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Effect of pharmacological inhibition of chloride transport on lung fluid balance in acute Escherichia coli pneumonia in mice
Critical Care volume 9, Article number: P90 (2005)
Clearance of fluid from the alveolar spaces primary depends on the active sodium transport across distal lung epithelium. Some experimental studies supported a potential role for the cystic fibrosis transmembrane conductance regulator (CFTR), especially in the cAMP-mediated upregulation of fluid clearance. Hypothetically, pharmacological inhibition of Cl-channels could worsen lung edema by decreasing the clearance of alveolar edema. In this study, we tested the affect of chloride transport inhibition on lung edema formation in acute pneumonia.
A mouse model of acute pneumonia was established using IT instillation of Escherichia coli (107 cfu). Basal and isoproterenol (0.1 mM)-stimulated alveolar fluid clearance were studied using the in situ mice model. Glibenclamide (0.1 mM) or a specific CFTR-inhibitor (100 mM CFTR-172) was instilled into the lung to study the effects of CFTR blockade.
In response to cAMP stimulation by isoproterenol, clearance was inhibited by glibenclamide or the CFTR-172 inhibitor (respectively, 12.2 ± 0.39% and 9.7 ± 3.5% versus 20.7 ± 2.9% in the control group, P < 0.05). Four hours after bacterial instillation, the lung wet-to-dry ratio and lung vascular permeability as measured by the extravascular accumulation of 125I-albumin were increased compared with the control group (respectively, 4.8 ± 0.18 g/g versus 3.8 ± 0.18 g/g, P < 0.05 and 61.8 ± 10.4 μl versus 20 ± 5.9 μl, P < 0.05). No significant statistical change was found among lung water and endothelial permeability in the glibenclamide or CFTR-172 inhibitor group.
These experiments indicated that the c-AMP-dependent fluid clearance from the distal airspaces of the lung involves chloride transport by CFTR. In vivo, we found no change in pulmonary edema formation following E. coli intratracheal instillation. These data suggest that chloride transport is not a major mechanism in lung edema formation in a mouse model of acute pneumonia.
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Robriquet, L., Song, Y., Folkesson, H. et al. Effect of pharmacological inhibition of chloride transport on lung fluid balance in acute Escherichia coli pneumonia in mice. Crit Care 9, P90 (2005). https://doi.org/10.1186/cc3153
- Cystic Fibrosis Transmembrane Conductance Regulator
- Intratracheal Instillation
- Chloride Transport