Potentiation by heparin fragments of thrombolysis induced with human tissue-type plasminogen activator or human single-chain urokinase-type plasminogen activator.
The effect of heparin and of two low molecular weight (low Mr) fractions of heparin on thrombolysis with recombinant human tissue-type plasminogen activator (rt-PA, Genentech Inc., So. San Francisco, CA) or human single chain urokinase-type plasminogen activator (scu-PA, Sandoz AG, Basle, Switzerland) was measured in a rabbit jugular vein thrombosis model. Four bolus injections of 200 anti-Factor Xa units/kg body weight of heparin (Liquemine, Hoffmann-La Roche, Basle, Switzerland), of 90 units/kg of CY 216 (Choay, Paris, France) or of 90 units/kg of CY 222 (Choay, Paris, France) were given intravenously, immediately after the start of the infusion of rt-PA or scu-PA and at hourly intervals during their intravenous infusion over 4 hours. The bolus injections resulted in anti-Factor Xa levels in plasma of 5.7 +/- 1.2 units/ml just before the repeat bolus injections of heparin with corresponding values of 3.9 +/- 0.2 units/ml for CY 216 and 1.6 +/- 0.2 units/ml for CY 222. Thrombolysis with 0.25 mg/kg rt-PA was 36 +/- 1 percent (n = 9) in the absence of anticoagulant, 40 +/- 1 percent (n = 7, p less than 0.05) in the presence of heparin, 49 +/- 5 percent (n = 7, p less than 0.02) with CY 216 and 62 +/- 5 percent (n = 7, p less than 0.01) with CY 222.(ABSTRACT TRUNCATED AT 250 WORDS)
Stassen
J M
JM
Center for Thrombosis and Vascular Research, University of Leuven, Belgium.
Juhan-Vague
I
I
Alessi
M C
MC
De Cock
F
F
Collen
D
D
D000818:Animals; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents; D006493:Heparin / Q000008:administration & dosage*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage; D010960:Plasminogen Activators / Q000008:administration & dosage*; D011817:Rabbits; D013924:Thrombophlebitis / Q000188:drug therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage*
D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D006493:Heparin; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator