ACUTE GASTRIC MUCOSAL ULCEROGENESIS IS DEPENDENT ON CONCENTRATION OF BILE-SALT

Abstract

Studies on animals implicating reflux of bile salts in formation of stress ulcer are often suspect because of the inordinately high intragastric concentrations of bile salts used to induce experimental acute gastric mucosal damage. The reflux of bile salt in 11 patients after operation was studied. Nine refluxed bile salts in a mean intragastric concentration of 1.87 .+-. 0.24 mM. (range, 0.34 to 4.88 mM.). 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 3 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[unit]/kg per 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 the net fluxes H+, Na+; the electrical potential difference (PD); the clearance of aminopyrine, a measure of mucosal blood flow (MBF); and the formation of lesions, graded 0-6 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 nonconcentration-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 < 0.01). 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.