Bile-induced adenosine triphosphate depletion and mucosal damage during reflux esophagitis

Background: This study was designed to investigate the role of bile in a la rge animal model of acute esophageal reflux disease. Methods: An agar elect rode was used to measure the transmucosal potential difference of the esoph agus in anaesthetized dogs. The vascular permeability index and the epithel ial permeability index of the mucosa were evaluated by means of the Evans b lue and the sodium-fluorescein clearance method, respectively. The tissue a denosine triphosphate (ATP) level and the myeloperoxidase activity were det ermined from tissue biopsies, while the degree of mucosal damage was evalua ted histologically on a grade 0-100 scale. Group 1 (n = 8) served as saline -treated control: groups 2 (n = 8), 3 (n = 5) and 4 (n = 5) were exposed fo r 3 h to canine bile alone, to hydrochloric acid + bile, or to hydrochloric acid alone, respectively. Results: In Groups 2, 3 and 4 the degree of muco sal damage was significantly increased, and a 4-fold elevation in myelopero xidase activity was observed. The transmucosal potential difference was dec reased significantly below the control level, while the vascular and epithe lial permeability indices were significantly increased compared with the co ntrol values. Bile, but not hydrochloric acid, evoked a significant (40%) d ecrease in the ATP level of the esophageal tissue. Conclusions: We propose that mucosal dysfunction. structural damage and leukocyte invasion during h ydrochloric acid-induced esophageal injury are exacerbated by bile-induced changes in tissue ATP concentrations during experimental esophageal reflux disease.