生物可降解镁支架治疗大鼠囊动脉瘤的实验研究--手术技术介绍
Özet
Reproducable 实验动物模型是需要的测试新的栓塞材料, 这是设计的治疗腔内闭塞动脉瘤 (IA)。本研究旨在建立一种安全、规范的手术方法, 在大鼠动物模型中囊动脉瘤支架栓塞术。
Abstract
在医疗的稳定进展, 可用于血管内治疗动脉瘤需要负担得起和 reproducable 实验动物模型, 以测试新的栓塞材料, 如支架和流分流。本项目的目的是设计一种安全, 快速, 标准化的外科技术, 支架辅助栓塞囊动脉瘤大鼠动物模型。
囊动脉瘤是从降主动脉动脉移植产生的。通过端侧吻合 microsurgically 移植下腹主动脉, 同雄性大鼠重度 > 500 克。动脉瘤吻合后, 采用气囊可膨胀镁支架 (2.5 毫米 x 6 毫米) 进行动脉瘤栓塞。采用改良 Seldinger 技术, 从下腹主动脉逆行引入支架系统。
根据6只动物的试验系列, 共有67只老鼠按照既定的标准操作程序操作。平均手术时间、平均吻合时间、动脉穿刺部位的平均缝合时间分别为167±22分钟、26±6分钟和11±5分钟。死亡率为 6% (n=4)。发病率为 7.5% (n=5), 并在4例中发现支架内血栓形成 (n=2 早, n=2 晚期在支架血栓形成中)。
结果表明, 在低发病率和死亡率的情况下, 标准化支架阻断囊侧壁动脉瘤的可行性。该支架栓塞术结合了机会, 研究新概念的支架或流动分流器的基础设备, 以及分子方面的愈合。
Introduction
由于颅内动脉瘤破裂引起的蛛网膜下腔出血与许多幸存者的高死亡率和不良神经结局有关。目前有两种咬合 IA 的一般方法: 显微外科切除术 (需要手术暴露动脉瘤), 或血管内闭塞。由于微创血管内线圈治疗狭窄颈 IA 已证明是与轻微低发病率 (特别是在后循环1,2), 血管内治疗方案已成为许多神经外科中心的首选模式。为了扩大血管内治疗的适应症, 克服了卷取后 IA 复发的主要缺陷, 研制了多种装置。颅内支架是特别有希望克服这些限制, 因为他们作为一个支架的新 endothelization 和线圈疝预防, 以及保护家长动脉和改善腔 intraaneurysmal 血栓引起的减少血液流入。在低成本动物模型中, 需要研究新型颅内支架;在宏观和分子水平。
本研究的目的是设计一个安全, 快速, 标准化的外科技术支架应用在已经建立的大鼠囊动脉瘤模型3,4,5。在本项目中, 我们评估了一个可生物降解的镁支架的作用。
Protocol
平均重量为592克 (±50 SD) 和平均年龄为20周的雄性大鼠被安置在动物设施, 室温为22-24 ° c 和十二小时的光/暗循环, 免费获得自来水和颗粒饲料。动物接受了关心从人与机构指南符合。这些实验得到了瑞士伯尔尼动物保育委员会 (102/13) 的批准。我们严格遵循动物研究的建议: 报告的在体内实验 (到达指南)。 1. 实验室设备、耗材、外科器械 使用一个安静, 无菌操作?…
Representative Results
手术的平均持续时间为 167 (± 22) min, 26 (± 6) 分钟, 这是动脉瘤的产生所需的, 另外 23 (± 7) 最小的支架应用和重建的切开 (图 3)。 死亡率, 发病率, 和宏观内支架血栓是该研究的主要终点。定期随访期分别为7天 (n=28) 和21天 (n=32)。死亡或多事的发病率导致该研究提早终止。手术中没有死亡。四动物 (6%) 在术?…
Discussion
吸收支架和动物模型
近年来, 医学的普遍趋势是远离永久性的植入物 (在病人的身体中保留终生) 到生物可吸收的材料。镁支架, 特别是, 已经相当建立在心脏病学8,9。不幸的是, 这些支架尚未被测试的其他应用, 如脑血管疾病。因此, 我们决定研究吸收支架在囊动脉瘤治疗中的实用性。这项研究是与老鼠一样的, 因为它们像其他的小实验动?…
Açıklamalar
The authors have nothing to disclose.
Acknowledgements
我们感谢 Eugen 霍夫曼和 Philine Zumstein 的卓越技术援助, 并分享他们在支架应用程序方面的专长。我们感谢 Majlinda Kalanderi 的解剖图纸。
Materials
| Medetomidine | any generic | ||
| Ketamin | any generic | ||
| Buprenorphine | any generic | ||
| Phosphate buffered saline | |||
| Sodium dodecyl sulfate (0.1%) | |||
| 3-0 resorbable suture | Ethicon Inc., USA | VCP428G | |
| 5-0 non absorbable suture | Ethicon Inc., USA | 8618G | |
| 6-0 non-absorbable suture | B. Braun, Germany | C0766070 | |
| 9-0 non-absorbable suture | B. Braun, Germany | G1111140 | |
| 10-0 non-absorbable suture | Covidien, USA | N2530 Monosof | |
| Operation microscope | Zeiss, Germany | ||
| Digital microscope camera | Sony, Japan | HXR-MC1P | |
| Standard surgical instruments | multiple | see protocol 7.a | |
| Microsurgical instruments | multiple | see protocol 7.b | |
| Vascular clip applicator | B. Braun, Germany | FT495T | |
| Temporary vascular clamps | B. Braun, Germany | ||
| 19G Puncture needle | Angiomed GmbH, Germany | 15820010 | |
| Hydrophobic guide wire | Cook Medical, USA | G00650 | |
| 4F sheat | Cordis Corporation, USA | 504-604A | |
| Inflation syringe | |||
| Laboratory shaker | Stuart | SRT6 | |
| Magnesium Stent 2.5/6 AMS with Polymer coating | Biotronik, Switzerland | ||
| Surgery drape | |||
| Sterile cellulose swabs | |||
| Syringes 1 ml and 2 ml | |||
| Hollow needles 18G and 26G | |||
| Isotonic sodium chloride | |||
| Microtubes | |||
| Eye ointment | Bausch + Lomb Inc, USA | Lacrinorm | any generic |
| Small animal shaver |
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Bu Makaleden Alıntı Yapın
Nevzati, E., Rey, J., Coluccia, D., D’Alonzo, D., Grüter, B., Remonda, L., Fandino, J., Marbacher, S. Biodegradable Magnesium Stent Treatment of Saccular Aneurysms in a Rat Model – Introduction of the Surgical Technique. J. Vis. Exp. (128), e56359, doi:10.3791/56359 (2017).