TY - JOUR
T1 - Hypercapnic acidosis impairs plasma membrane wound reseating in ventilator-injured lungs
AU - Doerr, Clinton H.
AU - Gajic, Ognjen
AU - Berrios, Jorge C.
AU - Caples, Sean
AU - Abdel, Matthew
AU - Lymp, James F.
AU - Hubmayr, Rolf D.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/6/15
Y1 - 2005/6/15
N2 - 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.
AB - 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.
KW - Permissive hypercapnia
KW - Plasma membrane wounding and repair
KW - Ventilator-induced lung injury
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U2 - 10.1164/rccm.200309-1223OC
DO - 10.1164/rccm.200309-1223OC
M3 - Article
C2 - 15695495
AN - SCOPUS:20444409437
VL - 171
SP - 1371
EP - 1377
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
SN - 1073-449X
IS - 12
ER -