In vivo model of intracranial stent implantation: a pilot study to examine the histological response of cerebral vessels after randomized implantation of heparin-coated and uncoated endoluminal stents in a blinded fashion
In vivo model of intracranial stent implantation: a pilot study to examine the histological response of cerebral vessels after randomized implantation of heparin-coated and uncoated endoluminal stents in a blinded fashion
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DOI：
10.3171/jns.2003.98.3.0544
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发表时间：
2003-03-01
影响因子：
4.1
通讯作者：
Hopkins, LN
中科院分区：
文献类型：
--
作者：
Levy, EI;Boulos, AS;Hopkins, LN
Object.目前还没有动物模型用于检查颅内血管腔内支架置入后发生的时间依赖性组织学变化。作者的目标是开发一种可重复的犬颅内血管支架植入体内模型，该模型能够证明植入涂层和未涂层器械后支架相关的血管变化。作者在11只杂种犬的基底动脉（BA）中植入肝素涂层或无涂层支架。在第12只动物中，将一枚涂层支架植入BA，将另一枚无涂层支架植入远端前脊髓动脉。所有器械尺寸过大，导致内膜损伤。存活的动物观察12周，之后在计划死亡和切除大脑之前进行重复的血管造影。对支架处理和未处理的BA切片进行组织学研究和计算机辅助形态测定分析，以评估狭窄、新生内膜增生、血管损伤和炎症的百分比。研究了部分被支架支柱覆盖的穿孔血管（“监禁”）的狭窄或闭塞证据。病理学家、介入医生、组织病理学家、组织病理学技术人员和放射科医生对支架类型不知情，在随访期间从观察的6只动物中取出7枚支架（3枚无涂层支架和4枚有涂层支架）。无涂层支架组的平均新生内膜增生为0.42 mm（2），肝素涂层器械组为0.18 mm（2）（p = 0.04）。无涂层支架组的新生内膜厚度显著增加（p = 0.04）。肝素涂层支架组的平均闭塞百分比较低（12%），而无涂层器械组为22%（p = 0.07）。当比较仅植入单枚支架的5只动物中植入的肝素涂层和无涂层器械的结果时，在新生内膜面积（p = 0.009）、新生内膜/中膜比（p = 0.001）、新生内膜厚度（p = 0.002）和闭塞百分比（p = 0.009）方面观察到更大的差异（表明肝素涂层支架的受益）。所有脑干穿支血管均保持通畅。开发了该体内颅内支架模型，以评估颅内血管系统中腔内支架植入的增殖和炎症反应。结果表明，与未涂层支架相比，肝素涂层支架植入后12周发生闭塞的百分比较低。
Object. No animal model currently exists for the examination of time-dependent histological changes occurring in intracranial vessels after endoluminal stent placement. The authors' goal was to develop a reproducible in vivo model of stent implantation in intracranial vessels in dogs that was capable of demonstrating stent-related vascular changes after the implantation of coated and uncoated devices.Methods. The authors implanted heparin-coated or uncoated stents in the basilar arteries (BAs) of 11 mongrel dogs. In a 12th animal, one coated stent was implanted in the BA and a second uncoated one was implanted in the distal anterior spinal artery. All the devices were oversized to induce intimal injury. Surviving animals were observed for 12 weeks, after which they underwent repeated angiography before planned death and removal of the brain. Histological studies and computer-assisted morphometric analyses were conducted on stent-treated and untreated sections of the BAs to assess the percentage of stenosis, neointimal proliferation, vessel injury, and inflammation. Perforating vessels partially covered by stent struts ("jailing") were studied for evidence of stenosis or occlusion. The pathologist, interventionists, histopathologist, histopathology technicians, and radiologist were blinded to the stent type.Seven stents (three uncoated and four coated) were removed from the six animals that were observed during the follow-up period. The mean neointimal proliferation was 0.42 mm(2) in the group treated with uncoated stents and 0.18 mm(2) in the group treated with heparin-coated devices (p = 0.04). Neointimal thickness was significantly increased in the group with uncoated stents (p = 0.04). The mean percentage of occlusion was less (12%) in the group with heparin-coated stents, compared with 22% in the group with uncoated devices (p = 0.07). When comparing results between the heparin-coated and uncoated devices implanted in the five animals that received a single stent only, greater differences (indicating a benefit from heparin-coated stents) were observed in neointimal area (p = 0.009), neointima/media ratio (p = 0.001), neointimal thickness (p = 0.002), and percentage of occlusion (p = 0.009). All brainstem perforating vessels covered by stent struts remained patent.Conclusions. This in vivo intracranial stent model was developed to assess proliferative and inflammatory responses to endoluminal stent implantation in the cerebrovasculature. The results indicate that a lower percentage of occlusion occurs 12 weeks after implantation of heparin-coated compared with uncoated stents.