title: Peritransplant Energy Changes and Their Correlation to Outcome After Human Liver Transplantation.
abstract: The ongoing shortage of donor livers for transplantation and the increased use of marginal livers necessitate the development of accurate pretransplant tests of viability. Considering the importance energy status during transplantation, we aimed to correlate peritransplant energy cofactors to posttransplant outcome and subsequently model this in an ex vivo setting.
  
  
  
  Sequential biopsies were taken from 19 donor livers postpreservation, as well as 30 minutes after portal venous reperfusion and hepatic arterial reperfusion and analyzed by liquid chromatography-mass spectrometry for energetic cofactors (adenosine triphosphate [ATP]/adenosine diphosphate [ADP]/adenosine monophosphate [AMP], nicotinamide adenine dinucleotide /NAD, nicotinamide adenine dinucleotide phosphate / nicotinamide adenine dinucleotide phosphate , flavin adenine dinucleotide , glutathione disulfide/glutathione). Energy status was correlated to posttransplant outcome. In addition, 4 discarded human donation after circulatory death livers were subjected to ex vivo reperfusion, modeling reperfusion injury and were similarly analyzed for energetic cofactors.
  
  
  
  A rapid shift toward higher energy adenine nucleotides was observed following clinical reperfusion, with a 2.45-, 3.17- and 2.12-fold increase in ATP:ADP, ATP:AMP and energy charge after portal venous reperfusion, respectively. Seven of the 19 grafts developed early allograft dysfunction. Correlation with peritransplant cofactors revealed a significant difference in EC between early allograft dysfunction and normal functioning grafts (0.09 vs 0.31, P < 0.05). In the simulated reperfusion model, a similar trend in adenine nucleotide changes was observed.
  
  
  
  A preserved energy status appears critical in the peritransplant period. Levels of adenine nucleotides change rapidly after reperfusion and ratios of ATP/ADP/AMP after reperfusion are significantly correlated to graft function. Using these markers as a viability test in combination with ex vivo reperfusion may provide a useful predictor of outcome that incorporates donor, preservation, and reperfusion factors.
authors.affiliation: 1 Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA. 2 Transplant Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA. 3 Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Bote G
authors.initials: BG
authors.lastname: Bruinsma
authors.forename: James H
authors.initials: JH
authors.lastname: Avruch
authors.forename: Gautham V
authors.initials: GV
authors.lastname: Sridharan
authors.forename: Pepijn D
authors.initials: PD
authors.lastname: Weeder
authors.forename: Marie Louise
authors.initials: ML
authors.lastname: Jacobs
authors.forename: Kerry
authors.initials: K
authors.lastname: Crisalli
authors.forename: Beth
authors.initials: B
authors.lastname: Amundsen
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Porte
authors.forename: James F
authors.initials: JF
authors.lastname: Markmann
authors.forename: Korkut
authors.initials: K
authors.lastname: Uygun
authors.forename: Heidi
authors.initials: H
authors.lastname: Yeh
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D016207:Cytokines / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010477:Perfusion / Q000009:adverse effects; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism; D012189:Retrospective Studies; D013997:Time Factors; D014019:Tissue Donors / Q000600:supply & distribution*; D014022:Tissue Survival; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000227:Adenine Nucleotides; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators