A thromboembolic model for the efficacy and safety evaluation of combined mechanical and pharmacologic revascularization strategies

A thromboembolic model for the efficacy and safety evaluation of combined mechanical and pharmacologic revascularization strategies
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DOI:
10.1136/neurintsurg-2012-010435
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发表时间:
2013-05-01
影响因子:
4.8
通讯作者:
Wakhloo, Ajay K.
Wakhloo, Ajay K.
中科院分区:
医学1区
文献类型:
--
作者:
Gounis, Matthew J.;Nogueira, Raul G.;Wakhloo, Ajay K.

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背景和目的动脉内纤维蛋白溶解治疗联合机械性血栓破裂介导的再通策略可能是比单独使用任何一种治疗更有效的治疗方法。有几个临床前动物模型来评估这些策略。在这里,我们报告一个模型,同时评估这两种治疗approaches.Methods同种异体血凝块通过6 F的引导导管后,新西兰白色兔的颈总动脉管腔狭窄>50%注入。狭窄在1小时后被释放,允许有足够的时间与凝块血管壁相互作用。确认闭塞,并将每根血管分配接受单独球囊血管成形术、动脉内组织纤溶酶原激活剂(tPA,阿替普酶,Genentech,San弗朗西斯科,加州,美国)、通过原型球囊输注导丝(NIT Therapeutics,Pittsburgh,Pennsylvania,美国)输送tPA、部分支架展开或局部输送tPA的部分支架展开。结果与其他治疗方法相比,球囊导丝治疗组的TICI评分稳定,且血管再通评分较高(TICI 2B),tPA用量较低。所有的治疗策略导致内皮剥脱和暴露的内部弹性lamina.Conclusions的动物模型允许可靠的和一致的血栓栓塞闭塞的目标脉管系统,并允许评估急性缺血性中风的药理学和机械血运重建策略。
Background and purpose Recanalization strategies mediated by intra-arterial fibrinolytic therapy in combination with mechanical clot disruption may be a more effective treatment approach than either therapy used alone. There are few preclinical animal models to evaluate these strategies. Here we report on a model to simultaneously evaluate both of these treatment approaches.Methods Allogeneic clot was injected through the 6 F guide catheter after creating >50% luminal stenosis of the common carotid arteries of New Zealand White rabbits. The stenosis was released after 1 h, allowing sufficient time for clot vessel wall interaction. Occlusion was confirmed and each vessel was assigned to receive either balloon angioplasty alone, intra-arterial tissue plasminogen activator (tPA, Alteplase, Genentech, San Francisco, California, USA), tPA delivery through prototype balloon infusion wire (NIT Therapeutics, Pittsburgh, Pennsylvania, USA), partial stent deployment or partial stent deployment with locally delivered tPA. The negative control received no treatment.Results In vivo revascularization Thrombolysis in Cerebral Infarction (TICI) score revealed that the balloon infusion wire achieved a stable and higher revascularization score of TICI 2B, with a lower dose of tPA in comparison with other treatment strategies. All treatment strategies resulted in endothelial denudation and exposure of the internal elastic lamina.Conclusions The proposed animal model permits reliable and consistent thromboembolic occlusion of the target vasculature and allows for an assessment of both pharmacologic and mechanical revascularization strategies for acute ischemic stroke.