Abstract
BackgroundSubnormothermic machine perfusion (SNMP) of liver grafts is currently less clinically developed than normothermic and hypothermic approaches, but may have logistical advantages. At intermediate temperatures, the oxygen demand of the graft is low enough to be satisfied with an acellular perfusate, obviating the need for oxygen carrying molecules. This intermediate metabolic rate, however, is sufficient to support the production of bile, which is emerging as an important indicator of graft injury and viability. In this study, we hypothesized that the biliary compartment would be more sensitive than perfusate in detecting graft injury during SNMP.MethodsTo test this hypothesis in a rat model, we performed liver transplants with DCD and control liver grafts after 1 h of acellular room temperature machine perfusion (acRTMP) or static cold storage (SCS). Point of care liver function tests were measured in biliary and perfusate samples after 1 h of machine perfusion. Following transplantation, rats were sacrificed at 24 h for assessment of post-transplant graft function and histology.ResultsAll point-of-care liver function tests were significantly more concentrated in the biliary compartment than the perfusate compartment during acRTMP. DCD liver grafts could be distinguished from control liver grafts by significantly higher markers of hepatocyte injury (AST, ALT) in the biliary compartment, but not in the perfusate compartment. Classical markers of cholangiocyte injury, such as gammy-glut amyl transferase (GGT), amylase (AML), and alkaline phosphatase were detectable in the biliary compartment, but not in the perfusate compartment. In comparison to SCS, graft preservation by acRTMP produced a significant survival benefit in DCD liver transplantation (75 vs. 0%, p < 0.0030).ConclusionTogether, these findings demonstrate that during acRTMP, the biliary compartment may be a more sensitive indicator of graft injury than the perfusate compartment. Moreover, acRTMP provides superior graft preservation to SCS in rat DCD liver transplantation.
Highlights
Ex vivo machine perfusion has emerged as a superior method for graft preservation over static cold storage (SCS) in liver transplantation [1, 2]
We demonstrate that markers of graft injury are all significantly more concentrated in the biliary compartment relative to perfusate, and that differences between DCD and control livers can only be distinguished by examination of the biliary compartment
Both control and DCD liver grafts were maintained at a fixed portal vein flow rate of 3 ml/min/gram tissue (Figure 3)
Summary
Ex vivo machine perfusion has emerged as a superior method for graft preservation over static cold storage (SCS) in liver transplantation [1, 2]. The oxygen requirement of the graft is low enough to be met with a simple acellular perfusate, yet the metabolic activity of the graft is sufficiently high to support the production of bile, which is emerging as an important indicator of graft injury and viability [4,5,6,7]. The oxygen demand of the graft is low enough to be satisfied with an acellular perfusate, obviating the need for oxygen carrying molecules. This intermediate metabolic rate, is sufficient to support the production of bile, which is emerging as an important indicator of graft injury and viability.
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