Biological and Thrombolytic Properties of Proenzyme and Active Forms of Human Urokinase – III. Thrombolytic Properties of Natural and Recombinant Urokinase in Rabbits with Experimental Jugular Vein Thrombosis

Summary

The thrombolytic properties of recombinant pro-urokinase (Rec-pro-UK), recombinant active urokinase (Rec-UK) and natural urinary urokinase (Nat-UK) were compared with those of tissue-type plasminogen activator (t-PA) in rabbits with a radiolabeled thrombus in the jugular vein. The thrombolytic agents were infused intravenously over a time period of 4 hr and the extent of thrombolysis measured two hours later.

In control animals the extent of thrombolysis was 11 ± 2% (n=8) after 6 hr. Nat-UK and Rec-UK had very similar thrombolytic properties. Significant thrombolysis was only obtained with infusion of 240,000 IU per kg (41 ± 2%, n=4 for Nat-UK and 37 ± 4%, n=4 for Rec-UK) and this was associated with a marked systemic activation of the fibrinolytic system, as evidenced by consumption of plasminogen and α₂-antiplasmin and fibrinogen breakdown.

Infusion of Rec-pro-UK induced thrombolysis at a dose of 60,000 IU per kg (44 ± 8%, n=3) but without associated systemic activation of the fibrinolytic system. In this respect the properties of Rec-pro-UK were similar to those of t-PA, which, however, had a 2- to 4-fold higher specific thrombolytic activity (30,000 IU/ kg yielding 48 ± 1% lysis, n=4).

It is concluded that Rec-UK has very similar thrombolytic properties as Nat-UK and that Rec-pro-UK has a beter thrombus- selectivity and less systemic side effects than the active enzymes.

Keywords

Thrombosis - Thrombolysis - Recombinant pro-urokinase - Recombinant urokinase - Natural urokinase

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