expression in donor lungs |
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