Differing ulcerogenic potential of dihydroxy and trihydroxy bile acids in canine gastric mucosa.

Although recent clinical reports suggest that greater than normal amounts of dihydroxy secondary bile acids appear in the gastric content of patients with postoperative alkaline reflux gastritis, the pathophysiologic significance of these observations is unclear. We addressed this problem by usiong chambered ex vivo wedges of proximal canine gastric wall. The effects of 1 and 2 mM concentrations of the dihydroxy secondary bile acid, taurodeoxycholic, were compared with those of its parent trihydroxy primary bile acid, taurocholic. The parameters of mucosal function evaluated included the net flux of hydrogen ion, the transmural electrical potential difference, mucosal blood flow determined by radiolabeled microsphere embolization, and the severity of mucosal damage induced in mucosa rendered ischemic by wedge-specific intra-arterial low-dose vasopressin infusin. The results indicate that at each concentration in both ischemic and nonischemic mucosa the dihydroxy secondary bile acid induced a greater depression in potential difference, a more profound increase in mucosal permeability to hydrogen ion, and in ischemic mucosa a more severe degree of gross mucosal damage than did the trihydroxy primary bile acid. These effects may be related to a greater lipid solubility and consequent capacity to disrupt cell membranes.