New insights into impairment of mucosal defense in portal hypertensive gastric mucosa

Portal hypertension (PHT) increases susceptibility of the gastric mucosa to injury. The aim of this study was to investigate whether PHT affects rat g astric mucosal defense mechanisms in vivo at the preepithelial, epithelial, and/or post-epithelial levels. PHT was produced in rats by staged portal v ein ligation and sham-operated (SO) rats served as controls. The gastric mu cosa was exposed, chambered, and continuously superfused with buffers under in vivo microscopy. We measured gastric mucosal gel layer thickness, surfa ce epithelial cell intracellular pH (pH(i)), mucosal blood flow, and mucosa l/serosal oxygenation. In PHT rats, gastric mucosal gel layer thickness was significantly reduced (88 +/- 16 mum in PHT rats vs. 135 +/- 25 mum in SO rats; P < 0.0001), and the surface epithelial cell pH(i) was significantly decreased (6.80 +/- 0.11 in PHT rats vs. 7.09 +/- 0.21 in SO rats; P < 0.01 ). Although total gastric mucosal blood flow was significantly increased in PHT rats by 72% (P < 0.05), the oxygenation of the gastric mucosal surface was decreased by 42% (P < 0.05) compared with SO rats. PHT impairs pre-epi thelial (mucosal gel layer thickness), epthelial (pH(i)), and post-epitheli al (maldistribution of blood flow) components of the gastric mucosal barrie r. These findings can explain the increased susceptibility of portal hypert ensive gastric mucosa to injury.