Fibrinolytic activity of immobilized plasminogen activator

Urokinase (UK) was immobilized onto the inner surface of 4-mm ID canine autogenous fibrocollagenous tubes in order to develop a fibrinolytic small-caliber vascular prosthesis. Using a glutaraldehyde entrapment process, the immobilized urokinase was compared to its soluble counterpart for its ability to degrade fibrin. Fibrin Degradation Product (FDP) levels increased with time for both soluble and immobilized urokinase, where FDP levels at complete lysis for both soluble and immobilized urokinase, where FDP levels at complete lysis were measured at 165.83 +/- 6.44 micrograms/ml. The rate of fibrinolysis was slower for the immobilized urokinase compared to its soluble form. The inhibitory effect of alpha-2 plasmin inhibitor was shown to be inimical to urokinase activity. Using a differential recirculation reactor apparatus and an esterolytic reaction involving N-alpha-acetyl-L-lysine methyl ester HCl, the amount of urokinase immobilized onto fibrocollagenous tubes (FCT) was measured to be 110 +/- 14 CTA units of UK per millimeter graft. The stability of immobilized urokinase was maintained for at least 75 hours of operation time, which corresponds to 1 year maintained for at least 75 hours of operation time, which corresponds to 1 year of storage time. Urokinase-bound fibrocollagenous tubes (UK-FCT), in addition to control FCT's, Perloff prostheses, and the autogenous saphenous vein, were interposed onto the carotid artery of canine mongrels using end-to-end anastomoses with 7-0 prolene sutures. Results indicate that the patency rates for UK-FCT's were 86% and 62% after 1 and 2 months, respectively. The Perloff graft and the control FCT had much lower patency rates. These results indicate that immobilizing urokinase is a viable method of producing a small-caliber biocompatible vascular prosthesis.