We are grateful to Dr. Clowes for first developing and describing this method. We are also thankful to Dr. Tulis for his detailed protocol which has been fundamentally helpful to our previous, current and future work. This work was supported by grants R01HL097111 and R01HL123364 from the NIH to M.T., and by American Heart Association grant 14GRNT18880008 to M.T.
We would like to thank Rachel Newton for her expert technical support and for her valuable help during the filming process.

注意：利用动物进行下面的实验已经进行了审查和批准的机构动物护理和使用委员会（IACUC）。 1.术前手续<ol style="margin-left: 40px;"><li>在使用前消毒手术器械。 <ol><li>高压灭菌所有手术器械24小时或更少的手术前。如果多次手术均在同一天进行的，通过在手术之间的干珠灭菌消毒的器械。 </li></ol></li><li>过滤消毒后再使用盐溶液。 </li><li>称量大鼠和计算的麻醉药物（氯胺酮80 mg / kg和赛拉嗪7毫克/千克）的剂量。 </li><li>施用麻醉药物腹膜内（IP）。 <ol><li>验证在5-10分钟镇静由脚趾捏是否足够。管理的附加的小剂量的药物（氯胺酮7 mg / kg和赛拉嗪0.6毫克/千克）如镇静是不完整的。 </li><li>确保针头是深足交付药物内每itoneally因为未交付的全部药液进入腹膜腔会引起镇静不足。 注：溃疡和脱发在皮肤注射部位会在手术后可见几天，由于无意皮下（sc）药液注入。 </li></ol></li><li>注入3毫升无菌生理盐水溶液皮下（SC）。用无菌棉签，将少量眼药膏对两眼以防止角膜干燥。 </li><li>准备加热设备。预温热垫通过微波或水浴。 </li><li>把动物仰起的手术台上。 <ol><li>去除头发在颈部腹侧区。用棉签涂于头发卸妆，等待30秒，完全擦去，用纱布。 </li><li>涂上碘伏擦洗和70％乙醇的脖子。 </li></ol></li><li>穿上个人防护设备，包括礼服，头发罩，口罩，眼镜。放在STER处理无菌手术器械和用品前ILE在结束手术手套。 </li><li>悬垂用无菌手术片的大鼠与只露出的颈部区域。 </li></ol> 2.外科手术<ol style="margin-left: 40px;"><li>在手术过程中，检查动物镇静深度在每15分钟脚趾捏。如果动物响应脚趾捏，添加氯胺酮和赛拉嗪的额外的小剂量（初始剂量的10％）。 </li><li>解剖左颈总动脉（CCA） <ol><li>用手术刀做一个直的纵向切口在颈部的中部。的皮肤切口的近似长度为1.5-2厘米，用于隔离动脉的1.5-2厘米部的目的。的长度可以变化取决于研究的目的。 </li><li>直截了当地解剖从皮肤的结缔组织。保持钳提示并确保不刺破皮肤或皮下组织。 </li><li>解剖肌肉层纵向ALON克气管的左侧。 </li><li>当打开了肌肉层，可视化的左CCA与迷走神经紧密相连。说白了剖析沿着左侧颈动脉非常谨慎，以最小的伸展分离迷走神经。 </li><li>解剖CCA到远端分叉。仔细剖析分岔和两个分支 - 颈内动脉（ICA）和颈外动脉（ECA）。 </li><li>保持周围的CCA解剖，直到1.5-2厘米的动脉大致一部分从周围组织中分离。 </li></ol></li><li>球囊损伤<ol><li>永久做出的ECA一个连字在约5mm远离分叉。永久结扎ECA的枕支，接近非洲经委会和ICA分叉。还永久结扎等分支机构，如果有的话，分叉和ECA结扎的定位 - 例如，甲状腺分支。缝合了用于所有连字是黑色4-0丝绸。夹在CCA的近端和ICA的远端。 注：现在，血流量已经停止或者通过永久结扎（非洲经委会）或临时通过削波（在CCA和ICA）。在分叉管腔面积内容已经分离从全身循环。 </li><li>就ECA的动脉切开术切口小，微型剪刀。确保该切口靠近远侧缝合线结。净血用生理盐水和棉签。 </li><li>将未充气2F球囊导管插入ECA流明。近端推进球囊导管的CCA流明。继续推进导管近端，直到它的末端到达那里的夹子保持。 </li><li>气囊充气装置连接到阴路厄锁在一个3路活塞和活塞3路的阳鲁尔锁定连接​​到气囊导管。 </li><li>慢慢膨胀时大约1.5个大气压压力的气球，以扩张颈动脉，以1.5倍的直径。 </l我&gt; <li>轻轻拉球旋转回分叉。 </li><li>放气的气球，并推进它回到近端。再次膨胀，并重复该拉回过程两次以上。 </li><li>从动脉管腔撤回球囊导管。 </li></ol></li><li>试剂腔内管理（ 例如，siRNA的药物） 注意：在此，使用的试剂是含有编码shRNA的任靶向基质相互作用分子1（STIM1）或非靶向shRNA的对照慢病毒颗粒的溶液。 STIM1是一个单一的跨膜内质网（ER）的蛋白质是一个ER的Ca 2+传感器控制质膜的Ca 2+通道的活化，是在血管平滑肌分化上调成增殖表型的洄游12,30-33。 <ol><li>附加一个血管内过度的注射针型导管到注射器（24克，1.6厘米）。测试REAG的吸30微升的解决方案经济需求测试。插入导管插入ECA同一切口。 </li><li>推进导管尖端进入CCA和领带一块缝合上的ECA单结固定导管，并暂时关闭切口。 </li><li>注入检测试剂溶液进入CCA的内腔中。保持在容器内腔中的溶液30分钟。保持暴露组织湿润用盐水和用一块湿纱布覆盖。 </li><li>孵育后，吸出剩余的溶液。松开单结，收回导管。 </li><li>领带ECA用一块缝合近端的动脉切开术的切口。使结尽可能接近分叉。 </li></ol></li><li>特写伤口。 <ol><li>由于球囊损伤和导管引入可能导致血管的泄漏或穿刺，卸下ICA的剪辑，并检查是否有泄漏。如果出血观察，申请一块纱布，并应用温和的压力止血。 </li><li>拆除CCA上的其他剪辑。 </li><li>确保有出血的迹象，然后删除所有夹具和其他手术器械。切掉多余的缝线。 </li><li>关闭伤口用皮肤缝合（4-0黑丝）。拭子上闭合伤口用聚烯吡酮碘或其它的抗感染性/杀菌剂/杀病毒剂剂的所有侧面。注资30毫升无菌生理盐水SC </li></ol></li></ol> 3.术后程序<ol style="margin-left: 40px;"><li>手术后继续隔热垫鼠。管理通过肌肉注射（IM）的大鼠0.05毫克/公斤丁丙诺啡一剂。在恢复过程中，保持动物的眼睛和嘴巴湿润。监测动物，直到它是清醒和走动。 </li><li>放在一个干净的笼子里的动物没有任何床上用品，直到其完全恢复。恢复后，将动物将被返回到动物室和单独圈养。 </li></ol>

