Dual Lactate Clearance in the Viability Assessment of Livers Donated After Circulatory Death With Ex Situ Normothermic Machine Perfusion

Background. Perfusate lactate clearance (LC) is considered one of the useful indicators of liver viability assessment during normothermic machine perfusion (NMP); however, the applicable scope and potential mechanisms of LC remain poorly defined in the setting of liver donation after circulatory dea...

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Autores principales:	Min Xu, MD, Fangyu Zhou, MD, Ola Ahmed, MD, Lucy V. Randle, BSc, Jun-Kyu Shin, PhD, Yuehui Zhu, PhD, Gundumi A. Upadhya, PhD, Kathleen Byrnes, MD, Brian Wong, PhD, Jae-Sung Kim, PhD, Yiing Lin, MD, PhD, William C. Chapman, MD
Formato:	article
Lenguaje:	EN
Publicado:	Wolters Kluwer 2021
Materias:	Surgery RD1-811
Acceso en línea:	https://doaj.org/article/a3a0dad254144335b8d47cdb3a5273e8
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spelling	oai:doaj.org-article:a3a0dad254144335b8d47cdb3a5273e82021-11-25T07:59:57ZDual Lactate Clearance in the Viability Assessment of Livers Donated After Circulatory Death With Ex Situ Normothermic Machine Perfusion2373-873110.1097/TXD.0000000000001243https://doaj.org/article/a3a0dad254144335b8d47cdb3a5273e82021-12-01T00:00:00Zhttp://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001243https://doaj.org/toc/2373-8731Background. Perfusate lactate clearance (LC) is considered one of the useful indicators of liver viability assessment during normothermic machine perfusion (NMP); however, the applicable scope and potential mechanisms of LC remain poorly defined in the setting of liver donation after circulatory death. Methods. The ex situ NMP of end-ischemic human livers was performed using the OrganOx Metra device. We further studied the extracellular signal-regulated kinases (phospho-extracellular signal-regulated kinase1/2 [pERK1/2]) pathway and several clinical parameters of these livers with successful LC (sLC, n = 5) compared with non-sLC (nLC, n = 5) in the perfusate (<2.2 mmol/L at 2 h, n = 5, rapid retrieval without normothermic regional perfusion). Results. We found the pERK1/2 level was substantially higher in the nLC livers than in the sLC livers (n = 5) at 2- and 6-h NMP (P = 0.035 and P = 0.006, respectively). Immunostaining showed that upregulation of pERK1/2 was in both the hepatocytes and cholangiocytes in the nLC livers. Successful LC was associated with a marginally higher glycogen restoration than nLC at 2 h NMP (n = 5, P = 0.065). Furthermore, bile lactate levels in all sLC livers were cleared into the normal range at 6 h NMP, whereas in the nLC group, only 2 livers had lower bile lactate levels, and the other livers had rising bile lactate levels in comparison with the corresponding perfusate lactate levels. The necrosis scores were higher in the nLC than in the sLC livers (n = 5) at 0- and 6-h NMP (P = 0.047 and P = 0.053, respectively). Conclusions. The dual LC in perfusate and bile can be helpful in evaluating the hypoxic injury of hepatocytes and cholangiocytes during the NMP of donation after circulatory death in liver donors.Min Xu, MDFangyu Zhou, MDOla Ahmed, MDLucy V. Randle, BScJun-Kyu Shin, PhDYuehui Zhu, PhDGundumi A. Upadhya, PhDKathleen Byrnes, MDBrian Wong, PhDJae-Sung Kim, PhDYiing Lin, MD, PhDWilliam C. Chapman, MDWolters KluwerarticleSurgeryRD1-811ENTransplantation Direct, Vol 7, Iss 12, p e789 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Surgery RD1-811
spellingShingle	Surgery RD1-811 Min Xu, MD Fangyu Zhou, MD Ola Ahmed, MD Lucy V. Randle, BSc Jun-Kyu Shin, PhD Yuehui Zhu, PhD Gundumi A. Upadhya, PhD Kathleen Byrnes, MD Brian Wong, PhD Jae-Sung Kim, PhD Yiing Lin, MD, PhD William C. Chapman, MD Dual Lactate Clearance in the Viability Assessment of Livers Donated After Circulatory Death With Ex Situ Normothermic Machine Perfusion
