Kimata H, Nakajima K, Suzuki H, Koide T, Narita T
Tokyo Research Laboratories, Kowa Co., Ltd., Japan.
J Pharmacobiodyn. 1991 Jul;14(7):399-406. doi: 10.1248/bpb1978.14.399.
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.
通过向大鼠左颈内动脉注射[125I]纤维蛋白凝块颗粒（20 - 100微米）制备实验性脑栓塞模型，并用γ射线探测器连续监测脑部放射性变化。脑横断面的放射自显影片显示左半脑小血管中有栓子存在。注射[125I]纤维蛋白凝块后，放射性在90分钟时自发降至初始放射性的一半。代表栓子溶解的放射性下降被抗纤溶药物反式-4-氨甲基环己烷羧酸显著抑制，这表明栓塞后在脑小血管中通过纤溶酶原激活产生了内源性纤维蛋白溶解。连续注射纤维蛋白凝块导致放射性累加，并降低每次栓子形成时的溶解速率。在第二次连续注射纤维蛋白凝块后，通过左颈内动脉输注溶栓药物30分钟。尽管在输注生理盐水期间观察到栓子的自发溶解，但组织型纤溶酶原激活剂（t-PA）以及尿激酶型纤溶酶原激活剂（u-PA）都进一步促进了溶解。分别以75微克/千克和10000国际单位/千克的剂量输注t-PA后60分钟，约一半的栓子消失。
