THE SYNTHETIC PENTASACCHARIDE SR-90107A ORG-31540 ENHANCES TISSUE-TYPE PLASMINOGEN ACTIVATOR-INDUCED THROMBOLYSIS IN RABBITS/

Current thrombolytic strategies have a number of shortcomings includin g resistance to recanalization and development of reocclusion. The pur pose of this study was to compare the effects of heparin and of the sy nthetic pentasaccharide SR 90107A, which represents the antithrombin I II binding site of heparin, on rt-PA-induced thrombolysis. The activit y of these compounds was evaluated by following rt-PA-induced lysis of standard-sized, [I-125]-fibrinogen-labelled thrombi produced in the e xternal jugular vein of rabbits. rt-PA alone (0.5 mg/kg/h for 4 h) ind uced a 43% thrombolysis. The i.v. co-administration of heparin (3 mg/k g, 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 an tithrombotic therapy during thrombolysis of occluded vessels.