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。

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
<ol><li>使用一个安静, 无菌操作室和保持温度在23±3° c。</li>
	<li>使用一个易于清洁和消毒的表面的手术台, 并覆盖它与手术的褶皱。在手术前和术后, 用一台摄像头的手术显微镜记录手术和红外线来温暖动物。</li>
	<li>获取以下耗材以创建侧壁动脉瘤并植入支架。<ol>
<li>获取更小和更大的无菌纤维素和纱布拭子, 注射器与18G 和26G 空心针和钝的倾斜的针为灌溉或容量替换。</li>
		<li>获得缝合材料, 包括吸收10-0 和9-0 显微缝合, 吸收6-0 和5-0 缝合, 可吸收3-0 缝合。</li>
		<li>为灌溉/容积置换获得0.9% 张氯化钠溶液, 确保手术过程中器械的清洁</li>
	</ol>
</li>
	<li>获得以下器械植入支架: 穿刺针 19G, 疏水导丝, 4 Fogaty 鞘, 和充气注射器的气球扩张。</li>
	<li>获得以下耗材为动脉瘤壁细胞:<ol>
<li>获得管内动脉瘤贮存在-24 ° c 和标识的标签, 以及实验室的振动筛, 以确保动脉瘤的全面化学治疗。</li>
		<li>获得0.1% 十二烷基硫酸钠 (SDS) 和磷酸盐缓冲盐水 (PBS) 为适当的细胞过程。</li>
	</ol>
</li>
	<li>获得下列标准手术器械:<ol>
<li>获得较粗的手术器械: 外科剪刀, 软组织钳, 软组织吊具, 直和弯曲钳, 三蚊钳, 针架。</li>
		<li>获得外科手术器械: 直和弯曲微剪刀, 直和弯曲微钳, 和四临时血管小夹子与相应的血管夹喷头。</li>
	</ol>
</li>
</ol>2. 麻醉
<ol><li>将大鼠放在气体室中, 麻醉, 混合异氟醚和氧 (4% 异氟醚)。保持吸入, 直到动物失去知觉。</li>
	<li>将麻醉动物从气室中取出, 并注入最终麻醉, 由盐酸 medetomidine (0.5 毫克/千克) 和盐酸氯胺酮 (50 毫克/千克) 的重量适应混合物 (通过注射到右侧或左下腹)。</li>
	<li>在手术过程中, 用有害的脚趾按压来监测麻醉深度, 以确认老鼠没有反应, 完全麻醉。如果有一个脚趾捏反射, readminster 的麻醉与重量适应腹腔注射氯胺酮和 medetomidine。在打开腹腔前需要足够的麻醉, 并进行端侧吻合和支架插入。</li>
	<li>将大鼠置于红外线加热灯下, 直到腹腔麻醉生效, 因为术前加温有效地避免了手术期间的广泛降温。</li>
</ol>3. 大鼠的外科准备和定位
<ol><li>称量大鼠, 提取舌头, 以确保上呼吸道, 并应用眼膏, 以避免角膜干燥。</li>
	<li>用胶带将老鼠固定在一个小的可洗的板子上, 避免对爪子施加任何压力或牵引。</li>
	<li>用小的动物剃须刀在操作区刮毛老鼠, 消毒手术区域。</li>
	<li>将两个厚的标记2-3 厘米分开的动物的背部, 使尽可能多的腰椎和胸腰椎前尽可能。这将确保更好地阐述后和更容易应用的支架。</li>
	<li>用无菌孔径褶皱覆盖大鼠, 并将其置于操作显微镜下。在动物旁边设置两个支撑物, 以利于实验者的双手更舒适的位置。</li>
	<li>洗手, 消毒, 戴上无菌手套。这是有用的, 有一个助理出席, 特别是为支架植入。</li>
	<li>根据实验室动物的建议, 在无菌条件下进行手术6,7。</li>
</ol>4. 动脉瘤接枝收获
<ol><li>全麻下, 在剑过程下开腹。首先, 用锋利的剪刀将 midventral 线上的皮肤切开, 并将皮肤从肌组织中分离出来。然后切开腹部肌组织, 并在胸腔的插入点处发现肝脏上方的隔膜。</li>
	<li>切开膜片和结缔组织用锋利的剪刀进入胸腔和切开肋骨用大剪刀一和半厘米在胸骨的右边和左边。</li>
	<li>当胸腔打开时, 用盐酸氯胺酮的心内剂量 (120 毫克/千克) 牺牲大鼠。</li>
	<li>在纤维素拭子的帮助下, 动员左肺并将其固定在右侧。</li>
	<li>在适当暴露的主动脉弧, 钳夹奇和左颅静脉静脉与两个蚊子钳以上的主动脉和切割之间。将夹钳留在切口末端, 避免逆行静脉出血。使用钳移动心脏和静脉的一侧, 使更好地获得主动脉弧和降主动脉。</li>
	<li>用显微剪刀和微钳技术对主动脉进行解剖。</li>
	<li>从降节向上追踪主动脉, 确定左锁骨下动脉和第一肋间动脉离开主动脉。</li>
