Antithrombotic and thrombolytic activity of sulodexide in rats

Abstract

We evaluated the ability of sulodexide, an extracted glycosaminoglycan, to prevent thrombus formation and to reduce a stabilized thrombus in a rat venous thrombosis model (vena cava ligature). Injection of sulodexide 10 min before induction of venous stasis, prevented thrombus formation in a dose-dependent manner (median effective dose 0.55 mg/kg). When given to rats with 6-h-old thrombi, sulodexide caused a marked reduction in thrombus size which reached 70% after 2 h with the highest dose tested (2 mg/kg). The effect of sulodexide on established thrombi appears to be due, at least in part, to a fibrinolysis-mediated mechanism, since it was significantly inhibited by epsilon-aminocaproic acid, a well-known antifibrinolytic drug. Treatment with sulodexide did not noticeably affect plasma levels of plasminogen activator and its specific inhibitor. We also showed that fluorescein-labelled sulodexide, when given to animals with 6-h-old thrombi, was present within the thrombi harvested 2 h later, but was then absent from blood. The fluorescence was mainly located in areas filled with amorphous material, that was identified as fibrin by staining with phosphotungstic acid-hematoxylin. No fluorescein-labelled material could be detected in rats treated with fluorescein alone. These findings indicate that, besides preventing venous thrombus formation, sulodexide is able to promote thrombus dissolution by a mechanism that is partly related to local fibrinolysis stimulation.

Review of pharmacodynamics, pharmacokinetics, and therapeutic properites of sulodexide

“…About 40% of the reduction of thrombus was counteracted by preinjection of the antifibrinolytic agent, indicating the fibrinolytic effect of sulodexide (Table III). 11 An increase of the plasminogen acti-vator in the euglobulin activity was demonstrated in these experiments. Administration of fluorescein-labeled sulodexide revealed diffused infiltration of the thrombus with the fluorescent compound, indicating binding as well as antithrombotic and profibrinolytic effects of sulodexide on the thrombus.…”

“…11 The effect of sulodexide on 6 h-old thrombosis showed a significant reduction in thrombus with increasing doses of sulodexide. 11 To investigate the fibrinolytic effect of sulodexide on preformed thrombosis, ⑀-aminocaproic acid as an antifibrinolytic agent was given to the thrombus-bearing animals immediately before sulodexide. About 40% of the reduction of thrombus was counteracted by preinjection of the antifibrinolytic agent, indicating the fibrinolytic effect of sulodexide (Table III).…”

Development and use of sulodexide in vascular diseases: implications for treatment

“…SDX intravenously administered in rats induces acceleration of spontaneous fibrinolysis-thrombolysis of preformed thrombi 33. This property is in accord with an increase in plasminogen activators – TPA and UPA in primates and other animals.…”

Sulodexide: A Renewed Interest in This Glycosaminoglycan

“…In addition to the antithrombotic effects of sulodexide, administration of the compound to animals with preexisting thrombi demonstrates a dose dependent reduction in thrombus size (4). It was suggested that this effect could be attributed to the activation of tissue plasminogenic activator and/or the inhibition of plasminogenic activator 1 (12,20).…”