%0 Journal Article
%T Airway response to acute mechanical stress in a human bronchial model of stretch
%A Christophe Faisy
%A Francisco M Pinto
%A Morgan Le Guen
%A Emmanuel Naline
%A Stanislas Grassin Delyle
%A Edouard Sage
%A Maria-Luz Candenas
%A Philippe Devillier
%J Critical Care
%D 2011
%I BioMed Central
%R 10.1186/cc10443
%X Bronchi were removed from 48 thoracic surgery patients. After preparation and equilibration in an organ bath, bronchial rings were stretched for 5 min using a force (2.5 กม basal tone) that corresponded to airway-inflation pressure > 30 cm H2O. The consequences of stretch were examined by using functional experiments, analysis of organ-bath fluid, and ribonucleic acid (RNA) isolation from tissue samples.Following removal of the applied force the airways immediately developed an increase in basal tone (P < 0.0001 vs. paired controls) that was sustained and it did so without significantly increasing responsiveness to acetylcholine. The spontaneous tone was abolished with a Rho-kinase inhibitor and epithelium removal, a leukotriene antagonist or nitric oxide synthase inhibitors reduced it, whereas indomethacin, sensory nerve inhibitors or antagonists for muscarinic, endothelin and histamine receptors had no effect. Stretch enhanced leukotriene-E4 production during the immediate spontaneous contraction of human bronchi (P < 0.05). Moreover, stretch up-regulated the early mRNA expression of genes involved in wingless-type mouse mammary tumor virus integration-site family (WNT)-signaling and Rho-kinase pathways.Stretching human bronchi for only 5 min induces epithelial leukotriene release via nitric oxide synthase activation and provokes a myogenic response dependent on Rho-kinase and WNT-signaling pathways. From a clinical perspective, these findings highlight the response of human airway to acute mechanical stress during excessive pulmonary inflation.In healthy subjects, air movement into and out of the lungs throughout respiration produces estimated pressure variations of 5 to 25 cm H2O, corresponding to functional residual capacity and total lung capacity, respectively. Airway inflation of the lungs induces mechanical strain and in turn causes either smooth muscle relaxation or contraction, which are mediated for the most part by airway epithelium and mechanosensors, s
%U http://ccforum.com/content/15/5/R208