Thrombolytic effect of tissue plasminogen activator in a cerebral embolic model

An experimental cerebral embolic model was prepared by an injection of [125I]fibrin clot particles (20-100 microns) into the left internal carotid artery in rats, and the changes in radioactivity of the brain were continuously monitored by a gamma-ray detector. The autoradiograms of the caput transections showed the existence of emboli in small vessels of the left hemicerebrum. After the injection of [125I]fibrin clots, the radioactivity spontaneously decreased to a half of the initial radioactivity at 90 min. The decrease in radioactivity which represented the embolus dissolution was markedly suppressed by an antiplasmin agent, trans-4-aminomethyl cyclohexane carboxylic acid, indicating that the endogenous fibrinolysis through the activation of plasminogen is generated in the cerebral small vessels after the embolization. Consecutive injection of fibrin clots caused a summation of the radioactivity and decreased the rate of dissolution at every embolus preparation. The thrombolytic agents were infused via the left internal carotid artery for 30 min after the second successive injection of fibrin clots. Although the spontaneous dissolution of emboli was observed during the infusion of saline, tissue plasminogen activator (t-PA) as well as urokinase plasminogen activator (u-PA) produced a further dissolution. Approximately half of the emboli disappeared 60 min after the infusion of t-PA at a dose of 75 micrograms/kg and at a dose of 10000 IU/kg, respectively.