Published ahead of print on February 1, 2005, doi:10.1164/rccm.200309-1223OC Am. J. Respir. Crit. Care Med., Volume 171, Number 12, June 2005, 1371-1377 A more recent version of this article appeared on June 15, 2005
Submitted on September 3, 2003 Hypercapnic Acidosis Impairs Plasma Membrane Wound Resealing in Ventilator Injured LungsClinton H Doerr1,1 Thoracic Diseases Research Unit, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA, 2 Department of Health Sciences Research, Division of Biostatistics, 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 and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA * To whom correspondence should be addressed. E-mail: rhubmayr{at}mayo.edu.
The objective of this study was to assess the effects of hypercapnic acidosis on lung cell injury and repair with 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, while 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, while 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 3 groups (0.50±0.19 vs 0.48±0.34 vs 0.43±0.20). However, compared to normocapnia the probability of wound repair was significantly reduced in hypercapnic lungs (63% vs 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 following mechanical injury is discussed. Key words: Ventilator Induced Lung Injury, Permissive Hypercapnia, Plasma Membrane Wounding and Repair
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