title: Acute gastric mucosal ulcerogenesis is dependent on the concentration of bile salt.
abstract: Studies on animals implicating reflux of bile salts in formation of "stress ulcer" often are suspect because of the inordinately high intragastric concentrations of bile salts used to induce experimental acute gastric mucosal damage. We studied reflux of bile salt in 11 patients after operation. Nine refluxed bile salts in a mean intragastric concentration of 1.87 +/- 0.24 mM. (range, 0.34 to 4.88 mM.). In the present study, therefore, the ulcerogenic potential of physiologic concentrations of bile salts was evaluated. With use of vascularized, chambered canine gastric mucosa, groups of animals were studied during three consecutive periods. Group A = topical acid test alone (ATS) during periods 1, 2, and 3; Group B = (1) ATS, (2) ATS, (3) ATS + vasopressin (VP = 0.1 U per Kg.-min. via the splenic artery); Group C = (1) ATS, (2) ATS + topical 1 mM. sodium taurocholate (TC), (3) ATS + 1 TC + VP; Group D = (1) ATS, (2) ATS + 2 TC, (3) ATS + 2 TC + VP; Group E = (1) ATS (2) ATS + 5 TC, (3) ATS + 5 TC + VP. Parameters evaluated were (1) net fluxes H+, Na+; (2) electrical potential difference  (PD); (3) clearance of aminopyrine, a measure of mucosal blood flow (MBF); and (4) formation of lesions, graded zero to six by an independent observer who used photographs. In nonischemic mucosa, bile salts produced no ulcers, a significant concentration-dependent increase in H+ "back diffusion" and fall in PD, and a noncentration-dependent increase in MBF. In ischemic mucosa, the combination of topical acid, topical bile salts, and mucosal ischemia was acutely ulcerogenic. The severity of mucosal injury was dependent on the concentration of bile salt (y = 0.108 + 1.53x, r = 0.90, p less than 0.01). These data indicate that acute mucosal damage occurs in the presence of physiologic concentrations of bile salt, i.e., those routinely found in the gastric contents of postoperative patients.
mesh_terms: D000208:Acute Disease; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism / Q000502:physiology; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply / Q000378:metabolism; D006801:Humans; D007511:Ischemia; D008297:Male; D008875:Middle Aged; D012995:Solubility; D013276:Stomach Ulcer / Q000209:etiology*
chemical_list: D001647:Bile Acids and Salts