title: Warm ischemic injury is reflected in the release of injury markers during cold preservation of the human liver.
abstract: BACKGROUND
  Liver transplantation plays a pivotal role in the treatment of patients with end-stage liver disease. Despite excellent outcomes, the field is strained by a severe shortage of viable liver grafts. To meet high demands, attempts are made to increase the use of suboptimal livers by both pretransplant recovery and assessment of donor livers. Here we aim to assess hepatic injury in the measurement of routine markers in the post-ischemic flush effluent of discarded human liver with a wide warm ischemic range.
  
  
  METHODS
  Six human livers discarded for transplantation with variable warm and cold ischemia times were flushed at the end of preservation. The liver grafts were flushed with NaCl or Lactated Ringer's, 2 L through the portal vein and 1 L through the hepatic artery. The vena caval effluent was sampled and analyzed for biochemical markers of injury; lactate dehydrogenase (LDH), alanine transaminase (ALT), and alkaline phosphatase (ALP). Liver tissue biopsies were analyzed for ATP content and histologically (H&E) examined.
  
  
  RESULTS
  The duration of warm ischemia in the six livers correlated significantly to the concentration of LDH, ALT, and ALP in the effluent from the portal vein flush. No correlation was found with cold ischemia time. Tissue ATP content at the end of preservation correlated very strongly with the concentration of ALP in the arterial effluent (P<0.0007, R2 = 0.96).
  
  
  CONCLUSIONS
  Biochemical injury markers released during the cold preservation period were reflective of the duration of warm ischemic injury sustained prior to release of the markers, as well as the hepatic energy status. As such, assessment of the flush effluent at the end of cold preservation may be a useful tool in evaluating suboptimal livers prior to transplantation, particularly in situations with undeterminable ischemic durations.
authors.affiliation: Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital/ Harvard Medical School, Boston, Massachusetts, United States; Department of Surgery (Surgical Laboratory), 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, Department of Surgery, Massachusetts General Hospital/ Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Wilson
authors.initials: W
authors.lastname: Wu
authors.affiliation: Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital/ Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Sinan
authors.initials: S
authors.lastname: Ozer
authors.affiliation: Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital/ Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Adam
authors.initials: A
authors.lastname: Farmer
authors.affiliation: Transplant Center, Massachusetts General Hospital/ Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: James F
authors.initials: JF
authors.lastname: Markmann
authors.affiliation: Transplant Center, Massachusetts General Hospital/ Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Heidi
authors.initials: H
authors.lastname: Yeh
authors.affiliation: Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital/ Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Korkut
authors.initials: K
authors.lastname: Uygun
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D050377:Cold Ischemia / Q000379:methods; D015925:Cryopreservation / Q000379:methods; D005260:Female; D006499:Hepatic Artery / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods; D008297:Male; D008875:Middle Aged; D009926:Organ Preservation / Q000379:methods; D019188:Organ Preservation Solutions / Q000378:metabolism; D011169:Portal Vein / Q000378:metabolism / Q000473:pathology; D052096:Warm Ischemia / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D019188:Organ Preservation Solutions; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
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