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Since its introduction the Wessler stasis rabbit model (Wessler, et al. J. Appl. Physiol. 14:(6), 943, 1959) has been widely used in the evaluation of the thrombogenic properties of prothrombin complex concentrates (activated and non-activated) and antithrombotic effects of various drugs. In order to study the antithrombotic actions of low molecular weight fractions and oligosaccharide fragments we used a modified stasis (rabbit) model with thrombogenic stimuli which produced a marked increase in circulating factor Xa levels. Male New Zealand rabbits ranging from 23 kg were injected (subcutaneous) with an analgesic muscle relaxant, xylazine (20 mg/kg) followed by ketamine (80 mg/ kg). Prothrombin complex concentrate (PCC) is injected within 2 minutes into a contralateral rabbit ear vein (25 units/kg) immediately followed by Russell’s viper venom (RVV). Within varying times after completion of the infusion, (1-15 minutes) previously exposed right and left jugular veins were gently isolated, kept in situ for 10 minutes, carefully excised and the clot formed was graded. Only minor changes were observed in the coagulation profile after the PCC/RW infusion, however measurable clots in both segments of the isolated vein were seen. Intravenous injection of heparin fractions (&lt;500 μg/kg) and oligosaccharide fragments (&lt;100 μg/kg)blocked the thrombotic effects of PCC/RW mixture in both the pretreatment and post-treatment regimens, whereas heparin at 500 μg/kg failed to show any antithrombotic effects. Bovine and human factor Xa concentrates, tissue thromboplastins, human serum, human and bovine a-thrombin, and arachidonic have also been employed as thrombogenic stimuli. Our studies show that the modified stasis rabbit model offers definite advantages over the existing model and provides a suitable in vivo standardized model to test antithrombotic effects of newly developed heparin fractions and fragments with high anti Xa and low anticoagulant action.

thrombosis and haemostasis

A Modified Stasis (Wessler) Rabbit Model To Evaluate The Antithrombotic Actions Of Heparin Fractions And Fragments With Low Anticoagulant – High Anti Xa Activities