title: Comparison of lung protective ventilation strategies in a rabbit model of acute lung injury.
abstract: OBJECTIVE
  To determine the impact of different protective and nonprotective mechanical ventilation strategies on the degree of pulmonary inflammation, oxidative damage, and hemodynamic stability in a saline lavage model of acute lung injury.
  
  
  METHODS
  A prospective, randomized, controlled, in vivo animal laboratory study.
  
  
  METHODS
  Animal research facility of a health sciences university.
  
  
  METHODS
  Forty-six New Zealand White rabbits.
  
  
  METHODS
  Mature rabbits were instrumented with a tracheostomy and vascular catheters. Lavage-injured rabbits were randomized to receive conventional ventilation with either a) low peak end-expiratory pressure (PEEP; tidal volume of 10 mL/kg, PEEP of 2 cm H2O); b) high PEEP (tidal volume of 10 mL/kg, PEEP of 10 cm H2O); c) low tidal volume with PEEP above Pflex (open lung strategy, tidal volume of 6 mL/kg, PEEP set 2 cm H2O > Pflex); or d) high-frequency oscillatory ventilation. Animals were ventilated for 4 hrs. Lung lavage fluid and tissue samples were obtained immediately after animals were killed. Lung lavage fluid was assayed for measurements of total protein, elastase activity, tumor necrosis factor-alpha, and malondialdehyde. Lung tissue homogenates were assayed for measurements of myeloperoxidase activity and malondialdehyde. The need for inotropic support was recorded.
  
  
  RESULTS
  Animals that received a lung protective strategy (open lung or high-frequency oscillatory ventilation) exhibited more favorable oxygenation and lung mechanics compared with the low PEEP and high PEEP groups. Animals ventilated by a lung protective strategy also showed attenuation of inflammation (reduced tracheal fluid protein, tracheal fluid elastase, tracheal fluid tumor necrosis factor-alpha, and pulmonary leukostasis). Animals treated with high-frequency oscillatory ventilation had attenuated oxidative injury to the lung and greater hemodynamic stability compared with the other experimental groups.
  
  
  CONCLUSIONS
  Both lung protective strategies were associated with improved oxygenation, attenuated inflammation, and decreased lung damage. However, in this small-animal model of acute lung injury, an open lung strategy with deliberate hypercapnia was associated with significant hemodynamic instability.
authors.affiliation: Division of Pediatric Critical Care, The Children's Hospital of Buffalo, State University of New York at Buffalo, Buffalo, NY 14222, USA. arotta@acsu.buffalo.edu
authors.forename: A T
authors.initials: AT
authors.lastname: Rotta
authors.forename: B
authors.initials: B
authors.lastname: Gunnarsson
authors.forename: B P
authors.initials: BP
authors.lastname: Fuhrman
authors.forename: L J
authors.initials: LJ
authors.lastname: Hernan
authors.forename: D M
authors.initials: DM
authors.lastname: Steinhorn
mesh_terms: D000818:Animals; D006439:Hemodynamics; D006611:High-Frequency Jet Ventilation; D015227:Lipid Peroxidation; D008954:Models, Biological; D011175:Positive-Pressure Respiration; D011817:Rabbits; D012121:Respiration, Artificial / Q000379:methods*; D012128:Respiratory Distress Syndrome / Q000517:prevention & control*