title: Liver preservation with machine perfusion and a newly developed cell-free oxygen carrier solution under subnormothermic conditions.
abstract: We describe a new preservation modality combining machine perfusion (MP) at subnormothermic conditions(21 °C) with a new hemoglobin-based oxygen carrier (HBOC) solution. MP (n=6) was compared to cold static preservation (CSP; n=6) in porcine orthotopic liver transplants after 9 h of cold ischemia and 5-day follow-up. Recipients' peripheral blood, serial liver biopsies, preservation solutions and bile specimens were collected before, during and after liver preservation. Clinical laboratorial and histological analyses were performed in addition to mitochondrial functional assays, transcriptomic, metabolomic and inflammatory inflammatory mediator analyses. Compared with CSP, MP animals had: (1) significantly higher survival (100%vs. 33%; p<0.05); (2) superior graft function (p<0.05);(3) eight times higher hepatic O2 delivery than O2 consumption (0.78 mL O2/g/h vs. 0.096 mL O2/g/h) during MP; and (4) significantly greater bile production (MP=378.5 ± 179.7; CS=151.6 ± 116.85). MP downregulated interferon (IFN)-α and IFN-γ in liver tissue. MP allografts cleared lactate, produced urea, sustained gluconeogenesis and produced hydrophilic bile after reperfusion. Enhanced oxygenation under subnormothermic conditions triggers regenerative and cell protective responses resulting in improved allograft function. MP at 21 °C with the HBOC solution significantly improves liver preservation compared to CSP.
authors.forename: P
authors.initials: P
authors.lastname: Fontes
authors.forename: R
authors.initials: R
authors.lastname: Lopez
authors.forename: A
authors.initials: A
authors.lastname: van der Plaats
authors.forename: Y
authors.initials: Y
authors.lastname: Vodovotz
authors.forename: M
authors.initials: M
authors.lastname: Minervini
authors.forename: V
authors.initials: V
authors.lastname: Scott
authors.forename: K
authors.initials: K
authors.lastname: Soltys
authors.forename: S
authors.initials: S
authors.lastname: Shiva
authors.forename: S
authors.initials: S
authors.lastname: Paranjpe
authors.forename: D
authors.initials: D
authors.lastname: Sadowsky
authors.forename: D
authors.initials: D
authors.lastname: Barclay
authors.forename: R
authors.initials: R
authors.lastname: Zamora
authors.forename: D
authors.initials: D
authors.lastname: Stolz
authors.forename: A
authors.initials: A
authors.lastname: Demetris
authors.forename: G
authors.initials: G
authors.lastname: Michalopoulos
authors.forename: J W
authors.initials: JW
authors.lastname: Marsh
mesh_terms: D064591:Allografts; D000818:Animals; D003080:Cold Temperature; D020869:Gene Expression Profiling; D006085:Graft Survival / Q000502:physiology; D006454:Hemoglobins; D008099:Liver / Q000502:physiology*; D016031:Liver Transplantation / Q000379:methods; D055432:Metabolomics; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions; D010100:Oxygen; D010477:Perfusion / Q000295:instrumentation* / Q000379:methods*; D034421:Sus scrofa
chemical_list: D006454:Hemoglobins; D019188:Organ Preservation Solutions; D010100:Oxygen