title: Biophysical determinants of alveolar epithelial plasma membrane wounding associated with mechanical ventilation.
abstract: Mechanical ventilation may cause harm by straining lungs at a time they are particularly prone to injury from deforming stress. The objective of this study was to define the relative contributions of alveolar overdistension and cyclic recruitment and "collapse" of unstable lung units to membrane wounding of alveolar epithelial cells. We measured the interactive effects of tidal volume (VT), transpulmonary pressure (PTP), and of airspace liquid on the number of alveolar epithelial cells with plasma membrane wounds in ex vivo mechanically ventilated rat lungs. Plasma membrane integrity was assessed by propidium iodide (PI) exclusion in confocal images of subpleural alveoli. Cyclic inflations of normal lungs from zero end-expiratory pressure to 40 cmH2O produced VT values of 56.9 ± 3.1 ml/kg and were associated with 0.12 ± 0.12 PI-positive cells/alveolus. A preceding tracheal instillation of normal saline (3 ml) reduced VT to 49.1 ± 6 ml/kg but was associated with a significantly greater number of wounded alveolar epithelial cells (0.52 ± 0.16 cells/alveolus; P < 0.01). Mechanical ventilation of completely saline-filled lungs with saline (VT = 52 ml/kg) to pressures between 10 and 15 cmH2O was associated with the least number of wounded epithelial cells (0.02 ± 0.02 cells/alveolus; P < 0.01). In mechanically ventilated, partially saline-filled lungs, the number of wounded cells increased substantially with VT, but, once VT was accounted for, wounding was independent of maximal PTP. We found that interfacial stress associated with the generation and destruction of liquid bridges in airspaces is the primary biophysical cell injury mechanism in mechanically ventilated lungs.
authors.affiliation: Mayo Clinic, Division of Pulmonary and Critical Care Medicine, 200 1st St. SW, Rochester, MN 55905. rhubmayr@mayo.edu.
authors.forename: Omar
authors.initials: O
authors.lastname: Hussein
authors.forename: Bruce
authors.initials: B
authors.lastname: Walters
authors.forename: Randolph
authors.initials: R
authors.lastname: Stroetz
authors.forename: Paul
authors.initials: P
authors.lastname: Valencia
authors.forename: Deborah
authors.initials: D
authors.lastname: McCall
authors.forename: Rolf D
authors.initials: RD
authors.lastname: Hubmayr
mesh_terms: D000818:Animals; D002462:Cell Membrane; D005260:Female; D008168:Lung / Q000502:physiology*; D008176:Lung Volume Measurements; D011650:Pulmonary Alveoli / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D020545:Respiratory Mucosa / Q000503:physiopathology*; D013312:Stress, Physiological; D013990:Tidal Volume; D055397:Ventilator-Induced Lung Injury / Q000503:physiopathology*
keywords: epithelial wounding; injury; lung mechanics