Impact of Subnormothermic Machine Perfusion Preservation in Severely Steatotic Rat Livers: A Detailed Assessment in an Isolated Setting

Current drastic shortage of donor organs has led to acceptance of extended-criteria donors for transplantation, despite higher risk of primary non-function. Here, we report the impact of subnormothermic machine perfusion (SMP) preservation on the protection of >50% macro-steatotic livers. Dietary hepatic steatosis was induced in Wistar rats via 2-day fasting and subsequent 3-day re-feeding with a fat-free, carbohydrate-rich diet. This protocol induces 50-60% macrovesicular steatosis, which should be discarded when preserved via cold storage (CS). The fatty livers were retrieved and preserved for 4 hours using either CS in histidine-tryptophan-ketoglutarate (HTK) or SMP in Polysol solution. Graft functional integrity was evaluated via oxygenated ex vivo reperfusion for 2 hours at 37°C. SMP resulted in significant reductions in not only parenchymal (ALT: p<0.001) but also mitochondrial (GLDH: p<0.001) enzyme release. Moreover, portal venous pressure (p=0.047), tissue adenosine triphosphate (p=0.001), bile production (p<0.001), HMGB-1 (p<0.001), lipid peroxidation and tissue glutathione were all significantly improved by SMP. Electron microscopy revealed that SMP alleviated deleterious alterations of sinusoidal microvasculature and hepatocellular mitochondria, both of which are characteristic disadvantages associated with steatosis. SMP could protect 50-60% macro-steatotic livers from preservation/reperfusion injury, and may thus represent a new means for expanding available donor pools. This article is protected by copyright. All rights reserved.