Endovascular external carotid artery occlusion for brain selective targeting: a cerebrovascular swine model.

Endovascular external carotid artery occlusion for brain selective targeting: a cerebrovascular swine model.
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DOI:
10.1186/s13104-015-1714-7
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发表时间:
2015-12-21
期刊:
影响因子:
1.8
通讯作者:
Pile-Spellman J
Pile-Spellman J
中科院分区:
其他
文献类型:
--
作者:
Mangla S;Choi JH;Barone FC;Novotney C;Libien J;Lin E;Pile-Spellman J

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脑血管研究动物模型的选择通常取决于要研究的疾病亚型(例如缺血性中风、出血、创伤)以及要测试的干预措施的性质(即医疗设备或药物)。许多初步研究都是在较小的动物身上进行的,因为它们具有成本效益,而且它们的脑脉管系统与人类的脑脉管系统非常接近。 当需要更高级别的确认或验证以及测试更大的设备时,也会使用非人类灵长类动物。然而,灵长类动物的研究既复杂又昂贵。中等大小的动物模型,例如猪和羊,可能代表了一种有价值的妥协。然而,由于天然的较高外颈动脉灌注和奇迹网的存在,它们的脑血管解剖结构面临着挑战。我们描述了对传统猪脑血管模型的修改,显着增强了选择性脑半球灌注,限制了颈外动脉灌注和稀释。我们研究了猪的外颈动脉分支的单侧血管内弹簧圈栓塞是否会导致脑灌注增加,改变脑循环,从而更接近地模拟人类脑循环。在栓塞前后将等量约4°C的冷盐水注射到6只约克夏猪的同侧颈总动脉中。获得栓塞前后的半球温度变化作为脑灌注的测量值,并使用非参数统计检验(Wilcoxon 符号秩检验、Mann-Whitney U 检验)进行平均和比较。根据半球温度随时间的绝对变化绘制图表,以确定冷推注后的峰值温降 (PTD) 和相应的达到峰值时间 (TTP)。栓塞后同侧大脑冷却增加了 288 ± 90%,表明由于这种血管改变,流向大脑的选择性血流有所改善。我们开发了一种有效的、选择性的猪血管脑模型,可作为实用且降低成本的中间步骤,用于评估中枢神经系统药物的目标剂量反应和大脑选择性干预(例如局部低温)。本文的在线版本 (doi:10.1186/s13104-015-1714-7) 包含补充材料,可供授权用户使用。
The choice of an animal model for cerebrovascular research is often determined by the disease subtype to be studied (e.g. ischemic stroke, hemorrhage, trauma), as well as the nature of the intervention to be tested (i.e. medical device or pharmaceutical). Many initial studies are performed in smaller animals, as they are cost-effective and their encephalic vasculature closely models that of humans. Non-human primates are also utilized when confirmation or validation is required on higher levels and to test larger devices. However, working with primates is complex and expensive. Intermediate sized animal models, such as swine and sheep, may represent a valuable compromise. Their cerebrovascular anatomy, however, comes with challenges because of the natural higher external carotid artery perfusion and the existence of a rete mirabile. We describe a modification to the traditional swine cerebrovascular model that significantly enhances selective brain hemispheric perfusion, limiting external carotid perfusion and dilution. We investigated whether unilateral endovascular coil-embolization of external carotid artery branches in swine would lead to increased brain perfusion, altering cerebral circulation so that it more closely models human cerebral circulation. Equal amounts of approximately 4 °C cold saline were injected in 6 Yorkshire pigs into the ipsilateral common carotid artery before and after embolization. Hemispheric temperature changes from pre- and post-embolization were obtained as a measure of brain perfusion and averaged and compared using non-parametric statistical tests (Wilcoxon signed rank test, Mann–Whitney U Test). Graphs were plotted with absolute changes in hemispheric temperature over time to determine peak temperature drop (PTD) and corresponding time to peak (TTP) following the cold bolus injection. There was a 288 ± 90 % increase in ipsilateral brain cooling after embolization indicating improved selective blood flow to the brain due to this vascular modification. We have developed an effective, selective vascular brain model in swine that may be useful as a practical and cost-reducing intermediate step for evaluating target dose–responses for central nervous system drugs and brain selective interventions, such as local hypothermia. The online version of this article (doi:10.1186/s13104-015-1714-7) contains supplementary material, which is available to authorized users.