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.

Autor:	Attard JA; National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, University of Birmingham, Birmingham, United Kingdom.; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.; Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom., Osei-Bordom DC; National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, University of Birmingham, Birmingham, United Kingdom.; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom., Boteon Y; National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, University of Birmingham, Birmingham, United Kingdom.; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.; Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom., Wallace L; National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, University of Birmingham, Birmingham, United Kingdom.; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom., Ronca V; National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, University of Birmingham, Birmingham, United Kingdom.; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom., Reynolds G; National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, University of Birmingham, Birmingham, United Kingdom.; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom., Perera MTPR; Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom., Oo YH; National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, University of Birmingham, Birmingham, United Kingdom.; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.; Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom.; Centre for Rare Disease, European Reference Network Centre (ERN RARE-LIVER), Hamburg, Germany., Mergental H; National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, University of Birmingham, Birmingham, United Kingdom.; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.; Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom., Mirza DF; Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom., Afford SC; National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, University of Birmingham, Birmingham, United Kingdom.; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
Jazyk:	angličtina
Zdroj:	Frontiers in surgery [Front Surg] 2021 Feb 17; Vol. 8, pp. 627332. Date of Electronic Publication: 2021 Feb 17 (Print Publication: 2021).
DOI:	10.3389/fsurg.2021.627332
Abstrakt:	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. Competing Interests: JA is a clinical research fellow at the Queen Elizabeth Hospital in Birmingham and employed by University Hospitals Birmingham. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Attard, Osei-Bordom, Boteon, Wallace, Ronca, Reynolds, Perera, Oo, Mergental, Mirza and Afford.)
Databáze:	MEDLINE
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