Comparison of the effect of super sulfated low molecular weight heparin and heparin on clot lysis induced by recombinant pro-urokinase in a CANINE MODEL of THROMBOSIS

The present study was conducted to compare the effect of commercial heparin and a super sulfated low molecular weight heparin (SSLMWHep) on clot lysis in a dog model of femoral artery thrombosis In two groups of dogs, Ilz5-labeled clots were formed in the femoral artery and were monitored continuously for loss of counts as an indicator of clot lysis. Femoral blood flow was measured simultaneously by an electromagnetic flow probe placed distal to the clot Blood samples were drawn periodically to monitor the activated partial thromboplastin time (APTT); template bleeding times (TBT) were performed at appropriate time points throughout the experiment. Group 1 received heparin (n = 11) as a 500 Unit loading bolus followed by a 600 U/hr maintenance infusion Group 2 received SSLMWHep (n = 11) as a 1.0 mg/kg loading bolus followed by a 0.5 mg/kg/hr maintenance infusion. Both treatment groups were given 2000 Units recombinant pro-urokinase (rpro-UK) as a 60-min intraarterial infusion at a site just proximal to the occlusive clot. Clot lysis at 2 hours in groups I and 2 was 36 ±8% and 49 ±8%, respectively APTTs were similar at 2 hrs in group 1 (2.0 times control) and group 2 (1.7 times control). TBT was markedly prolonged only in the heparin group. Therefore, while both agents produce similar effects on clot lysis induced by r-proUK, SSLMWHep exhibits an enhanced safety profile when compared to heparin in a canine model of femoral thrombosis.