An experimental study of local fibrinolysis using tissue plasminogen activator and urokinase in a canine common carotid artery thrombus model

Tissue-type plasminogen activator (t-PA) is thought to be a promising fibrinolytic agent because of its high affinity to fibrin without evidence of significant systemic fibrinolysis. The feasibility of t-PA and urokinase (UK) in local fibrinolytic therapy was investigated in a canine common carotid artery thrombus model. After the screening of coagulation-fibrinolytic activities, autologous blood clot was injected into the segment of intimal injured common carotid artery. The fibrinolytic agent was locally applied from the origin of the common carotid artery under temporary flow arrest with a double lumen balloon catheter. T-PA used in this study was produced by the cell culture technique of normal human cells. Its activity was-expressed by AK units (AKU), namely, the fibrinolytic area of the fibrin-agar plate induced by 10 AKU/ml of t-PA solution corresponds to that of 10 IU/ml of UK solution. The doses of t-PA required to produce angiographical recanalization were 600-1,200 AKU/kg (approximately 0.015-0.03 mg/kg) of t-PA, while 24,000 IU/kg was necessary for UK. In these doses, t-PA evoked no adverse effects on the plasma coagulation-fibrinolytic system, while UK produced significant decrease in plasma fibrinogen and alpha-2 plasmin inhibitor levels. Thus, t-PA may be considered to have higher fibrinolytic ability and lower adverse effect on the plasma coagulation-fibrinolytic system than UK. Local fibrinolytic therapy for acute cerebral infarction using t-PA is considered to be a promising intravascular therapeutic procedure with less systemic fibrinolytic complications such as hemorrhagic infarction.