Antithrombotic and thrombolytic effects of galactan polysulfate (DH 6322) in rats

Anticoagulant, fibrinolytic and thrombolytic effects of galactan polysulfate (DH 6322), a new semi-synthetic polysaccharide sulfate of bacterial origin, were studied in the rat in vitro, ex vivo and in vivo. Addition of DH 6322 to citrated plasma gave a 50% reduction in euglobulin lysis time at around 50 micrograms/ml and a 2-fold prolongation in plasma recalcification time at 40 micrograms/ml. Intravenous injection of DH 6322 caused significant acceleration of euglobulin clot lysis and urokinase-induced plasma clot lysis at doses as low as 2 mg/kg, and also significant prolongation of plasma recalcification time. Oral application of the compound gave similar effects only at an extremely high dose of 3 g/kg. When injected intravenously before induction of pulmonary thrombosis by lactic acid infusion, DH 6322 was found to be effective in preventing thrombus formation. In progressive venous thrombosis induced by insertion of a steel coil into the inferior vena cava, DH 6322 treatment also caused a significant reduction of thrombus size together with increase in the serum levels of fibrin degradation products. The findings indicate that the antithrombotic effects of DH 6322 result from its enhancement of the fibrinolytic potential as well as its anticoagulative action.