title: A novel porcine model of ventilator-associated pneumonia caused by oropharyngeal challenge with Pseudomonas aeruginosa.
abstract: BACKGROUND
  Animal models of ventilator-associated pneumonia (VAP) in primates, sheep, and pigs differ in the underlying pulmonary injury, etiology, bacterial inoculation methods, and time to onset. The most common ovine and porcine models do not reproduce the primary pathogenic mechanism of the disease, through the aspiration of oropharyngeal pathogens, or the most prevalent human etiology. Herein the authors characterize a novel porcine model of VAP due to aspiration of oropharyngeal secretions colonized by Pseudomonas aeruginosa.
  
  
  METHODS
  Ten healthy pigs were intubated, positioned in anti-Trendelenburg, and mechanically ventilated for 72 h. Three animals did not receive bacterial challenge, whereas in seven animals, a P. aeruginosa suspension was instilled into the oropharynx. Tracheal aspirates were cultured and respiratory mechanics were recorded. On autopsy, lobar samples were obtained to corroborate VAP through microbiological and histological studies.
  
  
  RESULTS
  In animals not challenged, diverse bacterial colonization of the airways was found and monolobar VAP rarely developed. In animals with P. aeruginosa challenge, colonization of tracheal secretion increased up to 6.39 ± 0.34 log colony-forming unit (cfu)/ml (P < 0.001). VAP was confirmed in six of seven pigs, in 78% of the cases developed in the dependent lung segments (right medium and lower lobes, P = 0.032). The static respiratory system elastance worsened to 41.5 ± 5.8 cm H2O/l (P = 0.001).
  
  
  CONCLUSIONS
  The authors devised a VAP model caused by aspiration of oropharyngeal P. aeruginosa, a frequent causative pathogen of human VAP. The model also overcomes the practical and legislative limitations associated with the use of primates. The authors' model could be employed to study pathophysiologic mechanisms, as well as novel diagnostic/preventive strategies.
authors.affiliation: From the Department of Pulmonary and Critical Care Medicine, Thorax Institute, Hospital Clínic, Barcelona, Spain (G.L.B., M.R., J.-D.M., L.S., O.T.R., V.G., N.L., M.R., M.E., L.F.-B., M.F., A.T.); Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (G.L.B., M.R., J.-D.M., I.R., L.M., L.F.-B., M.F., J.V., A.T.); Centro de Investigación Biomedica En Red- Enfermedades Respiratorias (CIBERES), Mallorca, Spain (G.L.B., M.R., O.T.R., V.G., M.R., M.E., L.F.-B., M.F., A.T.); Cardiology Department, Thorax Institute, Hospital Clínic, Barcelona, Spain (M.R.); Department of Clinical Microbiology, School of Medicine, and Barcelona Centre for International Health Research, (CRESIB, Hospital Clínic-Universitat de Barcelona), Barcelona, Spain (I.R., L.M., J.V.); Pathology Department, Hospital Clínic, Barcelona, Spain (M.C., J.R.); and University of Barcelona, Barcelona, Spain (J.V., J.R., A.T.).
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Li Bassi
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rigol
authors.forename: Joan-Daniel
authors.initials: JD
authors.lastname: Marti
authors.forename: Lina
authors.initials: L
authors.lastname: Saucedo
authors.forename: Otavio T
authors.initials: OT
authors.lastname: Ranzani
authors.forename: Ignasi
authors.initials: I
authors.lastname: Roca
authors.forename: Maria
authors.initials: M
authors.lastname: Cabanas
authors.forename: Laura
authors.initials: L
authors.lastname: Muñoz
authors.forename: Valeria
authors.initials: V
authors.lastname: Giunta
authors.forename: Nestor
authors.initials: N
authors.lastname: Luque
authors.forename: Mariano
authors.initials: M
authors.lastname: Rinaudo
authors.forename: Mariano
authors.initials: M
authors.lastname: Esperatti
authors.forename: Laia
authors.initials: L
authors.lastname: Fernandez-Barat
authors.forename: Miquel
authors.initials: M
authors.lastname: Ferrer
authors.forename: Jordi
authors.initials: J
authors.lastname: Vila
authors.forename: Jose
authors.initials: J
authors.lastname: Ramirez
authors.forename: Antoni
authors.initials: A
authors.lastname: Torres
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D009960:Oropharynx / Q000382:microbiology / Q000473:pathology*; D053717:Pneumonia, Ventilator-Associated / Q000453:epidemiology / Q000382:microbiology* / Q000473:pathology*; D011552:Pseudomonas Infections / Q000150:complications / Q000473:pathology*; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity; D013552:Swine