title: Assessing warm ischemic injury of pig livers at hypothermic machine perfusion.
abstract: BACKGROUND
  Livers originating from donation after circulatory death (DCD) donors are exposed to warm ischemia (WI) before liver transplantation (LTx). Currently, there are no objective tests to evaluate the damage sustained before LTx. This study aims to identify surrogate markers for liver injury that can be assessed during hypothermic machine perfusion (HMP) preservation. In addition, we want to use mathematical equation modeling combining these markers to improve our assessment of DCD livers for transplantation.
  
  
  METHODS
  Porcine livers were exposed to incremental periods of WI (0-120 min) and subsequently HMP preserved for 4 h. Biochemical and hemodynamic parameters were repeatedly measured in the perfusate during HMP. Subsequently, to mimic LTx, normothermic isolated-liver perfusion was applied for 2 h and the injury assessed using a morphological score.
  
  
  RESULTS
  With increasing WI periods, the perfusate became more acidotic, and levels of aspartate aminotransferase (AST), liver fatty acid binding protein, redox-active iron, and arterial vascular resistance increased. A damage index, combining AST and pH (damage index = 2 - 37 × β(AST) - 257 × β(pH)) based on multifactorial analysis of the changing pattern of these markers, had increased sensitivity and specificity to reflect WI and reperfusion injury.
  
  
  CONCLUSIONS
  This proof of concept study demonstrated the potential role for objective evaluation of DCD porcine livers during HMP and the advantage to use multifactorial analysis on the markers' changing pattern.
authors.affiliation: Liver Research Facility/Abdominal Transplant Surgery, Department of Surgery, Catholic University of Leuven, Leuven, Belgium.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Katrien
authors.initials: K
authors.lastname: Vekemans
authors.forename: Leonardo
authors.initials: L
authors.lastname: Iania
authors.forename: Mina
authors.initials: M
authors.lastname: Komuta
authors.forename: Jaakko
authors.initials: J
authors.lastname: Parkkinen
authors.forename: Veerle
authors.initials: V
authors.lastname: Heedfeld
authors.forename: Tine
authors.initials: T
authors.lastname: Wylin
authors.forename: Diethard
authors.initials: D
authors.lastname: Monbaliu
authors.forename: Jacques
authors.initials: J
authors.lastname: Pirenne
authors.forename: Jos
authors.initials: J
authors.lastname: van Pelt
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015415:Biomarkers; D005260:Female; D006863:Hydrogen-Ion Concentration; D007036:Hypothermia, Induced / Q000295:instrumentation; D008099:Liver / Q000098:blood supply*; D016031:Liver Transplantation; D009926:Organ Preservation; D010477:Perfusion; D013552:Swine; D014655:Vascular Resistance; D052096:Warm Ischemia / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D000255:Adenosine Triphosphate; D000410:Alanine Transaminase
keywords: Donation after cardiac death; Hypothermic machine perfusion; Liver; Marker; Preservation; Transplantation; Warm ischemia