Abstract
Urokinase (UK) was immobilized to the lumen of dacron-reinforced fibrocollagenous tubes (UK-FCT) using a glutaraldehyde entrapment process, in an effort to develop a fibrinolytic small diameter (i.e., 4 mm i.d.) vascular graft. Soluble and immobilized urokinase were evaluated for their ability to lyse synthetic clots made from purified physiologic substrates, alpha 2 plasmin inhibitor (alpha 2PI) mediated whole canine blood (WCB) and alpha 2PI-depleted WCB by measuring lysis time and fibrin degradation product (FDP) formation. Lysis times were orders of magnitude lower and FDP formation rates were orders of magnitude higher with synthetic clots compared with either alpha 2-mediated or alpha 2-depleted WCB clots as a substrate, using both soluble and immobilized UK. However, both soluble and immobilized UK catalyzed FDP formation at an enhanced rate for alpha 2PI-depleted WCB compared with the inhibitor-mediated substrate. These results suggest that both soluble and immobilized UK behave similarly when treated with either standard clots, alpha 2PI-mediated WCB and alpha 2PI-depleted WCB as substrates and the use of urokinase-bound fibrocollagenous tube may prove suitable as a fibrinolytic vascular prosthesis.
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