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.
Highlights
The main purpose of ex situ donor liver machine perfusion has been the development of superior modality of organ preservation to conventional static cold storage as well as a method to assess organ viability prior to transplantation [1]
In the United Kingdom, between April 2018 and March 2019, 15% of donor livers retrieved were not transplanted, representing a significant pool of potentially viable grafts [2] A recent randomized controlled clinical trial demonstrated that normothermic machine liver perfusion (NMLP) reduced discard rates of donor organs when compared to static cold storage, without jeopardizing transplant outcomes [3, 4]
Lactate levels were comparable at the start of perfusion, Start of Perfusion (T0), and decreased significantly in all lobes up until the end of the perfusion experiment, End of Perfusion after 6 h (T6) (Figure 4)
Summary
The main purpose of ex situ donor liver machine perfusion has been the development of superior modality of organ preservation to conventional static cold storage as well as a method to assess organ viability prior to transplantation [1]. The principal components include a blood reservoir, centrifugal pump, oxygen concentrator, heat exchanger and a circuit which continuously pumps perfusate through the liver via the organ’s inflow vessels (hepatic artery and/or portal vein) and recirculates this following drainage from the inferior vena cava [1]. These systems allow for extraction of perfusate for blood gas analysis, enabling real-time monitoring of oxygen and carbon dioxide levels, acid-base homeostasis as well as glucose levels [1] All these parameters have been described as markers for organ viability during machine perfusion [5]. 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, leading to more comparable results
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