sodium-taurodeoxycholate and Esophagitis

Pepsin and trypsin cause erosive, hemorrhagic lesions in our rabbit model of experimental esophagitis. Since the gastroduodenal contents of patients with reflux esophagitis may also contain bile salts, we used our model to determine the effect that a bile salt, taurodeoxycholate (TDC), would have on the esophageal mucosa when combined with either pepsin in an acid perfusate (pH 2) or trypsin in an alkaline perfusate (pH 7.5). Indexes of esophageal injury included gross appearance of the mucosa, microscopic examination, and mucosal barrier integrity as determined by permeability to hydrogen ion. We found that when 5 mM TDC was combined with pepsin (0.3 mg/ml), the gross and microscopic changes of esophagitis, as well as net hydrogen ion flux, were diminished when compared with those observed with pepsin exposure alone. When increasing concentrations of TDC (2 to 10 mM) were added to pepsin, the morphologic degree of injury as well as hydrogen ion flux decreased in a dose-dependent manner. In contrast, when 5 mM TDC was combined with trypsin (1000 U/ml) in the alkaline perfusate, the gross and microscopic changes of esophagitis and the net of hydrogen ion flux were increased when compared with either bile salt or trypsin alone. These effects were also dose dependent. These data demonstrate that bile salts present in the gastroduodenal contents of patients with reflux esophagitis have the capacity to modulate the effects of pepsin and trypsin on the esophageal mucosa.

Topics: Animals; Deoxycholic Acid; Disease Models, Animal; Esophagitis; Hydrogen-Ion Concentration; Pepsin A; Rabbits; Taurodeoxycholic Acid; Trypsin

Experimental esophageal mucosal injury has been characterized by an increase in mucosal permeability to acid and a fall in transmucosal electrical potential difference (PD). We have developed a technique for measuring transesophageal electrical resistance in an in vivo rabbit model of esophageal injury and have performed experiments to assess this parameter as an index of esophageal injury. As expected, tissue resistance varied inversely with mucosal area. The current-voltage plot for the esophagus with or without trypsin, bile, or acid injury remained linear with no "breakpoints." Tissue resistance was compared with standard indices of mucosal injury such as acid flux, PD, and morphologic change in experimental esophageal injury due to acid, bile, and trypsin. Our results show that tissue resistance is more sensitive than either PD or acid flux in detecting early esophageal injury due to low concentrations of acid or trypsin and, as opposed to PD, always showed a persistent, unidirectional change with injury. Thus these data show that in vivo measurement of transesophageal electrical resistance is a useful technique for assessing esophageal mucosal injury, in that it is the most sensitive indicator of esophageal injury we have observed.

Topics: Animals; Disease Models, Animal; Electric Conductivity; Electrophysiology; Esophagitis; Esophagus; Hydrogen-Ion Concentration; Mucous Membrane; Rabbits; Taurodeoxycholic Acid; Trypsin