<ol>
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American journal of physiology.</a> Cell Physiology. 295, C779-C790 (2008).</li><li>Bisaillon, J. M., 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=Essential+role+for+STIM1/Orai1-mediated+calcium+influx+in+PDGF-induced+smooth+muscle+migration.+American+journal+of+physiology.">Essential role for STIM1/Orai1-mediated calcium influx in PDGF-induced smooth muscle migration. American journal of physiology.</a> Cell Physiology. 298, C993-C1005 (2010).</li><li>Tulis, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rat+carotid+artery+balloon+injury+model.">Rat carotid artery balloon injury model.</a> Methods In Molecular Medicine. 139, 1-30 (2007).</li><li>Zhang, W., Trebak, M., Szallasi, A., B&#237;r&#243;, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Balloon+Injury+in+Rats+as+a+Model+for+Studying+TRP+Channel+Contribution+to+Vascular+Smooth+Muscle+Remodeling.">Balloon Injury in Rats as a Model for Studying TRP Channel Contribution to Vascular Smooth Muscle Remodeling.</a> T TRP Channels in Drug DiscoveryMethods in Pharmacology and Toxicology. , 101-111 (2012).</li><li>Tulis, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Histological+and+morphometric+analyses+for+rat+carotid+balloon+injury+model).">Histological and morphometric analyses for rat carotid balloon injury model).</a> Methods In Molecular Medicine. 139, 31-66 (2007).</li></ol>

