Novel oxygenation technique for hypothermic machine perfusion of liver grafts: Validation in porcine Donation after Cardiac Death (DCD) liver model
Hypothermic oxygenated machine perfusion improves outcomes in Liver Transplantation, but application is limited as O2 is supplied by a stationary circuit. A novel technique of O2 “pre-charge” in a portable pump would broaden use and further mitigate ischemia damage from organ transport. Porcine DCD...
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| Veröffentlicht in: | The American journal of surgery 2020-11, Vol.220 (5), p.1270-1277 |
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| creator | Panayotova, Guergana G. Rosado, Jesus Paterno, Flavio Deo, Dayanand Dikdan, George McCarty, Matthew A. Arrington, Ben Giudice, Anthony Fano, Adam Dhaduk, Nehal Lunsford, Keri E. Rao, Prakash Guarrera, James V. |
| description | Hypothermic oxygenated machine perfusion improves outcomes in Liver Transplantation, but application is limited as O2 is supplied by a stationary circuit. A novel technique of O2 “pre-charge” in a portable pump would broaden use and further mitigate ischemia damage from organ transport.
Porcine DCD livers were randomized to static cold storage (SCS, n = 8) or hypothermic machine perfusion (HMP). HMP was stratified into HMP-O2 (n = 5), non-O2 open to air HMP-RA (n = 5), and non-O2 with sealed lids or no air HMP-NA (n = 5). HMP-O2 was “pre-charged” using 100% O2 delivered at 10 L/min over 15 min. Perfusate and tissue O2 tension (pO2), liver biopsies, and fluid chemistries were analyzed.
“Pre-charge” achieves sustained tissue and perfusate pO2 vs others. HMP-O2 results in decreased markers of hepatocyte injury: ALT (p |
| doi_str_mv | 10.1016/j.amjsurg.2020.06.072 |
| format | Article |
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Porcine DCD livers were randomized to static cold storage (SCS, n = 8) or hypothermic machine perfusion (HMP). HMP was stratified into HMP-O2 (n = 5), non-O2 open to air HMP-RA (n = 5), and non-O2 with sealed lids or no air HMP-NA (n = 5). HMP-O2 was “pre-charged” using 100% O2 delivered at 10 L/min over 15 min. Perfusate and tissue O2 tension (pO2), liver biopsies, and fluid chemistries were analyzed.
“Pre-charge” achieves sustained tissue and perfusate pO2 vs others. HMP-O2 results in decreased markers of hepatocyte injury: ALT (p < 0.05) and LDH (p < 0.05), lower expression of CRP and higher expression of SOD1 vs SCS. This suggests decreased inflammation and improved ROS scavenging.
“Pre-charge” is an effective technique, which allows portability and transport without an O2 source and improves graft parameters.
•Oxygen “pre-charge” by 100% O2 for 15 min achieves high, persistent oxygen levels for perfusion.•HMP treatment leads to significant decrease in markers of injury: ALT and sCD-146.•Pre-charged HMP-O2 results in improved aerobic metabolism: decreased LDH.•HMP results in downregulation of CRP expression, a nonspecific marker of inflammation.•HMP results in upregulation of SOD1 expression, an ROS scavenger.