	<li>放置一个吸收6-0 缝合只是第一肋间动脉的头骨, 并把它绑起来。在近端, 切断左锁骨下动脉原点后的主动脉。重要的是要使用单一的垂直切口, 因为它降低了在切割边缘的血管移植的不规则的机会。最后, 删除新创建的动脉瘤, 切口就在绷带下面。</li>
	<li>在测量动脉瘤后, 立即将移植物移植到受体鼠体内。</li>
</ol>5. 动脉瘤的产生和支架的应用
<ol><li>手术方法<ol>
<li>用锋利的剪刀开始腹部远端的切口, 并在剑过程的远端 midventral 1 厘米的位置切割。小心地将皮肤和皮下组织从肌肉组织中分离出来。使用相同的剪刀打开腹部肌肉沿式阿尔巴。用镊子在切割时提高肌肉, 以避免损伤腹中器官。</li>
		<li>在剖腹手术后, 把小肠、盲肠和结肠移到右侧。使用自牵引器保持腹腔开放和修复器官。将棉签放在肝脏下方, 将其从手术区取出, 并增强腹膜后暴露。 注意: 如果脂肪体挡住了视线, 它可以放在腹腔外, 用湿纱布覆盖, 以避免大量的液体耗尽。</li>
		<li>排空膀胱以达到最大暴露下腹主动脉。这可以通过温和的压力膀胱壁, 或膀胱放电使用26G 空心针。</li>
		<li>保护膀胱和睾丸的脱水和广泛的操作, 在手术期间, 覆盖他们与湿无菌纤维素棉签。</li>
		<li>用两个钝钳打开覆盖腹主动脉的壁腹膜。注意几乎透明的输尿管、睾丸血管和肠系膜上动脉。一旦腹膜壁打开, 腹主动脉就会位于它的下方。它经常被一层薄薄的脂肪组织所覆盖。</li>
		<li>从腹部主动脉的钝性解剖开始, 用两个微钳将其从周围的腹膜后脂肪中释放出来, 直到血管的长长可见。继续使用微剪刀和微钳进行尖锐解剖。在这个过程中, 只有掌握膜, 以避免损坏容器壁。</li>
	</ol></li>
	<li>腹主动脉夹层 注意: 为了便于描述手术策略, 我们将腹主动脉分为三不同的部分 (图 1)。<ol>
<li>在远端段开始解剖-这在技术上更具挑战性。 注意: 远端段被细分为髂分岔和髂静脉和动脉。这段作为远端腹主动脉穿刺和支架插入的点。<ol>
<li>在两个血管的动脉外层的旁边切割, 用微剪刀和微钳从 v 静脉解剖主动脉。 注意: 小的腰椎动脉可能不常出现在腹主动脉背侧表面的节段血管中, 并干扰手术过程。血管的凝固和切割需要避免血管缝合时的逆行渗出。</li>
			<li>确定右髂动脉;它的起源可能在这段中有很大的差异, 但最常见的是更多的尾部比左相对。 注意: 这种情况很少干扰计划内支架插入穿刺部位的动脉, 但可能需要更远的穿刺点切除或-为最极端的解剖变异-血管结扎右髂动脉。</li>
			<li>在本段中准备主动脉后, 在血管下面放置一个小的彩色橡皮垫, 以指示动脉穿刺的位置。避免在这段中拉伸容器。血管壁上的拉伸会导致动脉穿刺后不受控制的血管破裂, 进而阻碍最终的重建。因此, 从动脉穿刺部位的所有粘连中释放主动脉并避免在主动脉下方放置纱布拭子是很重要的。</li>
		</ol>
</li>
		<li>解剖的主动脉从 v 静脉在中间部分与前面描述的相同的方式。 注意: 中间部分分为髂静脉和肾静脉。这段是用于动脉瘤植入和支架定位。<ol>
<li>从腹主动脉中鉴别肠系膜上动脉的来源, 并在所有手术过程中保留它。</li>
			<li>结扎或凝血动脉从主动脉的背表面在本节以及。为了避免腰骶神经丛损伤, 确保足够的冲洗, 并注意短凝血时间。</li>
			<li>在本段的主动脉解剖后建立支架的位置。在确定动脉瘤和支架的最终位置之前, 应预先预测支架与腹血管的可能干扰。</li>
			<li>在建立动脉瘤和支架的位置后, 在主动脉下放置一小块纱布和一个彩色橡胶垫, 以便更好地接触。</li>
		</ol>
</li>
		<li>最后解剖腹主动脉的近段。这在技术上比在远端和中段的相同程序更简单。 注意: 近端段位于肾静脉的近端。用于 Seldinger 技术支架植入术中最近端临时夹片的应用。<ol>
<li>打开壁腹膜后, 用两个钝钳将血管分离。</li>
			<li>在背环球的主动脉与弯曲, 钝钳, 放置在它下面的一个小块的彩色橡胶垫, 以方便以后的近端剪辑应用。</li>
		</ol>
</li>
	</ol></li>
	<li>动脉瘤的产生
	<ol>
<li>在中间部分先用远端钳夹住主动脉, 其次是近端, 以确保容器的稳固充填, 并便于随后的切开。</li>
		<li>在计划的吻合点处切除膜。用微钳抓膜, 用微剪刀小心切割, 不伤容器壁。</li>
		<li>用微钳提起一小块容器壁, 用微剪刀进行线性切口。切开应与动脉瘤基底大小相同。</li>
		<li>用钝尖的针头将两个方向的动脉冲洗成生理盐水。</li>
