Comparison of lung protective ventilation strategies in a rabbit model of acute lung injury

Alexandre T. Rotta, Björn Gunnarsson, Bradley P. Fuhrman, Lynn J. Hernan, David M. Steinhorn

Research output: Contribution to journalArticlepeer-review

105 Scopus citations


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. Design: A prospective, randomized, controlled, in vivo animal laboratory study. Setting: Animal research facility of a health sciences university. Subjects: Forty-six New Zealand White rabbits. Interventions: 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-α, and malondialdehyde. Lung tissue homogenates were assayed for measurements of myeloperoxidase activity and malondialdehyde. The need for inotropic support was recorded. Measurements and Main 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-α, 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.

Original languageEnglish (US)
Pages (from-to)2176-2184
Number of pages9
JournalCritical Care Medicine
Issue number11
StatePublished - 2001
Externally publishedYes


  • Acute lung injury
  • High frequency ventilation
  • Inflammation
  • Lung disease
  • Respiratory failure

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine


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