Acute Gastric Mucosal Damage Induced by Bile Salts, Acid, and Ischemia

Abstract

Intraluminal acid, gastric mucosal ischemia, and regurgitation of upper intestinal content have all been implicated in the pathogenesis of acute hemorrhagic gastritis in man. This study was designed to determine directly the ulcerogenic potential of topically applied acid and bile salts, alone and in combination with mucosal ischemia induced by intraarterial vasopressin (VP; 0.1 U per kg-min). In two groups of experimental dogs, vascularized full thickness wedges of gastric wall were mounted in lucite chambers, and , with the mucosa directly visualized, were studied during three consecutive 30-min periods. Group A (5 dogs) was subjected sequentially to (1) topical acid test solution alone (ATS), (2) ATS + VP, and (3) ATS + VP + 5 mM sodium taurocholate (TC). Group B (5 dogs) was subjected to (1) ATS, (2) ATS + TC, and (3) ATS + VP + TC. Three groups of control dogs were studied. Group A 1 was subjected to ATS + VP during periods 2 and 3. Group B 1 was subjected to ATS + TC during periods 2 and 3. Group C was subjected to (1) topical neutral test solution (NTS =160 mm NaCl), (2) NTS + TC, and (3) NTS + VP + TC. During each period, the net fluxes of volume, H + , and Na + , the electrical potential difference, and the aminopyrine clearance, a measure of gastric mucosal blood flow, were determined. Mucosal damage was assessed by an independent observer using photographs obtained after each period and graded 0 to 4. The results indicated that significant lesion formation occurred only in the presence of acid, bile salts, and ischemia. No lesions were noted during any period in the control animals. The data suggest that lesion formation was not a function of either back diffusion of H + or of mucosal ischemia, per se. Relative to period 1, mucosal blood flow was significantly increased in nonischemic mucosa exposed to bile salts, whereas a marked decrease was observed with topical bile salts during vasopressin infusion. Perhaps as a consequence, the combination of mucosal ischemia and topically applied acid and bile salts is severely, acutely, and uniquely ulcerogenic.