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Updated: Aug 9, 2026
Lavage-induced Surfactant Depletion in Pigs As a Model of the Acute Respiratory Distress Syndrome (ARDS)
Published on: September 7, 2016
Comparison of lung protective ventilation strategies in a rabbit model of acute lung injury
A T Rotta1, B Gunnarsson, B P Fuhrman
1Division 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
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.
