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  • 1
    ISSN: 1573-742X
    Keywords: enoxaparin ; inogatran ; electrolytic injury ; venous thrombosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The objective of this study was to compare the effectiveness of the low molecular weight heparin, enoxaparin (Lovenox®), and inogatran (a direct thrombin inhibitor) in a canine electrolytic injury model of venous thrombosis. Effectiveness was defined as the ability of either drug to prolong the following parameters: activated partial thromboplastin time (aPTT), thrombin time (TT), prothrombin time (PT), and time to formation of an occlusive thrombus in the vein. There were 5 dogs and 10 vessels for each group (the right and left femoral veins were used in each dog to measure time to occlusion). Dogs were randomly assigned to one of six groups: (1) saline controls; (2) low-dose inogatran (0.075 mg/kg IV bolus followed by a 5 μg/kg/min infusion); (3) mid-dose inogatran (0.25 mg/kg IV bolus followed by a 20 μg/kg/min infusion); (4) high-dose inogatran (0.75 mg/kg IV bolus followed by a 50 μg/kg/min infusion); (5) low-dose enoxaparin (100 units/kg IV bolus followed by a 50 U/kg/h infusion); and (6) high-dose enoxaparin (200 U/kg IV bolus followed by a 100 U/kg/h infusion). Administration of inogatran resulted in dose-dependent increases in aPTT, TT, and PT, and administration of enoxaparin resulted in dose-dependent increases in aPTT and TT. There were no changes in hemodynamics. The time to occlusion in the control group averaged 81.7 ± 9.9 minutes compared with 141.8 ± 12.7, 185.8 ± 17.6, and 226.9 ± 8.8 minutes with the low, mid, and high doses of inogatran, and 131 ± 20.3, and 183.0 ± 19.0 minutes with the low and high doses of enoxaparin. Bleeding times were elevated by inogatran and enoxaparin, but no appreciable differences were detected between the two compounds. In summary, the direct thrombin inhibitor inogatran, administered intravenously, was as effective as the low molecular weight heparin enoxaparin in a canine model of venous thrombosis induced by electrolytic injury, supporting the conclusion that direct antithrombins may prove useful for prevention and treatment of deep venous thrombosis.
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  • 2
    ISSN: 1573-742X
    Keywords: venous thrombosis ; antithrombotic ; direct thrombin inhibitor ; electrolytic injury
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Deep venous thrombosis (DVT) is a common cardiovascular disease, resulting in significant mortality each year in the United States. Direct thrombin inhibitors represent a new class of drugs that could potentially be better than conventional antithrombotic therapy based on indirect inhibition of coagulation factors with heparin and warfarin. BCH 2763 is a potent, selective bifunctional thrombin inhibitor that blocks both the active catalytic site and the anion binding exosite. The objective of this study is to test the antithrombotic efficacy of BCH 2763 in a canine model of DVT induced through electrolytic injury to the femoral vein. BCH 2763 was administered at three dose levels: 0.125 mg/kg bolus followed by 10 µg/kg/min IV infusion (low-dose; n = 5), 0.25 mg/kg bolus followed by 20 µg/kg/min infusion (mid-dose; n = 5), and 0.75 mg/kg bolus followed by 60 µg/kg/min (high-dose; n = 5). The control group (n = 5) received a 5-ml intravenous bolus of saline followed by a 1 mL/kg/h infusion. The parameters evaluated were changes in activated partial thromboplastin time (aPTT), thrombin time (TT), prothrombin time (PT), time to formation of an occlusive thrombus in the femoral vein, and the amount of venous blood flow delivered over the course of the experiment. There were significant dose-dependent increases in aPTT, TT, and PT in the BCH 2763-treated animals compared with the control group. The time to formation of an occlusive thrombus in the control group averaged 69.6 ± 9 minutes. Treatment with BCH 2763 prolonged the time to occlusion to 126.4 ± 13 minutes in the low-dose group, 155.4 ± 17 minutes in the mid-dose group, and 229 ± 7 minutes in the high-dose group (80% remained patent for the duration of the study), which were all significantly greater than the controls. Femoral venous blood flow was significantly greater in the mid-dose (51 ± 8%) and the high-dose (70 ± 6%) groups compared with the control vessels (22 ± 3%). In conclusion, the results of this study indicate that BCH 2763 is an effective intravenous antithrombotic agent in the canine electrolytic injury model of venous thrombosis.
    Type of Medium: Electronic Resource
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