		<li>放置前两针的端侧吻合, 这是执行与吸收9-0 缝合, 在近端和远端的切开。在缝合过程中尽可能少地抓住容器壁, 确保缝合线穿过容器壁的每一层。它们只应抓住主动脉腹侧部分, 以避免动脉狭窄;这可能导致血管破裂在支架应用。</li>
		<li>用间断缝合线闭合切口。从左边开始缝合, 然后继续到另一侧。当后壁完成后, 检查腔段的吻合处错误放置缝合线。 注意: 在这一点上, 可以引入不同的 intra-aneurysmal 疗法, 如线圈应用。</li>
		<li>完成吻合后, 先取下远端钳。放置额外的缝合线以防大出血。通过轻轻按压一小块纱布, 使出血源头管理小的渗出。脂肪组织或以前获得的外层也可以是有用的。现在去掉近端钳。</li>
		<li>冲洗的吻合部位, 并削减在动脉瘤圆顶绷带的剩余两端。</li>
		<li>用直接挤奶试验观察远端腹主动脉通畅。</li>
		<li>取下彩色橡皮垫下面的小纱布拭子, 因为在支架插入之前, 主动脉的所有段都应大致在相同的高度。避免用脂肪组织覆盖吻合缝合线, 因为支架在新造的动脉瘤下定位支架时必须可见。</li>
		<li>为了避免长期缺血造成的损伤, 在继续进行近端主动脉夹紧和支架插入之前, 允许10分钟再灌注。</li>
		<li>在植入支架前清空膀胱。</li>
	</ol></li>
	<li>支架植入 注意: 有一个助手手头上的步骤是有用的, 特别是对于最终的支架充气。<ol>
<li>先夹住远端段的动脉穿刺部位。从远端钳位开始, 并跟随近端。用微剪刀将疏松的结缔组织和 (部分) 膜在穿刺部位。</li>
		<li>在近端部放置一个大的临时钳夹, 避免动脉穿刺时大出血。</li>
		<li>用18G 穿刺针在远端段进行动脉穿刺。用微钳提起血管壁的小块, 以方便穿刺, 减少刺穿两个主动脉血管壁的风险。</li>
		<li>用钝尖的针头在两个方向上彻底冲洗动脉后用生理盐水。</li>
		<li>将疏水导丝插入穿刺部位, 并将下部夹钳移至远端段。</li>
		<li>将导丝向前推至近段的钳位水平。插入聚四氟乙烯介绍人根据 Seldinger 技术使用以前插入的指南导线。 注: 疏水性导丝比亲水的导线更合适, 因为它们具有优越的握持力, 并提供更好的手动控制。由于聚四氟乙烯引荐更容易插入比聚丙烯引荐, 他们减少了在穿刺现场失控的破裂的风险。</li>
		<li>将扩张向上推到吻合部位, 鞘位于下面半厘米处。</li>
		<li>取下导丝和扩张, 确保3路塞关闭, 以避免不必要的失血。</li>
		<li>在清空气球系统后, 用4福格蒂介绍人插入可吸收的镁支架。在除去介绍人装置之前, 用一条压力充气气球, 以保护折叠容器的内皮, 使其免受支撑损伤, 并降低在先前植入的 intraaneurysmal 中的支撑力变得纠缠的风险。材料 (图 2)。</li>
		<li>当支架处于其最后位置时, 小心充气气球与8-9 巴。持续检查端侧吻合缝合线是否可能撕裂。</li>
		<li>在适当的支架扩张和粘附到主动脉血管壁后, 放气并取出气球。</li>
		<li>当去除介绍人, 有一个临时夹子在手边为直接应用近接近于穿刺地点, 因为逆行渗出从近端的专利动脉可能是重要的。</li>
		<li>将下部夹放在远端段后, 取下下部段的临时夹钳。观察端侧吻合, 因为远端修剪引起的搏血压增加可能导致缝合部位出血。</li>
		<li>从两个方向的钝尖针上冲洗穿刺部位生理盐水。然后用吸收10-0 线程中断的技术缝合它。如有可能, 避免用微钳抓住容器壁, 确保每条缝合线穿过容器壁的所有层。在最血管穿刺部位缝合以避免血管狭窄。</li>
		<li>如果因回流而导致大出血, 则增加额外的缝合线。在轻微渗出的情况下, 通过用纱布拭子或先前保存的膜的部分, 通过温和的压力对出血部位进行安全止血。小块脂肪组织也有帮助。</li>
		<li>取下穿刺部位下面的彩色橡胶垫。主动脉的搏动在吻合口的近端和远端都清晰可见。用直接挤奶试验检查远端动脉通畅。</li>
	</ol></li>
</ol>6. 关闭
<ol><li>取出所有纱布拭子, 用 isotone 生理盐水轻轻冲洗腹腔, 清除任何杂物, 促进容积置换。</li>
	<li>取出软组织的吊具, 并将小肠、盲肠和脂肪块退回到正确的解剖位置。</li>
	<li>使用吸收5-0 缝合, 加入腹部肌肉。为了减少皮肤牵引, 放置一些皮下缝合使用可吸收3-0 缝合。用同样的3-0 缝合来闭合皮肤。</li>
	<li>关闭后, 消毒皮肤, 并放置在红外线下的动物, 以提供它的温暖。</li>
</ol>

