笔者想感谢恭Guesdon（雅培）的礼物Stentgrafts的。

方法已获批准由比沙德勃雷伦理委员会（N°2012-15/698-0074），该协议。 第一弹性蛋白酶灌注模型已在1990年1由Anidjar描述：腹主动脉瘤是由弹性蛋白酶灌注诱导雄性Wistar大鼠，年龄在8至9周，250-300克。 2至4周后，进行重新剖腹手术，直径为3毫米的覆盖冠状动脉stentgraft的用于排除动脉瘤。嫁接，插入通过远端aortotomy，部署下视力放大。两个星期后，前牺牲的左颈总动脉与主动脉造影证实stentgraft通畅。整个支架主动脉及周围组织，然后进行分析收获和空调。 协议 1。第1步：腹主动脉瘤感应（0天） <ol><li>异氟醚麻醉动物和性能一个腹腔penthobarbital的注射。 0.1 ml/100克penthobarbitol的是稀释在0.1信息毫升saline/100克动物体重。麻醉是足够的程序。 </li><li>剃腹部，并用酒精清洁皮肤。 </li><li>让Xypho耻骨切开皮肤，用刀片。腹部肌肉层，然后腹膜，避免内脏，用剪刀打开。将吊具和包裹肠道湿敷于动物的左侧。 </li><li>打开后腹膜直接以上的主动脉，不要撕破。我们的目标是，以防止未来的肠粘连经济清扫。 </li><li>结扎所有抵押品只有一个结扎左肾静脉至髂分叉，在原点的主动脉。如果主动脉被卡住的肠子或腔静脉，有一个高风险的第二次介入治疗期间出血，这往往是致命的影响。 </li><li>通过两次4-0丝线主动脉周围，15毫米以下来氟米特吨肾静脉。重要的是要完全解剖主动脉，约。左肾静脉和髂分叉近端，以允许插入吉尔伯特逼近夹15毫米以下。 </li><li>夹紧后的主动脉正下方的左肾静脉近侧和远侧正上方髂分叉除去外膜，近端的前端钳位未能执行小aortotomy。仔细冲洗用生理盐水棱角插管和所有剩余的血液清洗，以避免血栓栓塞时开放升主动脉。 </li><li>引进热锥形聚乙烯管（PE 10）顺利主动脉内，并通过4-0丝线主动脉周围（步骤1.6）和配合，以确保管，避免压力驱逐。 </li><li>注入弹性蛋白酶成10至13毫米长的主动脉（从近端钳丝）。 </li><li>注入725微升的细胞弹性蛋白酶溶液在30分钟内以恒定的速度速率为d。重要的是到小心地survey注射输液过程中，主动脉应扩大其正常直径140-150％。 </li><li>在输液结束，拔出导管，用生理盐水冲洗弹性蛋白酶，切丝，关闭aortotomy约3针10-0的聚丙烯。取下夹子：远端，近端。护理注意避免跨主动脉缝合。有了一些实践，并考虑小的aortotomy长度，主动脉血栓形成是极为罕见的。 </li><li>关闭腹壁，用连续的可吸收缝合线，与非中断的可吸收缝合线和皮肤。注射5毫克/千克剂量皮下，卡洛芬，以防止疼痛。大鼠返回到自己的笼子，并提供标准的大鼠实验室饲料和水libidum的。 </li></ol> 2。第2步：排除冠状动脉PTFE（聚四氟乙烯）有Stentgraft腹主动脉瘤（15-30天） <ol><li>在该操作之前，在1升水中稀释阿司匹林1,000毫克。每日娃后ml/100 10-12克/体重每天摄入量估计。 </li><li>如前面所述麻醉后，执行重新剖腹手术，小心避免附着到腹壁潜在的内部器官。同比增长50％以上相比，近端主动脉直径直视下主动脉瘤定义。根据我们的经验，成功率是90％，包括过早死亡，主要是由于主动脉爆裂（未发表的数据） </li><li>解剖主动脉主动脉分叉近端颈部。动脉瘤应出现的左肾静脉下方几毫米，这允许一个满意的前端的颈部之间的长度和插入导管的前端钳位，并缝合主动脉。 Stentgraft长度取决于动脉瘤的大小。近端和远端的脖子应涵盖至少2毫米。 </li><li>近端颈部周围包裹的是双回路的丝绸。夹以上的动脉瘤近端主动脉和below左肾动脉，远侧主动脉分叉以上。 </li><li>执行一个大型的的正上方aortotomy避免撕裂主动脉壁引入stentgraft时的上aortotomy。不要冲洗的主动脉血栓保存完整。推stentgraft向近端钳。取出钳和控制丝的张力，以允许移植进展。适应的输送导管周围的张力，直到近端的stentgraft边缘到达近端颈部，而且这将防止近侧钳拆除后大出血允许stentgraft进展。的气球和传送导管的近端可包括在肾动脉，但不是stentgraft的低于肾动脉，需部署。 </li><li>使用充气注射器直接的视觉控制在8个大气压的压力下的stentgraft部署。气球放气，同时收紧丝和移除气球轴。 </li><li>洗净的s用生理盐水tentgraft。放置的正下方靠近主动脉动脉瘤的末端部分，与中断的10-0的聚丙烯缝合线的夹紧。 </li><li>关闭伤口，皮下注入卡洛芬，并让动物返回到自己的笼子。提供标准的实验室饲料和水libidum的。 </li></ol> 3。第3步：控制的通畅Stentgraft（30天） 15天后插入stentgraft，执行控制的移植物通畅的动脉造影<ol><li>麻醉后，进行横向的肘部到肘部切口。左颈总动脉位于下方的颌下腺和舌下腺和下方的胸锁乳突肌。建议2厘米长曝光。 </li><li>结扎动脉远端用真丝4-0。后近端夹紧，插入18G导管逆行并两次经过颈动脉和周围绑丝4-0。有足够的长度，允许插入和固定导管前近侧钳被删除。如果它是很难暴露2cm的动脉，管，夹紧充满生理盐水后，可以推近端同时去除近端钳。 </li><li>通过导管直接透视下注入对比。执行一个血管造影stentgraft控制，，同时确认内漏的情况下，可能会导致不适当的部署stentgraft的，并确认stentgraft通畅。这一步是很重要的，因为高的侧支血管灌注甚至血栓stentgraft的允许足够的腿部。我们没有尝试进行多普勒超声：我们假定，钢结构stentgraft防止正确评估stentgraft通畅和内漏。 </li><li>牺牲大鼠放血的建议18，和动脉瘤，stentgraft，血栓及血管壁组织学或生物化学的研究收获。 </li></ol>

