title: Comparison between effects of pressure support and pressure-controlled ventilation on lung and diaphragmatic damage in experimental emphysema.
abstract: BACKGROUND
  In patients with emphysema, invasive mechanical ventilation settings should be adjusted to minimize hyperinflation while reducing respiratory effort and providing adequate gas exchange. We evaluated the impact of pressure-controlled ventilation (PCV) and pressure support ventilation (PSV) on pulmonary and diaphragmatic damage, as well as cardiac function, in experimental emphysema.
  
  
  METHODS
  Emphysema was induced by intratracheal instillation of porcine pancreatic elastase in Wistar rats, once weekly for 4 weeks. Control animals received saline under the same protocol. Eight weeks after first instillation, control and emphysema rats were randomly assigned to PCV (n = 6/each) or PSV (n = 6/each) under protective tidal volume (6 ml/kg) for 4 h. Non-ventilated control and emphysema animals (n = 6/group) were used to characterize the model and for molecular biology analysis. Cardiorespiratory function, lung histology, diaphragm ultrastructure alterations, extracellular matrix organization, diaphragmatic proteolysis, and biological markers associated with pulmonary inflammation, alveolar stretch, and epithelial and endothelial cell damage were assessed.
  
  
  RESULTS
  Emphysema animals exhibited cardiorespiratory changes that resemble human emphysema, such as increased areas of lung hyperinflation, pulmonary amphiregulin expression, and diaphragmatic injury. In emphysema animals, PSV compared to PCV yielded: no changes in gas exchange; decreased mean transpulmonary pressure (Pmean,L), ratio between inspiratory and total time (Ti/Ttot), lung hyperinflation, and amphiregulin expression in lung; increased ratio of pulmonary artery acceleration time to pulmonary artery ejection time, suggesting reduced right ventricular afterload; and increased ultrastructural damage to the diaphragm. Amphiregulin correlated with Pmean,L (r = 0.99, p < 0.0001) and hyperinflation (r = 0.70, p = 0.043), whereas Ti/Ttot correlated with hyperinflation (r = 0.81, p = 0.002) and Pmean,L (r = 0.60, p = 0.04).
  
  
  CONCLUSIONS
  In the model of elastase-induced emphysema used herein, PSV reduced lung damage and improved cardiac function when compared to PCV, but worsened diaphragmatic injury.
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Centro de Ciências da Saúde, Av. Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, Rio de Janeiro, RJ, 21941-902, Brazil.
authors.forename: Gisele de A
authors.initials: GA
authors.lastname: Padilha
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Centro de Ciências da Saúde, Av. Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, Rio de Janeiro, RJ, 21941-902, Brazil.
authors.forename: Lucas F B
authors.initials: LF
authors.lastname: Horta
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Centro de Ciências da Saúde, Av. Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, Rio de Janeiro, RJ, 21941-902, Brazil.
authors.forename: Lillian
authors.initials: L
authors.lastname: Moraes
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Centro de Ciências da Saúde, Av. Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, Rio de Janeiro, RJ, 21941-902, Brazil.
authors.forename: Cassia L
authors.initials: CL
authors.lastname: Braga
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Centro de Ciências da Saúde, Av. Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, Rio de Janeiro, RJ, 21941-902, Brazil.
authors.forename: Milena V
authors.initials: MV
authors.lastname: Oliveira
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Centro de Ciências da Saúde, Av. Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, Rio de Janeiro, RJ, 21941-902, Brazil.
authors.forename: Cíntia L
authors.initials: CL
authors.lastname: Santos
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.|National Center for Structural Biology and Bio-imaging, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Isalira P
authors.initials: IP
authors.lastname: Ramos
authors.affiliation: Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Morales
authors.affiliation: Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Vera Luiza
authors.initials: VL
authors.lastname: Capelozzi
authors.affiliation: Laboratory of Molecular and Cellular Cardiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Regina C S
authors.initials: RC
authors.lastname: Goldenberg
authors.affiliation: Pulmonary Engineering Group, Department of Anesthesiology and Intensive Care Therapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Marcelo Gama
authors.initials: MG
authors.lastname: de Abreu
authors.affiliation: Department of Surgical Sciences and Integrated Diagnostics, IRCCS AOU San Martino-IST, University of Genoa, Genoa, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Pelosi
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Centro de Ciências da Saúde, Av. Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, Rio de Janeiro, RJ, 21941-902, Brazil.
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Silva
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Centro de Ciências da Saúde, Av. Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, Rio de Janeiro, RJ, 21941-902, Brazil. prmrocco@gmail.com.
authors.forename: Patricia R M
authors.initials: PR
authors.lastname: Rocco
keywords: Amphiregulin; Diaphragm; Echocardiography; Emphysema; Pressure support ventilation