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.