Hypercapnic acidosis impairs plasma membrane wound reseating in ventilator-injured lungs

Clinton H. Doerr, Ognjen Gajic, Jorge C. Berrios, Sean Caples, Matthew Abdel, James F. Lymp, Rolf D. Hubmayr

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

The objective of this study was to assess the effects of hypercapnic acidosis on lung cell injury and repair by confocal microscopy in a model of ventilator-induced lung injury. Three groups of normocapnic, hypocapnic, and hypercapnic rat lungs were perfused ex vivo, either during or after injurious ventilation, with a solution containing the membrane-impermeant label propidium iodide. In lungs labeled during injurious ventilation, propidium iodide fluorescence identifies all cells with plasma membrane wounds, both permanent and transient, whereas in lungs labeled after injurious ventilation propidium iodide fluorescence identifies only cells with permanent plasma membrane wounds. Hypercapnia minimized the adverse effects of high-volume ventilation on vascular barrier function, whereas hypocapnia had the opposite effect. Despite CO2-dependent differences in lung mechanics and edema the number of injured subpleural cells per alveolus was similar in the three groups (0.48 ± 0.34 versus 0.51 ± 0.19 versus 0.43 ± 0.20 for hypocapnia, normocapnia, and hypercapnia, respectively). However, compared with normocapnia the probability of wound repair was significantly reduced in hypercapnic lungs (63 versus 38%; p < 0.02). This finding was subsequently confirmed in alveolar epithelial cell scratch models. The potential relevance of these observations for lung inflammation and remodeling after mechanical injury is discussed.

Original languageEnglish (US)
Pages (from-to)1371-1377
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume171
Issue number12
DOIs
StatePublished - Jun 15 2005

Keywords

  • Permissive hypercapnia
  • Plasma membrane wounding and repair
  • Ventilator-induced lung injury

ASJC Scopus subject areas

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

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