Gastric mucosal blood flow and neutrophil activation in aspirin-induced gastric mucosal damage in man.
Gastric and intestinal injury induced by nonsteroidal anti-inflammatory agents (NSAIDs) such as aspirin (ASA) is a common side effect of this class of drugs, but the mechanism by which these drugs act is not fully explained. In this study the effects of 3 days of continuous oral ASA administration (1 g twice daily) to eight healthy male volunteers were studied. To estimate the extent of mucosal damage, gastroscopy was performed before and after 3 days of ASA treatment, during which the mucosal blood flow was measured by means of laser-Doppler flowmetry. Before each endoscopy gastric microbleeding was measured. Since neutrophil activation has recently been suggested to be involved in the pathogenesis of ASA-induced gastric mucosal damage, we examined the influence of ASA treatment on the activation of leukocytes by determining their association with platelets in the blood. Aspirin-induced acute gastric damage reached about 3.5 in the endoscopic Lanza score. Mucosal blood flow increased significantly after ASA treatment, by about 50% in the oxyntic gland area and by 87% in the antral area. Gastric microbleeding rose from about 0.38 ml/day in the intact stomach to about 7.7 ml/day after ASA treatment. The platelet/neutrophil adherence increased significantly in both thrombin-unstimulated and thrombin-stimulated platelets. We conclude that acute 3 days' administration of ASA in man produces well-defined areas of gastric damage accompanied by a significant increase in gastric microbleeding and gastric blood flow and that ASA promotes platelet/neutrophil adhesion that may resemble the neutrophil/endothelium interaction in the gastric mucosa.
Konturek
J W
JW
Dept. of Medicine B, University of Münster, Germany.
Dembinski
A
A
Stoll
R
R
Konturek
M
M
Domschke
W
W
D000328:Adult; D001241:Aspirin / Q000009:adverse effects*; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects*; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D010973:Platelet Adhesiveness / Q000187:drug effects
D001241:Aspirin