Deformation-induced injury of alveolar epithelial cells: Effect of strain magnitude and amplitude

The alveolar epithelial lining of the lung undergoes significant increases in surface area at high lung volumes. These deformations may be critical in the development of pulmonary barotrauma. We tested the hypothesis that alveolar epithelial injury would increase both as a function of deformation amplitude, and maximal deformation. Alveolar type II cells from primary culture were seeded onto fibronectin coated silastic membranes and tested after 5 days in culture. Cells were exposed to uniform equi-biaxial deformations in a custom built device, and were subjected to changes in surface area of 12, 25, 37, and 50%, which correspond to lung inflation to ∼ 60, 80, 100, and > 100% of total lung capacity. Cells were also exposed to 0, 12, and 25% changes in surface area superimposed on a tonic deformation of 25%. Cells were continuously cycled for 1 hour at 15 cycles per minute. Alveolar epithelial injury was assessed quantitatively with a fluorescent cell viability assay, and defined as fraction of dead cells relative to total number of cells. Injury increased non-linearly with amplitude and maximum deformation (Figure), confirming our hypothesis. When deformation amplitude was reduced while maximal deformation was maintained constant, injury decreased. These findings implicate both peak volume and tidal volume in the development of barotrauma, and suggest that ventilation with PEEP and reduced tidal volumes, previously credited for enhancing alveolar recruitment, may also modulate epithelial injury by reducing the amplitude of cellular deformations. (Graph Presented).