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我什么都没有透露。

AAA两种型号都已经在我们的实验室：异种移植19和弹性蛋白酶诱导模型。1弹性蛋白酶模型是最相似的人主动脉瘤：一个大圆周腔内的血栓，然后排除动脉瘤腔内修复。 内漏是一个平常的并发症EVAR 14,15。很多问题依然未解：，AAA破裂已与低内漏，有时无瘤囊增大16。内漏是一个很平常的EVAR术后并发症，维持血液循环细胞和动脉瘤血栓之间的接?...

腔内的技能进步，因为第一腔内主动脉瘤修复术（EVAR）于1991年3帕罗迪，几乎所有腹主动脉瘤的一半现在都被视为EVAR 4。不像手术，EVAR叶血栓，但不包括从全身的血液。动脉瘤的特点是血红蛋白丰富的多层次的血栓，薄薄的媒体，和fibrosed和外膜发炎。三十年前已被证明的关键作用，在动脉瘤的进展蛋白水解5 6，7：血栓的动脉瘤囊与主动脉壁薄，弹性蛋白的裂解，在媒体上的平滑肌细胞的低密度，和高水平的免疫炎症外膜反应8,9。这些变化表明，蛋白水解酶的​​活性发生血栓，而不是直接在主动脉壁内。 此外，血栓管腔层是含有丰富的凝集的红细胞策LLS释放血红蛋白。它们主要涉及纤维蛋白形成，血小板活化和诱导凝血酶形成。最后，血栓引起的t-PA和纤溶酶原潴留，从而参与纤溶及招聘白细胞，中性粒细胞为主。这是更重要的12倍比在血液流10中的血栓。有关他们的存在是具有速率高型基质金属蛋白酶（MMP-8），MMP-9和弹性蛋白酶：他们释放颗粒丝氨酸蛋白酶和亲氧化剂降解纤维矩阵，并最终主动脉壁破裂9,11 -13。 选修瘤的干预旨在防止破裂。 EVAR叶瘤壁血栓完好。因此，动脉瘤灌注主动脉抵押品（腰动脉，肠系膜下动脉...），被命名为内漏，是一个特定的血管内介入治疗并发症的14,15，有时会导致破裂前夕低压内漏Ń。此外，在某些患者中，有动脉瘤直径16没有增加。循环血液和动脉瘤壁之间的相互作用维持上述管腔内血栓的生物活性。因此，V型内漏，定义为没有确定内漏瘤囊扩张，可以解释为瘤内血栓的酶的活性。 无论是放射成像（18FDG-PET扫描，血小板活化显像，铁OXYDE对比度MRI17），也不外周血采样（MMP-9，血小板衍生微粒，纤维蛋白溶酶/抗纤维蛋白溶酶复合物）用于直接探索人类主动脉瘤腔内影响评估生化途径。 在我们的知识，也没有任何重复性好，价格便宜的实验排除瘤动物模型。这一个允许前，后动脉瘤排除生物和组织学的修改加以探讨。

