Damage and protection of the human gastric mucosa. A multiparameter assessment

Studies in animals and humans have indicated that endogenous prostaglandins as well as synthetic prostaglandin analogues can prevent gastric mucosal damage induced by various agents. Methods were developed to assess induced damage and the effects of potentially protective agents (synthetic prostaglandin analogues and the histamine [H2]-receptor antagonist cimetidine) on the human gastric mucosa by measuring ion fluxes and transmucosal potential difference, as well as by observations with gastrointestinal endoscopy. Commonly ingested agents, such as aspirin, 1,300 mg, and 20 percent ethanol increased hydrogen ion and sodium ion fluxes, decreased potential difference, and caused gross mucosal damage, as observed by endoscopy. Conversely, acetaminophen, 2,600 mg, and 10 percent ethanol did not have any significant effects. Hyperosmolar solutions (1,800 and 3,600 mOsm/kg) also produced acute damage. Sodium taurocholate (10 mmol/liter) when instilled into the stomach, either at pH 1.1 or 7.0, produced both functional and structural damage. When given as a single dose, neither 15(R)15-methyl PGE2 nor the synthetic PGE1 analogue, misoprostol, prevented mucosal damage induced by aspirin and taurocholate (pH 1.1), respectively. Cimetidine, 400 mg orally, however, did reduce aspirin-induced mucosal damage, and this effect was independent of gastric acid inhibition.