Abstract
Today, the development of antithrombogenic medical materials is the important points in advance of medical therapy. For this purpose, we prepared the dacron fiber immobilized urokinase which was the most useful fibrinolytic medicament.
This report investigated the influence of disinfection against the fibrinolytic activity of this fiber and presented the two clinical cases who were implanted this fiber in Handley's operation for lymphedema. Figure 1 shows the procedure of immobilization of urokinase to dacron. In this procedure, polyethyleneimine and gantrez (maleic anhydride/methylvinyl ether copolymer) play the role of grafted copolymer in ordor to couple the urokinase in peptide linking. Fibrinolytic activity of this fiber was measured by standard human fibrin plate.
The prepared dacron fiber kept the remarkable fibrinolytic activity in the repeated fibrinolysis test after the 6 months storage. In basic experiment, we checked how the immobilized urokinase was stable to the handling of disinfection. The fiber was sorked in 0.5% chlorhexidine alcohol, boiled saline solution or ethyleneoxide gas. Figure 2 shows these results. The stability of immobilized urokinase was more superior in 0.5% chlorhexidine alcohol.
These experimental data suggest the possibility of clinical use of immobilized urokinase technique.
Then, we applied this immobilized urokinase technique to the lymphangioplasty in lymphedema which was called Handley's operation. We had already two clinical cases implanted dacron fiber immobilized urokinase. The first case had primary lymphedema of left lower extremity and the second case had secondary lymphedema of left lower extremity. These patients were implanted three pieces of dacron fibers of approximately a half meter into subcutaneous tissue from below the knee to above the groin. After the operations, they were injected intravenously the high concentration of urokinase solution once a month. In one patient, however, one of three pieces of dacron fiber was removed for the infection after 45 postoperative days. Figure 4 shows the histological finding of removed dacron fiber. The fiber was surrounded by the granulation tissue with giant cells. In peripheral portion, the spaces among the bundle were filled with granulation tissue, while in central portion, the some spaces were kept open. But the fibrinolytic activity of this removed material had been almost lost.
From these clinical cases, we fully realized the necessity to develop the new material immobilized urokinase which was able to maintain the strong fibrinolytic activity for a long period even in vivo.