<ol>
	<li>Molyneux, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=International+Subarachnoid+Aneurysm+Trial+(ISAT)+of+neurosurgical+clipping+versus+endovascular+coiling+in+2143+patients+with+ruptured+intracranial+aneurysms:+a+randomised+trial.">International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial.</a> Lancet. 360 (9342), 1267-1274 (2002).</li><li>Molyneux, A. 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S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+bare+metal+stent+and+paclitaxel-eluting+stent+using+a+novel+rat+aorta+stent+model.">Comparison of bare metal stent and paclitaxel-eluting stent using a novel rat aorta stent model.</a> J Vet Sci. 12 (2), 143-149 (2011).</li><li>Rouer, M., Meilhac, O., Delbosc, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+murine+model+of+endovascular+aortic+aneurysm+repair.">A new murine model of endovascular aortic aneurysm repair.</a> J Vis Exp. (77), e50740 (2013).</li><li>Hardhammar, P. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reduction+in+thrombotic+events+with+heparin-coated+Palmaz-Schatz+stents+in+normal+porcine+coronary+arteries.">Reduction in thrombotic events with heparin-coated Palmaz-Schatz stents in normal porcine coronary arteries.</a> Circulation. 93 (3), 423-430 (1996).</li><li>Guerrero, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antioxidant+effects+of+a+single+dose+of+acetylsalicylic+acid+and+salicylic+acid+in+rat+brain+slices+subjected+to+oxygen-glucose+deprivation+in+relation+with+its+antiplatelet+effect.">Antioxidant effects of a single dose of acetylsalicylic acid and salicylic acid in rat brain slices subjected to oxygen-glucose deprivation in relation with its antiplatelet effect.</a> Neurosci Lett. 358 (3), 153-156 (2004).</li><li>Niitsu, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Repeat+oral+dosing+of+prasugrel,+a+novel+P2Y12+receptor+inhibitor,+results+in+cumulative+and+potent+antiplatelet+and+antithrombotic+activity+in+several+animal+species.">Repeat oral dosing of prasugrel, a novel P2Y12 receptor inhibitor, results in cumulative and potent antiplatelet and antithrombotic activity in several animal species.</a> Eur J Pharmacol. 579 (1-3), 276-282 (2008).</li><li>Kastrati, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intracoronary+stenting+and+angiographic+results:+strut+thickness+effect+on+restenosis+outcome+(ISAR-STEREO)+trial.">Intracoronary stenting and angiographic results: strut thickness effect on restenosis outcome (ISAR-STEREO) trial.</a> Circulation. 103 (23), 2816-2821 (2001).</li><li>Lowe, H. 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这项工作得到了研究理事会的研究基金的支持, Kantonsspital Aarau, Aarau, 瑞士。可生物降解的镁支架由瑞士 Buelach 血管介入中心 Biotronik AG 提供。作者完全负责所提出的研究的设计和进行, 并声明没有相互竞争的利益。

