The synthetic pentasaccharide SR 90107A/Org 31540 enhances tissue-type plasminogen activator-induced thrombolysis in rabbits

Current thrombolytic strategies have a number of shortcomings including resistance to recanalization and development of reocclusion. The purpose of this study was to compare the effects of heparin and of the synthetic pentasaccharide SR 90107A, which represents the antithrombin III binding site of heparin, on rt-PA-induced thrombolysis. The activity of these compounds was evaluated by following rt-PA-induced lysis of standard-sized, [I-125]-fibrinogen-labelled thrombi produced in the external jugular vein of rabbits. rt-PA alone (0.5 mg/kg/h for 4 h) induced a 43% thrombolysis. The i.v. co-administration of heparin (3 mg/kg, i.v.) or SR 90107A (300 nmol/kg, i.v.) significantly enhanced rt-PA-induced thrombolysis (83 and 80%, respectively). The present results therefore suggest that SR 90107A may be considered as an adjunctive antithrombotic therapy during thrombolysis of occluded vessels.