title: Interactions of saruplase with acetylsalicylic acid, heparin, glyceryl trinitrate, tranexamic acid and aprotinin in a rabbit pulmonary thrombosis model.
abstract: In anesthetized rabbits with pulmonary embolized thrombi the interactions of saruplase (recombinant unglycosylated single-chain urokinase-type plasminogen activator, CAS 99149-95-8) with acetylsalicylic acid (ASA), glyceryl trinitrate (nitroglycerin, GTN), heparin, and the antifibrinolytics tranexamic acid and aprotinin have been studied. Lysis rates were evaluated as reduction of the weight and as reduction of the incorporated 125J-fibrin content of the embolized thrombi. In untreated controls the spontaneous 125J-fibrinolysis was 8.3 +/- 0.7% and the thrombus weight was reduced by 55.3 +/- 4.5% (mainly due to loss of H2O) at 195 min after the thromboembolization. Infusion of saruplase (21.5 micrograms/kg.min) for 60 min significantly increased the 125J-fibrinolysis to 36.8 +/- 3.7% and the reduction of the thrombus weight to 69.9 +/- 2.1%. ASA (50 mg/kg p.o.) by itself did not exert a lytic effect; in combination with saruplase ASA insignificantly augmented the 125J-fibrinolysis rate and significantly further increased the thrombus weight reduction. GTN (5.0 micrograms/kg.min i.v.) neither influenced the spontaneous nor the saruplase-mediated lysis rates. Treatment with heparin (200 IU/kg i.v.-bolus plus 50 IU/kg.min i.v.-infusion) resulted in significant greater thrombus weight reduction than observed in untreated controls; in combination with saruplase heparin significantly intensified the lytic effect. Tranexamic acid (30 mg/kg i.v.) and aprotinin (30.10(3) KIU/kg i.v.) completely abrogated the lytic effect of saruplase. Treatment with saruplase alone produced an insignificant decrease of the plasma level of fibrinogen by 23% to 200 +/- 20 mg/dl. ASA, GTN and aprotinin did not influence this slight fibrinogenolysis in saruplase-treated animals. A slight decrease of plasma fibrinogen levels was observed by heparin, whereas the decrease by tranexamic acid was significant.
authors.affiliation: Grünenthal GmbH, Center of Research, Aachen, Fed. Rep. of Germany.
authors.forename: J
authors.initials: J
authors.lastname: Schneider
mesh_terms: D000818:Animals; D007611:Aprotinin / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology*; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors*; D015849:Plasminogen Inactivators; D011655:Pulmonary Embolism / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D011817:Rabbits; D011994:Recombinant Proteins; D014148:Tranexamic Acid / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors*
chemical_list: D007457:Iodine Radioisotopes; D015849:Plasminogen Inactivators; D011994:Recombinant Proteins; D014148:Tranexamic Acid; D006493:Heparin; D007611:Aprotinin; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D005996:Nitroglycerin; D001241:Aspirin; C067551:saruplase