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首页> 外文期刊>Journal of stroke and cerebrovascular diseases: The official journal of National Stroke Association >Comparative analysis of fibrinolytic properties of Alteplase, Tenecteplase and Urokinase in an in vitro clot model of intracerebral haemorrhage
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Comparative analysis of fibrinolytic properties of Alteplase, Tenecteplase and Urokinase in an in vitro clot model of intracerebral haemorrhage

机译：脑内出血体外凝块模型中普雷酶，邻苯二甲酸酯和尿激酶纤维蛋白溶解特性的对比分析

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Objective: Hematoma lysis with recombinant tissue plasminogen activator (rtPA) has emerged as an alternative therapy for spontaneous intracerebral and intraventricular haemorrhage (ICH and IVH). However, the MISTIE III and CLEAR III trial failed to show significant improvement of favourable outcomes. Besides experimental and clinical trials revealed neurotoxic effects of rtPA. The demand for optimization of fibrinolytic therapy persists. Herein, we used our recently devised clot model of ICH to systematically analyse fibrinolytic properties of rtPA, tenecteplase and urokinase. Methods: In vitro clots of human blood (size: 25 ml and 50 ml; age: 1.5 tenecteplase, 24 tenecteplase and 48 tenecteplase) were produced and equipped with a catheter into the clot core for drug delivery and drainage. Various doses of tenecteplase and urokinase with different treatment periods were examined (overall 117 clots), assessing the optimal dose and treatment time of these fibrinolytics. Clots were weighed before and at the end of treatment. These results were compared with clots treated with 1 mg rtPA or with 0.9% sodium chloride solution. Results: The optimal treatment scheme of tenecteplase was found to be 100 IU with an incubation time of 30 min, for urokinase it was 50 000 IU with an incubation time of 20 min. The relative clot end weight of tenecteplase and urokinase (31.3 +/- 11.9%, 34.8 +/- 7.7%) was comparable to rtPA (36.7 +/- 10.7%). Larger clots were more effectively treated with tenecteplase compared to the control group (P=0.0013). urokinase and tenecteplase had similar lysis rates in aged clots and 90 min clots. One and two repetitive treatments with tenecteplase were as effective as two and three cycles of urokinase. Conclusions: In our in vitro clot model we could determine optimal treatment regimens of tenecteplase (100 IU, 30 min) and urokinase (50 000 IU, 20 min). Urokinase and tenecteplase were comparable in their fibrinolytic potential compared to 1mg rtPA in small clots and showed an effective lysis in aged clots. tenecteplase was more effective in larger clots. (c) 2020 Elsevier Inc. All rights reserved.
机译：目的：重组组织型纤溶酶原激活剂（rtPA）血肿溶解术已成为自发性脑内和脑室内出血（ICH和IVH）的替代疗法。然而，MISTIE III和CLEAR III试验未能显示有利结果的显著改善。此外，实验和临床试验显示rtPA具有神经毒性作用。优化纤溶治疗的需求依然存在。在此，我们使用我们最近设计的ICH血块模型系统地分析了rtPA、替尼替普酶和尿激酶的纤溶特性。方法：体外制备人血凝块（大小：25ml和50ml；年龄：1.5特奈替普酶、24特奈替普酶和48特奈替普酶），并将导管插入凝块核心进行药物输送和引流。对不同治疗期的不同剂量的替奈普酶和尿激酶进行检查（总共117个血栓），评估这些纤溶剂的最佳剂量和治疗时间。在治疗前和治疗结束时对血栓进行称重。这些结果与用1mg rtPA或0.9%氯化钠溶液处理的血栓进行了比较。结果：替奈普酶的最佳治疗方案为100IU，孵育时间为30min，尿激酶的最佳治疗方案为50000 IU，孵育时间为20min。替奈普酶和尿激酶的相对凝块末端重量（31.3+/-11.9%，34.8+/-7.7%）与rtPA（36.7+/-10.7%）相当。与对照组相比，使用替奈普酶治疗较大血栓更有效（P=0.0013）。尿激酶和替萘普酶在老年血栓和90分钟血栓中的溶解率相似。一个和两个重复的替奈普酶治疗与两个和三个周期的尿激酶一样有效。结论：在我们的体外血栓模型中，我们可以确定替奈普酶（100IU，30min）和尿激酶（50000 IU，20min）的最佳治疗方案。与1mg rtPA相比，尿激酶和替奈特普酶在小血栓中的纤溶潜力相当，并且在老年血栓中显示出有效的溶解作用。特奈替普酶对较大血栓更有效。（c） 2020爱思唯尔公司版权所有。

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