Kasper W, Hohnloser S H, Engler H, Meinertz T, Wilkens J, Roth E, Lang K, Limbourg P, Just H
Department of Cardiology, University Hospital Frieburg, Federal Republic of Germany.
J Am Coll Cardiol. 1990 Sep;16(3):733-8. doi: 10.1016/0735-1097(90)90367-x.
Pro-urokinase is a single chain precursor of two chain urokinase, which has been shown to induce fibrin-selective plasminogen activation. In the present study, thrombolytic efficacy of 9 million U of glycosylated pro-urokinase administered intravenously was compared with that of a combined regimen utilizing 4.5 million U of pro-urokinase and 0.2 million U of urokinase. Seventy-five patients with a first myocardial infarction were randomized to receive high dose pro-urokinase (n = 40, group A) or the combination therapy (n = 35, group B). Reperfusion of the infarct-related artery was assessed by repeat coronary angiography. Thrombolysis in Myocardial Infarction trial (TIMI) grade II or III reperfusion was achieved in 73% of group A patients compared with 66% of group B patients (p = NS). A trend toward faster reopening of the infarct-related artery was observed in patients in group B. Coronary artery reocclusion occurred in 5 (10%) of 49 patients in whom angiography was repeated within 36 h after the start of therapy. Clot-selective thrombolysis was indicated by a minimal fibrinogen decline (15% and 13%, respectively, in groups A and B). Alpha 2-antiplasmin levels, however, decreased more rapidly in patients in group B (p less than 0.05). This finding and the equivalent reperfusion rate in the combined treatment group strongly suggest synergistic interaction between these two thrombolytic agents. In summary, the high incidence of reperfusion, the low rate of early reocclusion and the paucity of side effects, particularly with regard to bleeding complications, indicate that pro-urokinase possesses the characteristics of an ideal thrombolytic agent.
单链尿激酶原是双链尿激酶的单链前体，已被证明可诱导纤维蛋白选择性纤溶酶原激活。在本研究中，将静脉注射900万单位糖基化单链尿激酶原的溶栓效果与使用450万单位单链尿激酶原和20万单位尿激酶的联合方案进行了比较。75例首次发生心肌梗死的患者被随机分为接受大剂量单链尿激酶原治疗组（n = 40，A组）或联合治疗组（n = 35，B组）。通过重复冠状动脉造影评估梗死相关动脉的再灌注情况。A组73%的患者实现了心肌梗死溶栓试验（TIMI）II级或III级再灌注，而B组为66%（p = 无显著性差异）。观察到B组患者梗死相关动脉有更快再通的趋势。在治疗开始后36小时内重复进行血管造影的49例患者中，有5例（10%）发生冠状动脉再闭塞。纤维蛋白原最低下降表明为凝块选择性溶栓（A组和B组分别为15%和13%）。然而，B组患者的α2-抗纤溶酶水平下降更快（p < 0.05）。这一发现以及联合治疗组中相当的再灌注率强烈提示这两种溶栓剂之间存在协同相互作用。总之，再灌注发生率高、早期再闭塞率低以及副作用少，特别是在出血并发症方面，表明单链尿激酶原具有理想溶栓剂的特性。
