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Ex situ Normothermic Split Liver Machine Perfusion: Protocol for Robust Comparative Controls in Liver Function Assessment Suitable for Evaluation of Novel Therapeutic Interventions in the Pre-clinical Setting

Background: Ex situ donor liver machine perfusion is a promising tool to assess organ viability prior to transplantation and platform to investigate novel therapeutic interventions. However, the wide variability in donor and graft characteristics between individual donor livers limits the comparabil...

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Autores principales: Attard, Joseph A., Osei-Bordom, Daniel-Clement, Boteon, Yuri, Wallace, Lorraine, Ronca, Vincenzo, Reynolds, Gary, Perera, M. T. P. R., Oo, Ye Htun, Mergental, Hynek, Mirza, Darius F., Afford, Simon C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925992/
https://www.ncbi.nlm.nih.gov/pubmed/33681282
http://dx.doi.org/10.3389/fsurg.2021.627332
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author Attard, Joseph A.
Osei-Bordom, Daniel-Clement
Boteon, Yuri
Wallace, Lorraine
Ronca, Vincenzo
Reynolds, Gary
Perera, M. T. P. R.
Oo, Ye Htun
Mergental, Hynek
Mirza, Darius F.
Afford, Simon C.
author_facet Attard, Joseph A.
Osei-Bordom, Daniel-Clement
Boteon, Yuri
Wallace, Lorraine
Ronca, Vincenzo
Reynolds, Gary
Perera, M. T. P. R.
Oo, Ye Htun
Mergental, Hynek
Mirza, Darius F.
Afford, Simon C.
author_sort Attard, Joseph A.
collection PubMed
description Background: Ex situ donor liver machine perfusion is a promising tool to assess organ viability prior to transplantation and platform to investigate novel therapeutic interventions. However, the wide variability in donor and graft characteristics between individual donor livers limits the comparability of results. We investigated the hypothesis that the development of a split liver ex situ machine perfusion protocol provides the ideal comparative controls in the investigation of machine perfusion techniques and therapeutic interventions, thus leading to more comparable results. Methods: Four discarded human donor livers were surgically split following identification and separation of right and left inflow and outflow vessels. Each lobe, on separate perfusion machines, was subjected to normothermic perfusion using an artificial hemoglobin-based oxygen carrier solution for 6 h. Metabolic parameters as well as hepatic artery and portal vein perfusion parameters monitored. Results: Trends in hepatic artery and portal vein flows showed a general increase in both lobes throughout each perfusion experiment, even when normalized for tissue weight. Progressive decreases in perfusate lactate and glucose levels exhibited comparable trends in between lobes. Conclusion: Our results demonstrate comparability between right and left lobes when simultaneously subjected to normothermic machine perfusion. In the pre-clinical setting, this model provides the ideal comparative controls in the investigation of therapeutic interventions.
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spelling pubmed-79259922021-03-04 Ex situ Normothermic Split Liver Machine Perfusion: Protocol for Robust Comparative Controls in Liver Function Assessment Suitable for Evaluation of Novel Therapeutic Interventions in the Pre-clinical Setting Attard, Joseph A. Osei-Bordom, Daniel-Clement Boteon, Yuri Wallace, Lorraine Ronca, Vincenzo Reynolds, Gary Perera, M. T. P. R. Oo, Ye Htun Mergental, Hynek Mirza, Darius F. Afford, Simon C. Front Surg Surgery Background: Ex situ donor liver machine perfusion is a promising tool to assess organ viability prior to transplantation and platform to investigate novel therapeutic interventions. However, the wide variability in donor and graft characteristics between individual donor livers limits the comparability of results. We investigated the hypothesis that the development of a split liver ex situ machine perfusion protocol provides the ideal comparative controls in the investigation of machine perfusion techniques and therapeutic interventions, thus leading to more comparable results. Methods: Four discarded human donor livers were surgically split following identification and separation of right and left inflow and outflow vessels. Each lobe, on separate perfusion machines, was subjected to normothermic perfusion using an artificial hemoglobin-based oxygen carrier solution for 6 h. Metabolic parameters as well as hepatic artery and portal vein perfusion parameters monitored. Results: Trends in hepatic artery and portal vein flows showed a general increase in both lobes throughout each perfusion experiment, even when normalized for tissue weight. Progressive decreases in perfusate lactate and glucose levels exhibited comparable trends in between lobes. Conclusion: Our results demonstrate comparability between right and left lobes when simultaneously subjected to normothermic machine perfusion. In the pre-clinical setting, this model provides the ideal comparative controls in the investigation of therapeutic interventions. Frontiers Media S.A. 2021-02-17 /pmc/articles/PMC7925992/ /pubmed/33681282 http://dx.doi.org/10.3389/fsurg.2021.627332 Text en Copyright © 2021 Attard, Osei-Bordom, Boteon, Wallace, Ronca, Reynolds, Perera, Oo, Mergental, Mirza and Afford. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Surgery
Attard, Joseph A.
Osei-Bordom, Daniel-Clement
Boteon, Yuri
Wallace, Lorraine
Ronca, Vincenzo
Reynolds, Gary
Perera, M. T. P. R.
Oo, Ye Htun
Mergental, Hynek
Mirza, Darius F.
Afford, Simon C.
Ex situ Normothermic Split Liver Machine Perfusion: Protocol for Robust Comparative Controls in Liver Function Assessment Suitable for Evaluation of Novel Therapeutic Interventions in the Pre-clinical Setting
title Ex situ Normothermic Split Liver Machine Perfusion: Protocol for Robust Comparative Controls in Liver Function Assessment Suitable for Evaluation of Novel Therapeutic Interventions in the Pre-clinical Setting
title_full Ex situ Normothermic Split Liver Machine Perfusion: Protocol for Robust Comparative Controls in Liver Function Assessment Suitable for Evaluation of Novel Therapeutic Interventions in the Pre-clinical Setting
title_fullStr Ex situ Normothermic Split Liver Machine Perfusion: Protocol for Robust Comparative Controls in Liver Function Assessment Suitable for Evaluation of Novel Therapeutic Interventions in the Pre-clinical Setting
title_full_unstemmed Ex situ Normothermic Split Liver Machine Perfusion: Protocol for Robust Comparative Controls in Liver Function Assessment Suitable for Evaluation of Novel Therapeutic Interventions in the Pre-clinical Setting
title_short Ex situ Normothermic Split Liver Machine Perfusion: Protocol for Robust Comparative Controls in Liver Function Assessment Suitable for Evaluation of Novel Therapeutic Interventions in the Pre-clinical Setting
title_sort ex situ normothermic split liver machine perfusion: protocol for robust comparative controls in liver function assessment suitable for evaluation of novel therapeutic interventions in the pre-clinical setting
topic Surgery
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925992/
https://www.ncbi.nlm.nih.gov/pubmed/33681282
http://dx.doi.org/10.3389/fsurg.2021.627332
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