title: Metabolic profiling during ex vivo machine perfusion of the human liver.
abstract: As donor organ shortages persist, functional machine perfusion is under investigation to improve preservation of the donor liver. The transplantation of donation after circulatory death (DCD) livers is limited by poor outcomes, but its application may be expanded by ex vivo repair and assessment of the organ before transplantation. Here we employed subnormothermic (21 °C) machine perfusion of discarded human livers combined with metabolomics to gain insight into metabolic recovery during machine perfusion. Improvements in energetic cofactors and redox shifts were observed, as well as reversal of ischemia-induced alterations in selected pathways, including lactate metabolism and increased TCA cycle intermediates. We next evaluated whether DCD livers with steatotic and severe ischemic injury could be discriminated from 'transplantable' DCD livers. Metabolomic profiling was able to cluster livers with similar metabolic patterns based on the degree of injury. Moreover, perfusion parameters combined with differences in metabolic factors suggest variable mechanisms that result in poor energy recovery in injured livers. We conclude that machine perfusion combined with metabolomics has significant potential as a clinical instrument for the assessment of preserved livers.
authors.affiliation: Center for Engineering in Medicine, Dept. of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.|Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Bote G
authors.initials: BG
authors.lastname: Bruinsma
authors.affiliation: Center for Engineering in Medicine, Dept. of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Gautham V
authors.initials: GV
authors.lastname: Sridharan
authors.affiliation: Center for Engineering in Medicine, Dept. of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.|Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Pepijn D
authors.initials: PD
authors.lastname: Weeder
authors.affiliation: Transplant Center, Dept. of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Avruch
authors.affiliation: Center for Engineering in Medicine, Dept. of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Nima
authors.initials: N
authors.lastname: Saeidi
authors.affiliation: Center for Engineering in Medicine, Dept. of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Sinan
authors.initials: S
authors.lastname: Özer
authors.affiliation: Center for Engineering in Medicine, Dept. of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Geerts
authors.affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Porte
authors.affiliation: Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Michal
authors.initials: M
authors.lastname: Heger
authors.affiliation: Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: van Gulik
authors.affiliation: Transplant Division, Dept. of Surgery, University of Massachusetts, Worcester, MA, USA.
authors.forename: Paulo N
authors.initials: PN
authors.lastname: Martins
authors.affiliation: Transplant Center, Dept. of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Markmann
authors.affiliation: Transplant Center, Dept. of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Heidi
authors.initials: H
authors.lastname: Yeh
authors.affiliation: Center for Engineering in Medicine, Dept. of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Korkut
authors.initials: K
authors.lastname: Uygun
mesh_terms: D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism*; D016031:Liver Transplantation; D008297:Male; D055442:Metabolome; D009926:Organ Preservation / Q000295:instrumentation / Q000379:methods; D010477:Perfusion / Q000295:instrumentation / Q000379:methods