Antithrombotic effects of recombinant hirudin in different animal models.
The effect of recombinant hirudin (r-hirudin; HBW 023) was studied in four different models of thrombosis as well as on bleeding time. Arteriolar thrombus formation was induced in rats either by argon laser injury or by photochemical reaction. r-Hirudin, given by intravenous infusion, significantly inhibited arteriolar thrombus formation and arterial bleeding time at a dose of 40 micrograms/kg.min. In rabbit jugular veins and carotid arteries, occluding thrombi were produced by stenosis and endothelial damage. r-Hirudin reduced the incidence of thrombosis dose dependently (ED50 0.7 and 1.0 mg/kg i.v. in arteries and veins, respectively). Caval vein thrombosis was initiated in rats by insertion of a stainless steel coil. This thrombosis was dose dependently reduced by the injection of r-hirudin (ED50 0.16 mg/kg i.v.). The duration of the antithrombotic effect of 0.25 mg/kg of r-hirudin in caval veins was about 60 min, whereas the arterial bleeding time was significantly prolonged in these rats for only 20 min. The plasma level of r-hirudin had dropped to 0.12 micrograms/ml 60 min after injection. These results suggest that the duration of the effect on bleeding time may be shorter than the antithrombotic action of r-hirudin.
Just
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M
Department of Pharmacology, Cassella AG, Frankfurt am Main, FRG.
Tripier
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Seiffge
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D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications; D001760:Bleeding Time; D002341:Carotid Artery Thrombosis / Q000188:drug therapy / Q000209:etiology; D003911:Dextrans / Q000528:radiation effects / Q000633:toxicity; D004195:Disease Models, Animal; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives*; D005452:Fluoresceins / Q000528:radiation effects / Q000633:toxicity; D024764:Hirudin Therapy; D007601:Jugular Veins; D007834:Lasers / Q000009:adverse effects; D008297:Male; D008638:Mesenteric Arteries / Q000293:injuries; D010777:Photochemistry; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000627:therapeutic use; D013927:Thrombosis / Q000188:drug therapy* / Q000209:etiology; D014684:Venae Cavae
D003911:Dextrans; D005452:Fluoresceins; D011994:Recombinant Proteins; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate