Published ahead of print on December 12, 2002, doi:10.1164/rccm.200208-889OC
Am. J. Respir. Crit. Care Med., Volume 167, Number 8, April 2003, 1057-1063
A more recent version of this article appeared on April 15, 2003
Submitted on August 21, 2002
Accepted on December 9, 2002
Ventilator-Induced Cell Wounding and Repair in the Intact Lung
Ognjen Gajic1*, Jaeho Lee1, Clinton H Doerr1, Jorge C Berrios1, Jeffrey L Myers2, and Rolf D Hubmayr3
1 Thoracic Diseases Research Unit, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA,
2 Department of Pathology, Mayo Clinic, Rochester, MN, USA,
3 Thoracic Diseases Research Unit, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA; Department of Physiology & Biophysics, Mayo Clinic, Rochester, MN, USA
* To whom correspondence should be addressed. E-mail: gajic.ognjen{at}mayo.edu.
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 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 while 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.
Key words: ventilator-induced lung injury, plasma membrane resealing, confocal microscopy, isolated perfused rat lung, stress failure
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Copyright © 2002 American Thoracic Society
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