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?...

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。

<table><tbody><tr><td>Medetomidine</td><td></td><td></td><td>any generic</td></tr><tr><td>Ketamin</td><td></td><td></td><td>any generic</td></tr><tr><td>Buprenorphine</td><td></td><td></td><td>any generic</td></tr><tr><td>Phosphate buffered saline</td><td></td><td></td><td></td></tr><tr><td>Sodium dodecyl sulfate (0.1%)</td><td></td><td></td><td></td></tr><tr><td>3-0 resorbable suture</td><td>Ethicon Inc., USA</td><td>VCP428G</td><td></td></tr><tr><td>5-0 non absorbable suture</td><td>Ethicon Inc., USA</td><td>8618G</td><td></td></tr><tr><td>6-0 non-absorbable suture</td><td>B. Braun, Germany</td><td>C0766070</td><td></td></tr><tr><td>9-0 non-absorbable suture</td><td>B. Braun, Germany</td><td>G1111140</td><td></td></tr><tr><td>10-0 non-absorbable suture</td><td>Covidien, USA</td><td>N2530 Monosof</td><td></td></tr><tr><td>Operation microscope</td><td>Zeiss, Germany</td><td></td><td></td></tr><tr><td>Digital microscope camera</td><td>Sony, Japan</td><td>HXR-MC1P</td><td></td></tr><tr><td>Standard surgical instruments</td><td></td><td>multiple</td><td>see protocol 7.a</td></tr><tr><td>Microsurgical instruments</td><td></td><td>multiple</td><td>see protocol 7.b</td></tr><tr><td>Vascular clip applicator</td><td>B. Braun, Germany</td><td>FT495T</td><td></td></tr><tr><td>Temporary vascular clamps</td><td>B. Braun, Germany</td><td></td><td></td></tr><tr><td>19G Puncture needle&amp;nbsp;</td><td>Angiomed GmbH, Germany</td><td>15820010</td><td></td></tr><tr><td>Hydrophobic guide wire</td><td>Cook Medical, USA</td><td>G00650</td><td></td></tr><tr><td>4F sheat</td><td>Cordis Corporation, USA</td><td>504-604A</td><td></td></tr><tr><td>Inflation syringe</td><td></td><td></td><td></td></tr><tr><td>Laboratory shaker</td><td>Stuart</td><td>SRT6</td><td></td></tr><tr><td>Magnesium Stent 2.5/6 AMS with Polymer coating</td><td>Biotronik, Switzerland</td><td></td><td></td></tr><tr><td>Surgery drape&amp;nbsp;</td><td></td><td></td><td></td></tr><tr><td>Sterile cellulose swabs</td><td></td><td></td><td></td></tr><tr><td>Syringes 1 ml and 2 ml</td><td></td><td></td><td></td></tr><tr><td>Hollow needles 18G and 26G</td><td></td><td></td><td></td></tr><tr><td>Isotonic sodium chloride</td><td></td><td></td><td></td></tr><tr><td>Microtubes</td><td></td><td></td><td></td></tr><tr><td>Eye ointment</td><td>Bausch + Lomb Inc, USA</td><td>Lacrinorm</td><td>any generic</td></tr><tr><td>Small animal shaver</td><td></td><td></td><td></td></tr></tbody></table>

biodegradable magnesium stent treatment of saccular aneurysms in a rat model - introduction of the surgical technique

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。

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?...

Watch this Scientific Journal Video about Biodegradable Magnesium Stent Treatment of Saccular Aneurysms in a Rat Model - Introduction of the Surgical Technique at JoVE.com

Biodegradable Magnesium Stent Treatment of Saccular Aneurysms in a Rat Model - Introduction of the Surgical Technique

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。

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

The steady progess in the armamentarium of techniques available for endovascular treatment of intracranial aneurysms requires affordable and reproducable ...

biodegradable-magnesium-stent-treatment-saccular-aneurysms-rat-model

Research

JoVE Journal

Neuroscience

11.0K 次观看.  Kantonsspital Aarau. 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。

视频: Biodegradable Magnesium Stent Treatment of Saccular Aneurysms in a Rat Model - Introduction of the Surgical Technique

A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis

Despite the considerable progress made in the stent development in the last decades, cardiovascular diseases remain the main cause of death in western countries. Beside the benefits offered by the development of different drug-eluting stents, the coronary revascularization bears also the life-threatening risks of in-stent thrombosis and restenosis. Research on new therapeutic strategies is impaired by the lack of appropriate methods to study stent implantation and restenosis processes. Here, we describe a rapid and accessible procedure of stent implantation in mouse carotid artery, which offers the possibility to study in a convenient way the molecular mechanisms of vessel remodeling and the effects of different drug coatings.

A model of stent implantation in mouse carotid artery is described. Compared to other similar methods, this procedure is very rapid, simple and accessible, offering the possibility to study in a convenient way the vascular wall reaction to different drug-eluting stents and the molecular mechanisms of restenosis.

颈动脉支架植入再狭窄的研究的小鼠模型

Despite  the considerable progress made in the stent development in the last decades,  cardiovascular diseases remain the main cause of death in western ...

科研

医学

A New Murine Model of Endovascular Aortic Aneurysm Repair

Endovascular aneurysm exclusion is a validated technique to prevent aneurysm rupture. Long-term results highlight technique limitations and new aspects of Abdominal aortic aneurysm (AAA) pathophysiology. There is no abdominal aortic aneurysm endograft exclusion model cheap and reproducible, which would allow deep investigations of AAA before and after treatment. We hereby describe how to induce, and then to exclude with a covered coronary stentgraft an abdominal aortic aneurysm in a rat. The well known elastase induced AAA model was first reported in 19901 in a rat, then described in mice2. Elastin degradation leads to dilation of the aorta with inflammatory infiltration of the abdominal wall and intra luminal thrombus, matching with human AAA. Endovascular exclusion with small covered stentgraft is then performed, excluding any interactions between circulating blood and the aneurysm thrombus. Appropriate exclusion and stentgraft patency is confirmed before euthanasia by an angiography thought the left carotid artery. Partial control of elastase diffusion makes aneurysm shape different for each animal. It is difficult to create an aneurysm, which will allow an appropriate length of aorta below the aneurysm for an easy stentgraft introduction, and with adequate proximal and distal neck to prevent endoleaks. Lots of failure can result to stentgraft introduction which sometimes lead to aorta tear with pain and troubles to stitch it, and endothelial damage with post op aorta thrombosis. Giving aspirin to rats before stentgraft implantation decreases failure rate without major hemorrhage. Clamping time activates neutrophils, endothelium and platelets, and may interfere with biological analysis.

