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


Journal Article

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-alpha, 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-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.

Full Text

Duke Authors

Cited Authors

  • Rotta, AT; Gunnarsson, B; Fuhrman, BP; Hernan, LJ; Steinhorn, DM

Published Date

  • November 2001

Published In

Volume / Issue

  • 29 / 11

Start / End Page

  • 2176 - 2184

PubMed ID

  • 11700418

Pubmed Central ID

  • 11700418

Electronic International Standard Serial Number (EISSN)

  • 1530-0293

International Standard Serial Number (ISSN)

  • 0090-3493

Digital Object Identifier (DOI)

  • 10.1097/00003246-200111000-00021


  • eng