title: Hypothermic machine preservation attenuates ischemia/reperfusion markers after liver transplantation: preliminary results.
abstract: BACKGROUND
  Hypothermic machine perfusion (HMP) has shown significant benefits in renal transplantation but is still in its infancy in liver transplantation. Potential benefits include diminished preservation injury and improved early graft function.
  
  
  METHODS
  We analyzed liver tissue and effluent collected during our Phase 1 trial of liver HMP. Liver allografts underwent HMP for 4-7 h using dual centrifugal perfusion with Vasosol solution at 4-8°C were transplanted and compared with cold stored (CS) transplant controls. Histology, reverse transcription-polymerase chain reaction (RT-PCR), and immunohistochemistry on liver biopsies compared histology and expression of early proinflammatory cytokines, IL-8 and TNF-α, and intracellular adhesion molecule-1 (ICAM-1). Gel electrophoresis was used to evaluate effluent protein content representing residual metabolism.
  
  
  RESULTS
  We saw no differences between HMP and CS in early histologic findings after reperfusion. RT-PCR of reperfusion biopsy samples in the CS group showed high expression of proinflammatory cytokines and ICAM-1. This up-regulation was significantly attenuated by HMP (ICAM-1; P = 0.0152) (IL-8; P = 0.0014) (TNF-α; P = 0.0284). This was confirmed with immunohistochemistry. Albumin was identified in the perfusate throughout HMP.
  
  
  CONCLUSIONS
  HMP significantly reduced proinflammatory cytokine expression compared with CS controls. Further studies of human liver HMP with detailed molecular investigations are now warranted to elucidate benefits of HMP in liver transplantation.
authors.affiliation: Department of Surgery, Center for Liver Disease and Transplantation, Columbia University College of Physicians and Surgeons, 622 West 168th Street PH 14 Center, Room 202, New York, NY 10032, USA. jjg46@columbia.edu
authors.forename: James V
authors.initials: JV
authors.lastname: Guarrera
authors.forename: Scot D
authors.initials: SD
authors.lastname: Henry
authors.forename: Sean W C
authors.initials: SW
authors.lastname: Chen
authors.forename: Tod
authors.initials: T
authors.lastname: Brown
authors.forename: Eugenia
authors.initials: E
authors.lastname: Nachber
authors.forename: Ben
authors.initials: B
authors.lastname: Arrington
authors.forename: Jason
authors.initials: J
authors.lastname: Boykin
authors.forename: Benjamin
authors.initials: B
authors.lastname: Samstein
authors.forename: Robert S
authors.initials: RS
authors.lastname: Brown
authors.forename: Jean C
authors.initials: JC
authors.lastname: Emond
authors.forename: H Thomas
authors.initials: HT
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D006801:Humans; D007036:Hypothermia, Induced / Q000295:instrumentation* / Q000379:methods*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D016031:Liver Transplantation / Q000502:physiology*; D008875:Middle Aged; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016209:Interleukin-8; D019188:Organ Preservation Solutions; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1