title: Impact of Subnormothermic Machine Perfusion Preservation in Severely Steatotic Rat Livers: A Detailed Assessment in an Isolated Setting.
abstract: The current drastic shortage of donor organs has led to acceptance of extended-criteria donors for transplantation, despite higher risk of primary nonfunction. Here, we report the impact of subnormothermic machine perfusion (SMP) preservation on the protection of >50% macrosteatotic 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 h using either CS in histidine-tryptophan-ketoglutarate or SMP in polysol solution. Graft functional integrity was evaluated via oxygenated ex vivo reperfusion for 2 h at 37°C. SMP resulted in significant reductions in not only parenchymal alanine aminotransferase (p < 0.001), but also mitochondrial glutamate dehydrogenase (p < 0.001) enzyme release. Moreover, portal venous pressure (p = 0.047), tissue adenosine triphosphate (p = 0.001), bile production (p < 0.001), high-mobility group box protein-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% macrosteatotic livers from preservation/reperfusion injury, and may thus represent a new means for expanding available donor pools.
authors.affiliation: Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Okamura
authors.affiliation: Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hata
authors.affiliation: Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hirao
authors.affiliation: Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kubota
authors.affiliation: Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Inamoto
authors.affiliation: Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: S
authors.identifier: http://orcid.org/0000-0002-2398-2428
authors.initials: S
authors.lastname: Kageyama
authors.affiliation: Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Tamaki
authors.affiliation: Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Yermek
authors.affiliation: Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Yoshikawa
authors.affiliation: Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Uemoto
mesh_terms: D000818:Animals; D005234:Fatty Liver / Q000503:physiopathology*; D016031:Liver Transplantation; D008297:Male; D009926:Organ Preservation; D010101:Oxygen Consumption; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury; D012720:Severity of Illness Index
keywords: animal models: murine; basic (laboratory) research/science; donors and donation: extended criteria; ischemia reperfusion injury (IRI); liver transplantation/hepatology; organ procurement and allocation