</description><identifier>ISSN: 0002-9610</identifier><identifier>EISSN: 1879-1883</identifier><identifier>DOI: 10.1016/j.amjsurg.2020.06.072</identifier><identifier>PMID: 32892979</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Antibodies ; Biomarkers - metabolism ; Biopsy ; Circuits ; Cold storage ; Cryopreservation ; Death ; Ex vivo perfusion ; Gene expression ; Heart ; Hypothermic machine perfusion ; Hypothermic oxygenated machine perfusion ; Ischemia ; Ischemia/reperfusion injury ; Laboratories ; Liver ; Liver - metabolism ; Liver graft preservation ; Liver Transplantation ; Liver transplants ; Models, Animal ; Organ Preservation - methods ; Oxygen - administration & dosage ; Oxygenation ; Perfusion ; Perfusion - methods ; Random Allocation ; Scavenging ; Sensors ; Superoxide dismutase ; Swine ; Tissue and Organ Procurement - methods ; Transplantation ; Transplants & implants</subject><ispartof>The American journal of surgery, 2020-11, Vol.220 (5), p.1270-1277</ispartof><rights>2020 Elsevier Inc.</rights><rights>Copyright © 2020 Elsevier Inc. All rights reserved.</rights><rights>2020. Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-c94deea8ca02eb41b6e448026c9098aa8ae5c8c1d9535ec670c8de544fb1fc733</citedby><cites>FETCH-LOGICAL-c393t-c94deea8ca02eb41b6e448026c9098aa8ae5c8c1d9535ec670c8de544fb1fc733</cites><orcidid>0000-0002-4049-1049 ; 0000-0002-7540-4478 ; 0000-0002-4156-1774 ; 0000-0002-7370-3861 ; 0000-0001-7212-2646</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0002961020304268$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32892979$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Panayotova, Guergana G.</creatorcontrib><creatorcontrib>Rosado, Jesus</creatorcontrib><creatorcontrib>Paterno, Flavio</creatorcontrib><creatorcontrib>Deo, Dayanand</creatorcontrib><creatorcontrib>Dikdan, George</creatorcontrib><creatorcontrib>McCarty, Matthew A.</creatorcontrib><creatorcontrib>Arrington, Ben</creatorcontrib><creatorcontrib>Giudice, Anthony</creatorcontrib><creatorcontrib>Fano, Adam</creatorcontrib><creatorcontrib>Dhaduk, Nehal</creatorcontrib><creatorcontrib>Lunsford, Keri E.</creatorcontrib><creatorcontrib>Rao, Prakash</creatorcontrib><creatorcontrib>Guarrera, James V.</creatorcontrib><title>Novel oxygenation technique for hypothermic machine perfusion of liver grafts: Validation in porcine Donation after Cardiac Death (DCD) liver model</title><title>The American journal of surgery</title><addtitle>Am J Surg</addtitle><description>Hypothermic oxygenated machine perfusion improves outcomes in Liver Transplantation, but application is limited as O2 is supplied by a stationary circuit. A novel technique of O2 “pre-charge” in a portable pump would broaden use and further mitigate ischemia damage from organ transport.
Porcine DCD livers were randomized to static cold storage (SCS, n = 8) or hypothermic machine perfusion (HMP). HMP was stratified into HMP-O2 (n = 5), non-O2 open to air HMP-RA (n = 5), and non-O2 with sealed lids or no air HMP-NA (n = 5). HMP-O2 was “pre-charged” using 100% O2 delivered at 10 L/min over 15 min. Perfusate and tissue O2 tension (pO2), liver biopsies, and fluid chemistries were analyzed.
“Pre-charge” achieves sustained tissue and perfusate pO2 vs others. HMP-O2 results in decreased markers of hepatocyte injury: ALT (p < 0.05) and LDH (p < 0.05), lower expression of CRP and higher expression of SOD1 vs SCS. This suggests decreased inflammation and improved ROS scavenging.
“Pre-charge” is an effective technique, which allows portability and transport without an O2 source and improves graft parameters.
