溶栓
医学
纤维蛋白
组织纤溶酶原激活剂
血栓
血管性血友病因子
冲程(发动机)
血栓形成
大脑中动脉
磁共振成像
血小板
纤溶酶原激活剂
内科学
血小板活化
心脏病学
缺血
免疫学
放射科
心肌梗塞
机械工程
工程类
作者
Marc Vincent Adriaan van Moorsel,Steven de Maat,Kristof Vercruysse,Esther M. van Leeuwen,Charlène Jacqmarcq,Thomas Bonnard,Denis Vivien,H. Bart van der Worp,Rick M. Dijkhuizen,Coen Maas
出处
期刊:Blood
[American Society of Hematology]
日期:2022-12-29
卷期号:140 (26): 2844-2848
被引量:5
标识
DOI:10.1182/blood.2022016342
摘要
Abstract Recombinant human tissue plasminogen activator (rh-tPA) is an important thrombolytic agent for treatment of acute ischemic stroke. It requires fibrin binding for plasminogen activation. In contrast, Microlyse, a novel thrombolytic agent, requires von Willebrand factor (VWF) binding for plasminogen activation. We compared rh-tPA with Microlyse, administered 20 minutes after inducing thrombosis, in 2 randomized blinded acute ischemic stroke mouse models. Thrombosis was induced in the middle cerebral artery with different experimental triggers. Where thrombin infusion generates fibrin-rich thrombi, topical FeCl3 application generates platelet-rich thrombi. In the fibrin-rich model, both rh-tPA and Microlyse increased cortical reperfusion (determined by laser speckle imaging) 10 minutes after therapy administration (35.8 ± 17.1%; P = .001 39.3 ± 13.1%; P < .0001; 15.6 ± 7.5%, respectively, vs vehicle). In addition, both thrombolytic agents reduced cerebral lesion volume (determined by magnetic resonance imaging) after 24 hours (18.9 ± 11.2 mm3; P = .033; 16.1 ± 13.9 mm3; P = .018; 26.6 ± 5.6 mm3, respectively, vs vehicle). In the platelet-rich model, neither rh-tPA nor Microlyse increased cortical reperfusion 10 minutes after therapy (7.6 ± 8.8%; P = .216; 16.3 ± 13.9%; P = .151; 10.1 ± 7.9%, respectively, vs vehicle). However, Microlyse, but not rh-tPA, decreased cerebral lesion volumes (13.9 ± 11.4 mm3; P < .001; 23.6 ± 11.1 mm3; P = .188; 30.3 ± 10.9 mm3, respectively, vs vehicle). These findings support broad applicability of Microlyse in ischemic stroke, irrespective of the thrombus composition.
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