New derivative of staphylokinase SAK-RGD-K2-Hirul exerts thrombolytic effects in the arterial thrombosis model in rats

Sak-rgd-k2-hir and sak-rgd-k2-hirul are recombinant proteins that are derivatives of r-sak (recombinant staphylokinase). they are characterized by their fibrin-specific plasminogen activation properties and their antithrombin and antiplatelet activities. the difference between these proteins is the presence of the antithrombotic fragment (hirudin or hirulog) in the c-terminal portion of the r-sak. the aim of the present study was to examine the thrombolytic potentials of sak-rgd-k2-hir and sak-rgd-k2-hirul in an electrically induced carotid artery thrombosis model in rats and to compare the potentials to that of r-sak. we determined that a bolus injection of sak-rgd-k2-hirul was more effective than one of r-sak in the improvement and maintenance of carotid patency and in arterial thrombus weight reduction; however,it had the same potency as sak-rgd-k2-hir. the bleeding time,prothrombin time and activated partial thromboplastin time were significantly prolonged in the animals that were treated with either dose (1.5 or 3.0 mg/kg) of sak-rgd-k2-hir or sak-rgd-k2-hirul,whereas no changes were observed in the plasma fibrinogen concentration or the α2 plasmin inhibitor level. r-sak alone did not change the bleeding time or coagulation parameters. in conclusion,our findings demonstrate the thrombolytic activity of intravenous bolus injection of the novel thrombolytic agent sak-rgd-k2-hirul in rats. although this protein compares favorably with r-sak,we were unable to show the presence of any beneficial effects of sak-rgd-k2-hirul over those of sak-rgd-k2-hir. furthermore,our results suggest that high doses of sak-rgd-k2-hirul bear the risk of bleeding. copyright © 2011 by institute od pharmacology polish academy of sciences.