•Oxygen “pre-charge” by 100% O2 for 15 min achieves high, persistent oxygen levels for perfusion.•HMP treatment leads to significant decrease in markers of injury: ALT and sCD-146.•Pre-charged HMP-O2 results in improved aerobic metabolism: decreased LDH.•HMP results in downregulation of CRP expression, a nonspecific marker of inflammation.•HMP results in upregulation of SOD1 expression, an ROS scavenger.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Biomarkers - metabolism</subject><subject>Biopsy</subject><subject>Circuits</subject><subject>Cold storage</subject><subject>Cryopreservation</subject><subject>Death</subject><subject>Ex vivo perfusion</subject><subject>Gene expression</subject><subject>Heart</subject><subject>Hypothermic machine perfusion</subject><subject>Hypothermic oxygenated machine perfusion</subject><subject>Ischemia</subject><subject>Ischemia/reperfusion injury</subject><subject>Laboratories</subject><subject>Liver</subject><subject>Liver - metabolism</subject><subject>Liver graft preservation</subject><subject>Liver Transplantation</subject><subject>Liver transplants</subject><subject>Models, Animal</subject><subject>Organ Preservation - methods</subject><subject>Oxygen - administration & dosage</subject><subject>Oxygenation</subject><subject>Perfusion</subject><subject>Perfusion - methods</subject><subject>Random Allocation</subject><subject>Scavenging</subject><subject>Sensors</subject><subject>Superoxide dismutase</subject><subject>Swine</subject><subject>Tissue and Organ Procurement - methods</subject><subject>Transplantation</subject><subject>Transplants & implants</subject><issn>0002-9610</issn><issn>1879-1883</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkU-P1CAYh4nRuLOrH0FD4mU9tAKlFLxszMz6J9noRb0Shr6d0rSlQjtxPodfWCZTPXjxRN7k-T0v8EPoBSU5JVS86XIzdHEJh5wRRnIiclKxR2hDZaUyKmXxGG0IISxTgpIrdB1jl0ZKefEUXRVMKqYqtUG_Pvsj9Nj_PB1gNLPzI57BtqP7sQBufMDtafJzC2FwFg_Gtm4EPEFolnhmfYN7d4SAD8E0c3yLv5ve1RePG_Hkgz0Hdn51JyjBWxNqZyzegZlbfLvb7l6vmsHX0D9DTxrTR3i-njfo2_v7r9uP2cOXD5-27x4yW6hizqziNYCR1hAGe073AjiXhAmriJLGSAOllZbWqixKsKIiVtZQct7saWOrorhBtxfvFHx6bpz14KKFvjcj-CVqxjkRoiwFSeirf9DOL2FMt0uUoCWnrKCJKi-UDT7GAI2eghtMOGlK9Lk13em1NX1uTROhU2sp93K1L_sB6r-pPzUl4O4CQPqOo4Ogo3UwWqhdADvr2rv_rPgNUqKtng</recordid><startdate>202011</startdate><enddate>202011</enddate><creator>Panayotova, Guergana G.</creator><creator>Rosado, Jesus</creator><creator>Paterno, Flavio</creator><creator>Deo, Dayanand</creator><creator>Dikdan, George</creator><creator>McCarty, Matthew A.</creator><creator>Arrington, Ben</creator><creator>Giudice, Anthony</creator><creator>Fano, Adam</creator><creator>Dhaduk, Nehal</creator><creator>Lunsford, Keri E.</creator><creator>Rao, Prakash</creator><creator>Guarrera, James V.</creator><general>Elsevier Inc</general><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>3V.</scope><scope>7QO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4049-1049</orcidid><orcidid>https://orcid.org/0000-0002-7540-4478</orcidid><orcidid>https://orcid.org/0000-0002-4156-1774</orcidid><orcidid>https://orcid.org/0000-0002-7370-3861</orcidid><orcidid>https://orcid.org/0000-0001-7212-2646</orcidid></search><sort><creationdate>202011</creationdate><title>Novel oxygenation technique for hypothermic machine perfusion of liver grafts: Validation in porcine Donation after Cardiac Death (DCD) liver model</title><author>Panayotova, Guergana G. ; Rosado, Jesus ; Paterno, Flavio ; Deo, Dayanand ; Dikdan, George ; McCarty, Matthew A. ; Arrington, Ben ; Giudice, Anthony ; Fano, Adam ; Dhaduk, Nehal ; Lunsford, Keri E. ; Rao, Prakash ; Guarrera, James V.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-c94deea8ca02eb41b6e448026c9098aa8ae5c8c1d9535ec670c8de544fb1fc733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Antibodies</topic><topic>Biomarkers - 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Academic</collection><jtitle>The American journal of surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Panayotova, Guergana G.