Add time:07/17/2019         Source:sciencedirect.com

Enhancement by anticoagulation of thrombolysis with infused or bolus-injected Saruplase (cas 99149-95-8) (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 36, reperfusion time 42 ± 3 min and reocclusion rate 23; 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 66 after a reperfusion time of 39 ± 7 min; reocclusion rate was 36 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 66 after 26 ± 5 min; no reocclusion occured and final patency rate was 100 % (p < 0.05 vs saruplase alone). Bolus injection of 6 mg/kg saruplase achieved reperfusion in 56 arteries after 15 ± 3 min, but reocclusion rate was 45; final patency rate was 17 %. Combination of bolus-injected saruplase with heparin resulted in a reperfusion rate of 46 after 8 ± 3 min and no reocclusion occured; patency rate was 67 %. With combination of argatroban and bolus-injected saruplase 66 arteries were reperfused after 8 ± 3 min; reocclusion was prevented and final patency rate was 100 % (p < 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.

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