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Frequency and peak stretch magnitude affect alveolar epithelial permeability

Dept of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA

CORRESPONDENCE: S. S. Margulies, Dept of Bioengineering, 210 South 33rd St, University of Pennsylvania, Philadelphia, PA 19104-6321, USA. Fax: 1 2155732071. E-mail: margulie{at}seas.upenn.edu

Keywords: Barrier properties, tight junction, ventilator-induced lung injury

Received: October 25, 2007
Accepted June 24, 2008

The present study measured stretch-induced changes in transepithelial permeability to uncharged tracers (1.5–5.5 Å) using cultured monolayers of alveolar epithelial 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 (SA) for 1 h.

Significant changes in permeability of cell monolayers were observed when stretched from 0% to 37% SA at all frequencies, and from 0% to 25% SA only at high frequency (1 Hz), but not at all when stretched from 0% to 12% SA compared with unstretched controls. At stretch oscillation amplitudes of 25 and 37% SA, imposed at 1 Hz, tracer permeability increased compared with that at 0.25 Hz. Cells subjected to a single stretch cycle at 37% 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% 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.