Ventilator-induced cell wounding and repair in the intact lung

Ognjen Gajic, Jaeho Lee, Clinton H. Doerr, Jorge C. Berrios, Jeffrey L. Myers, Rolf D. Hubmayr

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

We tested the hypothesis that cells of ventilator-injured lungs are subject to reversible plasma membrane stress failure. Rat lungs were perfused with the membrane impermeable fluorescent marker propidium iodide and randomized to one of four ventilation strategies. Subpleural lung regions were imaged with confocal microscopy, and cell injury was quantified as the number of propidium iodide-positive cells per alveolus. The number of injured cells was significantly greater in lungs ventilated with large tidal volumes and zero end-expiratory pressure than in lungs ventilated with small tidal volumes and positive end-expiratory pressure (p < 0.01). Cell injury correlated with lung weight gain, change in dynamic compliance, and histologic injury scores. In a second set of experiments, lungs were mechanically ventilated for 30 minutes at high tidal volume settings, whereas propidium iodide was perfused either during or after injurious ventilation. Labeling after removal of injurious stress revealed significantly fewer injured cells (0.2.5 ± 0.09 to 0.08 ± 0.08, p < 0.01). We conclude that cells of ventilator-injured lungs are subject to reversible plasma membrane stress failure.

Original languageEnglish (US)
Pages (from-to)1057-1063
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume167
Issue number8
DOIs
StatePublished - Apr 15 2003

Keywords

  • Confocal microscopy
  • Isolated perfused rat lung
  • Plasma membrane resealing
  • Stress failure
  • Ventilator-induced lung injury

ASJC Scopus subject areas

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

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