BACKGROUND: The response of the oesophageal microcirculation to luminal damaging agents may play an important role in reflux-induced mucosal injury. We characterized the microcirculatory consequences of exposure to bile with or without hydrochloric acid, and determined the changes in the constitutive nitric oxide synthase and inducible nitric oxide synthase activities in a canine model of acute reflux oesophagitis. METHODS: Group 1 served as a saline-treated control, while groups 2-4 were exposed for 3 h to bile alone, to hydrochloric acid, or to bile + hydrochloric acid, respectively. The mucosal microcirculation was observed continuously by means of intravital videomicroscopy with an orthogonal polarization spectral imaging technique. Myeloperoxidase, constitutive and inducible nitric oxide synthase activities were measured via tissue biopsies, while the degree of mucosal damage was evaluated histologically. RESULTS: Bile evoked deep tissue damage and leucocyte accumulation in the mucosa and muscle layer. The capillary red blood cell velocity and the relative vessel area increased significantly (P < 0.05). The constitutive NO synthase activity was decreased, and the inducible NO synthase activity was increased significantly. In the hydrochloric acid-treated group the functional capillary density decreased, the mucosal damage was less severe, the constitutive NO synthase activity did not change, whereas the inducible NO synthase activity was increased significantly. The constitutive NO synthase activity did not change after the bile + hydrochloric acid treatment either. CONCLUSION: Reflux components induce characteristic microcirculatory alterations. The structural damage and leucocyte invasion are accompanied by bile-induced constitutive NO synthase inhibition when hydrochloric acid production is suppressed.
BACKGROUND: The response of the oesophageal microcirculation to luminal damaging agents may play an important role in reflux-induced mucosal injury. We characterized the microcirculatory consequences of exposure to bile with or without hydrochloric acid, and determined the changes in the constitutive nitric oxide synthase and inducible nitric oxide synthase activities in a canine model of acute reflux oesophagitis. METHODS: Group 1 served as a saline-treated control, while groups 2-4 were exposed for 3 h to bile alone, to hydrochloric acid, or to bile + hydrochloric acid, respectively. The mucosal microcirculation was observed continuously by means of intravital videomicroscopy with an orthogonal polarization spectral imaging technique. Myeloperoxidase, constitutive and inducible nitric oxide synthase activities were measured via tissue biopsies, while the degree of mucosal damage was evaluated histologically. RESULTS: Bile evoked deep tissue damage and leucocyte accumulation in the mucosa and muscle layer. The capillary red blood cell velocity and the relative vessel area increased significantly (P < 0.05). The constitutive NO synthase activity was decreased, and the inducible NO synthase activity was increased significantly. In the hydrochloric acid-treated group the functional capillary density decreased, the mucosal damage was less severe, the constitutive NO synthase activity did not change, whereas the inducible NO synthase activity was increased significantly. The constitutive NO synthase activity did not change after the bile + hydrochloric acid treatment either. CONCLUSION: Reflux components induce characteristic microcirculatory alterations. The structural damage and leucocyte invasion are accompanied by bile-induced constitutive NO synthase inhibition when hydrochloric acid production is suppressed.
Authors: Hendrik Bracht; Vladimir Krejci; Luzius Hiltebrand; Sebastian Brandt; Gisli Sigurdsson; Syed Z Ali; Jukka Takala; Stephan M Jakob Journal: Intensive Care Med Date: 2008-05-31 Impact factor: 17.440