title: Time and tidal volume-dependent ventilator-induced lung injury in healthy rats.
abstract: OBJECTIVE
  We evaluated the effect of duration of mechanical ventilation with different tidal volumes (VT) on ventilator-induced lung injury in healthy rats.
  
  
  METHODS
  Anaesthetized rats were ventilated with VT between 9 and 45 mL kg[-1] for 1 or 7 h with a positive end-expiratory pressure of 2.5 cmH2O.
  
  
  RESULTS
  After 1 h, rats ventilated even with the highest applied VT (36 and 45 mL kg[minus sign]1, resulting in average peak airway pressures of 30 +/-3 and 37 +/- 4 cmH2O), had no detectable alterations in dynamic or static lung mechanics, gas exchange or pulmonary permeability, but a moderate degree of lung inflammation (neutrophil accumulation in broncho-alveolar lavage) observed in all groups. In contrast, after 3 h of ventilation, rats ventilated with the highest VT (36 and 45 mL kg[minus sign]1) died from progressive circulatory failure and high-permeability pulmonary oedema, manifested by hypoxaemia, an increased alveolar-arterial protein concentration ratio and a reduced static lung compliance (mortality rate at 7 h, 62.5% and 100%). Animals with lower VT all survived and presented no changes in the measured variables.
  
  
  CONCLUSIONS
  These results in normal rats demonstrate the preponderant effect of the duration (>3 h) of 'aggressive' ventilation and the cut-off value of the level of VT applied (>27 mL kg[minus sign]1).
authors.affiliation: University Hospitals of Geneva, Division of Anaesthiological Investigations, Geneva, Switzerland. Bernard.walder@hcuge.ch
authors.forename: B
authors.initials: B
authors.lastname: Walder
authors.forename: E
authors.initials: E
authors.lastname: Fontao
authors.forename: M
authors.initials: M
authors.lastname: Totsch
authors.forename: D R
authors.initials: DR
authors.lastname: Morel
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D019559:Capillary Leak Syndrome / Q000503:physiopathology; D003627:Data Interpretation, Statistical; D008168:Lung / Q000473:pathology; D008170:Lung Compliance / Q000502:physiology; D055370:Lung Injury; D009504:Neutrophils / Q000502:physiology; D010100:Oxygen / Q000097:blood; D011506:Proteins / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism; D011659:Pulmonary Gas Exchange / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D015656:Respiratory Mechanics / Q000502:physiology; D013990:Tidal Volume / Q000502:physiology*
chemical_list: D011506:Proteins; D010100:Oxygen