Mechanisms of surface-tension-induced epithelial cell damage in a model of pulmonary airway reopening

TLDR

Mechanical ventilation causes airway collapse and reopening that mechanically stresses airway walls, injuring surfactant‑compromised lungs. The study modeled airway reopening with a semi‑infinite bubble in a narrow fluid‑occluded channel and used computational simulations to identify the steep pressure gradient near the bubble front as the likely injurious stress component. Cell damage rose as opening velocity decreased, but was fully prevented by the surfactant Infasurf, confirming that mechanical stresses—particularly steep pressure gradients—injure epithelial cells and that surfactant protects them.

Abstract

Airway collapse and reopening due to mechanical ventilation exerts mechanical stress on airway walls and injures surfactant-compromised lungs. The reopening of a collapsed airway was modeled experimentally and computationally by the progression of a semi-infinite bubble in a narrow fluid-occluded channel. The extent of injury caused by bubble progression to pulmonary epithelial cells lining the channel was evaluated. Counterintuitively, cell damage increased with decreasing opening velocity. The presence of pulmonary surfactant, Infasurf, completely abated the injury. These results support the hypotheses that mechanical stresses associated with airway reopening injure pulmonary epithelial cells and that pulmonary surfactant protects the epithelium from this injury. Computational simulations identified the magnitudes of components of the stress cycle associated with airway reopening (shear stress, pressure, shear stress gradient, or pressure gradient) that may be injurious to the epithelial cells. By comparing these magnitudes to the observed damage, we conclude that the steep pressure gradient near the bubble front was the most likely cause of the observed cellular damage.