<table border="1">
<tbody>
 <tr>
 <td></td>
 <td></td>
 <td></td>
 <td>Animals </td>
 </tr>
 <tr>
 <td>Wistar rats</td>
 <td></td>
 <td></td>
 <td>aged from 8 to 9 weeks. Weight range from 350 to 400 g</td>
 </tr>
 <tr>
 <td></td>
 <td></td>
 <td></td>
 <td>Instruments</td>
 </tr>
 <tr>
 <td>Isoflurane anesthesic system</td>
 <td></td>
 <td></td>
 <td>4,5% at the beginning, then 2%</td>
 </tr>
 <tr>
 <td>Penthobarbital</td>
 <td>Ceva sante animale, Libourne, France</td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Dissection stereomicroscope</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Steriles gloves</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Microsurgical Steriles instruments</td>
 <td>Moria, Antony, France</td>
 <td></td>
 <td>Needle holder,	Forceps, Scissors,Gilbert approximator
o	3 Micro clamps</td>
 </tr>
 <tr>
 <td>N&deg;40 Silk string</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Prolen 9-0 and 10-0</td>
 <td>Ethicon, Johnson &amp; Johnson, Auneau, France</td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Heat-tapered polyethylene tubing</td>
 <td>PE 10</td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Syringe infusion pump</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Porcine pancreatic elastase</td>
 <td>Sigma, St. Louis, Mo., USA</td>
 <td></td>
 <td>550 &mu;l of salin is mixed with 175 &mu;l of elastase</td>
 </tr>
 <tr>
 <td>Indeflator</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>9 to 16 mm length, 3 mm diameter coronary PTFE covered stentgraft</td>
 <td>Abbott, Abbott Park, Illinois, USA</td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>C-Arm OEC 9800</td>
 <td>GE Medical Systems, Milwaukee, WI</td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Aspegic 1000 mg</td>
 <td>Aspirin, Sanofi-Aventis, Paris, France</td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td></td>
 <td></td>
 <td></td>
 <td>Reagent</td>
 </tr>
 <tr>
 <td>Aerane isoflurane 100ML</td>
 <td>Baxter</td>
 <td>Aerane</td>
 <td></td>
 </tr>
 <tr>
 <td>Penthobarbital</td>
 <td>Centravet</td>
 <td>053pen203</td>
 <td></td>
 </tr>
 <tr>
 <td>Silk Suture 4-0</td>
 <td>Fine Science</td>
 <td>18020-40</td>
 <td></td>
 </tr>
 <tr>
 <td>Microsurgical steriles instruments</td>
 <td>Moria</td>
 <td>9980-9983-9987-204/A-204/D-8148-4877A-4878A</td>
 <td></td>
 </tr>
 <tr>
 <td>Prolen 9-0 and 10-0</td>
 <td>Ethicon</td>
 <td>W2829 &ndash; NS2850</td>
 <td></td>
 </tr>
 <tr>
 <td>Heat tapered Polyethylene tubing : PE 10</td>
 <td>Bioseb</td>
 <td>MRE-010</td>
 <td></td>
 </tr>
 <tr>
 <td>Infusion pump</td>
 <td>World precision instrument</td>
 <td>AL-1000</td>
 <td></td>
 </tr>
 <tr>
 <td>Porcine pancreatic elastase</td>
 <td>Sigma</td>
 <td>E1250-100MG</td>
 <td></td>
 </tr>
 <tr>
 <td>Indeflator</td>
 <td>Longreal</td>
 <td>KY025 25 100</td>
 <td></td>
 </tr>
 <tr>
 <td>Aspegic 1000mg (Aspirin)</td>
 <td>Sanofi-Aventis</td>
 <td>3400931898191</td>
 <td></td>
 </tr>
 <tr>
 <td>C-Arm OEC 9800</td>
 <td>General electric.</td>
 <td>OEC 9800</td>
 <td></td>
 </tr>
 <tr>
 <td>Stentgraft : Jostent</td>
 <td>Abbott</td>
 <td>210CG1230 
 210CG1630</td>
 <td></td>
 </tr>
</tbody>
</table>

