The effect of metiamide, an H2-receptor antagonist, in the prevention of experimental stress ulcers

Because of evidence that Metiamide, an H2-receptor antagonist, strongly inhibits gastric acid secretion, the present study was designed to test the hypothesis that Metiamide will prevent bile salt-induced stress ulcers during hemorrhagic shock. Forty dogs were bled and maintained for 4 1/2 hr at a mean blood pressure of 40 to 50 mm Hg. In group A, 10 dogs received 300 mg of Metiamide orally 45 min before bleeding and 10 dogs received normal saline. The pylorus was occluded before bleeding and 100 ml of 15 mM bile salt were instilled into the stomach and aspirated at the end of 4 1/2 hr. At the time the animal was killed after 48 hr, no ulcers were seen in the stomachs of dogs treated with Metiamide. Sixty per cent of the dogs in the untreated group developed multiple gross ulcers. In group B the effect of Metiamide on the disappearance rate of H+ ion was measured by instillation of 50 mM HCl + 15 mM bile acid. No difference was noted in the rate of H+ ion disappearance between Metiamide-treated and control dogs. Also, in 5 normotensive dogs the rate of H+ ion disappearance was measured before and after treatment with Metiamide, and the loss of H+ was identical for both periods. Metiamide was effective in preventing stress ulcer in this experimental model. The protective effect of Metiamide is probably due to its inhibitory effect of H+ ion secretion.