Regular articleAntithrombotic Effects and Bleeding Time of Thrombin Inhibitors and Warfarin in the Rat
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Materials and Methods
Male Sprague-Dawley rats (body weight 350–425 g; Møllegaard Breeding Centre, Skensved, Denmark) were used in this study. The animal care and use was approved by Gothenburg Local Ethical Committee on Animal Experiments, a body within The National Board for Laboratory Animals, Sweden. The animals were anaesthetized with an intraperitoneal injection of sodium pentobarbital (80 mg/kg; NordVacc, Malmö, Sweden) followed by a continuous infusion (12 mg/kg per hour) throughout the experiment. The body
Antithrombotic Effect versus Dose and Plasma Concentration
The doses and the mean plasma concentrations are summarized in Table 1. In rats, given vehicle (group 1) the thrombus size was 18.8±1.2 in AU. Figure 2 shows the antithrombotic effects of warfarin, inogatran, melagatran, and heparin. A 50% antithrombotic effect for warfarin was obtained with 0.40 μmol/kg per day for 4 days and for inogatran and melagatran at a dose of 0.92 and 0.13 μmol/kg per hour when given as a continuous infusion during the experiment. The slopes of the dose-response curves
Discussion
The arterial thrombosis model used in this study, where application of ferric chloride to the carotid artery was used as a thrombogenic stimulus, was slightly modified from that used previously [15]. In that study, a 50% antithrombotic effect was obtained at a plasma concentration of 0.14–0.12 μmol l−1 for hirudin and melagatran, respectively. In the present study, the plasma concentration at 50% antithrombotic effect was 0.15 μmol/l for melagatran.
The turnover for the individual coagulation
Acknowledgements
The authors acknowledge Therese Hultstrand for technical assistance with the bleeding time experiments.
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