Histological and biochemical modifications after aneurysm endograft exclusion are still unclear. We describe a new model of endograft implantation on a murine aneurysm. Through thrombus analysis with and without persistant circulating blood stream interface, and new endovascular biomaterials evaluation, this model will help to better understand endovascular aneurysm exclusion pathobiology.

一种新的小鼠模型主动脉瘤腔内修复

Endovascular aneurysm exclusion is a validated technique to prevent aneurysm rupture. Long-term results highlight technique limitations and new aspects of ...

Imaging In-Stent Restenosis: An Inexpensive, Reliable, and Rapid Preclinical Model

Preclinical models of restenosis are essential to unravel the pathophysiological processes that lead to in-stent restenosis and to optimize existing and future drug-eluting stents.
A variety of antibodies and transgenic and knockout strains are available in rats. Consequently, a model for in-stent restenosis in the rat would be convenient for pathobiological and pathophysiological studies. 
In this video, we present the full procedure and pit-falls of a rat stent model suitable for high throughput stent research. We will show the surgical procedure of stent deployment, and the assessment of in-stent restenosis using the most elegant technique of OCT (Optical Coherence Tomography). This technique provides high accuracy in assessing plaque CSAs (cross section areas) and correlates well with histological sections, which require special and time consuming embedding and sectioning techniques. OCT imaging further allows longitudinal monitoring of the development of in-stent restenosis within the same animal compared to one-time snapshots using histology.

This video demonstrates how to use a preclinical inexpensive and reliable model to study pathobiological and pathophysiological processes of in-stent restenosis development. Longitudinal in vivo monitoring using OCT (Optical Coherence Tomography) and analysis of OCT images are also demonstrated.

支架内再狭窄的影像：一种廉价的，可靠，快速的临床前模型

Preclinical models of restenosis are essential to unravel the pathophysiological processes that lead to in-stent restenosis and to optimize existing and ...

生物学

The Helsinki Rat Microsurgical Sidewall Aneurysm Model

Experimental saccular aneurysm models are necessary for testing novel surgical and endovascular treatment options and devices before they are introduced into clinical practice. Furthermore, experimental models are needed to elucidate the complex aneurysm biology leading to rupture of saccular aneurysms.
Several different kinds of experimental models for saccular aneurysms have been established in different species. Many of them, however, require special skills, expensive equipment, or special environments, which limits their widespread use. A simple, robust, and inexpensive experimental model is needed as a standardized tool that can be used in a standardized manner in various institutions.
The microsurgical rat abdominal aortic sidewall aneurysm model combines the possibility to study both novel endovascular treatment strategies and the molecular basis of aneurysm biology in a standardized and inexpensive manner. Standardized grafts by means of shape, size, and geometry are harvested from a donor rat&#39;s descending thoracic aorta and then transplanted to a syngenic recipient rat. The aneurysms are sutured end-to-side with continuous or interrupted 9-0 nylon sutures to the infrarenal abdominal aorta.
We present step-by-step procedural instructions, information on necessary equipment, and discuss important anatomical and surgical details for successful microsurgical creation of an abdominal aortic sidewall aneurysm in the rat.

Microsurgical sidewall aneurysms in rats are created by end-to-side anastomosis of an aortic graft to the abdominal aorta. We present step-by-step instructions and discuss anatomical and surgical details for successful experimental saccular aneurysm creation.

赫尔辛基鼠显微旁瘤模型

Experimental saccular aneurysm models are necessary for testing novel surgical and endovascular treatment options and devices before they are introduced ...

Use of a Rat Model to Study Ventral Abdominal Hernia Repair

Ventral abdominal hernia is a relatively common clinical condition that sometimes requires herniorraphy (surgical repair). The repair of ventral abdominal hernia typically requires implantation of a material to serve as a mechanical bridge across the defect in the abdominal wall. Biomaterials, such as porcine small intestinal submucosa (SIS), also serve as a lattice for cell growth into the implant and can naturally incorporate into the host tissue. Development of such repair materials benefits from use of animal models in which experimental abdominal wall defects are easily created and are amenable to repair in a reproducible fashion. The method offered here describes surgical creation and repair of ventral abdominal hernia in a rat model. When SIS is used to repair an experimental ventral abdominal hernia in this model, it is rapidly incorporated into host tissue within 28 days of implantation. Histologically, incorporation of their implanted material into host tissue is characterized by a robust fibrovascular response. Future refinements and applications of the rat abdominal hernia model may likely involve diabetic and/or obese animals as a means to more closely mimic common co-morbidities of man.

This manuscript describes methods associated with creation and repair of a ventral abdominal wall defect (hernia). This model can be used to study repair strategies such as those that use implanted materials. In this manuscript, repair of the experimental hernia with porcine small intestinal submucosa is presented as an example.

大鼠模型在腹腹疝修补术中的应用研究

Ventral abdominal hernia is a relatively common clinical condition that sometimes requires herniorraphy (surgical repair). The repair of ventral abdominal ...

