MUCOSAL ADAPTATION TO ASPIRIN-INDUCED GASTRIC DAMAGE IN HUMANS - STUDIES ON BLOOD-FLOW, GASTRIC-MUCOSAL GROWTH, AND NEUTROPHIL ACTIVATION

The gastropathy associated with the ingestion of non-steroidal anti-in flammatory drugs (NSAIDs) such as aspirin is a common side effect of t his class of drugs, but the precise mechanisms by which they cause muc osal damage have not been fully explained. During continued use of an injurious substance, such as aspirin, the extent of gastric mucosal da mage decreases and this phenomenon is named gastric adaptation. To ass ess the extent of mucosal damage by aspirin and subsequent adaptation the effects of 14 days of continuous, oral administration of aspirin ( 2 g per day) to eight healthy male volunteers was studied. To estimate the rate of mucosal damage, gastroscopy was performed before (day 0) and at days 3, 7, 14 of aspirin treatment. Gastric microbleeding and g astric mucosal blood flow were measured using laser Doppler flowmeter and mucosal biopsy specimens were taken for the estimation of tissue D NA synthesis and RNA and DNA concentration. In addition, the activatio n of neutrophils in peripheral blood was assessed by measuring their a bility to associate with platelets. Aspirin induced acute damage mainl y in gastric corpus, reaching at day 3 about 3.5 on the endoscopic Lan za score but lessened to about 1.5 at day 14 pointing to the occurrenc e of gastric adaptation. Mucosal blood flow increased at day 3 by abou t 50% in the gastric corpus and by 88% in the antrum. The in vitro DNA synthesis and RNA concentration, an index of mucosal growth, were red uced at day 3 but then increased to reach about 150% of initial value at the end of aspirin treatment. The gastric microbleeding rate rose f rom about 0.38 ml/day at day 0 to about 7.7 ml/day at day 3 but then d ecreased significantly to virtually normal values at the end of the st udy. The neutrophil/platelet adherence showed significant increase dur ing aspirin treatment. It is concluded that the treatment with aspirin in humans induces gastric adaptation to this agent, which entails the increase in mucosal blood flow, the rise in neutrophil activation, an d the enhancement in mucosal growth.