The authors declare that they have no competing financial interests.

大鼠颈动脉球囊损伤一直深受Tulis在2007年34说明，它已全面通过Tulis博士讨论了此过程的所有细节。谁是有意执行此过程的读者强烈推荐阅读Tulis“协议。然而，有一件事我们不Tulis博士同意：除了充气用生理盐水或任何液体的气球，我们建议与空气膨胀了。根据我们的个人经验，液体膨胀难以避免气泡。此外，它更难以灵活调整损伤过程中的压力，并可能导致额外的压力和伤害到动脉。另一个技术技巧是...

气囊导管在血管成形术的过程中使用，以扩大或动脉粥样硬化血栓阻塞网站，在血管的目的的医疗器械。变窄的血管腔被强制由膨胀的气球，以开放和血液供应将被顺序地恢复到解除下游局部缺血症状，例如心绞痛，心肌梗塞，和腿痛。然而，血管成形术的巨大成功已经减少了术后并发症如力结果引起血管气压伤（球囊损伤），即血管壁重塑，在很多情况下，再狭窄的血管腔（再狭窄）1。 已经开发了许多动物模型模仿血管成形术，以帮助研究人员了解球囊损伤有关的血管壁重塑2背后的机制。在所有的用于建模的动物物种，鼠是最经常使用的一个。 Çompared到兔，狗和猪，鼠的优势是其成本低，其相对的易用性和大鼠生理学的现有知识。虽然小鼠具有一个额外的优势在广泛基因操作的菌株，小鼠容器太小，插入气囊导管。在过去的三十年里，实验组大鼠已使研究人员能够更好地了解支撑内膜增生及血管重塑3-6的分子和细胞机制。超越球囊损伤，血管重塑也参与大多数主要血管疾病，如动脉粥样硬化7,8，高血压9和动脉瘤10。因此，知识通过球囊损伤模型，获得了在一般的整体血管壁病变的研究是有益的。 大鼠球囊损伤模型的总体目标是不仅要进一步理解的血管疾病，而且，以测试新的药剂的效力为疾病控制11,12。目前临床药物治疗再狭窄是由血管成形术后右经血管腔放置药物洗脱支架应用。在动物模型中，一个高效而更经济的方式为新代理的测试是一个发达的地方腔内灌注的方法。已通过这种方法进行了测试候选药物包括小分子药物13,14，细胞因子或生长因子15,16，基因操纵剂（cDNA克隆，的siRNA 等 ）17-20，以及新颖的药物制剂21,22。 到目前为止，大鼠球囊损伤模型仍然是研究血管疾病/病症的最有用的模型之一。它是从台架的基本步骤到床头，通常作为第一步骤，从体外移动到体内 ，但它不应该是最后一个。大鼠实验的结果需要被审议和进一步的特征在于转换到人体之前临床使用时，由于在血管床和容器解剖学以及人和大鼠23-26之间的内在物种差异的差异。尽管如此，它仍然是在转化医学研究的重要工具。虽然这种研究用于因缺乏转基因鼠的限制，它已不再是一个问题，因为新的基因组的方法，如锌指核酸酶27，TALENS 28和CRISPR-CAS 29取得淘汰赛大鼠方便。

