Prevention of stress ulcerations using H 2 receptor antagonists

Abstract

Cimetidine, an H 2 receptor antagonist, was instilled transorally into the stomachs of several groups of rats prior to a period of stress in order to study its possible prophylactic effect upon the formation of stress ulcers and its effect on gastric mucosal membrane potentials and pH. Each group consisted of seven rats. The control group (group I) was given 0.5 ml of saline every 6 hours for three days and then was stressed using a combination of restraint and cold. After the animals were sacrificed, the mean number of gastric ulcers was 7.3 and the pH of the gastric fluid was 1.3. These results were compared with the results obtained in five experimental groups of rats pretreated for varying amounts of time with cimetidine (5 mg/100 g) given every 6 hours. Group II had only two doses of cimetidine, which were then followed by a period of stress. Groups III, IV, V, and VI were pretreated with cimetidine for one, two, three, and four days, respectively, prior to stress. A statistically significant decrease in ulcers was present in those groups receiving cimetidine pretreatment for at least two days. Three additional groups were then studied to investigate the transmucosal membrane potentials of stressed rats with and without cimetidine and in a group of unstressed controls. The mean membrane potentials with and without cimetidine were −29 mv and −9 mv, respectively (p < 0.001), and in the group of unstressed controls the transmucosal potential difference was −26 mv. Cimetidine, therefore, apparently protects the gastric mucosa against this decrease in the transmucosal potential difference during stress and may have a protective effect on the formation of stress ulcers. These studies suggest that cimetidine may be useful for the prevention of stress ulcers in patients subjected to severe traumatic or clinical stress.