Loscalzo J, Wharton T P, Kirshenbaum J M, Levine H J, Flaherty J T, Topol E J, Ramaswamy K, Kosowsky B D, Salem D N, Ganz P
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Circulation. 1989 Apr;79(4):776-82. doi: 10.1161/01.cir.79.4.776.
Recognition that myocardial infarction is caused by coronary thrombosis has stimulated a search for a safe, rapidly acting, and effective thrombolytic regimen. Tissue plasminogen activator (t-PA) can provide relatively clot-selective thrombolysis, but one quarter of patients fail to achieve reperfusion, lysis speed is not optimal, and higher doses have been associated with an increased incidence of hemorrhagic stroke. We report the results of a multicenter study of pro-urokinase, a second naturally occurring plasminogen activator that has structural similarities to t-PA but has a different mechanism of action. Pro-urokinase was administered 3.9 +/- 1.1 hours after the onset of chest pain to 40 patients with acute myocardial infarction with angiographically confirmed complete coronary occlusion (TIMI grade 0). After a 90-minute intravenous infusion of pro-urokinase (4.7-9 million units, 36-69 mg) 51% (20 of 39) of the patients demonstrated reperfusion (TIMI grade 2 or 3) occurring 64.8 +/- 22.3 minutes after initiation of therapy. Fibrinogen levels fell only 10 +/- 17% from baseline, confirming the fibrin specificity of pro-urokinase. As with t-PA, however, this specificity was only relative. alpha 2-Antiplasmin decreased to 39% and plasminogen decreased to 64% of initial values. Fibrinogen degradation products increased 63% and the fibrin-specific D-dimer increased 8.7-fold. Thus, pro-urokinase produces relatively clot-selective coronary thrombolysis similar to that produced by t-PA, but the use of either pro-urokinase or t-PA alone in higher doses would be likely to produce more nonspecific effects.
认识到心肌梗死是由冠状动脉血栓形成引起的，这激发了人们寻找一种安全、起效迅速且有效的溶栓方案的努力。组织型纤溶酶原激活剂（t-PA）可提供相对具有凝块选择性的溶栓作用，但四分之一的患者未能实现再灌注，溶栓速度不理想，且较高剂量与出血性中风发生率增加有关。我们报告了一项关于尿激酶原的多中心研究结果，尿激酶原是另一种天然存在的纤溶酶原激活剂，其结构与t-PA相似，但作用机制不同。在胸痛发作后3.9±1.1小时，对40例经血管造影证实冠状动脉完全闭塞（TIMI 0级）的急性心肌梗死患者给予尿激酶原。在静脉输注尿激酶原90分钟（470万 - 900万单位，36 - 69毫克）后，51%（39例中的20例）患者在治疗开始后64.8±22.3分钟出现再灌注（TIMI 2级或3级）。纤维蛋白原水平仅比基线下降10±17%，证实了尿激酶原的纤维蛋白特异性。然而，与t-PA一样，这种特异性只是相对的。α2 - 抗纤溶酶降至初始值的39%，纤溶酶原降至初始值的64%。纤维蛋白原降解产物增加63%，纤维蛋白特异性D - 二聚体增加8.7倍。因此，尿激酶原产生的冠状动脉溶栓作用与t-PA产生的作用相似，具有相对的凝块选择性，但单独使用较高剂量的尿激酶原或t-PA都可能产生更多非特异性效应。