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			<td height="21" style="height:21px;">Fogarty balloon embolectomy catheters, 2 French&#160;</td>
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			<td height="21" style="height:21px;">Deltaphase Operating Board - Includes 2 Pads &#38; 2 Insulators</td>
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			<td height="21" style="height:21px;">Hartmann Mosquito Forceps 4&#8221; curved</td>
			<td>Apiary Medical, Inc. San Diego, CA</td>
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			<td height="21" style="height:21px;">Crile Retractor 4&#8221; double ended</td>
			<td>Apiary Medical, Inc.</td>
			<td>gS 34.1934</td>
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			<td height="21" style="height:21px;">Other surgical instruments</td>
			<td>Roboz Surgical Instrument Company, Inc., Gaithersburg, MD</td>
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vascular balloon injury and intraluminal administration in rat carotid artery

大鼠颈动脉球囊损伤模型已经确立了二十多年。它仍然是学习与之相关的血管平滑肌分化，形成内膜和血管重塑的分子和细胞机制的重要方法。雄性Sprague-Dawley大鼠是最经常使用的动物为这种模式。雌性大鼠不优选的，因为雌激素是保护性防止血管疾病，因而引入一个变化成此过程。左颈通常受伤与右颈动脉作为阴性对照。左颈损伤是由膨胀的气球是滥伐内皮和扩张S中的血管壁造成的。损伤后，潜在的治疗策略，例如使用药物化合物和任一基因或shRNA转移的进行评估。典型地，对于基因或shRNA转移，血管腔的受伤部分被局部转30分钟，用viral粒子交付和表达了受伤的血管壁或者编码蛋白质或shRNA。新内膜增厚较增殖的血管平滑肌细胞通常损伤后峰值在2周。船只大多收获用于细胞和分子的细胞信号转导途径的分析以及基因和蛋白表达该时间点。容器也可收获在较早时间点，以确定一个特定的蛋白质或途径的表达和/或活化的发作，这取决于预期的实验目的。容器可以被表征和评价使用组织染色，免疫组织化学，蛋白质/表达测定法，和活性测定。来自同一动物的完整右颈动脉是一种理想的内部控制。在分子和细胞损伤的参数引起的变化可以通过动脉受伤比较内部右控制动脉进行评估。同样地，治疗方法可以通过比较损伤进行评估D和治疗动脉控制只受伤的动脉。

伤后两周内，颈动脉被收获，切片并进行形态分析。动脉是横切片并用H＆E（ 图1，图2B，C和3）。大鼠颈动脉壁包含四层弹性膜，它显示为粉色系。最外层片材，外弹性膜（EEL）和最内层椎板之间的区域，内弹性膜（IEL）是媒体平滑肌层（ 图1）。在IEL的内侧的区域为内膜，内皮细胞完好容器的单层;或内膜增生血管损伤。在受损的颈动脉中，媒体比因平滑肌细胞增殖的控?...

Watch this Scientific Journal Video about Vascular Balloon Injury and Intraluminal Administration in Rat Carotid Artery at JoVE.com

Vascular Balloon Injury and Intraluminal Administration in Rat Carotid Artery

该协议使用球囊导管引起的大鼠颈动脉腔内损伤，从此引起内膜增生。这是一个公认的模型用于研究在响应损伤的血管重塑的机制。它也被广泛使用，以确定潜在的治疗方法的有效性。

血管球囊损伤和腔内管理在大鼠颈动脉

The carotid artery balloon injury model in rats has been well established for over two decades. It remains an important method to study the molecular and ...

vascular-balloon-injury-intraluminal-administration-rat-carotid

Research

JoVE Journal

Medicine

16.2K 次观看.  State University of New York College of Nanoscale Science and Engineering (SUNY CNSE). 该协议使用球囊导管引起的大鼠颈动脉腔内损伤，从此引起内膜增生。这是一个公认的模型用于研究在响应损伤的血管重塑的机制。它也被广泛使用，以确定潜在的治疗方法的有效性。 

视频: Vascular Balloon Injury and Intraluminal Administration in Rat Carotid Artery