生物工程

Vascular Gene Transfer from Metallic Stent Surfaces Using Adenoviral Vectors Tethered through Hydrolysable Cross-linkers

In-stent restenosis presents a major complication of stent-based revascularization procedures widely used to re-establish blood flow through critically narrowed segments of coronary and peripheral arteries. Endovascular stents capable of tunable release of genes with anti-restenotic activity may present an alternative strategy to presently used drug-eluting stents. In order to attain clinical translation, gene-eluting stents must exhibit predictable kinetics of stent-immobilized gene vector release and site-specific transduction of vasculature, while avoiding an excessive inflammatory response typically associated with the polymer coatings used for physical entrapment of the vector. This paper describes a detailed methodology for coatless tethering of adenoviral gene vectors to stents based on a reversible binding of the adenoviral particles to polyallylamine bisphosphonate (PABT)-modified stainless steel surface via hydrolysable cross-linkers (HC). A family of bifunctional (amine- and thiol-reactive) HC with an average t1/2 of the in-chain ester hydrolysis ranging between 5 and 50 days were used to link the vector with the stent. The vector immobilization procedure is typically carried out within 9 hr&#160;and consists of several steps: 1) incubation of the metal samples in an aqueous solution of PABT (4 hr); 2) deprotection of thiol groups installed in PABT with tris(2-carboxyethyl) phosphine (20 min); 3) expansion of thiol reactive capacity of the metal surface by reacting the samples with polyethyleneimine derivatized with pyridyldithio (PDT) groups (2 hr); 4) conversion of PDT groups to thiols with dithiothreitol (10 min); 5) modification of adenoviruses with HC (1 hr); 6) purification of modified adenoviral particles by size-exclusion column chromatography (15 min) and 7) immobilization of thiol-reactive adenoviral particles on the thiolated steel surface (1 hr). This technique has wide potential applicability beyond stents, by facilitating surface engineering of bioprosthetic devices to enhance their biocompatibility through the substrate-mediated gene delivery to the cells interfacing the implanted foreign material.

These studies report on reversible attachment of adenoviral gene vectors to coatless metal surfaces of stents and model mesh disks. Sustained release of transduction-competent viral particles contingent upon hydrolysis of cross-linkers used for vector immobilization results in a durable site-specific transgene expression in vascular cells and in stented arteries.

从金属支架表面使用的腺病毒载体栓通过水解的交联剂血管基因转移

In-stent restenosis presents a major complication of stent-based revascularization procedures widely used to re-establish blood flow through critically ...

Creation of a Rodent Model of Abdominal Aortic Aneurysm by Blocking Adventitial Vasa Vasorum Perfusion

The adventitial vasa vasorum (VV) provides oxygen and nourishment to the aortic wall. Hypoxia in the aortic wall can cause enlarged abdominal aortic aneurysms (AAAs). This article introduces and describes a standard protocol used to induce AAAs through adventitial VV hypoperfusion created with a combination of polyurethane catheter insertion into the aortic lumen and suture ligation of the infrarenal abdominal aorta.
The protocol involves the use of male rats weighing 300-400 g, which are provided food and water ad libitum. After laparotomy with a ventral midline abdominal incision, exfoliation of the aorta is performed, which blocks blood flow from the perivascular tissue. Aortotomy involving a small incision adjacent to the renal artery branches is performed, and a polyurethane catheter is inserted using an 18-gauge indwelling needle. After repairing the incision, tight ligation of the aorta over the catheter blocks VV blood flow from the proximal direction through the aortic wall without disturbing the aortic blood flow. This technique can induce an AAA with progressive aortic dilatation.
The greatest benefit of this model is that VV hypoperfusion causes tissue hypoxia and the development of an infrarenal AAA, which has morphological and pathological characteristics similar to those of a human AAA.

Polyurethane catheter insertion into the aortic lumen and suture ligation of the aorta induce chronic hypoxia due to hypoperfusion of the adventitial vasa vasorum. This article describes a novel animal model of abdominal aortic aneurysm (AAA) with characteristics similar to those of AAA in humans.

阻断外瓦萨血管灌注对腹主动脉瘤鼠模型的建立

The adventitial vasa vasorum (VV) provides oxygen and nourishment to the aortic wall. Hypoxia in the aortic wall can cause enlarged abdominal aortic ...

A Rat Model of Orthotopic Liver Transplantation Using a Novel Magnetic Anastomosis Technique for Suprahepatic Vena Cava Reconstruction

The rat model of orthotopic liver transplantation (OLT) is essential for transplant research. It is a very sophisticated animal model and requires a steep learning curve. The introduction of the cuff technique for anastomosis of the portal vein (PV) and infrahepatic vena cava (IHVC) has significantly simplified the transplant procedure in rats. However, due to the short anterior wall of the recipients' suprahepatic vena cava (SHVC), the cuff technique is very difficult to use for the reconstruction of the SHVC. Most researchers in this field still use the hand-suture technique for SHVC reconstruction, which makes it the bottleneck step in rat orthotopic liver transplantation. The magnetic anastomosis technique (i.e., magnamosis) is a method of connecting two vessels using the attractive force between two magnets. Our recent study has shown that the magnetic anastomosis technique is superior to the hand-suture technique for SHVC reconstruction in rats. In this article, we show a step-by-step protocol for SHVC reconstruction in rats using the novel magnetic anastomosis technique. In this model, the reconstruction of the PV and IHVC was performed by the standard cuff technique, while the reconstruction of the bile duct (BD) was performed by a stent technique. The hepatic re-arterialization was not performed. The magnetic anastomosis technique made SHVC reconstruction much easier and significantly shortened the anphepatic phase. After a reasonable learning curve, even researchers without advanced microsurgical skills can produce reliable and reproducible results using this rat model of OLT.

