title: Kinetics of lactate metabolism during acellular normothermic ex vivo lung perfusion.
abstract: BACKGROUND
  Plasma lactate has been used as a marker of poor prognosis in clinical conditions. However, the relationship between lactate production and lung function during acellular normothermic ex vivo lung perfusion (EVLP) is unclear. We investigated the kinetics of lactate metabolism during EVLP and the correlation of this marker with outcomes after transplant.
  
  
  METHODS
  Human donor lungs in our clinical EVLP trial (CLs; n = 28) and rejected donor lungs for experimental use (Els; n = 8) were perfused ex vivo using the Toronto technique. Lactate level, lactate/pyruvate (L/P) ratio, and glucose level in the perfusate were measured. In CLs, we examined the relationship between lactate metabolism during EVLP and early post-transplant outcomes. The hypoxia-inducible factor 1 sub-unit 1α (HIF-1α) level in lung tissue was examined in ELs.
  
  
  RESULTS
  We performed double-lung EVLP in CLs and single-lung EVLP in ELs. In CLs, the lactate and L/P ratios at the end of EVLP had no correlation with early post-transplant outcomes despite lactate elevation during EVLP. Although lactate elevation was also present in all ELs, we were able to identify 2 groups based on L/P ratio at the end of EVLP. The group with the high L/P ratio had higher airway pressure during EVLP and higher HIF-1α in lung tissue at the end of EVLP.
  
  
  CONCLUSIONS
  Lactate increases seen in the EVLP perfusate most often represent physiologic lactate production by the lung in a setting with reduced lactate clearance. Thus, patients who underwent transplantation after EVLP had good outcomes despite lactate elevation during EVLP.
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, Toronto Lung Transplant Program, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Terumoto
authors.initials: T
authors.lastname: Koike
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Yeung
authors.forename: Marcelo
authors.initials: M
authors.lastname: Cypel
authors.forename: Matthew
authors.initials: M
authors.lastname: Rubacha
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sato
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Waddell
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007773:Lactates / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D016040:Lung Transplantation / Q000379:methods*; D017063:Outcome Assessment, Health Care; D010477:Perfusion / Q000379:methods*; D011773:Pyruvates / Q000378:metabolism
chemical_list: D015415:Biomarkers; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007773:Lactates; D011773:Pyruvates