Deformation-induced injury of alveolar epithelial cells - Effect of frequency, duration, and amplitude

The onset of ventilator-induced lung injury (VILI) is linked to a number of possible mechanisms. To isolate the possible role of alveolar epithelial d eformation in the development of VILI, we have developed an in vitro system in which changes in alveolar epithelial cell viability can be measured aft er exposure to tightly controlled and physiologically relevant deformations . We report here a study of the relative effect of deformation frequency, d uration, and amplitude on cell viability. We exposed rat primary alveolar e pithelial cells to a variety of biaxial stretch protocols, and assessed def ormation-induced cell injury quantitatively, using a fluorescent cell viabi lity assay. Deformation-induced injury was found to depend on repetitive st retching, with cyclic deformations significantly more damaging than tonical ly held deformations. In cyclically deformed cells, injury occurred rapidly , with the majority of cell death occurring during the first 5 min of defor mation. Deformation-induced injury was increased with the frequency of sust ained cyclic deformations, but was not dependent on the deformation rate du ring a single stretch. Reducing the amplitude of cell deformations by super imposing small cyclic deformations on a tonic deformation significantly red uced cell death as compared with large-amplitude deformations with the same peak deformation.