The reconstruction of the suprahepatic vena cava (SHVC) remains a difficult step in rat orthotopic liver transplantation. In this article, we show a step-by-step protocol for SHVC reconstruction in rats using a novel magnetic anastomosis technique.

应用新型磁吻合技术 Suprahepatic 腔静脉重建大鼠原位肝移植模型的研究

The rat model of orthotopic liver transplantation (OLT) is essential for transplant research. It is a very sophisticated animal model and requires a steep ...

Implantation of Human-Sized Coronary Stents into Rat Abdominal Aorta Using a Trans-Femoral Access

Percutaneous coronary intervention (PCI), combined with the deployment of a coronary stent, represents the gold standard in interventional treatment of coronary artery disease. In-stent restenosis (ISR) is determined by an excessive proliferation of neointimal tissue within the stent and limits the long-term success of stents. A variety of animal models have been used to elucidate pathophysiological processes underlying in-stent restenosis (ISR), with the porcine coronary and the rabbit iliac artery models being the most frequently used. Murine models provide the advantages of high throughput, ease of handling and housing, reproducibility, and a broad availability of molecular markers. The apolipoprotein E deficient (apoE-/- ) mouse model has been widely used to study cardiovascular diseases. However, stents must be miniaturized to be implanted into mice, involving important changes of their mechanical and (potentially) biological properties. The use of apoE-/- rats can overcome these shortcomings as apoE-/- rats allow for the evaluation of human-sized coronary stents while at the same time providing an atherogenic phenotype. This makes them an excellent and reliable model to investigate ISR after stent implantation. Here, we describe, in detail, the implantation of commercially available human coronary stents into the abdominal aorta of rats with an apoE-/- background using a trans-femoral access.

This protocol describes the implantation of human coronary stents into the abdominal aorta of rats with an apoE-/- background using a trans-femoral access. Compared with other animal models, murine models carry the advantages of high throughput, reproducibility, ease of handling and housing, and a broad availability of molecular markers.

使用跨女性访问将人类大小的冠状动脉支架植入大鼠腹主动脉

Percutaneous coronary intervention (PCI), combined with the deployment of a coronary stent, represents the gold standard in interventional treatment of ...

Using a Cell-Tracer Injection to Investigate the Origin of Neointima-Forming Cells in a Rat Saccular Side Wall Model

Microsurgical clipping creates a subsequent barrier of blood flow into intracranial aneurysms, whereas endovascular treatment relies on neointima and thrombus formation. The source of endothelial cells covering the endoluminal layer of the neointima remains unclear. Therefore, the aim of the present study was to investigate the origin of neointima-forming cells after cell-tracer injection in the already well-established Helsinki rat microsurgical sidewall aneurysm model.
Sidewall aneurysms were created by suturing decellularized or vital arterial pouches end-to-side to the aorta in male Lewis rats. Before arteriotomy with aneurysm suture, a cell-tracer injection containing CM-Dil dye was performed into the clamped aorta to label endothelial cells in the adjacent vessel and track their proliferation during follow-up (FU). Treatment followed by coiling (n = 16) or stenting (n = 15). At FU (7 days or 21 days), all rats underwent fluorescence angiography, followed by aneurysm harvesting and macroscopic and histological evaluation with immunohistological cell counts for specific regions of interest. 
None of the 31 aneurysms had ruptured upon follow-up. Four animals died prematurely. Macroscopically residual perfusion was observed in 75.0% coiled and 7.0% of stented rats. The amount of cell-tracer-positive cells was significantly elevated in decellularized stented compared to coiled aneurysms with respect to thrombus on day 7 (p = 0.01) and neointima on day 21 (p = 0.04). No significant differences were found in thrombus or neointima in vital aneurysms. 
These findings confirm worse healing patterns in coiled compared to stented aneurysms. Neointima formation seems particularly dependent on the parent artery in decellularized aneurysms, whereas it is supported by the recruitment from aneurysm wall cells in vital cell-rich walls. In terms of translation, stent treatment might be more appropriate for highly degenerated aneurysms, whereas coiling alone might be adequate for aneurysms with mostly healthy vessel walls.

We performed a one-point, lipophilic cell-tracer injection to track endothelial cells, followed by an arteriotomy and suturing of sidewall aneurysms on the abdominal rat aorta. Neointima formation seemed dependent on the parent artery in decellularized aneurysms and was promoted by the recruitment from aneurysm wall cells in vital cell-rich walls.

使用细胞示踪剂注射研究大鼠囊侧壁模型中新内膜形成细胞的起源

Microsurgical clipping creates a subsequent barrier of blood flow into intracranial aneurysms, whereas endovascular treatment relies on neointima and ...