title: Ex vivo rehabilitation of non-heart-beating donor lungs in preclinical porcine model: delayed perfusion results in superior lung function.
abstract: OBJECTIVE
  Ex vivo lung perfusion (EVLP) is a promising modality for the evaluation and treatment of marginal donor lungs. The optimal timing of EVLP initiation and the potential for rehabilitation of donor lungs with extended warm ischemic times is unknown. The present study compared the efficacy of different treatment strategies for uncontrolled non-heart-beating donor lungs.
  
  
  METHODS
  Mature swine underwent hypoxic arrest, followed by 60 minutes of no-touch warm ischemia. The lungs were harvested and flushed with 4°C Perfadex. Three groups (n = 5/group) were stratified according to the preservation method: cold static preservation (CSP; 4 hours of 4°C storage), immediate EVLP (I-EVLP: 4 hours EVLP at 37°C), and delayed EVLP (D-EVLP; 4 hours of CSP followed by 4 hours of EVLP). The EVLP groups were perfused with Steen solution supplemented with heparin, methylprednisolone, cefazolin, and an adenosine 2A receptor agonist. The lungs then underwent allotransplantation and 4 hours of recipient reperfusion before allograft assessment for resultant ischemia-reperfusion injury.
  
  
  RESULTS
  The donor blood oxygenation (partial pressure of oxygen/fraction of inspired oxygen ratio) before death was not different between the groups. The oxygenation after transplantation was significantly greater in the D-EVLP group than in the I-EVLP or CSP groups. The mean airway pressure, pulmonary artery pressure, and expression of interleukin-8, interleukin-1β, and tumor necrosis factor-α were all significantly reduced in the D-EVLP group. Post-transplant oxygenation exceeded the acceptable clinical levels only in the D-EVLP group.
  
  
  CONCLUSIONS
  Uncontrolled non-heart-beating donor lungs with extended warm ischemia can be reconditioned for successful transplantation. The combination of CSP and EVLP in the D-EVLP group was necessary to obtain optimal post-transplant function. This finding, if confirmed clinically, will allow expanded use of nonheart-beating donor lungs.
authors.affiliation: Department of Surgery, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Mulloy
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Stone
authors.forename: Ivan K
authors.initials: IK
authors.lastname: Crosby
authors.forename: Damien J
authors.initials: DJ
authors.lastname: Lapar
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Sharma
authors.forename: David V
authors.initials: DV
authors.lastname: Webb
authors.forename: Christine L
authors.initials: CL
authors.lastname: Lau
authors.forename: Victor E
authors.initials: VE
authors.lastname: Laubach
authors.forename: Irving L
authors.initials: IL
authors.lastname: Kron
mesh_terms: D000818:Animals; D062186:Arterial Pressure; D002951:Citrates / Q000494:pharmacology; D050377:Cold Ischemia; D003080:Cold Temperature; D004195:Disease Models, Animal; D005260:Female; D006323:Heart Arrest / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D016040:Lung Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D019188:Organ Preservation Solutions / Q000494:pharmacology; D010477:Perfusion / Q000009:adverse effects / Q000379:methods*; D011651:Pulmonary Artery / Q000503:physiopathology / Q000601:surgery; D011659:Pulmonary Gas Exchange; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology; D012129:Respiratory Function Tests; D034421:Sus scrofa; D013997:Time Factors; D014019:Tissue Donors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D052096:Warm Ischemia
chemical_list: D002951:Citrates; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016209:Interleukin-8; D019188:Organ Preservation Solutions; C070005:Perfadex; D014409:Tumor Necrosis Factor-alpha