title: Ventilator-induced cell wounding and repair in the intact lung.
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 (0.25 +/- 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.
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Thoracic Diseases Research Unit, Mayo Clinic, Rochester, Minnesota 55905, USA. gajic.ognjen@mayo.edu
authors.forename: Ognjen
authors.initials: O
authors.lastname: Gajic
authors.forename: Jaeho
authors.initials: J
authors.lastname: Lee
authors.forename: Clinton H
authors.initials: CH
authors.lastname: Doerr
authors.forename: Jorge C
authors.initials: JC
authors.lastname: Berrios
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Myers
authors.forename: Rolf D
authors.initials: RD
authors.lastname: Hubmayr
mesh_terms: D000818:Animals; D002462:Cell Membrane; D008168:Lung / Q000166:cytology* / Q000276:immunology; D055370:Lung Injury; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D014945:Wound Healing