New England Center for Stroke Research, Department of Radiology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
St George's University School of Medicine, Grenada, West Indies.
J Neurointerv Surg. 2019 Dec;11(12):1243-1248. doi: 10.1136/neurintsurg-2019-014969. Epub 2019 May 18.
To develop a preclinical model of stroke with a large vessel occlusion treated with mechanical thrombectomy.
An ischemic stroke model was created in dogs by the introduction of an autologous clot into the middle cerebral artery (MCA). A microcatheter was navigated to the clot and a stent retriever thrombectomy was performed with the goal to achieve Thrombolysis in Cerebral Ischemia (TICI) 2b/3 reperfusion. Perfusion and diffusion MRI was acquired after clot placement and following thrombectomy to monitor the progression of restricted diffusion as well as changes in ischemia as a result of mechanical thrombectomy. Post-mortem histology was done to confirm MCA territory infarct volume.
Initial MCA occlusion with TICI 0 flow was documented in all six hound-cross dogs entered into the study. TICI 2b/3 revascularization was achieved with one thrombectomy pass in four of six animals (67%). Intra-procedural events including clot autolysis leading to spontaneous revascularization (n=1) and unresolved vasospasm (n=1) accounted for thrombectomy failure. In one case, iatrogenic trauma during microcatheter navigation resulted in a direct arteriovenous fistula at the level of the cavernous carotid. Analysis of MRI indicated that a volume of tissue from the initial perfusion deficit was spared with reperfusion following thrombectomy, and there was also a volume of tissue that infarcted between MRI and ultimate recanalization.
We describe a large animal stroke model in which mechanical thrombectomy can be performed. This model may facilitate, in a preclinical setting, optimization of complex multimodal stroke treatment paradigms for clinical translation.
建立一种采用机械取栓治疗的大血管闭塞性卒中的临床前模型。
通过将自体血栓引入大脑中动脉(MCA),在犬中创建缺血性卒中模型。将微导管导航至血栓处,并进行支架取栓术,以实现血栓溶解(TICI)2b/3 再灌注。在放置血栓后和取栓后采集灌注和弥散 MRI,以监测受限弥散的进展以及机械取栓引起的缺血变化。进行死后组织学检查以确认 MCA 区域梗死体积。
在纳入研究的 6 只猎犬中,所有动物均出现初始 MCA 闭塞伴 TICI 0 血流。在 6 只动物中的 4 只(67%)中,通过一次取栓操作实现了 TICI 2b/3 再通。术中事件包括血栓自溶导致自发再通(n=1)和未解决的血管痉挛(n=1),导致取栓失败。在 1 例中,微导管导航过程中的医源性创伤导致在海绵窦颈动脉水平形成直接动静脉瘘。MRI 分析表明,在取栓后再灌注时,初始灌注缺损的组织中有一部分得以保留,并且在 MRI 和最终再通之间还有一部分组织发生梗死。
我们描述了一种可进行机械取栓的大动物卒中模型。该模型可在临床前环境中促进复杂多模态卒中治疗方案的优化,以便进行临床转化。