title: Optimal ex vivo lung perfusion techniques with oxygenated perfusate.
abstract: BACKGROUND
  Accumulating evidence supports an increasing role of ex vivo lung perfusion (EVLP) in clinical lung transplantation. However, EVLP has adverse effects on the quality of lung grafts, which have rarely been discussed. Careful optimization of current EVLP protocols might improve outcomes. This study examined effects of different levels of oxygenation of the perfusate circulated through the lungs during EVLP and the impact on post-transplant functional outcomes.
  
  
  METHODS
  We compared results of 4 different oxygenation levels in the perfusate during EVLP: 6% oxygen (O2), 40% O2, 60% O2, and 100% O2. We evaluated lung function, compliance, and vascular resistance and levels of glucose and other markers in the perfusate. After EVLP, lung grafts were transplanted, and post-transplant outcomes were compared.
  
  
  RESULTS
  Lungs perfused with 40% O2on EVLP had the lowest glucose consumption compared with the other perfusates. Lungs treated with 40% O2or 60% O2exhibited significantly less inflammation, as indicated by reduced pro-inflammatory cytokine messenger RNA levels compared with lungs perfused with 6% O2or 100% O2. Significantly more oxidative damage was noted after 4 hours of EVLP perfused with 100% O2. After transplantation, lungs perfused with 40% O2during EVLP had the best post-transplant functional outcomes.
  
  
  CONCLUSIONS
  Optimization of O2levels in the perfusate during EVLP improved outcomes in this rat model. Deoxygenated perfusate, the current standard during EVLP, exhibited significantly more inflammation with compromised cellular metabolic activity and compromised post-transplant outcomes.
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Noda
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Shinya
authors.initials: S
authors.lastname: Tane
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Haam
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Awori J
authors.initials: AJ
authors.lastname: Hayanga
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Jonathan
authors.initials: J
authors.lastname: D'Cunha
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: James D
authors.initials: JD
authors.lastname: Luketich
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Electronic address: shigemuran@upmc.edu.
authors.forename: Norihisa
authors.initials: N
authors.lastname: Shigemura
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005112:Extracorporeal Circulation / Q000379:methods*; D016040:Lung Transplantation / Q000379:methods*; D008297:Male; D023421:Models, Animal; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000737:chemistry*; D010100:Oxygen / Q000502:physiology*; D010477:Perfusion / Q000379:methods*; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D016207:Cytokines; D019188:Organ Preservation Solutions; D010100:Oxygen
keywords: ex vivo lung perfusion; extracorporeal membrane oxygenation; hyperoxia; lung preservation; lung transplantation; microvasculature; tissue hypoxia