Effects of Argatroban and Unfractionated Heparin on t-PA Induced Thrombolysis
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The effects of argatroban (a selective thrombin inhibitor) and unfractionated heparin (UFH) on t-PA induced thrombolysis were compared in an experimental thrombosis using the microvasculature of hamster cheek pouch. The thrombus was produced by irradiation of ultraviolet light (intensity; 20mW/mm2, wave length; 400-500nm) in combination with the intravascular administration of fluorescein sodium (50mg/kg), until the development of thrombus stenosed 99% of the luminal area of the venule (50-70μm). Thrombolytic process mediated by t-PA was observed on a color television through a high gain video camera and recorded on videotape. The effects of these anticoagulants administered with t-PA were evaluated by the percent stenosis of lumen and the percent area of thrombus, which were calculated by the computed video analyzer. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were measured on plasma samples obtained one hour after the injection of anticoagulants. Bleeding time was measured on the shaved left medial hind leg with blade before sampling the blood. Argatroban (0.1-0.3mg/kg·hr) significantly enhanced thrombolysis by t-PA (72×104 IU/kg·hr) in one and two hours after infusion of t-PA. Argatroban (0.1-0.3mg/kg·hr) prolonged PT, aPTT and bleeding time dose dependently and significantly at the dose of 0.3mg/kg/·hr. Argatroban (0.3mg/kg·hr) enhanced thrombolysis by t-PA (72×104 IU/kg·hr), but UFH (12.5 anti-X U/kg·hr) delayed it. Argatroban (0.3mg/kg·hr) did not significantly prolonged PT and aPTT as compared with UFH (12.5 anti-X U/kg·hr). From these results, argatroban was suggested to be a useful additional anticoagulant in thrombolytic therapy using t-PA.
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