a new murine model of endovascular aortic aneurysm repair

血管内动脉瘤排除是经过验证的技术，以防止动脉瘤破裂。长期业绩突出的腹主动脉瘤（AAA）的病理生理技术的局限性和新的方面。有没有腹主动脉瘤移植物排斥模型便宜和可重复性，这将使治疗前后的AAA级深调查。我们在此描述了如何诱导，然后一个覆盖冠状动脉stentgraft的腹主动脉瘤的大鼠排除。众所周知的弹性蛋白酶诱导AAA模型首次报道于1990年1大鼠，小鼠2然后描述。弹性蛋白的降解导致的主动脉扩张的腹壁和管腔内血栓的炎性浸润，配合人力AAA。腔内隔绝小覆盖stentgraft，然后执行，不包括血液循环和动脉瘤血栓之间的任何互动。适当的的排斥和stentgraft通畅是通过血管造影证实之前安乐死，认为左侧颈动脉。部分的弹性蛋白酶扩散的控制，使得每个动物的动脉瘤形状不同。这是很难创建一个动脉瘤，这将允许一个适当长度的主动脉在动脉瘤一个简单的stentgraft的引入以下，并有足够的近端和远端颈部，以防止内漏。大量的失败可能会导致有时会导致主动脉撕裂的痛苦和烦恼十字绣stentgraft介绍，与后运算主动脉血栓形成和血管内皮损伤。到大鼠植入stentgraft前给予阿司匹林，降低故障率没有大的出血。钳位时间激活嗜中性粒细胞，血管内皮细胞和血小板，并且可能会干扰生物分析。

<html>瘤固定在4％多聚甲醛溶液中24小时，然后进入的磷酸盐缓冲盐溶液，直到固定在树脂中的集团。我们使用HPS（苏木精Phloxin赛峰）（ 图1）染色，示出愈合增殖细胞周围的PTFE（ 图2）。然后，间充质细胞，其特征在于由α-肌动蛋白染色（ 图3）。 <img src="/files/ftp_upload/50740/50740fig1.jpg" alt="图1" /> 图1?...

Watch this Scientific Journal Video about A New Murine Model of Endovascular Aortic Aneurysm Repair at JoVE.com

A New Murine Model of Endovascular Aortic Aneurysm Repair

动脉瘤的组织学和生化修改后移植物排斥目前仍不清楚。我们描述了一种新的模式移植物植入对小鼠动脉瘤。通过血栓并没有持久性循环血液流接口，和新的血管内的生物材料评价的分析，这种模式将有助于更好地了解血管内动脉瘤排除病理学。

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 ...

a-new-murine-model-of-endovascular-aortic-aneurysm-repair

Research

JoVE Journal

Medicine

14.3K 次观看.  Hôpital X. Bichat, AP-HP, Paris. 动脉瘤的组织学和生化修改后移植物排斥目前仍不清楚。我们描述了一种新的模式移植物植入对小鼠动脉瘤。通过血栓并没有持久性循环血液流接口，和新的血管内的生物材料评价的分析，这种模式将有助于更好地了解血管内动脉瘤排除病理学。

视频: A New Murine Model of Endovascular Aortic Aneurysm Repair

Reproducable Paraplegia by Thoracic Aortic Occlusion in a Murine Model of Spinal Cord Ischemia-reperfusion

