title: Inspiratory resistive breathing induces acute lung injury.
abstract: BACKGROUND
  Resistive breathing is associated with large negative intrathoracic pressures. Increased mechanical stress induces high-permeability pulmonary edema and lung inflammation.
  
  
  OBJECTIVE
  To determine the effects of resistive breathing on the healthy lung.
  
  
  METHODS
  Anesthetized rats breathed through a two-way nonrebreathing valve. The inspiratory line was connected to a resistance setting peak inspiratory tracheal pressure at 50% of maximum (inspiratory resistive breathing), while 100% oxygen was supplied to prevent hypoxemia. Quietly breathing animals (100% oxygen) served as controls. Lung injury was evaluated after 3 and 6 hours of resistive breathing.
  
  
  RESULTS
  After both 3 and 6 hours of resistive breathing, lung permeability was increased, as assessed by (99m)Tc-diethylenetriaminepentaacetic acid scintigraphy and Evans blue dye extravasation. Tissue elasticity, measured on the basis of static pressure-volume curves and by the low-frequency forced oscillation technique, was also increased. After both 3 and 6 hours of resistive breathing, gravimetric measurements revealed the presence of pulmonary edema and analysis of bronchoalveolar lavage showed increased total protein content, whereas the total cell count was elevated only after 6 hours of resistive breathing. Cytokine levels were assessed in bronchoalveolar lavage fluid and lung tissue by ELISA and were increased after 6 hours compared with controls. Western blot analysis showed early activation of Src kinase via phosphorylation (at 30 min), and Erk1/2 and IκBα (nuclear factor-κB inhibitor) were phosphorylated at 3 and 6 hours. Pathology revealed the presence of lung injury after resistive breathing.
  
  
  CONCLUSIONS
  Resistive breathing induces acute lung injury and inflammation.
authors.affiliation: Department of Critical Care and Pulmonary Services, Evangelismos Hospital, University of Athens Medical School, Athens, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Toumpanakis
authors.forename: George A
authors.initials: GA
authors.lastname: Kastis
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Zacharatos
authors.forename: Ioanna
authors.initials: I
authors.lastname: Sigala
authors.forename: Tatiana
authors.initials: T
authors.lastname: Michailidou
authors.forename: Maroussa
authors.initials: M
authors.lastname: Kouvela
authors.forename: Constantinos
authors.initials: C
authors.lastname: Glynos
authors.forename: Maziar
authors.initials: M
authors.lastname: Divangahi
authors.forename: Charis
authors.initials: C
authors.lastname: Roussos
authors.forename: Stamatios E
authors.initials: SE
authors.lastname: Theocharis
authors.forename: Theodoros
authors.initials: T
authors.lastname: Vassilakopoulos
mesh_terms: D055371:Acute Lung Injury / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001249:Asthma / Q000503:physiopathology; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002199:Capillary Permeability / Q000502:physiology; D002452:Cell Count; D016207:Cytokines / Q000032:analysis; D005260:Female; D007150:Immunohistochemistry; D008168:Lung / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration; D013314:Stress, Mechanical; D014939:Work of Breathing / Q000502:physiology*
chemical_list: D016207:Cytokines