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

Daniel J. Tschumperlin, Jane Oswari, Susan S. Margulies

Research output: Contribution to journalArticlepeer-review

250 Scopus citations


The onset of ventilator-induced lung injury (VILI) is linked to a number of possible mechanisms. To isolate the possible role of alveolar epithelial deformation in the development of VILI, we have developed an in vitro system in which changes in alveolar epithelial cell viability can be measured after exposure to tightly controlled and physiologically relevant deformations. We report here a study of the relative effect of deformation frequency, duration, and amplitude on cell viability. We exposed rat primary alveolar epithelial cells to a variety of biaxial stretch protocols, and assessed deformation-induced cell injury quantitatively, using a fluorescent cell viability assay. Deformation-induced injury was found to depend on repetitive stretching, with cyclic deformations significantly more damaging than tonically held deformations. In cyclically deformed cells, injury occurred rapidly, with the majority of cell death occurring during the first 5 min of deformation. Deformation-induced injury was increased with the frequency of sustained cyclic deformations, but was not dependent on the deformation rate during a single stretch. Reducing the amplitude of cell deformations by superimposing small cyclic deformations on a tonic deformation significantly reduced cell death as compared with large-amplitude deformations with the same peak deformation.

Original languageEnglish (US)
Pages (from-to)357-362
Number of pages6
JournalAmerican journal of respiratory and critical care medicine
Issue number2 I
StatePublished - 2000

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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