Exploration of Optimal pH in Hypothermic Machine Perfusion for Rat Liver Grafts Retrieved after Circulatory Death
Ex vivo hypothermic machine perfusion (HMP) is a strategy for controlling ischemia-reperfusion injury in donation after circulatory death (DCD) liver transplantation. The pH of blood increases with a decrease in temperature and water dissociation, leading to a decrease in [H ]. This study aimed to v...
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| Veröffentlicht in: | Journal of clinical medicine 2023-06, Vol.12 (11), p.3845 |
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| creator | Sakamoto, Sodai Bochimoto, Hiroki Shibata, Kengo Zin, Nur Khatijah Mohd Fukai, Moto Nakamura, Kosei Ishikawa, Takahisa Fujiyoshi, Masato Shimamura, Tsuyoshi Taketomi, Akinobu |
| description | Ex vivo hypothermic machine perfusion (HMP) is a strategy for controlling ischemia-reperfusion injury in donation after circulatory death (DCD) liver transplantation. The pH of blood increases with a decrease in temperature and water dissociation, leading to a decrease in [H
]. This study aimed to verify the optimal pH of HMP for DCD livers. Rat livers were retrieved 30 min post-cardiac arrest and subjected to 3-h cold storage (CS) in UW solution (CS group) or HMP with UW-gluconate solution (machine perfusion [MP] group) of pH 7.4 (original), 7.6, 7.8, and 8.0 (MP-pH 7.6, 7.8, 8.0 groups, respectively) at 7-10 °C. The livers were subjected to normothermic perfusion to simulate reperfusion after HMP. All HMP groups showed greater graft protection compared to the CS group due to the lower levels of liver enzymes in the former. The MP-pH 7.8 group showed significant protection, evidenced by bile production, diminished tissue injury, and reduced flavin mononucleotide leakage, and further analysis by scanning electron microscopy revealed a well-preserved structure of the mitochondrial cristae. Therefore, the optimum pH of 7.8 enhanced the protective effect of HMP by preserving the structure and function of the mitochondria, leading to reduced reperfusion injury in the DCD liver. |
| doi_str_mv | 10.3390/jcm12113845 |
| format | Article |
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]. This study aimed to verify the optimal pH of HMP for DCD livers. Rat livers were retrieved 30 min post-cardiac arrest and subjected to 3-h cold storage (CS) in UW solution (CS group) or HMP with UW-gluconate solution (machine perfusion [MP] group) of pH 7.4 (original), 7.6, 7.8, and 8.0 (MP-pH 7.6, 7.8, 8.0 groups, respectively) at 7-10 °C. The livers were subjected to normothermic perfusion to simulate reperfusion after HMP. All HMP groups showed greater graft protection compared to the CS group due to the lower levels of liver enzymes in the former. The MP-pH 7.8 group showed significant protection, evidenced by bile production, diminished tissue injury, and reduced flavin mononucleotide leakage, and further analysis by scanning electron microscopy revealed a well-preserved structure of the mitochondrial cristae. Therefore, the optimum pH of 7.8 enhanced the protective effect of HMP by preserving the structure and function of the mitochondria, leading to reduced reperfusion injury in the DCD liver.</description><identifier>ISSN: 2077-0383</identifier><identifier>EISSN: 2077-0383</identifier><identifier>DOI: 10.3390/jcm12113845</identifier><identifier>PMID: 37298042</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Bile ducts ; Clinical medicine ; Enzymes ; Health aspects ; Hydrogen-ion concentration ; Isolation perfusion (Physiology) ; Laboratory animals ; Liver ; Management ; Methods ; Preservation of organs, tissues, etc ; Quality management ; Respiration ; Temperature ; Transplantation ; Veins & arteries</subject><ispartof>Journal of clinical medicine, 2023-06, Vol.12 (11), p.3845</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c477t-a07c27820493dc0abb2843a2979371fb3cbaada24c3d549d6e52ef2d1e59b313</citedby><cites>FETCH-LOGICAL-c477t-a07c27820493dc0abb2843a2979371fb3cbaada24c3d549d6e52ef2d1e59b313</cites><orcidid>0000-0002-8593-2258 ; 0000-0002-7995-8419 ; 0000-0002-1951-4015 ; 0000-0002-1708-0348 ; 0000-0001-5942-1211</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10253457/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10253457/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37298042$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sakamoto, Sodai</creatorcontrib><creatorcontrib>Bochimoto, Hiroki</creatorcontrib><creatorcontrib>Shibata, Kengo</creatorcontrib><creatorcontrib>Zin, Nur Khatijah Mohd</creatorcontrib><creatorcontrib>Fukai, Moto</creatorcontrib><creatorcontrib>Nakamura, Kosei</creatorcontrib><creatorcontrib>Ishikawa, Takahisa</creatorcontrib><creatorcontrib>Fujiyoshi, Masato</creatorcontrib><creatorcontrib>Shimamura, Tsuyoshi</creatorcontrib><creatorcontrib>Taketomi, Akinobu</creatorcontrib><title>Exploration of Optimal pH in Hypothermic Machine Perfusion for Rat Liver Grafts Retrieved after Circulatory Death</title><title>Journal of clinical medicine</title><addtitle>J Clin Med</addtitle><description>Ex vivo hypothermic machine perfusion (HMP) is a strategy for controlling ischemia-reperfusion injury in donation after circulatory death (DCD) liver transplantation. The pH of blood increases with a decrease in temperature and water dissociation, leading to a decrease in [H
