Split-Liver Ex Situ Machine Perfusion: A Novel Technique for Studying Organ Preservation and Therapeutic Interventions

Abstract

Ex situ machine perfusion is a promising technology to help improve organ viability prior to transplantation. However, preclinical studies using discarded human livers to evaluate therapeutic interventions and optimize perfusion conditions are limited by significant graft heterogeneity. In order to improve the efficacy and reproducibility of future studies, a split-liver perfusion model was developed to allow simultaneous perfusion of left and right lobes, allowing one lobe to serve as a control for the other. Eleven discarded livers were surgically split, and both lobes perfused simultaneously on separate perfusion devices for 3 h at subnormothermic temperatures. Lobar perfusion parameters were also compared with whole livers undergoing perfusion. Similar to whole-liver perfusions, each lobe in the split-liver model exhibited a progressive decrease in arterial resistance and lactate levels throughout perfusion, which were not significantly different between right and left lobes. Split liver lobes also demonstrated comparable energy charge ratios. Ex situ split-liver perfusion is a novel experimental model that allows each graft to act as its own control. This model is particularly well suited for preclinical studies by avoiding the need for large numbers of enrolled livers necessary due to the heterogenous nature of discarded human liver research.

Ischemia-Reperfusion Injury in Marginal Liver Grafts and the Role of Hypothermic Machine Perfusion: Molecular Mechanisms and Clinical Implications

“…Another specific issue in liver transplantation is the need for allograft-recipient size matching and the unique ability of the liver to regenerate. In this context, machine perfusion may provide a possible platform for ex vivo splitting or size reduction of donor allografts [89,90].…”

Organ Restoration With Normothermic Machine Perfusion and Immune Reaction

“…Huang et al (27) used sub-normothermic machine liver perfusion (SNMLP) in whole and split liver NMLP. The study highlighted that ATP generation during perfusion is a potential viability marker that may be predictive of allograft function after transplantation.…”

The New Horizon of Split‐Liver Transplantation: Ex Situ Liver Splitting During Hypothermic Oxygenated Machine Perfusion

“…(2) For technical or logistical reasons, SLT often involves the extension of CIT, which increases the ischemia damage and negatively impacts the outcomes of split grafts. (1) On the basis of the proprieties of D-HOPE (2) and preclinical models, (3,4) in the current case wherein prolonged CIT was expected, we decided to perform the splitting procedure during D-HOPE. Our goals were to minimize ischemia damage due to long transport times and ex situ splitting plus LLS hyperreduction as well as to limit the IRI of the ERG, which would have an even longer ischemia time for being a sequential transplantation.…”