title: A physiologic and biochemical profile of clinically rejected lungs on a normothermic ex vivo lung perfusion platform.
abstract: BACKGROUND
  Although ex vivo lung perfusion (EVLP) is increasingly being used to evaluate and manipulate potential donor lungs before lung transplantation (LTx), data on the biochemistry of lungs during EVLP are limited. In this study, we examined the physiology and biochemistry of human lungs on an EVLP circuit.
  
  
  METHODS
  We recovered unallocated double lungs in standard fashion and split them into single lungs. All lungs received a nebulized arginase inhibitor, 2-S-amino-6-boronohexanoic acid (ABH), at either the onset (n = 6) or after 3 h (n = 8) of EVLP. Serial biochemical analysis included levels of arginase, endogenous nitric oxide synthase (eNOS), cyclic guanosine monophosphate, and reactive oxygen species. We considered lungs transplantable if they sustained a PaO2:FiO2 ≥ 350 in addition to stable pulmonary function during EVLP.
  
  
  RESULTS
  We recovered a total of 14 single lungs. We deemed three single lungs from different donors to be transplantable after EVLP. These lungs had superior oxygenation, lower carbon dioxide, and more stable pulmonary artery pressures. Transplantable lungs had higher baseline levels of eNOS and higher final levels of cyclic guanosine monophosphate than non-transplantable lungs. Early ABH administration was associated with a transient increase in dynamic compliance.
  
  
  CONCLUSIONS
  In this biochemical characterization of lungs deemed unsuitable for LTx, early levels of eNOS and late levels of cyclic guanosine monophosphate appear to be associated with improved allograft function during EVLP. In addition, nebulized ABH is associated with a significant increase in dynamic compliance. These data suggest that biochemical markers during EVLP may predict acceptable allograft function, and that this platform can be used to biochemically manipulate donor lungs before LTx.
authors.affiliation: Department of Surgery, Division of Cardiac Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: George
authors.forename: George J
authors.initials: GJ
authors.lastname: Arnaoutakis
authors.forename: Claude A
authors.initials: CA
authors.lastname: Beaty
authors.forename: Simran K
authors.initials: SK
authors.lastname: Jandu
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Santhanam
authors.forename: Dan E
authors.initials: DE
authors.lastname: Berkowitz
authors.forename: Ashish S
authors.initials: AS
authors.lastname: Shah
mesh_terms: D000293:Adolescent; D000328:Adult; D001119:Arginase / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000737:chemistry / Q000502:physiology*; D008170:Lung Compliance; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009926:Organ Preservation; D010477:Perfusion; D011312:Pressure; D011659:Pulmonary Gas Exchange; D017382:Reactive Oxygen Species / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D017382:Reactive Oxygen Species; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D001119:Arginase; D006152:Cyclic GMP