title: Variable ventilation improves pulmonary function and reduces lung damage without increasing bacterial translocation in a rat model of experimental pneumonia.
abstract: Variable ventilation has been shown to improve pulmonary function and reduce lung damage in different models of acute respiratory distress syndrome. Nevertheless, variable ventilation has not been tested during pneumonia. Theoretically, periodic increases in tidal volume (VT) and airway pressures might worsen the impairment of alveolar barrier function usually seen in pneumonia and could increase bacterial translocation into the bloodstream. We investigated the impact of variable ventilation on lung function and histologic damage, as well as markers of lung inflammation, epithelial and endothelial cell damage, and alveolar stress, and bacterial translocation in experimental pneumonia.
  
  
  
  Thirty-two Wistar rats were randomly assigned to receive intratracheal of Pseudomonas aeruginosa (PA) or saline (SAL) (n = 16/group). After 24-h, animals were anesthetized and ventilated for 2 h with either conventional volume-controlled (VCV) or variable volume-controlled ventilation (VV), with mean VT= 6 mL/kg, PEEP = 5cmH2O, and FiO2= 0.4. During VV, tidal volume varied randomly with a coefficient of variation of 30% and a Gaussian distribution. Additional animals assigned to receive either PA or SAL (n = 8/group) were not ventilated (NV) to serve as controls.
  
  
  
  In both SAL and PA, VV improved oxygenation and lung elastance compared to VCV. In SAL, VV decreased interleukin (IL)-6 expression compared to VCV (median [interquartile range]: 1.3 [0.3-2.3] vs. 5.3 [3.6-7.0]; p = 0.02) and increased surfactant protein-D expression compared to NV (2.5 [1.9-3.5] vs. 1.2 [0.8-1.2]; p = 0.0005). In PA, compared to VCV, VV reduced perivascular edema (2.5 [2.0-3.75] vs. 6.0 [4.5-6.0]; p < 0.0001), septum neutrophils (2.0 [1.0-4.0] vs. 5.0 [3.3-6.0]; p = 0.0008), necrotizing vasculitis (3.0 [2.0-5.5] vs. 6.0 [6.0-6.0]; p = 0.0003), and ultrastructural lung damage scores (16 [14-17] vs. 24 [14-27], p < 0.0001). Blood colony-forming-unit (CFU) counts were comparable (7 [0-28] vs. 6 [0-26], p = 0.77). Compared to NV, VCV, but not VV, increased expression amphiregulin, IL-6, and cytokine-induced neutrophil chemoattractant (CINC)-1 (2.1 [1.6-2.5] vs. 0.9 [0.7-1.2], p = 0.025; 12.3 [7.9-22.0] vs. 0.8 [0.6-1.9], p = 0.006; and 4.4 [2.9-5.6] vs. 0.9 [0.8-1.4], p = 0.003, respectively). Angiopoietin-2 expression was lower in VV compared to NV animals (0.5 [0.3-0.8] vs. 1.3 [1.0-1.5], p = 0.01).
  
  
  
  In this rat model of pneumonia, VV improved pulmonary function and reduced lung damage as compared to VCV, without increasing bacterial translocation.
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Raquel F
authors.initials: RF
authors.lastname: de Magalhães
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Samary
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Raquel S
authors.initials: RS
authors.lastname: Santos
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Milena V
authors.initials: MV
authors.lastname: de Oliveira
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Nazareth N
authors.initials: NN
authors.lastname: Rocha
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Cintia L
authors.initials: CL
authors.lastname: Santos
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Jamil
authors.initials: J
authors.lastname: Kitoko
authors.affiliation: Laboratory of Immunopharmacology, Oswaldo Cruz Institute - Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Carlos A M
authors.initials: CA
authors.lastname: Silva
authors.affiliation: Laboratory of Immunopharmacology, Oswaldo Cruz Institute - Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Hildebrandt
authors.affiliation: Laboratory of Immunopharmacology, Oswaldo Cruz Institute - Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Cassiano F
authors.initials: CF
authors.lastname: Goncalves-de-Albuquerque
authors.affiliation: Laboratory of Immunopharmacology, Oswaldo Cruz Institute - Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Adriana R
authors.initials: AR
authors.lastname: Silva
authors.affiliation: Laboratory of Immunopharmacology, Oswaldo Cruz Institute - Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Hugo C
authors.initials: HC
authors.lastname: Faria-Neto
authors.affiliation: Department of Pathology, University of São Paulo, Av. Doutor Arnaldo, 455, 01246-903, São Paulo, SP, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Martins
authors.affiliation: Department of Pathology, University of São Paulo, Av. Doutor Arnaldo, 455, 01246-903, São Paulo, SP, Brazil.
authors.forename: Vera L
authors.initials: VL
authors.lastname: Capelozzi
authors.affiliation: Pulmonary Engineering Group, Department of Anesthesiology and Intensive Care Therapy, University Hospital Carl Gustav Carus, Dresden University of Technology, Fetschertsrasse 74, 01307, Dresden, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Huhle
authors.affiliation: Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Biophysics Institute, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, s/n, Bloco G2-048, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Morales
authors.affiliation: Laboratory of Clinical Bacteriology and Immunology, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.|Carlos Chagas Filho Biophysics Institute, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, s/n, Bloco G2-048, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Olsen
authors.affiliation: IRCCS AOU San Martino-IST, Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Largo Rosanna Benzi 8, 16132, Genoa, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Pelosi
authors.affiliation: Pulmonary Engineering Group, Department of Anesthesiology and Intensive Care Therapy, University Hospital Carl Gustav Carus, Dresden University of Technology, Fetschertsrasse 74, 01307, Dresden, Germany.
authors.forename: Marcelo Gama
authors.initials: MG
authors.lastname: de Abreu
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil.
authors.forename: Patricia R M
authors.initials: PR
authors.lastname: Rocco
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil. pedro.leme@gmail.com.|Laboratory of Pulmonary Investigation, Centro de Ciências da Saúde, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Avenida Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil. pedro.leme@gmail.com.
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Silva
mesh_terms: D000465:Algorithms; D000818:Animals; D018988:Bacterial Translocation; D042783:Endothelial Cells / Q000473:pathology; D004847:Epithelial Cells / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D008168:Lung / Q000503:physiopathology* / Q000648:ultrastructure; D018410:Pneumonia, Bacterial / Q000382:microbiology / Q000503:physiopathology / Q000628:therapy*; D011552:Pseudomonas Infections / Q000382:microbiology / Q000503:physiopathology / Q000628:therapy*; D011650:Pulmonary Alveoli / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial / Q000379:methods*; D012129:Respiratory Function Tests; D013990:Tidal Volume
keywords: Inflammation; Lung damage; Lung mechanics; Molecular biology; Pneumonia; Variable ventilation