We set up a new model of gastric
bleeding induced by the
luminal perfusion of
aspirin (ASA) in rats pretreated with
clopidogrel under conditions where
acid secretion is stimulated, and examined the effect of antiulcer drugs on the
bleeding. Under
urethane anesthesia,
acid secretion was stimulated by i.v. infusion of
histamine (8 mg/kg/h), and two
catheters were inserted into the stomach, one from the esophagus and another from the duodenum. The stomach was perfused with 25 mM ASA at a rate of 0.1 ml/min using an
infusion pump, and gastric
bleeding was measured as
hemoglobin concentration in the perfusate collected every 15 min.
Clopidogrel (30 mg/kg) was given orally 24 h before the perfusion. Various antiulcer drugs were given intraduodenally 30 min before the ASA treatment. Perfusion of the stomach with ASA provoked little gastric
bleeding or damage even when
acid secretion was stimulated. Pretreatment with
clopidogrel significantly increased the
bleeding and damage caused by ASA. The
bleeding and lesions produced by ASA plus
clopidogrel were significantly prevented by pretreatment with
famotidine and
omeprazole. Mucosal
protective drugs such as
rebamipide,
irsogladine and
teprenone also prevented gastric
bleeding response to ASA/
clopidogrel under conditions of
acid secretion, although the effect was less pronounced than that of the antisecretory drugs. We conclude that
clopidogrel increases gastric
bleeding induced by ASA when
acid secretion is stimulated. Both antisecretory and mucosal
protective drugs are effective in reducing gastric
bleeding under such conditions. This model is useful for the screening of drugs that protect against gastric
bleeding.