Joseph A Attard1,2,3, Daniel-Clement Osei-Bordom1,2, Yuri Boteon1,2,3, Lorraine Wallace1,2, Vincenzo Ronca1,2, Gary Reynolds1,2, M T P R Perera3, Ye Htun Oo1,2,3,4, Hynek Mergental1,2,3, Darius F Mirza3, Simon C Afford1,2. 1. 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. 2. Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom. 3. Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom. 4. Centre for Rare Disease, European Reference Network Centre (ERN RARE-LIVER), Hamburg, Germany.
Abstract
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.
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.
Authors: Hynek Mergental; Barney Tf Stephenson; Richard W Laing; Paolo Muiesan; M Thamara Pr Perera; Simon C Afford; Darius F Mirza Journal: Ann Surg Open Date: 2022-02-03
Authors: Dimitri Sneiders; Anne-Baue R M van Dijk; Wojciech G Polak; Darius F Mirza; M Thamara P R Perera; Hermien Hartog Journal: Transpl Int Date: 2021-12-02 Impact factor: 3.842