description	Background. Perfusate lactate clearance (LC) is considered one of the useful indicators of liver viability assessment during normothermic machine perfusion (NMP); however, the applicable scope and potential mechanisms of LC remain poorly defined in the setting of liver donation after circulatory death. Methods. The ex situ NMP of end-ischemic human livers was performed using the OrganOx Metra device. We further studied the extracellular signal-regulated kinases (phospho-extracellular signal-regulated kinase1/2 [pERK1/2]) pathway and several clinical parameters of these livers with successful LC (sLC, n = 5) compared with non-sLC (nLC, n = 5) in the perfusate (<2.2 mmol/L at 2 h, n = 5, rapid retrieval without normothermic regional perfusion). Results. We found the pERK1/2 level was substantially higher in the nLC livers than in the sLC livers (n = 5) at 2- and 6-h NMP (P = 0.035 and P = 0.006, respectively). Immunostaining showed that upregulation of pERK1/2 was in both the hepatocytes and cholangiocytes in the nLC livers. Successful LC was associated with a marginally higher glycogen restoration than nLC at 2 h NMP (n = 5, P = 0.065). Furthermore, bile lactate levels in all sLC livers were cleared into the normal range at 6 h NMP, whereas in the nLC group, only 2 livers had lower bile lactate levels, and the other livers had rising bile lactate levels in comparison with the corresponding perfusate lactate levels. The necrosis scores were higher in the nLC than in the sLC livers (n = 5) at 0- and 6-h NMP (P = 0.047 and P = 0.053, respectively). Conclusions. The dual LC in perfusate and bile can be helpful in evaluating the hypoxic injury of hepatocytes and cholangiocytes during the NMP of donation after circulatory death in liver donors.
format	article
author	Min Xu, MD Fangyu Zhou, MD Ola Ahmed, MD Lucy V. Randle, BSc Jun-Kyu Shin, PhD Yuehui Zhu, PhD Gundumi A. Upadhya, PhD Kathleen Byrnes, MD Brian Wong, PhD Jae-Sung Kim, PhD Yiing Lin, MD, PhD William C. Chapman, MD
author_facet	Min Xu, MD Fangyu Zhou, MD Ola Ahmed, MD Lucy V. Randle, BSc Jun-Kyu Shin, PhD Yuehui Zhu, PhD Gundumi A. Upadhya, PhD Kathleen Byrnes, MD Brian Wong, PhD Jae-Sung Kim, PhD Yiing Lin, MD, PhD William C. Chapman, MD
author_sort	Min Xu, MD
title	Dual Lactate Clearance in the Viability Assessment of Livers Donated After Circulatory Death With Ex Situ Normothermic Machine Perfusion
title_short	Dual Lactate Clearance in the Viability Assessment of Livers Donated After Circulatory Death With Ex Situ Normothermic Machine Perfusion
title_full	Dual Lactate Clearance in the Viability Assessment of Livers Donated After Circulatory Death With Ex Situ Normothermic Machine Perfusion
title_fullStr	Dual Lactate Clearance in the Viability Assessment of Livers Donated After Circulatory Death With Ex Situ Normothermic Machine Perfusion
title_full_unstemmed	Dual Lactate Clearance in the Viability Assessment of Livers Donated After Circulatory Death With Ex Situ Normothermic Machine Perfusion
title_sort	dual lactate clearance in the viability assessment of livers donated after circulatory death with ex situ normothermic machine perfusion
publisher	Wolters Kluwer
publishDate	2021
url	https://doaj.org/article/a3a0dad254144335b8d47cdb3a5273e8
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Dual Lactate Clearance in the Viability Assessment of Livers Donated After Circulatory Death With Ex Situ Normothermic Machine Perfusion

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