title: Airway pressure release ventilation during ex vivo lung perfusion attenuates injury.
abstract: Critical organ shortages have resulted in ex vivo lung perfusion gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of donation after circulatory death organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation during ex vivo lung perfusion improves lung function after transplantation.
  
  
  
  Two groups (n = 4 animals/group) of porcine donation after circulatory death donor lungs were procured after hypoxic cardiac arrest and a 2-hour period of warm ischemia, followed by a 4-hour period of ex vivo lung perfusion rehabilitation with standard conventional volume-based ventilation or pressure-based airway pressure release ventilation. Left lungs were subsequently transplanted into recipient animals and reperfused for 4 hours. Blood gases for partial pressure of oxygen/inspired oxygen fraction ratios, airway pressures for calculation of compliance, and percent wet weight gain during ex vivo lung perfusion and reperfusion were measured.
  
  
  
  Airway pressure release ventilation during ex vivo lung perfusion significantly improved left lung oxygenation at 2 hours (561.5 ± 83.9 mm Hg vs 341.1 ± 136.1 mm Hg) and 4 hours (569.1 ± 18.3 mm Hg vs 463.5 ± 78.4 mm Hg). Likewise, compliance was significantly higher at 2 hours (26.0 ± 5.2 mL/cm H2O vs 15.0 ± 4.6 mL/cm H2O) and 4 hours (30.6 ± 1.3 mL/cm H2O vs 17.7 ± 5.9 mL/cm H2O) after transplantation. Finally, airway pressure release ventilation significantly reduced lung edema development on ex vivo lung perfusion on the basis of percentage of weight gain (36.9% ± 14.6% vs 73.9% ± 4.9%). There was no difference in additional edema accumulation 4 hours after reperfusion.
  
  
  
  Pressure-directed airway pressure release ventilation strategy during ex vivo lung perfusion improves the rehabilitation of severely injured donation after circulatory death lungs. After transplant, these lungs demonstrate superior lung-specific oxygenation and dynamic compliance compared with lungs ventilated with standard conventional ventilation. This strategy, if implemented into clinical ex vivo lung perfusion protocols, could advance the field of donation after circulatory death lung rehabilitation to expand the lung donor pool.
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Va.
authors.forename: J Hunter
authors.initials: JH
authors.lastname: Mehaffey
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Va.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Charles
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Va.
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Sharma
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Va.
authors.forename: Dustin T
authors.initials: DT
authors.lastname: Money
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Va.
authors.forename: Yunge
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pathology, University of Virginia, Charlottesville, Va.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Stoler
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Va.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Lau
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Va.
authors.forename: Curtis G
authors.initials: CG
authors.lastname: Tribble
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Va.
authors.forename: Victor E
authors.initials: VE
authors.lastname: Laubach
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Va.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Roeser
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Va. Electronic address: ilk@virginia.edu.
authors.forename: Irving L
authors.initials: IL
authors.lastname: Kron
mesh_terms: D000818:Animals; D001469:Barotrauma / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D045422:Continuous Positive Airway Pressure / Q000009:adverse effects; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006085:Graft Survival; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D008170:Lung Compliance; D055370:Lung Injury / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D016040:Lung Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D020556:Neutrophil Infiltration; D010477:Perfusion / Q000009:adverse effects / Q000379:methods*; D011013:Pneumonectomy; D011312:Pressure; D011654:Pulmonary Edema / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D012119:Respiration; D034421:Sus scrofa; D013997:Time Factors; D052096:Warm Ischemia
chemical_list: D016207:Cytokines
keywords: APRV; EVLP; airway pressure release ventilation; ex vivo lung perfusion; ischemia reperfusion; lung injury; lung transplant