Introduction

Ischemic stroke treatment has advanced in the last two decades and intravenous thrombolysis is now considered the standard of care for selected patients. Recanalization can also be achieved by mechanical endovascular treatment for patients with large vessel occlusions. Complicating treatment-related symptomatic intracerebral hemorrhage and prolonged needle-to-recanalization times have been identified as major determinants of poor three-month functional outcomes. A hybrid mechanical-thrombolytic system with a patch imbued with an ultra-low dose of thrombolytic agents loaded onto a stent-retriever has been developed.

Methods

In this study, the in situ dose–response relationship of the thrombolytic patch imbued with up to 1000 IU of urokinase plasminogen activator (uPA) was quantified using Raman spectroscopy.

Results

Thrombi of up to 400 μm thickness dissolved within 15 min when patches imbued with < 1% of the conventional thrombolysis therapy dosage were applied. The results demonstrated that low-dose thrombolytic patches can dissolve normal clots compressed in the blood vessel in a short time. 500 IU is the threshold uPA dosage in the thrombolytic patch that most effectively dissolves the clots.

Conclusion

This study suggests that a novel endovascular stent-retriever loaded with an ultra-low drug dose fibrinolytic patch may be a suitable treatment for patients who are ineligible for conventional thrombolytic therapy.

中文翻译：

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具有超低剂量贴片的新型混合机械溶栓系统的剂量-反应关系和阈值药物剂量识别

介绍

在过去的二十年中，缺血性中风治疗取得了进展，静脉溶栓现在被认为是选定患者的标准治疗方法。对于大血管闭塞的患者，也可以通过机械血管内治疗来实现再通。复杂的治疗相关症状性脑出血和延长的针头再通时间已被确定为三个月功能结果不佳的主要决定因素。已经开发了一种混合机械溶栓系统，该系统带有一个贴片，该贴片充满了加载到支架回收器上的超低剂量溶栓剂。

方法

在这项研究中，使用拉曼光谱对注入高达 1000 IU 尿激酶纤溶酶原激活剂 (uPA) 的溶栓贴剂的原位剂量-反应关系进行了量化。

结果

当使用小于 1% 的常规溶栓治疗剂量的贴片时，厚度高达 400  μm的血栓在 15 分钟内溶解。结果表明，低剂量溶栓贴片可以在短时间内溶解压缩在血管中的正常凝块。500 IU 是溶栓贴剂中最有效溶解凝块的阈值 uPA 剂量。

结论

这项研究表明，一种新型血管内支架回收器装载了超低药物剂量的纤溶贴片，可能是不适合常规溶栓治疗的患者的合适治疗方法。