Enhanced thrombolytic and antithrombotic potency of a fibrin-targeted plasminogen activator in baboons
Enhanced thrombolytic and antithrombotic potency of a fibrin-targeted plasminogen activator in baboons
复制标题
DOI：
10.1161/01.cir.94.6.1412
复制
发表时间：
1996-09-15
期刊：
影响因子：
37.8
通讯作者：
Hanson, SR
中科院分区：
文献类型：
--
作者：
Runge, MS;Harker, LA;Hanson, SR
背景：溶栓治疗可降低急性心肌梗死患者的死亡率，但目前可用药物的使用存在显著的局限性。在本报告中，我们描述了由抗纤维蛋白抗体59D8 （AFA）和低分子量单链尿激酶型纤溶酶原激活剂（scuPA）组成的混合重组纤溶酶原激活剂的溶栓和抗血栓活性。方法和结果建立了一个在幼年狒狒体内形成血栓的溶栓模型，比较了AFA-scuPA、重组组织纤溶酶原激活剂（rTPA）和重组scuPa （rscuPA）对非闭塞性in- 111标记的富血小板动脉型血栓和i -125标记的富纤维蛋白静脉型血栓的溶栓效果。全身输注1.89 nmol/kg fa - scupa所产生的溶栓效果与更高剂量的TPA （14.2 nmol/kg）和rscuPA （28.5 nmol/kg）所产生的溶栓效果相当。当稳态血浆浓度归一化时，AFA-scuPA溶解血栓的速度比scuPA和TPA快6倍
Background Thrombolytic therapy reduces mortality in patients with acute myocardial infarction, but significant limitations exist with the use of currently available agents. In the present report, we describe the thrombolytic and antithrombotic potencies of a hybrid recombinant plasminogen activator consisting of an antifibrin antibody 59D8 (AFA) and low-molecular-weight single-chain urokinase-type plasminogen activator (scuPA).Methods and Results A thrombolysis model in which thrombi are preformed in vivo in juvenile baboons was developed to compare the potencies of AFA-scuPA, recombinant tissue plasminogen activator (rTPA), and recombinant scuPa (rscuPA) in lysing nonocclusive In-111-labeled platelet-rich arterial-type thrombi and I-125-labeled fibrin-rich venous-type thrombi. Systemic infusion of 1.89 nmol/kg AFA-scuPA produced thrombolysis that was comparable to that obtained with much higher doses of TPA (14.2 nmol/kg) and rscuPA (28.5 nmol/kg). When steady-state plasma concentrations are normalized, AFA-scuPA lyses thrombi sixfold more rapidly than scuPA and TPA (P