Zarich S W, Kowalchuk G J, Weaver W D, Loscalzo J, Sassower M, Manzo K, Byrnes C, Muller J E, Gurewich V
Cardiovascular Division, Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
J Am Coll Cardiol. 1995 Aug;26(2):374-9. doi: 10.1016/0735-1097(95)80009-6.
The present study was designed to test the efficacy and safety of a sequential combination of recombinant tissue-type plasminogen activator (rt-PA) and pro-urokinase in patients with acute myocardial infarction.
Efforts continue to identify a thrombolytic regimen that induces rapid, complete and sustained coronary artery patency in acute myocardial infarction. The two endogenous plasminogen activators rt-PA and pro-urokinase have been shown experimentally to induce fibrinolysis by sequential and complementary mechanisms. As a result, certain combinations of these activators have been found to be synergistic in vitro and in vivo.
In a multicenter observational study with core facilities for angiographic and laboratory analysis, 101 patients with acute myocardial infarction were enrolled and given a low dose bolus of rt-PA (5 to 10 mg) followed by a 90-min infusion of pro-urokinase (40 mg/h). All patients received intravenous heparin and oral aspirin. Coronary angiography was performed in all patients at 90 min.
Angiography at 90 min showed the infarct-related artery to be patent (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow) in 77% of patients, and 60% achieved TIMI grade 3 flow. At one center, angiography was repeated at 24 h to detect a possible reocclusion. All 28 patients with a patent infarct-related artery at 90 min had patency at 24 h (82% achieved TIMI grade 3 flow). Treatment was well tolerated, with bleeding complications essentially confined to arterial puncture site hematomas. There was only one in-hospital death.
A sequential combination of low dose rt-PA and reduced-dose pro-urokinase produced a high TIMI 3 patency rate, was well tolerated and was associated with a low reocclusion rate.
本研究旨在测试重组组织型纤溶酶原激活剂（rt-PA）与尿激酶原序贯联合应用于急性心肌梗死患者的疗效和安全性。
人们一直在努力寻找一种能在急性心肌梗死中诱导冠状动脉迅速、完全且持续通畅的溶栓方案。实验表明，两种内源性纤溶酶原激活剂rt-PA和尿激酶原可通过相继且互补的机制诱导纤维蛋白溶解。因此，已发现这些激活剂的某些组合在体外和体内具有协同作用。
在一项具备血管造影和实验室分析核心设施的多中心观察性研究中，纳入了101例急性心肌梗死患者，先给予低剂量推注rt-PA（5至10毫克），随后90分钟输注尿激酶原（40毫克/小时）。所有患者均接受静脉肝素和口服阿司匹林治疗。所有患者在90分钟时进行冠状动脉造影。
90分钟时的血管造影显示，77%的患者梗死相关动脉通畅（心肌梗死溶栓治疗[TIMI]2级或3级血流），60%达到TIMI 3级血流。在一个中心，24小时时重复进行血管造影以检测可能的再闭塞情况。90分钟时梗死相关动脉通畅的所有28例患者在24小时时仍保持通畅（82%达到TIMI 3级血流）。治疗耐受性良好，出血并发症基本局限于动脉穿刺部位血肿。院内仅1例死亡。
低剂量rt-PA与减量尿激酶原的序贯联合产生了较高的TIMI 3级通畅率，耐受性良好且再闭塞率低。
