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-inflammatory drugs (NSAIDs) such as aspirin is a common side effect of this class of drugs, but the precise mechanisms by which they cause mucosal damage have not been fully explained. During continued use of an injurious substance, such as aspirin, the extent of gastric mucosal damage decreases and this phenomenon is named gastric adaptation. To assess 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 gastric mucosal blood flow were measured using laser Doppler flowmeter and mucosal biopsy specimens were taken for the estimation of tissue DNA synthesis and RNA and DNA concentration. In addition, the activation of neutrophils in peripheral blood was assessed by measuring their ability to associate with platelets. Aspirin induced acute damage mainly in gastric corpus, reaching at day 3 about 3.5 on the endoscopic Lanza score but lessened to about 1.5 at day 14 pointing to the occurrence of gastric adaptation. Mucosal blood flow increased at day 3 by about 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 reduced at day 3 but then increased to reach about 150% of initial value at the end of 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, and the enhancement in mucosal growth.
Department of Medicine B, University of Münster, Germany.
J W
JW
Konturek
A
A
Dembinski
R
R
Stoll
W
W
Domschke
S J
SJ
Konturek
D000222:Adaptation, Physiological; D000328:Adult; D001241:Aspirin / Q000009:adverse effects*; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology / Q000502:physiology; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced; D005773:Gastroscopy; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D013272:Stomach Diseases / Q000139:chemically induced
D001241:Aspirin