Training a Sophisticated Microsurgical Technique: Interposition of External Jugular Vein Graft in the Common Carotid Artery in Rats

Neointimal hyperplasia is one the primary causes of stenosis in arterialized veins that are of great importance in arterial coronary bypass surgery, in peripheral arterial bypass surgery as well as in arteriovenous fistulas.1-5 The experimental procedure of vein graft interposition in the common carotid artery by using the cuff-technique has been applied in several research projects to examine the aetiology of neointimal hyperplasia and therapeutic options to address it. 6-8 The cuff prevents vessel anastomotic remodeling and induces turbulence within the graft and thereby the development of neointimal hyperplasia.
Using the superior caval vein graft is an established small-animal model for venous arterialization experiment.9-11 This current protocol refers to an established jugular vein graft interposition technique first described by Zou et al., 9 as well as others.12-14 Nevertheless, these cited small animal protocols are complicated.
To simplify the procedure and to minimize the number of experimental animals needed, a detailed operation protocol by video training is presented. This video should help the novice surgeon to learn both the cuff-technique and the vein graft interposition. Hereby, the right external jugular vein was grafted in cuff-technique in the common carotid artery of 21 female Sprague Dawley rats categorized in three equal groups that were sacrificed on day 21, 42 and 84, respectively. Notably, no donor animals were needed, because auto-transplantations were performed. The survival rate was 100 % at the time point of sacrifice. In addition, the graft patency rate was 60 % for the first 10 operated animals and 82 % for the remaining 11 animals. The blood flow at the time of sacrifice was 8&plusmn;3 ml/min. In conclusion, this surgical protocol considerably simplifies, optimizes and standardizes this complicated procedure. It gives novice surgeons easy, step-by-step instruction, explaining possible pitfalls, thereby helping them to gain expertise fast and avoid useless sacrifice of experimental animals.

Neointimal hyperplasia is the primary cause of stenosis in arterialized veins. We propose a new protocol whereby the right external jugular vein is grafted using the cuff technique in the common carotid artery of Sprague Dawley rats. The survival rate was 100 % at the time point of sacrifice.

培养一个精密的显微外科技术在大鼠颈总动脉，颈外静脉移植：介入

Neointimal hyperplasia is one the primary causes of stenosis in arterialized veins that are of great importance in arterial coronary bypass surgery, in ...

科研

医学

Optimized System for Cerebral Perfusion Monitoring in the Rat Stroke Model of Intraluminal Middle Cerebral Artery Occlusion

The translational potential of pre-clinical stroke research depends on the accuracy of experimental modeling. Cerebral perfusion monitoring in animal models of acute ischemic stroke allows to confirm successful arterial occlusion and exclude subarachnoid hemorrhage. Cerebral perfusion monitoring can also be used to study intracranial collateral circulation, which is emerging as a powerful determinant of stroke outcome and a possible therapeutic target. Despite a recognized role of Laser Doppler perfusion monitoring as part of the current guidelines for experimental cerebral ischemia, a number of technical difficulties exist that limit its widespread use. One of the major issues is obtaining a secure and prolonged attachment of a deep-penetration Laser Doppler probe to the animal skull. In this video, we show our optimized system for cerebral perfusion monitoring during transient middle cerebral artery occlusion by intraluminal filament in the rat. We developed in-house a simple method to obtain a custom made holder for twin-fibre (deep-penetration) Laser Doppler probes, which allow multi-site monitoring if needed. A continuous and prolonged monitoring of cerebral perfusion could easily be obtained over the intact skull.

Cerebral perfusion monitoring has been demonstrated to improve accuracy in ischemic stroke models. Technical difficulties often limit the use of this essential tool for cerebrovascular research. In this video, an optimized system is shown to obtain a single or multi-site hemodynamic monitoring during intraluminal middle cerebral artery occlusion in rats.