Background 
Lower extremity paralysis continues to complicate aortic interventions. The lack of understanding of the underlying pathology has hindered advancements to decrease the occurrence this injury.&#160;The current model demonstrates reproducible lower&#160;extremity paralysis following thoracic aortic occlusion.
Methods 
Adult male C57BL6 mice were anesthetized with isoflurane. Through a cervicosternal incision the aorta was exposed. The descending thoracic aorta and left subclavian arteries were identified without entrance into pleural space. Skeletonization of these arteries was followed by immediate closure (Sham) or occlusion for 4 min (moderate ischemia) or 8 min (prolonged ischemia). The sternotomy and skin were closed and the mouse was transferred to warming bed for recovery.&#160; Following recovery, functional analysis was obtained at 12 hr intervals until 48 hr.
Results 
Mice that underwent sham surgery showed no observable hind&#160;limb deficit. Mice subjected to moderate ischemia for 4 min had minimal functional deficit at 12 hr followed by progression to complete paralysis at 48 hr. Mice subjected to prolonged ischemia had an immediate paralysis with no observable hind-limb movement at any point in the postoperative period. There was no observed intraoperative or post&#160;operative mortality.
Conclusion 
Reproducible lower extremity paralysis whether immediate or delayed can be achieved in a murine model. Additionally, by using a median sternotomy and careful dissection, high survival rates, and reproducibility can be achieved.

The lack of mechanistic understanding of spinal cord ischemia-reperfusion injury has hindered further adjuncts to prevent paraplegia following high risk aortic operations. Thus, the development of animal models is imperative. This manuscript demonstrates reproducible lower extremity paralysis following thoracic aortic occlusion in a murine model.

可重放截瘫胸主动脉阻断脊髓缺血再灌注的小鼠模型

Background
Lower extremity paralysis continues to complicate aortic interventions. The lack of understanding of the underlying pathology has hindered ...

科研

医学

Open Tracheostomy Gastric Acid Aspiration Murine Model of Acute Lung Injury Results in Maximal Acute Nonlethal Lung Injury

Acid pneumonitis is a major cause of sterile acute lung injury (ALI) in humans. Acid pneumonitis spans the clinical spectrum from asymptomatic to acute respiratory distress syndrome (ARDS), characterized by neutrophilic alveolitis, and injury to both alveolar epithelium and vascular endothelium. Clinically, ARDS is defined by acute onset of hypoxemia, bilateral patchy pulmonary infiltrates and non-cardiogenic pulmonary edema. Human studies have provided us with valuable information about the physiological and inflammatory changes in the lung caused by ARDS, which has led to various hypotheses about the underling mechanisms. Unfortunately, difficulties determining the etiology of ARDS, as well as a wide range of pathophysiology have resulted in a lack of critical information that could be useful in developing therapeutic strategies.
Translational animal models are valuable when their pathogenesis and pathophysiology accurately reproduce a concept proven in both in vitro and clinical settings. Although large animal models (e.g., sheep) share characteristics of the anatomy of human trachea-bronchial tree, murine models provide a host of other advantages including: low cost; short reproductive cycle lending itself to greater data acquisition; a well understood immunologic system; and a well characterized genome leading to the availability of a variety of gene deletion and transgenic strains. A robust model of low pH induced ARDS requires a murine ALI that targets mainly the alveolar epithelium, secondarily the vascular endothelium, as well as the small airways leading to the alveoli. Furthermore, a reproducible injury with wide differences between different injurious and non-injurious insults is important.
The murine gastric acid aspiration model presented here using hydrochloric acid employs an open tracheostomy and recreates a pathogenic scenario that reproduces the low pH pneumonitis injury in humans. Additionally, this model can be used to examine interaction of a low pH insult with other pulmonary injurious entities (e.g., food particles, pathogenic bacteria).

This protocol induces acute lung injury in a mouse that has close fidelity to the pathogenesis of acid pneumonitis observed in humans. We generate a maximal acute nonlethal low pH lung injury and account for differences in rodent-human anatomic respiratory structure using an open tracheostomy coupled with circumferential pressure release.

