Fibrolase thrombosis model systems

FIBROLASE, AN ACTIVE THROMBOLYTIC ENZYME IN ARTERIAL AND VENOUS THROMBOSIS MODEL SYSTEMS... 

The present report outlines studies with fibrolase in several different animal thrombosis model systems. Infusion of fibrolase proximal to an occlusive thrombus produces rapid and effective thrombolysis in carotid (22) and renal arterial, and iliac venous thrombosis model systems (23). Recently the recombinant form of fibrolase has been purified from a yeast expression system (24). It appears to be identical in all respects to the natural enzyme and has been used successfully in the carotid arterial thrombosis model system (22). Both natural and recombinant forms of the enzyme have effective thrombolytic activity in the different animal models employed there are no observable side effects nor toxicity, and minimal or no observable hemorrhaging. 

In the iliac venous thrombosis model system six animals were studied with good lysis observed venographically in five (23). Figure 2 presents representative venograms illustrating the effectiveness of thrombolysis induced by selective application of natural fibrolase. No toxicity, little or no hemorrhaging, and no evidence of other side effects were observed in the animals studied. These studies again demonstrate the favorable therapeutic potential of native fibrolase. 

The present results demonstrate that natural fibrolase exhibits effective in vivo thrombolytic activity in several animal thrombosis model systems. Infusion of the enzyme proximal to an occlusive thrombus induced rapid and specific thrombolysis in rabbit renal arterial and iliac venous thrombosis model systems. No evidence of hemorrhaging or alterations to the hemostatic system were observed in these studies. Additionally, no toxicity was observed and no angiographic, histologic, or functional evidence of side effects were obtained. The enzyme rapidly lysed 48 hr aged thrombi in the venous thrombosis model. This suggests that one of the primary mechanisms of thrombus resistance to PA-based agents. 

The present investigations, although limited to the local application of fibrolase, demonstrate that under these conditions the enzyme lyses venous or arterial thrombi rapidly and with no observable systemic or hematologic side effects. In these thrombosis model systems the enzyme, either alone or in combination with antiplatelet therapy, offers a unique, safe, and specific mechanism for clot dissolution and may prove useful as a clinically effective alternative to, or for use in synergistic combination with, presently used thrombolytic agents. 

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