The defensive factors that prevent the human duodenal mucosa from acidic and peptic damage have not been fully evaluated. To determine whether duodenal mucosal bicarbonate production was altered in patients with inactive duodenal ulcer, we measured basal and acid-stimulated bicarbonate output from the duodenal bulb and the distal duodenum in healthy subjects and patients with inactive duodenal ulcer. As compared with 16 normal subjects, the 12 patients had significantly less mean (+/- SE) basal proximal duodenal mucosal bicarbonate secretion (185 +/- 13 vs. 107 +/- 18 mumol per centimeter per hour; P less than 0.001). Moreover, in response to a physiologic amount of hydrochloric acid (2 mmol per five minutes) instilled directly into the duodenal bulb, peak proximal duodenal bicarbonate output in the patients was 41 percent of the normal response (263 +/- 65 vs. 642 +/- 77 mumol per centimeter per hour; P less than 0.01). There was little overlap between groups. In contrast, bicarbonate outputs in the distal duodenum were similar in the two groups. We conclude that most patients with duodenal ulcer disease have decreased proximal duodenal mucosal bicarbonate production at rest, in response to hydrochloric acid, and in relation to peak gastric acid secretion. Impaired proximal duodenal mucosal bicarbonate secretion may be an important factor in the development and natural history of duodenal ulcer.

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Nonsteroidal anti-inflammatory drugs are a frequent cause of gastric and duodenal mucosal injury. We examined the effect of indomethacin on duodenal mucosal bicarbonate secretion and prostaglandin output in healthy subjects. Subjects received either 50 mg of indomethacin or placebo orally 13 hours and 1 hour before study. A 4-cm segment of proximal (the duodenal bulb) or distal (10 to 14 cm beyond the pylorus) duodenum was isolated and perfused with 154 mM NaCl containing a nonabsorbable marker. In the proximal duodenum indomethacin reduced both basal and acid-stimulated bicarbonate secretion by approximately 65% (p less than 0.01); in the distal duodenum indomethacin decreased basal and acid-stimulated bicarbonate output by approximately 45% (p less than 0.01). Oral indomethacin inhibited basal and acid-stimulated duodenal prostaglandin E2 output in both the proximal and distal duodenum. We conclude that, by decreasing duodenal mucosal bicarbonate production and prostaglandin output in humans, oral indomethacin, in two doses of 50 mg each, impairs an important duodenal defense mechanism.

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