急性肺损伤开放气管切开胃酸吸入小鼠模型结果在急性最大非致命性肺损伤

Acid pneumonitis is a major cause of sterile acute lung injury (ALI) in humans. Acid pneumonitis spans the clinical spectrum from asymptomatic to acute ...

Reproducible Arterial Denudation Injury by Infrarenal Abdominal Aortic Clamping in a Murine Model

Percutaneous vascular interventions uniformly result in arterial denudation injuries that subsequently lead to thrombosis and restenosis. These complications can be attributed to impairments in re-endothelialization within the wound margins. Yet, the cellular and molecular mechanisms of re-endothelialization remain to be defined. While several animal models to study re-endothelialization after arterial denudation are available, few are performed in the mouse because of surgical limitations. This undermines the opportunity to exploit transgenic mouse lines and investigate the contribution of specific genes to the process of re-endothelialization. Here, we present a step-by-step protocol for creating a highly reproducible murine model of arterial denudation injury in the infrarenal abdominal aorta using external vascular clamping. Immunocytochemical staining of injured aortas for fibrinogen and &#946;-catenin demonstrate the exposure of a pro-thrombotic surface and the border of intact endothelium, respectively. The method presented here has the advantages of speed, excellent overall survival rate, and relative technical ease, creating a uniquely practical tool for imposing arterial denudation injury in transgenic mouse models. Using this method, investigators may elucidate the mechanisms of re-endothelialization under normal or pathological conditions.

Understanding the cellular and molecular mechanisms of re-endothelialization following arterial denudation injury is of paramount importance in preventing thrombosis and restenosis of arteries. Here we describe a protocol for reproducible arterial denudation injury of the infrarenal abdominal aorta. The procedure was developed to investigate the underlying mechanisms that regulate endothelial regeneration using mouse models.

重复性的动脉剥脱损伤腹主动脉阻断在小鼠模型

Percutaneous vascular interventions uniformly result in arterial denudation injuries that subsequently lead to thrombosis and restenosis. These ...

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 ...

Quantitative Micro-CT Analysis of Aortopathy in a Mouse Model of &#946;-aminopropionitrile-induced Aortic Aneurysm and Dissection

Aortic aneurysm and dissection is associated with significant morbidity and mortality in the population and can be highly lethal. While animal models of aortic disease exist, in vivo imaging of the vasculature has been limited. In recent years, micro-computerized tomography (micro-CT) has emerged as a preferred modality for imaging both large and small vessels both in vivo and ex vivo. In conjunction with a method of vascular casting, we have successfully used micro-CT to characterize the frequency and distribution of aortic pathology in &#946;-aminopropionitrile-treated C57/Bl6 mice. Technical limitations of this method include variations in the quality of the perfusion introduced by poor animal preparation, the application of proper methodologies for vessel size quantification, and the non-survivability of this procedure. This article details a methodology for the intravascular perfusion of a lead-based radiopaque silicone rubber for the quantitative characterization of aortopathy in a mouse model of aneurysm and dissection. In addition to visualizing aortic pathology, this method may be used for examining other vascular beds in vivo or vascular beds removed post-mortem.

Quantitative Micro-CT Analysis of Aortopathy in a Mouse Model of &amp;#946;-aminopropionitrile-induced Aortic Aneurysm and Dissection

This article describes a detailed methodology of using a radiopaque lead-based silicone rubber to perfuse the murine vasculature for aortic diameter quantification in a mouse model of aortic aneurysm and dissection.

β-aminopropionitrile 诱发主动脉瘤和解剖小鼠模型 Aortopathy 的定量显微 CT 分析

Aortic aneurysm and dissection is associated with significant morbidity and mortality in the population and can be highly lethal. While animal models of ...

Murine Cervical Aortic Transplantation Model using a Modified Non-Suture Cuff Technique

With the introduction of powerful immunosuppressive protocols, distinct advances are possible in the prevention and therapy of acute rejection episodes. However, only minor improvement in the long-term results of transplanted solid organs could be observed over the past decades. In this context, chronic allograft vasculopathy (CAV) still represents the leading cause of late organ failure in cardiac, renal and pulmonary transplantation.
Thus far, the underlying pathogenesis of CAV development remains unclear, explaining why effective treatment strategies are presently missing and emphasizing a need for relevant experimental models in order to study the underlying pathophysiology leading to CAV formation. The following protocol describes a murine heterotopic cervical aortic transplantation model using a modified non-suture cuff technique. In this technique, a segment of the thoracic aorta is interpositioned in the right common carotid artery. With the use of the non-suture cuff technique, an easy to learn and reproducible model can be established, minimizing the possible heterogeneity of sutured vascular micro anastomoses.