优化系统的脑灌注监测在中风模型大鼠的大脑中动脉闭塞腔内

The translational potential of pre-clinical stroke research depends on the accuracy of experimental modeling. Cerebral perfusion monitoring in animal ...

Catheterization of the Carotid Artery and Jugular Vein to Perform Hemodynamic Measures, Infusions and Blood Sampling in a Conscious Rat Model

The success of a small animal model to study critical illness is, in part, dependent on the ability of the model to simulate the human condition. Intra-tracheal inoculation of a known amount of bacteria has been successfully used to reproduce the pathogenesis of pneumonia which then develops into sepsis. Monitoring hemodynamic parameters and providing standard clinical treatment including infusion of antibiotics, fluids and drugs to maintain blood pressure is critical to simulate routine supportive care in this model but to do so requires both arterial and venous vascular access. The video details the surgical technique for implanting carotid artery and common jugular vein catheters in an anesthetized rat. Following a 72 hr recovery period, the animals will be re-anesthetized and connected to a tether and swivel setup attached to the rodent housing which connects the implanted catheters to the hemodynamic monitoring system. This setup allows free movement of the rat during the study while continuously monitoring pressures, infusing fluids and drugs (antibiotics, vasopressors) and performing blood sampling.

Vascular accesses to measure hemodynamics, provide fluids and perform blood sampling are important to any small animal model study. We present a technique for implanting catheters into the carotid artery and the common jugular vein in an anesthetized rat for connecting to a system to perform monitoring, infusions and sampling.

颈动脉和颈静脉导管在有意识大鼠模型进行血流动力学措施，输液和血液采样

The success of a small animal model to study critical illness is, in part, dependent on the ability of the model to simulate the human condition. ...

Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study model. As the use of mouse models are often a vital step in preclinical drug discovery and drug development1-8, it is necessary to design a system to introduce drugs into mice in a uniform, reproducible manner. Ideally, the system should permit the collection of blood samples at regular intervals over a set time course. The ability to measure drug concentrations by mass-spectrometry, has allowed investigators to follow the changes in plasma drug levels over time in individual mice1, 9, 10. In this study, paclitaxel was introduced into transgenic mice as a continuous arterial infusion over three hours, while blood samples were simultaneously taken by retro-orbital bleeds at set time points. Carotid artery infusions are a potential alternative to jugular vein infusions, when factors such as mammary tumors or other obstructions make jugular infusions impractical. Using this technique, paclitaxel concentrations in plasma and tissue achieved similar levels as compared to jugular infusion. In this tutorial, we will demonstrate how to successfully catheterize the carotid artery by preparing an optimized catheter for the individual mouse model, then show how to insert and secure the catheter into the mouse carotid artery, thread the end of the catheter out through the back of the mouse&#8217;s neck, and hook the mouse to a pump to deliver a controlled rate of drug influx. Multiple low volume retro-orbital bleeds allow for analysis of plasma drug concentrations over time.

This method was developed with the goal of delivering a steady drug solution via the carotid artery, to assess the pharmacokinetics of novel drugs in mouse models.

颈动脉输液的紫杉烷类化合物在小鼠体内的药代动力学和药效学分析

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study ...

Ferric Chloride-induced Thrombosis Mouse Model on Carotid Artery and Mesentery Vessel

Severe thrombosis and its ischemic consequences such as myocardial infarction, pulmonary embolism and stroke are major worldwide health issues. The ferric chloride injury is now a well-established technique to rapidly and accurately induce the formation of thrombi in exposed veins or artery of small and large diameter. This model has played a key role in the study of the pathophysiology of thrombosis, in the discovery and validation of novel antithrombotic drugs and in the understanding of the mechanism of action of these new agents. Here, the implementation of this technique on a mesenteric vessel and carotid artery in mice is presented. The method describes how to label circulating leukocytes and platelets with a fluorescent dye and to observe, by intravital microscopy on the exposed mesentery, their accumulation at the injured vessel wall which leads to the formation of a thrombus. On the carotid artery, the occlusion caused by the clot formation is measured by monitoring the blood flow with a Doppler probe.

