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 gastric mucosal defense mechanisms in vivo at the preepithelial, epithelial, and/or post-epithelial levels. PHT was produced in rats by staged portal vein ligation and sham-operated (SO) rats served as controls. The gastric mucosa was exposed, chambered, and continuously superfused with buffers under in vivo microscopy. We measured gastric mucosal gel layer thickness, surface epithelial cell intracellular pH (pH₁), mucosal blood flow, and mucosal/serosal oxygenation. In PHT rats, gastric mucosal gel layer thickness was significantly reduced (88 ±16 μm in PHT rats vs. 135 ±25 μm in SO rats; P <0.0001), and the surface epithelial cell pH₁ 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-epithelial (mucosal gel layer thickness), epithelial (pH₁), and post-epithelial (maldistribution of blood flow) components of the gastric mucosal barrier. These findings can explain the increased susceptibility of portal hypertensive gastric mucosa to injury. Supported by Veterans Affairs Medical Research Service Merit Review Awards (J.D.K., I.J.S., and AS.T.) and a REAP award. Presented at the Fortieth Annual Meeting of The Society for Surgery of the Alimentary Tract, Orlando, Fla., May 16–19, 1999.