Here, we present a protocol of heterotopic aortic transplantation in mice using the non-suture cuff technique in a cervical murine model. This model can be used to study the underlying pathology of chronic allograft vasculopathy (CAV) and can help evaluate new therapeutic agents in order to prevent its formation.

使用改性非缝合铐技术的宫颈主动脉移植模型

With the introduction of powerful immunosuppressive protocols, distinct advances are possible in the prevention and therapy of acute rejection episodes. ...

Murine Surgical Model of Topical Elastase Induced Descending Thoracic Aortic Aneurysm

According to the Center for Disease Control, aortic aneurysms (AAs) were considered a leading cause of death in all races and both sexes from 1999-2016. An aneurysm forms as a result of progressive weakening and eventual dilation of the aorta, which can rupture or tear once it reaches a critical diameter. Aneurysms of the descending aorta in the chest, called descending thoracic aortic aneurysms (dTAA), make up a large proportion of aneurysm cases in the United States. Uncontained dTAA rupture is almost universally lethal, and elective repair has a high rate of morbidity and mortality. The purpose of our model is to study dTAA specifically, to elucidate the pathophysiology of dTAA and to search for molecular targets to halt the growth or reduce the size of dTAA. By having a murine model to study thoracic pathology precisely, targeted therapies can be developed to specifically test dTAA. The method is based on the placement of porcine pancreatic elastase (PPE) directly on the outer murine aortic wall after surgical exposure. This creates a destructive and inflammatory reaction, which weakens the aortic wall and allows for aneurysm formation over weeks to months. Though murine models possess limitations, our dTAA model produces robust aneurysms of predictable size. Furthermore, this model can be used to test genetic and pharmaceutical targets which may arrest dTAA growth or prevent rupture. In human patients, interventions such as these could help avoid aneurysm rupture, and difficult surgical intervention.

We describe a surgical protocol to consistently induce robust descending thoracic aortic aneurysms in mice. The procedure involves left thoracotomy, thoracic aorta exposure, and placement of a sponge soaked in porcine pancreatic elastase on the aortic wall.

局部性乳酸酶诱导下降胸腔主动脉瘤的毛尿外科模型

According to the Center for Disease Control, aortic aneurysms (AAs) were considered a leading cause of death in all races and both sexes from 1999-2016. ...

Porcine Model of Infrarenal Abdominal Aortic Aneurysm

Large animal models to study abdominal aortic aneurysms are sparse. The purpose of this model is to create reproducible, clinically significant infrarenal abdominal aortic aneurysms (AAA) in swine. To achieve this, we use a combination of balloon angioplasty, elastase and collagenase, and a lysyl oxidase inhibitor, called &#946;-aminopropionitrile (BAPN), to create clinically significant infrarenal aortic aneurysms, analogous to human disease.
Noncastrated male swine are fed BAPN for 7 days prior to surgery to achieve a steady state in the blood. A midline laparotomy is performed and the infrarenal aorta is circumferentially dissected. An initial measurement is recorded prior to aneurysm induction with a combination of balloon angioplasty, elastase (500 units)/collagenase (8000 units) perfusion, and topical elastase application. Swine are fed BAPN daily until terminal procedure on either postoperative day 7, 14, or 28, at which time the aneurysm is measured, and tissue procured. BAPN + surgery pigs are compared to pigs that underwent surgery alone.
Swine treated with BAPN and surgery had a mean aortic dilation of 89.9% &#177; 47.4% at day 7, 105.4% &#177; 58.1% at day 14, and 113.5% &#177; 30.2% at day 28. Pigs treated with surgery alone had significantly smaller aneurysms compared to BAPN + surgery animals at day 28 (p &#60; 0.0003). The BAPN + surgery group had macroscopic and immunohistochemical evidence of end stage aneurysmal disease.
Clinically significant infrarenal AAA can be induced using balloon angioplasty, elastase/collagenase perfusion and topical application, supplemented with oral BAPN. This model creates large, clinically significant AAA with hallmarks of human disease. This has important implications for the elucidation of AAA pathogenesis and testing of novel therapies and devices for the treatment of AAA. Limitations of the model include variation in BAPN ingested by swine, quality of elastase perfusion, and cost of BAPN.&#160;

This novel model creates robust infrarenal abdominal aortic aneurysms in swine using a combination of balloon angioplasty, elastase/collagenase perfusion, topical elastase application, and oral compound &#946;-aminopropionitrile administration, which interferes with collagen cross-linking.

