OBJECTIVES: : To analyze alveolar dynamics in healthy and acid-injured lungs of ventilated mice. Protective ventilation is potentially lifesaving in patients with acute lung injury. However, optimization of ventilation strategies is hampered by an incomplete understanding of the effects of mechanical ventilation at the alveolar level.

DESIGN: : In anesthetized and ventilated Balb/c mice, subpleural alveoli were visualized by darkfield intravital microscopy and optical coherence tomography.

SETTING: : Animal research laboratory.

SUBJECTS: : Male Balb/c mice.

INTERVENTIONS: : Lung injury was induced by intratracheal instillation of hydrochloric acid. In control animals and mice with lung injury, ventilation pressures were varied between 0 and 24 cm H2O at baseline, 60 mins, and 120 mins, and alveolar distension and cyclic opening and collapse of alveolar clusters were analyzed.

MEASUREMENTS AND MAIN RESULTS: : In normal lungs, alveolar clusters distend with increasing ventilation pressure in a sigmoid relationship. Although an increase in ventilation pressure from 0 to 24 cm H2O increases alveolar size by 41.5 +/- 2.3% in normal lungs, alveolar distension is reduced to 20.6 +/- 2.2% 120 mins after induction of lung injury by acid aspiration. Cyclic opening and collapse of alveolar clusters are neither observed in normal nor acid-injured lungs. Alveolar compliance is highest in small and distensible alveolar clusters, which are also most prone to acid-induced injury.

CONCLUSIONS: : Over the applied pressure range, volume changes in control and acid-injured mouse lungs result predominantly from alveolar distension rather than cyclic opening and collapse of alveolar clusters. Preferential loss of compliance in small alveolar clusters redistributes tidal volume to larger alveoli, which increases spatial heterogeneity in alveolar inflation and may promote alveolar overdistension.