RATIONALE: Lung injury results in intra-tidal alveolar recruitment and derecruitment (R/D) and alveolar collapse, creating stress concentrators that increase strain and aggravate injury. OBJECTIVE: To describe alveolar micromechanics during mechanical ventilation in bleomycin-induced lung injury and surfactant replacement therapy. METHODS: Structure and function were assessed in rats one (D1) and three (D3) days after intratracheal bleomycin instillation and subsequent to surfactant replacement therapy (SRT). Pulmonary system mechanics were measured during ventilation with positive end-expiratory pressures (PEEP) between 1 and 10 cmH2O followed by perfusion fixation at end-expiratory airway opening pressures (Pao) of 1, 5, 10, and 20cmH2O for quantitative analyses of lung structure. Lung structure and function were used to parameterize a physiologically-based multi-compartment computational model of alveolar micromechanics. MEASUREMENTS AND MAIN RESULTS: In healthy controls, numbers of open alveoli remained stable in a range of Pao=1-20cmH2O while bleomycin-challenged lungs demonstrated progressive alveolar derecruitment with Pao<10cmH2O. At D3, approximately 40% of alveoli remained closed at high Pao while alveolar size heterogeneity increased. Simulations of injured lungs predicted that alveolar recruitment pressures were much greater than the derecruitment pressures so that minimal intra-tidal R/D occurred during mechanical ventilation with a tidal volume of 10ml/kg bodyweight over a range of PEEP. However, the simulations also predicted a dramatic increase in alveolar strain with injury that we attribute to alveolar interdependence. CONCLUSION: In progressive lung injury, alveolar collapse with increased distension of patent (open) alveoli dominates alveolar micromechanics. PEEP and surfactant substitution reduce alveolar collapse and dynamic strain but increase static strain.
- Knudsen, L.
- Lopez-Rodriguez, E.
- Berndt, L.
- Steffen, L.
- Ruppert, C.
- Bates, J. H. T.
- Ochs, M.
- Smith, B. J.
Keywords
- acute lung injury
- alveolar dynamics
- modeling
- stereology
- surfactant