Rationale Positive pressure ventilation exposes the lung to mechanical stresses that can exacerbate injury. The exact mechanism of this pathological process remains elusive. Objectives Describe Recruitment/Derecruitment (R/D) at acinar length scales over short time frames and test the hypothesis that mechanical interdependence between neighboring lung units determines the spatial and temporal distributions of R/D, using a computational model. Methods Experiments were performed in anaesthetized rabbits ventilated in Pressure Controlled mode (PCV). The lung was consecutively imaged at ~1.5 min intervals, at each Positive End-Expiratory Pressure (PEEP) of 12, 9, 6, 3 and 0 cmH2O before and after injury. The extent and spatial distribution of R/D was analyzed by subtracting subsequent images. In a realistic lung structure we implemented a mechanistic model in which each unit has individual pressures and speeds of opening and closing. Derecruited and Recruited lung fractions (Fderecruited, Frecruited) were computed based on the comparison of the aerated volumes at successive time points. Results Alternative R/D occurred in neighboring alveoli over short time scales in all tested PEEP levels and despite stable PCV. The computational model reproduced this behavior only when parenchymal interdependence between neighboring acini was accounted for. Simulations closely mimicked the experimental magnitude of Fderecruited and Frecruited when mechanical interdependence was included, while its exclusion gave Frecruited values of zero at PEEP ≥ 3 cmH2O. Conclusions These findings give further insight into the microscopic behavior of the injured lung and provide a means of testing protective-ventilation strategies to prevent R/D and subsequent lung damage.

Objectives: Airway closure is involved in adverse effects of mechanical ventilation under both general anesthesia and in acute respiratory distress syndrome patients. However, direct evidence and characterization of individual airway closure is lacking. Here, we studied the same individual peripheral airways in intact lungs of anesthetized and mechanically ventilated rabbits, at baseline and following lung injury, using high-resolution synchrotron phase-contrast CT. Design: Laboratory animal investigation. Setting: European synchrotron radiation facility. Subjects: Six New-Zealand White rabbits. Interventions: The animals were anesthetized, paralyzed, and mechanically ventilated in pressure-controlled mode (tidal volume, 6 mL/kg; respiratory rate, 40; Fio 2, 0.6; inspiratory:expiratory, 1:2; and positive end-expiratory pressure, 3 cm H2O) at baseline. Imaging was performed with a 47.5 × 47.5 × 47.5 μm voxel size, at positive end-expiratory pressure 12, 9, 6, 3, and 0 cm H2O. The imaging sequence was repeated after lung injury induced by whole-lung lavage and injurious ventilation in four rabbits. Cross-sections of the same individual airways were measured. Measurements and Main Results: The airways were measured at baseline (n = 48; radius, 1.7 to 0.21 mm) and after injury (n = 32). Closure was observed at 0 cm H2O in three of 48 airways (6.3%; radius, 0.35 ± 0.08 mm at positive end-expiratory pressure 12) at baseline and five of 32 (15.6%; radius, 0.28 ± 0.09 mm) airways after injury. Cross-section was significantly reduced at 3 and 0 cm H2O, after injury, with a significant relation between the relative change in cross-section and airway radius at 12 cm H2O in injured, but not in normal lung (R = 0.60; p < 0.001). Conclusions: Airway collapsibility increases in the injured lung with a significant dependence on airway caliber. We identify “compliant collapse” as the main mechanism of airway closure in initially patent airways, which can occur at more than one site in individual airways.