]. This study aimed to verify the optimal pH of HMP for DCD livers. Rat livers were retrieved 30 min post-cardiac arrest and subjected to 3-h cold storage (CS) in UW solution (CS group) or HMP with UW-gluconate solution (machine perfusion [MP] group) of pH 7.4 (original), 7.6, 7.8, and 8.0 (MP-pH 7.6, 7.8, 8.0 groups, respectively) at 7-10 °C. The livers were subjected to normothermic perfusion to simulate reperfusion after HMP. All HMP groups showed greater graft protection compared to the CS group due to the lower levels of liver enzymes in the former. The MP-pH 7.8 group showed significant protection, evidenced by bile production, diminished tissue injury, and reduced flavin mononucleotide leakage, and further analysis by scanning electron microscopy revealed a well-preserved structure of the mitochondrial cristae. Therefore, the optimum pH of 7.8 enhanced the protective effect of HMP by preserving the structure and function of the mitochondria, leading to reduced reperfusion injury in the DCD liver.</description><subject>Bile ducts</subject><subject>Clinical medicine</subject><subject>Enzymes</subject><subject>Health aspects</subject><subject>Hydrogen-ion concentration</subject><subject>Isolation perfusion (Physiology)</subject><subject>Laboratory animals</subject><subject>Liver</subject><subject>Management</subject><subject>Methods</subject><subject>Preservation of organs, tissues, etc</subject><subject>Quality management</subject><subject>Respiration</subject><subject>Temperature</subject><subject>Transplantation</subject><subject>Veins & arteries</subject><issn>2077-0383</issn><issn>2077-0383</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNptkk1rGzEQhpfS0oQ0p96LoJdCcapPS3sqwU3jgktKyF1otaNYZne1kbSm_veVEzc4pdJBo9EzrzSaqar3BF8wVuMvG9sTSghTXLyqTimWcoaZYq-P7JPqPKUNLkMpTol8W50wSWuFOT2tHq5-j12IJvswoODQzZh9bzo0LpEf0HI3hryG2HuLfhq79gOgXxDdlPa4CxHdmoxWfgsRXUfjckK3kKOHLbSobIt74aOdOpND3KFvYPL6XfXGmS7B-WE9q-6-X90tlrPVzfWPxeVqZrmUeWawtFQqinnNWotN01DFmaG1rJkkrmG2MaY1lFvWCl63cxAUHG0JiLphhJ1VX59kx6npobUw5Gg6PcaSXtzpYLx-eTL4tb4PW00wFYwLWRQ-HRRieJggZd37ZKHrzABhSpoqyueqVoIV9OM_6CZMcSjpPVK41OfxSQfq3nSg_eBCudjuRfWlFJRLIebzQl38hyqzhVKGMIDzxf8i4PNTgI0hpQjuOUmC9b5J9FGTFPrD8b88s39bgv0Bz_i2-A</recordid><startdate>20230604</startdate><enddate>20230604</enddate><creator>Sakamoto, Sodai</creator><creator>Bochimoto, Hiroki</creator><creator>Shibata, Kengo</creator><creator>Zin, Nur Khatijah Mohd</creator><creator>Fukai, Moto</creator><creator>Nakamura, Kosei</creator><creator>Ishikawa, Takahisa</creator><creator>Fujiyoshi, Masato</creator><creator>Shimamura, Tsuyoshi</creator><creator>Taketomi, Akinobu</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8593-2258</orcidid><orcidid>https://orcid.org/0000-0002-7995-8419</orcidid><orcidid>https://orcid.org/0000-0002-1951-4015</orcidid><orcidid>https://orcid.org/0000-0002-1708-0348</orcidid><orcidid>https://orcid.org/0000-0001-5942-1211</orcidid></search><sort><creationdate>20230604</creationdate><title>Exploration of Optimal pH in Hypothermic Machine Perfusion for Rat Liver Grafts Retrieved after Circulatory Death</title><author>Sakamoto, Sodai ; 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The pH of blood increases with a decrease in temperature and water dissociation, leading to a decrease in [H
]. This study aimed to verify the optimal pH of HMP for DCD livers. Rat livers were retrieved 30 min post-cardiac arrest and subjected to 3-h cold storage (CS) in UW solution (CS group) or HMP with UW-gluconate solution (machine perfusion [MP] group) of pH 7.4 (original), 7.6, 7.8, and 8.0 (MP-pH 7.6, 7.8, 8.0 groups, respectively) at 7-10 °C. The livers were subjected to normothermic perfusion to simulate reperfusion after HMP. All HMP groups showed greater graft protection compared to the CS group due to the lower levels of liver enzymes in the former. The MP-pH 7.8 group showed significant protection, evidenced by bile production, diminished tissue injury, and reduced flavin mononucleotide leakage, and further analysis by scanning electron microscopy revealed a well-preserved structure of the mitochondrial cristae. Therefore, the optimum pH of 7.8 enhanced the protective effect of HMP by preserving the structure and function of the mitochondria, leading to reduced reperfusion injury in the DCD liver.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>37298042</pmid><doi>10.3390/jcm12113845</doi><orcidid>https://orcid.org/0000-0002-8593-2258</orcidid><orcidid>https://orcid.org/0000-0002-7995-8419</orcidid><orcidid>https://orcid.org/0000-0002-1951-4015</orcidid><orcidid>https://orcid.org/0000-0002-1708-0348</orcidid><orcidid>https://orcid.org/0000-0001-5942-1211</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Bile ducts Clinical medicine Enzymes Health aspects Hydrogen-ion concentration Isolation perfusion (Physiology) Laboratory animals Liver Management Methods Preservation of organs, tissues, etc Quality management Respiration Temperature Transplantation Veins & arteries |
| title | Exploration of Optimal pH in Hypothermic Machine Perfusion for Rat Liver Grafts Retrieved after Circulatory Death |
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