肾上腺腹动脉瘤的猪模型

Large animal models to study abdominal aortic aneurysms are sparse. The purpose of this model is to create reproducible, clinically significant infrarenal ...

A Murine Model of Hemodialysis Access-Related Hand Dysfunction

Chronic kidney disease is a major public health problem, and the prevalence of end-stage renal disease (ESRD) requiring chronic renal replacement therapies such as hemodialysis continues to increase. Autogenous arteriovenous fistula (AVF) placement remains a primary vascular access option for ESRD patients. Unfortunately, approximately half of the hemodialysis patients experience dialysis access-related hand dysfunction (ARHD), ranging from subtle paresthesia to digital gangrene. Notably, the underlying biologic drivers responsible for ARHD are poorly understood, and no adequate animal model exists to elucidate the mechanisms and/or develop novel therapeutics for the prevention/treatment of ARHD. Herein, we describe a new mouse model in which an AVF is created between the left common iliac artery and vein, thereby facilitating the assessment of limb pathophysiology. The microsurgery includes vessel isolation, longitudinal venotomy, creation of arteriovenous anastomosis, and venous reconstruction. Sham surgeries include all the critical steps except for AVF creation. Iliac AVF placement results in clinically relevant alterations in central hemodynamics, peripheral ischemia, and impairments in hindlimb neuromotor performance. This novel preclinical AVF model provides a useful platform that recapitulates common neuromotor perturbations reported by hemodialysis patients, allowing researchers to investigate the mechanisms of ARHD pathophysiology and test potential therapeutics.

This protocol details the surgical steps of murine common iliac arteriovenous fistula creation. We developed this model to study hemodialysis access-related limb pathophysiology.

血液透析通路相关手功能障碍的小鼠模型

Chronic kidney disease is a major public health problem, and the prevalence of end-stage renal disease (ESRD) requiring chronic renal replacement ...

Drug Treatment by Central Venous Catheter in a Mouse Model of Angiotensin II Induced Abdominal Aortic Aneurysm and Monitoring by 3D Ultrasound

Since pharmaceutical treatment options are lacking in the clinical management of abdominal aortic aneurysm (AAA), animal models, in particular mouse models, are applied to advance the understanding of the disease pathogenesis and to identify potential therapeutic targets. Testing novel drug candidates to block AAA growth in these models generally requires repeated drug administration during the time course of the experiment. Here, we describe a compiled protocol for AAA induction, insertion of an intravenous catheter to facilitate prolonged therapy, and serial AAA monitoring by 3D ultrasound. Aneurysms are induced in apolipoprotein E (ApoE) deficient mice by angiotensin II release over 28 days from osmotic mini-pumps implanted subcutaneously into the mouse back. Subsequently, the surgical procedure for external jugular vein catheterization is conducted to allow for daily intravenous drug treatment or repeated blood sampling via a subcutaneous vascular access button. Despite the two dorsal implants, the monitoring of AAA development is readily facilitated by sequential semi-automated 3D ultrasound analysis, which yields comprehensive information on the expansion of aortic diameter and volume and on aneurysm morphology, as illustrated by experimental examples.

This protocol describes the consecutive implantation of an osmotic pump to induce abdominal aortic aneurysm by angiotensin II release in apolipoprotein E (ApoE) deficient mice and of a vascular access port with a jugular vein catheter for repeated drug treatment. Monitoring of aneurysm development by 3D ultrasound is effectively conducted despite dorsal implants.

血管紧张素II诱导的腹主动脉瘤小鼠模型中中心静脉导管的药物治疗及3D超声监测

Since pharmaceutical treatment options are lacking in the clinical management of abdominal aortic aneurysm (AAA), animal models, in particular mouse ...