Bednar M M, Raymond S J, Gross C E
Division of Neurosurgery, University of Vermont, Burlington 05405.
Neurol Res. 1993 Dec;15(6):405-8. doi: 10.1080/01616412.1993.11740173.
The thrombolytic activity of tissue plasminogen activator was evaluated in a rabbit model of thromboembolic stroke using both various concentrations (3, 5, and 10 mg/kg; 20% bolus with the remaining 80% given over 30 min.) and routes of administration (intravenous versus regional intra-arterial). An autologous tin-tagged clot was embolized to the brain via the carotid artery. Tissue plasminogen activator was then given at the doses and routes noted (n = 3 in all groups). Thrombolytic activity was followed by serial x-rays of the tin-laden clot over a four-hour period. The brains were then removed and subjected to gross inspection. Only the intravenous dose of 5 mg/kg tissue plasminogen activator produced greater than 50% clot lysis in all animals. Doses of t-PA higher (10 mg/kg) or lower (3 mg/kg) than this were less effective in producing thrombolysis, demonstrating greater than 50% clot lysis in only one animal of each group. We conclude that in this model of thromboembolic stroke the intravenous administration of tissue plasminogen activator is more effective than intra-arterial, and that the optimal dose is in the range of 5 mg/kg.
在兔血栓栓塞性中风模型中，使用不同浓度（3、5和10毫克/千克；20%推注，其余80%在30分钟内给予）和给药途径（静脉注射与局部动脉内注射）评估组织型纤溶酶原激活剂的溶栓活性。通过颈动脉将自体锡标记的血凝块栓塞到大脑。然后按照上述剂量和途径给予组织型纤溶酶原激活剂（所有组n = 3）。在4小时内通过对含锡血凝块进行系列X射线检查来跟踪溶栓活性。然后取出大脑进行大体检查。只有静脉注射5毫克/千克组织型纤溶酶原激活剂在所有动物中产生了大于50%的血凝块溶解。高于（10毫克/千克）或低于（3毫克/千克）此剂量的组织型纤溶酶原激活剂在产生溶栓方面效果较差，每组仅在一只动物中显示出大于50%的血凝块溶解。我们得出结论，在该血栓栓塞性中风模型中，静脉注射组织型纤溶酶原激活剂比动脉内注射更有效，且最佳剂量在5毫克/千克范围内。
