Frequency and peak stretch magnitude affect alveolar epithelial permeability

The present study measured stretch-induced changes in transepithelial permeability to uncharged tracers (1.5-5.5 angstrom) using cultured monolayers of alveolar epithellial type-I like cells. Cultured alveolar epithelial cells were subjected to uniform cyclic (0, 0.25 and 1.0 Hz) biaxial stretch from 0% to 12, 25 or 37% change in surface area (Delta SA) for 1 h. Significant changes in permeability of cell monolayers were observed when stretched from 0% to 37% Delta SA at all frequencies, and from 0% to 25% Delta SA only at high frequency (1 Hz) but not at all when stretched from 0% to 12% Delta SA compared with unstretched controls. At stretch oscillation amplitudes of 25 and 37% Delta SA, imposed at 1 Hz tracer permeability increased compared with that at 0.25 Hz. Cells subjected to a single stretch cycle at 37% Delta SA (0.25 Hz), to simulate a deep sigh, were not distinguishable from unstretched controls. Reducing stretch oscillation amplitude while maintaining a peak stretch of 37% Delta SA (0.25 Hz) via the application of a simulated post-end-expiratory pressure did not protect barrier properties. In conclusion, peak stretch magnitude and stretch frequency were the primary determining factors for epithelial barrier dysfunction, as opposed to oscillation amplitude.