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

Objective., To determine the impact of different protective and nonprotecti ve mechanical ventilation strategies on the degree of pulmonary inflammatio n, oxidative damage, and hemodynamic stability in a saline lavage model of acute lung injury. Design: A prospective, randomized, controlled, in vivo animal laboratory st udy. 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 vas cular catheters. Lavage-injured rabbits were randomized to receive conventi onal ventilation with either a) low peak end-expiratory pressure (PEEP; tid al 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) h igh-frequency oscillatory ventilation. Animals were ventilated for 4 hrs. L ung lavage fluid and tissue samples were obtained immediately after animals were killed. Lung lavage fluid was assayed for measurements of total prote in, elastase activity, tumor necrosis factor-alpha, and malondialdehyde. Lu ng tissue homogenates were assayed for measurements of myeloperoxidase acti vity and malondialdehyde. The need for inotropic support was recorded. Measurements and Main Results. Animals that received a lung protective stra tegy (open lung or high-frequency oscillatory ventilation) exhibited more f avorable 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 leukos tasis). Animals treated with high-frequency oscillatory ventilation had att enuated oxidative injury to the lung and greater hemodynamic stability comp ared with the other experimental groups. Conclusions: Both lung protective strategies were associated with improved oxygenation, attenuated inflammation, and decreased lung damage. However, i n this small-animal model of acute lung injury, an open lung strategy with deliberate hypercapnia was associated with significant hemodynamic instabil ity.