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Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion

There continues to be significant debate regarding the most effective mode of ex situ machine perfusion of livers for transplantation. Subnormothermic (SNMP) and normothermic machine perfusion (NMP) are two methods with different benefits. We examined the metabolomic profiles of discarded steatotic...

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Autores principales: Karimian, Negin, Raigani, Siavash, Huang, Viola, Nagpal, Sonal, Hafiz, Ehab O. A., Beijert, Irene, Mahboub, Paria, Porte, Robert J., Uygun, Korkut, Yarmush, Martin, Yeh, Heidi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918199/
https://www.ncbi.nlm.nih.gov/pubmed/31652927
http://dx.doi.org/10.3390/metabo9110246
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author Karimian, Negin
Raigani, Siavash
Huang, Viola
Nagpal, Sonal
Hafiz, Ehab O. A.
Beijert, Irene
Mahboub, Paria
Porte, Robert J.
Uygun, Korkut
Yarmush, Martin
Yeh, Heidi
author_facet Karimian, Negin
Raigani, Siavash
Huang, Viola
Nagpal, Sonal
Hafiz, Ehab O. A.
Beijert, Irene
Mahboub, Paria
Porte, Robert J.
Uygun, Korkut
Yarmush, Martin
Yeh, Heidi
author_sort Karimian, Negin
collection PubMed
description There continues to be significant debate regarding the most effective mode of ex situ machine perfusion of livers for transplantation. Subnormothermic (SNMP) and normothermic machine perfusion (NMP) are two methods with different benefits. We examined the metabolomic profiles of discarded steatotic human livers during three hours of subnormothermic or normothermic machine perfusion. Steatotic livers regenerate higher stores of ATP during SNMP than NMP. However, there is a significant depletion of available glutathione during SNMP, likely due to an inability to overcome the high energy threshold needed to synthesize glutathione. This highlights the increased oxidative stress apparent in steatotic livers. Rescue of discarded steatotic livers with machine perfusion may require the optimization of redox status through repletion or supplementation of reducing agents.
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spelling pubmed-69181992019-12-24 Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion Karimian, Negin Raigani, Siavash Huang, Viola Nagpal, Sonal Hafiz, Ehab O. A. Beijert, Irene Mahboub, Paria Porte, Robert J. Uygun, Korkut Yarmush, Martin Yeh, Heidi Metabolites Article There continues to be significant debate regarding the most effective mode of ex situ machine perfusion of livers for transplantation. Subnormothermic (SNMP) and normothermic machine perfusion (NMP) are two methods with different benefits. We examined the metabolomic profiles of discarded steatotic human livers during three hours of subnormothermic or normothermic machine perfusion. Steatotic livers regenerate higher stores of ATP during SNMP than NMP. However, there is a significant depletion of available glutathione during SNMP, likely due to an inability to overcome the high energy threshold needed to synthesize glutathione. This highlights the increased oxidative stress apparent in steatotic livers. Rescue of discarded steatotic livers with machine perfusion may require the optimization of redox status through repletion or supplementation of reducing agents. MDPI 2019-10-24 /pmc/articles/PMC6918199/ /pubmed/31652927 http://dx.doi.org/10.3390/metabo9110246 Text en © 2019 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Karimian, Negin
Raigani, Siavash
Huang, Viola
Nagpal, Sonal
Hafiz, Ehab O. A.
Beijert, Irene
Mahboub, Paria
Porte, Robert J.
Uygun, Korkut
Yarmush, Martin
Yeh, Heidi
Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion
title Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion
title_full Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion
title_fullStr Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion
title_full_unstemmed Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion
title_short Subnormothermic Machine Perfusion of Steatotic Livers Results in Increased Energy Charge at the Cost of Anti-Oxidant Capacity Compared to Normothermic Perfusion
title_sort subnormothermic machine perfusion of steatotic livers results in increased energy charge at the cost of anti-oxidant capacity compared to normothermic perfusion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918199/
https://www.ncbi.nlm.nih.gov/pubmed/31652927
http://dx.doi.org/10.3390/metabo9110246
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