Lyden P D, Zivin J A, Clark W A, Madden K, Sasse K C, Mazzarella V A, Terry R D, Press G A
Department of Neurology, Veterans Administration Medical Center, San Diego, CA 92093.
Neurology. 1989 May;39(5):703-8. doi: 10.1212/wnl.39.5.703.
Tissue plasminogen activator (tPA) dissolves intravascular thrombus and restores blood flow after thromboembolic vascular occlusion. The utility of this agent for treatment of stroke in humans may be limited by post-reperfusion hemorrhagic complications. We studied tPA-mediated thrombolysis in an animal model of cerebrovascular occlusion in order to determine what factors, if any, predispose tPA-treated animals to suffer hemorrhage. Small blood clot emboli were injected into the internal carotid arteries of rabbits. Angiograms confirmed occlusion of the middle cerebral artery or internal carotid artery in 100% of subjects. tPA or saline was administered as a 30-minute infusion at various times after embolization. Hemorrhage rates were similar in all groups regardless of treatment. tPA increased the prothrombin time and the thrombin time but not the partial thromboplastin time. There was no correlation between these changes in blood coagulation and the finding of cerebral hemorrhage. We observed a significant association between stroke severity and cerebral hemorrhage. We conclude that tPA treatment successfully causes thrombolysis of cerebral emboli without causing an increase in the incidence of cerebral hemorrhage in rabbits.
组织型纤溶酶原激活剂（tPA）可溶解血管内血栓，并在血栓栓塞性血管闭塞后恢复血流。该药物用于人类中风治疗的效用可能会受到再灌注后出血并发症的限制。我们在脑血管闭塞的动物模型中研究了tPA介导的溶栓作用，以确定是否有任何因素使接受tPA治疗的动物易发生出血。将小血块栓子注入兔颈内动脉。血管造影证实100%的受试对象大脑中动脉或颈内动脉闭塞。在栓塞后的不同时间给予tPA或生理盐水30分钟输注。无论治疗如何，所有组的出血率相似。tPA延长了凝血酶原时间和凝血酶时间，但未延长部分凝血活酶时间。这些凝血变化与脑出血的发现之间没有相关性。我们观察到中风严重程度与脑出血之间存在显著关联。我们得出结论，tPA治疗成功地导致了兔脑栓塞的溶栓，而不会导致脑出血发生率增加。