The FeCl3 induced thrombosis model in mice is described herein. A method to monitor thrombus growth by intravital microscopy observation on a mesenteric vessel and by blood flow measurement in the carotid artery is presented.

三氯化铁诱发血栓形成小鼠模型上的颈动脉和肠系膜血管

Severe thrombosis and its ischemic consequences such as myocardial infarction, pulmonary embolism and stroke are major worldwide health issues. The ferric ...

A Rat Carotid Balloon Injury Model to Test Anti-vascular Remodeling Therapeutics

The rat carotid balloon injury is a well-established surgical model that has been used to study arterial remodeling and vascular cell proliferation. It is also a valuable model system to test, and to evaluate therapeutics and drugs that negate maladaptive remodeling in the vessel. The injury, or barotrauma, in the vessel lumen caused by an inflated balloon via an inserted catheter induces subsequent neointimal growth, often leading to hyperplasia or thickening of the vessel wall that narrows, or obstructs the lumen. The method described here is sufficiently sensitive, and the results can be obtained in relatively short time (2 weeks after the surgery). The efficacy of the drug or therapeutic against the induced-remodeling can be evaluated either by the post-mortem pathological and histomorphological analysis, or by ultrasound sonography in live animals. In addition, this model system has also been used to determine the therapeutic window or the time course of the administered drug. These studies can leadto the development of a better administrative strategy and a better therapeutic outcome. The procedure described here provides a tool for translational studies that bring drug and therapeutic candidates from bench research to clinical applications.

The rat carotid balloon injury model described below allows researchers to evaluate drugs or therapeutics that negate injury-induced arterial hyperplasia. Detailed pre-surgical preparation, surgical procedure, and post-surgical cares of the animal are described.

大鼠颈动脉球囊损伤模型试验抗血管重建治疗

The rat carotid balloon injury is a well-established surgical model that has been used to study arterial remodeling and vascular cell proliferation. It is ...

Intraluminal Drug Delivery to the Mouse Arteriovenous Fistula Endothelium

Delivery of therapeutic agents to enhance arteriovenous fistula (AVF) maturation can be administered either via intraluminal or external routes. The simple murine AVF model was combined with intraluminal administration of drug solution to the venous endothelium at the same time as fistula creation. Technical aspects of this model are discussed. Under general anesthesia, an abdominal incision is made and the aorta and inferior vena cava (IVC) are exposed. The infra-renal aorta and IVC are dissected for clamping. After proximal and distal clamping, the puncture site is exposed and a 25 G needle is used to puncture both walls of the aorta and into the IVC. Immediately after the puncture, a reporter gene-expressing viral vector was infused in the IVC via the same needle, followed by 15 min of incubation. The intraluminal administration method enabled more robust viral gene delivery to the venous endothelium compared to administration by the external route. This novel method of delivery will facilitate studies that explore the role of the endothelium in AVF maturation and enable intraluminal drug delivery at the time of surgical operation.

After puncturing the aorta through the inferior vena cava (IVC) to create an aorto-caval fistula in the mouse, solution containing a drug is infused into the IVC via the same needle, followed by incubation. This method enables more robust drug delivery to the venous endothelium compared to the external route.

腔内药物输送到鼠标动静脉瘘内皮

Delivery of therapeutic agents to enhance arteriovenous fistula (AVF) maturation can be administered either via intraluminal or external routes. The ...

