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用于脑动静脉畸形的非粘性液体栓塞剂:猪奇网的初步组织病理学研究

Nonadhesive liquid embolic agent for cerebral arteriovenous malformations: preliminary histopathological studies in swine rete mirabile.

作者信息

Murayama Y, Viñuela F, Ulhoa A, Akiba Y, Duckwiler G R, Gobin Y P, Vinters H V, Greff R J

机构信息

Division of Interventional Neuroradiology, and Leo G. Rigler Radiological Research Center, University of California, Los Angeles, School of Medicine 90024, USA.

出版信息

Neurosurgery. 1998 Nov;43(5):1164-75. doi: 10.1097/00006123-199811000-00081.

DOI:10.1097/00006123-199811000-00081
PMID:9802860
Abstract

OBJECTIVE

To assess acute and chronic histopathological changes observed in a swine arteriovenous malformation model after endovascular delivery of Embolyx E (Micro Therapeutics Inc., San Clemente, CA) and its organic solvent dimethyl sulfoxide (DMSO). To develop standard endovascular delivery techniques of Embolyx through microcatheters into swine rete mirabile (RMB).

METHODS

Forty RMBs in 22 swine were used to analyze acute and chronic angiographic and histological changes after superselective delivery of Embolyx E and/or its organic solvent (DMSO). Four RMBs (two for DMSO and two for Embolyx E study) were used as control specimens. Angiographic and histological evaluations were obtained 18 days, 1 month, 3 months, and 6 months after the procedure. Particular attention was paid to the presence of focal or diffuse angionecrosis, arterial revascularization, and perivascular inflammatory response.

RESULTS

Staged and/or continuous delivery of Embolyx E were performed through the DMSO-compatible microcatheters without untoward catheter "gluing." All subacute/chronic specimens embolized with Embolyx E showed no evidence of angiographic recanalization. Twelve RMBs were used in acute studies, and all specimens showed no evidence of angionecrosis or aggressive inflammatory reaction. Subacute and chronic (total, n = 14) histological examinations of the RMBs showed mild inflammatory response manifested by monocellular infiltration and scattered foreign body giant cell reaction. In the 9 of 14 subacute and chronic specimens, focal disruption of elastica was observed along with embolic materials. Fourteen RMBs in eight swine were used to determine the safety range for DMSO injection. Two RMBs were used as control specimens. Rapid intra-arterial delivery (0.5 ml/5-15 s, n = 6) of DMSO caused angiographic vasospasm and histological endothelial necrosis. Slow injection (0.5 ml/30-120 s, n = 8) of DMSO showed minimum or no angiographic vasospasm, minimal adventitial inflammatory response, and no clinical complications.

CONCLUSION

Embolyx E, an occlusive and nonadhesive embolic agent, is capable of producing permanent occlusion of swine RMB with the development of mild intra- and perivascular inflammatory changes and no clinical complications. The slow endovascular delivery of DMSO produces no untoward angiographic, pathological, or clinical changes. A fast injection of DMSO causes endothelial necrosis and severe inflammatory response in the arterial wall. This embolic material seems to have appropriate biochemical, anatomic, and histopathological characteristics to be used in the treatment of cerebral arteriovenous malformations or vascular cranial base tumors.

摘要

目的

评估在猪动静脉畸形模型中,经血管内递送Embolyx E(微治疗公司,加利福尼亚州圣克莱门特)及其有机溶剂二甲基亚砜(DMSO)后观察到的急性和慢性组织病理学变化。开发通过微导管将Embolyx输送到猪奇网(RMB)的标准血管内递送技术。

方法

使用22头猪的40个RMB来分析Embolyx E和/或其有机溶剂(DMSO)超选择性递送后的急性和慢性血管造影及组织学变化。4个RMB(2个用于DMSO研究,2个用于Embolyx E研究)用作对照标本。在操作后18天、1个月、3个月和6个月进行血管造影和组织学评估。特别关注局灶性或弥漫性血管坏死、动脉再血管化和血管周围炎症反应的存在。

结果

通过与DMSO兼容的微导管进行Embolyx E的分阶段和/或连续递送,未出现不良的导管“粘连”。所有用Embolyx E栓塞的亚急性/慢性标本均未显示血管造影再通的证据。12个RMB用于急性研究,所有标本均未显示血管坏死或侵袭性炎症反应的证据。RMB的亚急性和慢性(共14个)组织学检查显示轻度炎症反应,表现为单核细胞浸润和散在的异物巨细胞反应。在14个亚急性和慢性标本中的9个中,观察到弹性组织的局灶性破坏以及栓塞物质。8头猪中的14个RMB用于确定DMSO注射的安全范围。2个RMB用作对照标本。DMSO的快速动脉内递送(0.5 ml/5 - 15秒,n = 6)导致血管造影血管痉挛和组织学内皮坏死。DMSO的缓慢注射(0.5 ml/30 - 120秒,n = 8)显示最小或无血管造影血管痉挛、最小的外膜炎症反应且无临床并发症。

结论

Embolyx E是一种闭塞性和非粘性栓塞剂,能够使猪RMB产生永久性闭塞,伴有轻度血管内和血管周围炎症变化且无临床并发症。DMSO的缓慢血管内递送不会产生不良的血管造影、病理或临床变化。快速注射DMSO会导致内皮坏死和动脉壁严重炎症反应。这种栓塞材料似乎具有适用于治疗脑动静脉畸形或颅底血管肿瘤的合适生化、解剖和组织病理学特征。

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