A Novel Oxygenated Machine Perfusion System for Preservation of the Liver

Abstract

Machine perfusion (MP) is a potential method to increase the donor pool for organ transplantation. However, MP systems for liver grafts remain difficult to use because of organ-specific demands. Our aim was to test a novel, portable MP system for hypothermic preservation of the liver. A portable, pressure-regulated, oxygenated MP system designed for kidney preservation was adapted to perfuse liver grafts via the portal vein (PV). Three porcine livers underwent 20 h of hypothermic perfusion using Belzer MP solution. The MP system was assessed for perfusate flow, temperature, venous pressure, and pO2 /pCO2 during the preservation period. Biochemical and histological parameters were analyzed to determine postpreservation organ damage. Perfusate flow through the PV increased over time from 157 ± 25 mL/min at start to 177 ± 25 mL/min after 20 h. PV pressure remained stable at 13 ± 1 mm Hg. Perfusate temperature increased from 9.7 ± 0.6°C at the start to 11.0 ± 0.0°C after 20 h. Aspartate aminotransferase and lactate dehydrogenase increased from 281 ± 158 and 308 ± 171 U/L after 1 h to 524 ± 163 and 537 ± 168 U/L after 20 h, respectively. Blood gas analysis showed a stable pO2 of 338 ± 20 mm Hg before perfusion of the liver and 125 ± 14 mm Hg after 1 h perfusion. The pCO2 increased from 15 ± 5 mm Hg after 1 h to 53 ± 4 mm Hg after 20 h. No histological changes were found after 20 h of MP. This study demonstrated the feasibility of a portable MP system for preservation of the liver and showed that continuous perfusion via the PV can be maintained with an oxygen-driven pump system without notable preservation damage of the organ.

Hypothermic Oxygenated Liver Perfusion: Basic Mechanisms and Clinical Application

“…Importantly, the rate of oxygen consumption during HMP decreases rapidly during the first hour and ceases after 90 min at a low baseline level because of downregulation of mitochondrial respiration despite increasing ADP and sufficient levels of substrates (oxygen and electron donors) [15, 23, 24]. Accordingly, during hypothermic oxygenated liver perfusion, mitochondria switch from a high-flux electron transfer stage at the beginning of machine perfusion to a low-flux electron transfer stage during approximately 60-90 min of perfusion.…”

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“…This study showed that continuous perfusion via the portal vein can be maintained with an oxygen-driven pump system without notable preservation damage of the organ. 17 In a porcine liver transplant model, Vekemans and associates studied SCS-discarded human liver grafts to either 4 hours of HMP or an additional 4 hours of SCS. All livers were then warm reperfused to mimic ischemia-reperfusion injury ex vivo.…”

Liver ex situ machine perfusion preservation: A review of the methodology and results of large animal studies and clinical trials

“…In contrast to NMP settings, HMP settings are by definition not particularly physiologic, with perfusate temperature most commonly defined as 4°C. Many porcine HMP studies used kidney perfusion solution (KPS‐1), also known as UW solution of Belzer MP . Bessems et al was unique in comparing Celsior perfusate versus Polysol with the result that Celsior solution was more damaging than Polysol, increasing AST/ALT and intravascular resistance to a greater extent .…”