title: Heparin and the thrombin inhibitor argatroban enhance fibrinolysis by infused or bolus-injected saruplase (r-scu-PA) in rabbit femoral artery thrombosis.
abstract: Enhancement by anticoagulation of thrombolysis with infused or bolus-injected saruplase (r-scu-PA) has been studied using heparin and the thrombin inhibitor argatroban. In a rabbit femoral artery thrombosis model infusion of saruplase (3 - 12 mg/kg, 60 min) caused a dose-dependent thrombolysis. Reperfusion rate after infusion of 3 mg/kg saruplase alone was 3/6, reperfusion time 42 +/- 3 min and reocclusion rate 2/3; final patency rate at 120 min was 17%. Combination of 3 mg/kg saruplase with heparin (150 U/kg + 100 U/kg.hr i.v.; 5.3-fold PTT-prolongation) resulted in a reperfusion rate of 6/6 after a reperfusion time of 39 +/- 7 min; reocclusion rate was 3/6 and final patency rate was 50%. Argatroban (1 mg/kg + 3 mg/kg.hr i.v.; 2.3-fold PTT prolongation) in combination with saruplase resulted in a reperfusion rate of 6/6 after 26 +/- 5 min; no reocclusion occured and final patency rate was 100% (p less than 0.05 vs saruplase alone). Bolus injection of 6 mg/kg saruplase achieved reperfusion in 5/6 arteries after 15 +/- 3 min, but reocclusion rate was 4/5; final patency rate was 17%. Combination of bolus-injected saruplase with heparin resulted in a reperfusion rate of 4/6 after 8 +/- 3 min and no reocclusion occured; patency rate was 67%. With combination of argatroban and bolus-injected saruplase 6/6 arteries were reperfused after 8 +/- 3 min; reocclusion was prevented and final patency rate was 100% (p less than 0.05 vs saruplase-bolus alone). Systemic fibrinogenolysis was more pronounced with bolus injection than infusion of saruplase. The results indicate that arterial thrombolysis with saruplase can be enhanced by heparin and the thrombin inhibitor argatroban. The bolus injection of saruplase resulted in persistent reperfusion when simultaneous anticoagulation was performed. Despite less PTT prolongation, enhancement of saruplase-induced thrombolysis was more effective with argatroban than with heparin in rabbit femoral artery thrombosis.
authors.affiliation: Grünenthal GmbH, Center of Research, Aachen, FRG.
authors.forename: J
authors.initials: J
authors.lastname: Schneider
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D000991:Antithrombins / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004792:Enzyme Precursors / Q000008:administration & dosage; D005263:Femoral Artery; D005342:Fibrinolysis / Q000187:drug effects*; D006493:Heparin / Q000627:therapeutic use; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D010875:Pipecolic Acids / Q000627:therapeutic use; D010960:Plasminogen Activators / Q000008:administration & dosage; D011817:Rabbits; D011994:Recombinant Proteins; D013449:Sulfonamides; D013927:Thrombosis / Q000188:drug therapy*; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D004792:Enzyme Precursors; D010875:Pipecolic Acids; D011994:Recombinant Proteins; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; C031942:argatroban; C067551:saruplase