airway response to acute mechanical stress in a human bronchial model of stretch气道反应在人类支气管急性机械应力拉伸模型.pdfVIP

Faisy et al. Critical Care 2011, 15:R208 /content/15/5/R208 RESEARCH Open Access Airway response to acute mechanical stress in a human bronchial model of stretch 1,2* 3 1 1 1 Christophe Faisy , Francisco M Pinto , Morgan Le Guen , Emmanuel Naline , Stanislas Grassin Delyle , Edouard Sage4, Maria-Luz Candenas3 and Philippe Devillier1 Abstract Introduction: Lung inflation may have deleterious effects on the alveoli during mechanical ventilation. However, the consequences of stretch during excessive lung inflation on basal tone and responsiveness of human bronchi are unknown. This study was undertaken to devise an experimental model of acute mechanical stretch in isolated human bronchi and to investigate its effect on airway tone and responsiveness. Methods: 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 × 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. Results: 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 enhance