The Rabbit Model of Accelerated Atherosclerosis: A Methodological Perspective of the Iliac Artery Balloon Injury

Acute coronary syndrome resulting from coronary occlusion following atherosclerotic plaque development and rupture is the leading cause of death in the industrialized world. New Zealand White (NZW) rabbits are widely used as an animal model for the study of atherosclerosis. They develop spontaneous lesions when fed with atherogenic diet; however, this requires long time of 4 - 8 months. To further enhance and accelerate atherogenesis, a combination of atherogenic diet and mechanical endothelial injury is often employed. The presented procedure for inducing atherosclerotic plaques in rabbits uses a balloon catheter to disrupt the endothelium in the left iliac artery of NZW rabbits fed with atherogenic diet. Such mechanical damage caused by the balloon catheter induces a chain of inflammatory reactions initiating neointimal lipid accumulation in a time dependent fashion. Atherosclerotic plaque following balloon injury show neointimal thickening with extensive lipid infiltration, high smooth muscle cell content and presence of macrophage derived foam cells. This technique is simple, reproducible and produces plaque of controlled length within the iliac artery. The whole procedure is completed within 20 - 30 min. The procedure is safe with low mortality and also offers high success in obtaining substantial intimal lesions. The procedure of balloon catheter induced arterial injury results in atherosclerosis within two weeks. This model can be used for investigating the disease pathology, diagnostic imaging and to evaluate new therapeutic strategies.

Animal models of atherosclerosis are essential to understand the mechanism and to investigate newer approaches to prevent plaque development or rupture, a leading cause of death in the industrialized world. This protocol uses a combination of balloon injury and cholesterol rich diet to induce atherosclerotic plaques in rabbit iliac artery.

家兔加速动脉粥样硬化模型的研究--髂动脉球囊损伤的方法学观察

Acute coronary syndrome resulting from coronary occlusion following atherosclerotic plaque development and rupture is the leading cause of death in the ...

Phase Contrast Magnetic Resonance Imaging in the Rat Common Carotid Artery

Phase contrast magnetic resonance imaging (PC-MRI) is a noninvasive approach that can quantify flow-related parameters such as blood flow. Previous studies have shown that abnormal blood flow may be associated with systemic vascular risk. Thus, PC-MRI can facilitate the translation of data obtained from animal models of cardiovascular diseases to pertinent clinical investigations. In this report, we describe the procedure for measuring blood flow in the common carotid artery (CCA) of rats using cine-gated PC-MRI and discuss relevant analysis methods. This procedure can be performed in a live, anesthetized animal and does not require euthanasia after the procedure. The proposed scanning parameters yield repeatable measurements for blood flow, indicating excellent reproducibility of the results. The PC-MRI procedure described in this article can be used for pharmacological testing, pathophysiological assessment, and cerebral hemodynamics evaluation.

The overall goal of this procedure is to measure the blood flow in the rat common carotid artery by using noninvasive phase contrast magnetic resonance imaging.

大鼠颈总动脉的相位对比磁共振成像

Phase contrast magnetic resonance imaging (PC-MRI) is a noninvasive approach that can quantify flow-related parameters such as blood flow. Previous ...

Ferric Chloride-induced Canine Carotid Artery Thrombosis: A Large Animal Model of Vascular Injury

Occlusive arterial thrombosis leading to cerebral ischemic stroke and myocardial infarction contributes to ~13 million deaths every year globally. Here, we have translated a vascular injury model from a small animal into a large animal (canine), with slight modifications that can be used for pre-clinical screening of prophylactic and thrombolytic agents. In addition to the surgical methods, the modified protocol describes the step-by-step methods to assess carotid artery canalization by angiography, detailed instructions to process both the brain and carotid artery for histological analysis to verify carotid canalization and cerebral hemorrhage, and specific parameters to complete an assessment of downstream thromboembolic events by utilizing magnetic resonance imaging (MRI). In addition, specific procedural changes from the previously well-established small animal model necessary to translate into a large animal (canine) vascular injury are discussed.

Here, we present the modifications necessary to a well characterized and commonly used small animal ferric chloride-induced (FeCl3) carotid artery injury model for use in a large animal vascular injury model. The resulting model can be utilized for pre-clinical trial assessment of both prophylactic and thrombolytic pharmacological and mechanical interventions.

氯化铁诱导的犬颈动脉血栓形成: 一种大的血管损伤动物模型

Occlusive arterial thrombosis leading to cerebral ischemic stroke and myocardial infarction contributes to ~13 million deaths every year globally. Here, ...