Antithrombotic mechanisms of urokinase immobilized polyurethane.
Urokinase immobilized polymer is highly antithrombotic, which cannot be explained only by fibrinolysis. We immobilized 10 IU/cm2 of urokinase to polyurethane by using maleic anhydride methylvinyl ether copolymer as a carrier. Then we incubated blood in circular tubes made of this material, measured the clotting factors and observed the surface of the tubes after incubation by scanning electronmicroscopy and immunofluorescence microscopy. After 5 min incubation, the relative activities of factors V, VIII, IX, X and XII, fibrinogen, plasminogen and alpha 2 plasmin inhibitor decreased, but the activity of factor VII increased. No platelet adhesion to the surface of the urokinase immobilized polyurethane was observed and there was no significant adsorption of serum proteins, including fibrinogen, fibronectin and vWF antigen, on the surface. Urokinase-immobilized polyurethane catalyzed the digestion of clotting factors as well as fibrinolysis and also inhibited platelet adhesion on its surface probably by inhibiting protein adsorption and its clinical application including vessel prosthesis should be developed further.
Kitamoto
Y
Y
Third Department of Internal Medicine, Kumamoto University Medical School, Japan.
Tomita
M
M
Kiyama
S
S
Inoue
T
T
Yabushita
Y
Y
Sato
T
T
Ryoda
H
H
Sato
T
T
D001779:Blood Coagulation Factors / Q000032:analysis / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects*; D004800:Enzymes, Immobilized / Q000494:pharmacology*; D005343:Fibrinolytic Agents; D006801:Humans; D010664:Phenylmethylsulfonyl Fluoride / Q000031:analogs & derivatives; D011140:Polyurethanes; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D001779:Blood Coagulation Factors; D004800:Enzymes, Immobilized; D005343:Fibrinolytic Agents; D011140:Polyurethanes; D010664:Phenylmethylsulfonyl Fluoride; C027226:(4-amidinophenyl)methanesulfonyl fluoride; D014568:Urokinase-Type Plasminogen Activator