title: Preemptive therapy with steroids but not macrolides improves gas exchange in caustic-injured donor lungs.
abstract: BACKGROUND
  Donor lungs are susceptible to aspiration in the period before and after brain death. We hypothesized that preemptive anti-inflammatory treatment may result in better graft performance as evaluated during ex vivo lung perfusion (EVLP).
  
  
  METHODS
  Pigs (27.4 ± 8.3kg) were divided into four groups (n = 6). Group [S] was treated with steroids (methylprednisolone 10 mg/kg), group [M] with macrolides (clarithromycin 250 mg), and group [P] with placebo (saline). In all groups, treatment was given i.v. 25, 18, and 1 h before instillation of 4 mL/kg gastric juice (GJ). Group [C] without GJ instillation served as a control group. Two hours after the onset of acute lung injury, lungs were flushed, explanted, and stored cold for 75 min. Graft performance was then assessed during EVLP for 2 h. Aerodynamic and hemodynamic parameters and oxygenation capacity (∆PO(2)) were recorded every 30 min (T30-T120). BAL samples were collected and analyzed for total and differential cells, IL-6, IL-1β, 8- isoprostane, and CRP levels. Wet-to-dry weight ratio [W/D] was measured and tissue samples were collected for histology.
  
  
  RESULTS
  ΔPO(2) in [S] was comparable to [C] and was higher versus [M] (P < 0.05) and [P] (P < 0.01). No differences were observed in pulmonary vascular resistance, lung compliance, and mean airway pressure. No additional edema was noticed after 2 h of EVLP. Cellular and biomolecular changes in BAL fluid and histologic alterations were comparable among the three study groups.
  
  
  CONCLUSIONS
  Preemptive treatment of donors with steroids but not macrolides improves gas exchange in a porcine lung injury model independently from its anti-inflammatory activity.
authors.affiliation: Laboratory for Experimental Thoracic Surgery, KU Leuven, Leuven, Belgium.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Meers
authors.forename: Shana
authors.initials: S
authors.lastname: Wauters
authors.forename: Eric
authors.initials: E
authors.lastname: Verbeken
authors.forename: Hans
authors.initials: H
authors.lastname: Scheers
authors.forename: Bart
authors.initials: B
authors.lastname: Vanaudenaerde
authors.forename: Geert M
authors.initials: GM
authors.lastname: Verleden
authors.forename: Dirk
authors.initials: D
authors.lastname: Van Raemdonck
mesh_terms: D055371:Acute Lung Injury / Q000503:physiopathology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015415:Biomarkers; D017291:Clarithromycin / Q000627:therapeutic use*; D006439:Hemodynamics; D008168:Lung / Q000473:pathology; D016040:Lung Transplantation; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D010477:Perfusion; D011015:Pneumonia, Aspiration / Q000150:complications*; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D013552:Swine; D014019:Tissue Donors
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D017291:Clarithromycin; D008775:Methylprednisolone