イヌ大たい静脈血せんモデルにおける組織性プラスミノーゲンアクチベーターの効果

Abstract

Tissue plasminogen activator (TPA) was purified either as a single chain or as a two chain form from the culture medium of a human melanoma cell line. The thrombolytic activity of TPA was investigated in beagle dogs with an experimental femoral vein thrombosis and compared with urokinase. The 125I-fibrinogen labeled thrombus was formed in the femoral vein, and the thrombolytic agents were infused over a 4 hour period. The degree of thrombolysis was measured as the difference between the injected and recovered 125I. In six control animals with a saline infusion, the degree of thrombolysis was 16.3±3.8 percent (mean±S. E. M.), in 5 dogs receiving 100, 000IU urokinase, 17.4±3.7 percent and in 4 dogs with 1, 000, 000IU urokinase, 40.6±4.8 percent. Infusion of 100, 000IU single chain TPA in 5 dogs resulted in 33.5±7.8 percent lysis and of 100, 000IU two chain TPA in 5 dogs in 60.1±10.8 percent. Infusion of 300, 000IU one chain TPA yielded 57.5 percecent lysis and of the same amount of two chain TPA 72.9 percent. Significant activation of plasminogen, consumption of α2-antiplasmin and fibrinogen breakdown was only observed in the animals receiving the high dosis of urokinase but not in the saline, TPA or the low dose urokinase groups. It is thus concluded that in this thrombosis model, human TPA has a higher specific thrombolytic effect than urokinase, without systemic fibrinolytic activation and fibrinogen breakdown.