title: Lung Lavage and Surfactant Replacement During Ex Vivo Lung Perfusion for Treatment of Gastric Acid Aspiration-Induced Donor Lung Injury.
abstract: BACKGROUND
  Ex vivo lung perfusion (EVLP) provides opportunities to treat injured donor lungs before transplantation. We investigated whether lung lavage, to eliminate inflammatory inhibitory components, followed by exogenous surfactant replacement, could aid lung recovery and improve post-transplant lung function after gastric aspiration injury.
  
  
  METHODS
  Gastric acid aspiration was induced in donor pigs, which were ventilated for 6 hours to develop lung injury. After retrieval and 10 hours of cold preservation, EVLP was performed for 6 hours. The lungs were randomly divided into 4 groups (n = 5, each): (1) no treatment (control), (2) lung lavage, (3) surfactant administration, and (4) lung lavage, followed by surfactant administration. After another 2-hour period of cold preservation, the left lung was transplanted and reperfused for 4 hours.
  
  
  RESULTS
  Physiologic lung function significantly improved after surfactant administration during EVLP. The EVLP perfusate from the lavage + surfactant group showed significantly lower levels of interleukin (IL)-1β, IL-6, IL-8, and secretory phospholipase A2. Total phosphatidylcholine was increased, and minimum surface tension was recovered to normal levels (≤5 mN/m) in the bronchioalveolar fluid after surfactant administration. Lysophosphatidylcholine in bronchioalveolar fluid was significantly lower in the lavage + surfactant group than in the surfactant group. Post-transplant lung function was significantly better in the lavage + surfactant group compared with all other groups.
  
  
  CONCLUSIONS
  Lung lavage, followed by surfactant replacement during EVLP, reduced inflammatory mediators and prevented hydrolysis of phosphatidylcholine, which contributed to the superior post-transplant function in donor lungs with aspiration injury.
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakajima
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ohsumi
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Kalaf
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ilker
authors.initials: I
authors.lastname: Iskender
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Hsin
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanou
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Manyin
authors.initials: M
authors.lastname: Chen
authors.affiliation: the Department of Physiology and Pharmacology, Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada.
authors.forename: Brandon
authors.initials: B
authors.lastname: Baer
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Rafael
authors.initials: R
authors.lastname: Coutinho
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Lucas
authors.initials: L
authors.lastname: Maahs
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Paula
authors.initials: P
authors.lastname: Behrens
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sassan
authors.initials: S
authors.lastname: Azad
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Tereza
authors.initials: T
authors.lastname: Martinu
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Waddell
authors.affiliation: the Department of Physiology and Pharmacology, Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada.
authors.forename: James F
authors.initials: JF
authors.lastname: Lewis
authors.affiliation: the Physiology and Experimental Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Post
authors.affiliation: the Department of Physiology and Pharmacology, Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada.
authors.forename: Ruud A W
authors.initials: RAW
authors.lastname: Veldhuizen
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Cypel
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, and University of Toronto, Toronto, Ontario, Canada. Electronic address: shaf.keshavjee@uhn.ca.
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018893:Bronchoalveolar Lavage / Q000379:methods*; D004195:Disease Models, Animal; D005112:Extracorporeal Circulation / Q000379:methods; D005744:Gastric Acid; D055370:Lung Injury / Q000503:physiopathology / Q000601:surgery*; D016040:Lung Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D011300:Preoperative Care / Q000379:methods; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D011897:Random Allocation; D015427:Reperfusion Injury / Q000517:prevention & control*; D012129:Respiratory Function Tests; D018709:Statistics, Nonparametric; D034421:Sus scrofa; D013552:Swine; D014019:Tissue Donors
chemical_list: D011663:Pulmonary Surfactants
keywords: aspiration; ex vivo lung perfusion; lung lavage; lung transplantation; surfactant