</au><au>Rosado, Jesus</au><au>Paterno, Flavio</au><au>Deo, Dayanand</au><au>Dikdan, George</au><au>McCarty, Matthew A.</au><au>Arrington, Ben</au><au>Giudice, Anthony</au><au>Fano, Adam</au><au>Dhaduk, Nehal</au><au>Lunsford, Keri E.</au><au>Rao, Prakash</au><au>Guarrera, James V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel oxygenation technique for hypothermic machine perfusion of liver grafts: Validation in porcine Donation after Cardiac Death (DCD) liver model</atitle><jtitle>The American journal of surgery</jtitle><addtitle>Am J Surg</addtitle><date>2020-11</date><risdate>2020</risdate><volume>220</volume><issue>5</issue><spage>1270</spage><epage>1277</epage><pages>1270-1277</pages><issn>0002-9610</issn><eissn>1879-1883</eissn><abstract>Hypothermic oxygenated machine perfusion improves outcomes in Liver Transplantation, but application is limited as O2 is supplied by a stationary circuit. A novel technique of O2 “pre-charge” in a portable pump would broaden use and further mitigate ischemia damage from organ transport.
Porcine DCD livers were randomized to static cold storage (SCS, n = 8) or hypothermic machine perfusion (HMP). HMP was stratified into HMP-O2 (n = 5), non-O2 open to air HMP-RA (n = 5), and non-O2 with sealed lids or no air HMP-NA (n = 5). HMP-O2 was “pre-charged” using 100% O2 delivered at 10 L/min over 15 min. Perfusate and tissue O2 tension (pO2), liver biopsies, and fluid chemistries were analyzed.
“Pre-charge” achieves sustained tissue and perfusate pO2 vs others. HMP-O2 results in decreased markers of hepatocyte injury: ALT (p < 0.05) and LDH (p < 0.05), lower expression of CRP and higher expression of SOD1 vs SCS. This suggests decreased inflammation and improved ROS scavenging.
“Pre-charge” is an effective technique, which allows portability and transport without an O2 source and improves graft parameters.
•Oxygen “pre-charge” by 100% O2 for 15 min achieves high, persistent oxygen levels for perfusion.•HMP treatment leads to significant decrease in markers of injury: ALT and sCD-146.•Pre-charged HMP-O2 results in improved aerobic metabolism: decreased LDH.•HMP results in downregulation of CRP expression, a nonspecific marker of inflammation.•HMP results in upregulation of SOD1 expression, an ROS scavenger.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>32892979</pmid><doi>10.1016/j.amjsurg.2020.06.072</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-4049-1049</orcidid><orcidid>https://orcid.org/0000-0002-7540-4478</orcidid><orcidid>https://orcid.org/0000-0002-4156-1774</orcidid><orcidid>https://orcid.org/0000-0002-7370-3861</orcidid><orcidid>https://orcid.org/0000-0001-7212-2646</orcidid></addata></record> |
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| ispartof | The American journal of surgery, 2020-11, Vol.220 (5), p.1270-1277 |
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| subjects | Animals Antibodies Biomarkers - metabolism Biopsy Circuits Cold storage Cryopreservation Death Ex vivo perfusion Gene expression Heart Hypothermic machine perfusion Hypothermic oxygenated machine perfusion Ischemia Ischemia/reperfusion injury Laboratories Liver Liver - metabolism Liver graft preservation Liver Transplantation Liver transplants Models, Animal Organ Preservation - methods Oxygen - administration & dosage Oxygenation Perfusion Perfusion - methods Random Allocation Scavenging Sensors Superoxide dismutase Swine Tissue and Organ Procurement - methods Transplantation Transplants & implants |
| title | Novel oxygenation technique for hypothermic machine perfusion of liver grafts: Validation in porcine Donation after Cardiac Death (DCD) liver model |
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