Preventive effect of argatroban on ellagic acid-induced cerebral thromboembolism in rats.
The preventive effect of argatroban, a synthetic thrombin inhibitor, on cerebral infarction was evaluated with ellagic acid (EA)-induced cerebral thromboembolism in rats. Platelet-rich thrombi containing fibrin and EA crystal were formed in the microarteries in the affected hemisphere by the injection of EA suspension into the cerebral arteries. The mortality in saline control was over 80% 6 h after the EA injection. Argatroban decreased the mortality to 0% at a dose of 3 mg/kg/h, and significantly reduced the ischemic area in the affected cerebral hemisphere. Heparin also decreased the mortality to 30% at a dose of 600 U/kg/h, but marked bleeding was observed at the incised wound. These findings suggest that argatroban is a more effective and safer anticoagulant than heparin for the prevention of ischemic damage on cerebral thrombosis.
Exploratory Research Laboratories II, Daiichi Pharmaceutical Co., Tokyo, Japan.
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Hara
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Iwamoto
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Ishihara
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Tomikawa
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives; D002545:Brain Ischemia / Q000209:etiology / Q000517:prevention & control*; D002544:Cerebral Infarction / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004610:Ellagic Acid / Q000633:toxicity; D006493:Heparin / Q000627:therapeutic use; D007275:Injections, Intravenous; D002542:Intracranial Embolism and Thrombosis / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D008297:Male; D010875:Pipecolic Acids / Q000627:therapeutic use*; D051381:Rats; D013053:Spectrophotometry; D013449:Sulfonamides; D015996:Survival Rate; D013917:Thrombin / Q000037:antagonists & inhibitors
D010875:Pipecolic Acids; D013449:Sulfonamides; D004610:Ellagic Acid; D006493:Heparin; D001120:Arginine; D013917:Thrombin; C031942:argatroban