Bile acid efflux precedes mucosal barrier disruption in the rabbit esophagus

In a rabbit model of esophagitis, bile acids are one of the agents capable of disrupting the normal esophageal mucosal barrier to diffusion. They are of particular interest because they may play a central role in causing reflux esophagitis, a major clinical problem. Bile acid efflux from the lumen of the esophagus occurs when bile acids disrupt the normal esophageal barrier. Whether this entry of bile acids into the mucosa is a critical step in the pathophysiology of bile acid injury to the mucosa or a result of the injury that is occurring by some other means is unknown. To differentiate these two possibilities, the temporal relation between bile acid efflux from the esophageal lumen and disruption of the mucosal barrier was studied with an in vivo perfused model of esophagitis in anesthetized New Zealand White rabbits. Solutions containing taurocholic acid or chenodeoxycholic acid at pH 2 or 7 were perfused for 4 h while bile acid, hydrogen ion, glucose, and erythritol flux rates were measured. In each case in which the bile acid caused barrier disruption, the highest rate of bile acid efflux occurred during the 1st h of perfusion. In contrast, the increase in flux rates of hydrogen ion, glucose, and erythritol, indicators of mucosal barrier disruption, were the highest during the 2nd or 3rd h of exposure. These data suggest that entry of bile acids into the esophageal mucosa is a cause rather than an effect of the bile-induced increase in mucosal permeability.