Acute Respiratory Distress Syndrome (ARDS) is a common and devastating lung disorder. In spite of the tremendous amount of research on this subject, many of the mechanisms responsible for the initiation and progression of this disease are not understood. Although the mechanical forces generated by ventilating patients with large volumes have been investigated, the consequences of the fluid mechanical and surface tension forces generated at low lung volumes as well as the role of cellular mechanics on this disease is unknown. The main objective of this dissertation research is to design and implement an in-vitro cell culture model in order to investigate the responses of lung epithelial cells (EC) to the fluid mechanical forces generated during the low lung volume ventilation of ARDS patients. In this model, the collapse and reopening of small airways is mimicked by progressing micron sized air bubbles over EC populations. EC were found to be very sensitive to the hydrodynamic stresses, especially to large spatial gradients in pressure near the bubble tip during bubble progressions. Additionally, compared to single bubble propagation, multiple bubble passages created additional injury, but the most of the injury happened after the first bubble propagation. In addition to hydrodynamic stresses, EC' morphological, biomechanical and microstructural properties also played a major role on cellular injury during bubble progressions. As these cells become more liquid-like, their resistance to injurious stresses increases significantly. The knowledge gained from this study may be useful to understand the injury mechanisms of EC during low volume ventilation and therefore to establish new ventilatory protocols and pharmaceutical treatments for ARDS patients.
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