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J Appl Physiol (March 5, 2004). doi:10.1152/japplphysiol.01288.2003
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Submitted on December 2, 2003
Accepted on March 3, 2004

Pressure gradient, not exposure duration, determines the extent of epithelial cell damage in a model of pulmonary airway reopening

Sarina S Kay1, Anastacia M Bilek1, Kay C Dee1, and Donald P Gaver1*

1 Biomedical Engineering, Tulane University, New Orleans, LA, USA

* To whom correspondence should be addressed. E-mail: donald.gaver{at}tulane.edu.

The reduction of tidal volume during mechanical ventilation has been shown to reduce mortality of patients with acute respiratory distress syndrome (ARDS), but epithelial cell injury can still result from mechanical stresses imposed by the opening of occluded airways. To study these stresses, a fluid filled parallel-plate flow chamber lined with epithelial cells was used as an idealized model of an occluded airway. Airway reopening was modeled by the progression of a semi-infinite bubble of air through the length of the channel, which cleared the fluid. In our prior study, the magnitude of the pressure gradient near the bubble tip was directly correlated to the epithelial cell layer damage [1]. However, in that study it was not possible to discriminate the stress magnitude from the stimulus duration because the bubble propagation velocity varied between experiments. In the present study, the stress magnitude is modified by varying the viscosity of the occlusion fluid while fixing the reopening velocity across experiments. This approach causes the stimulus duration to be inversely related to the magnitude of the pressure gradient. Nevertheless, cell damage remains directly correlated with the pressure gradient, not the duration of stress exposure. The present study thus provides additional evidence that the magnitude of the pressure gradient induces cellular damage in this model of airway reopening. We explore the mechanism for acute damage and also demonstrate that repeated reopening and closure is shown to damage the epithelial cell layer even under conditions that would not lead to extensive damage from a single reopening event.




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