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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

Authors :
Joseph A. Attard
Daniel-Clement Osei-Bordom
Yuri Boteon
Lorraine Wallace
Vincenzo Ronca
Gary Reynolds
M. T. P. R. Perera
Ye Htun Oo
Hynek Mergental
Darius F. Mirza
Simon C. Afford
Source :
Frontiers in Surgery, Vol 8 (2021), Frontiers in Surgery
Publication Year :
2021
Publisher :
Frontiers Media S.A., 2021.

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.

Details

Language :
English
Volume :
8
Database :
OpenAIRE
Journal :
Frontiers in Surgery
Accession number :
edsair.doi.dedup.....128bfdc88a5ae37adfbb6ec91c975fd3
Full Text :
https://doi.org/10.3389/fsurg.2021.627332/full