Name: reproducible arterial denudation injury by infrarenal abdominal aortic clamping in a murine model
Uploaded: 2016-11-24T12:30:00.000+00:00
Duration: 8 min 33 s
Description: Watch this Scientific Journal Video about Reproducible Arterial Denudation Injury by Infrarenal Abdominal Aortic Clamping in a Murine Model at JoVE.com

这项工作是由从礼与再生医学的Edythe广泛中心补助和与健康（HL130290）的国家机构来支持MLIA加州大学洛杉矶分校训练计划干细胞研究，以ASS和AIM，菲利普·J.·惠特科姆奖学金到AIM。

注:此协议已在美国加州洛杉矶大学被批准的动物研究委员会。 1.术前准备及麻醉<ol><li>一定要在整个过程中遵守无菌技术。 </li><li>使用消毒蒸汽高压灭菌器的所有手术用品。 </li><li>打开麻醉诱导之前加热啮齿动物手术平台使得它可以温热至在外科手术过程适当的温度（37℃）并置于立体显微镜可视化。 </li><li>鼠标放置在麻醉诱导室，并以1升/分钟的流速，用4％异氟烷诱导。 <ol><li>仔细监测小鼠诱导时的呼吸频率和足底皮肤的颜色。 </li><li>呼吸速率的减缓后，从感应腔移开鼠标和放置在外科手术制备以面在2.5％分离鼻锥和维护的异氟烷浓度温热垫。 </li><li>执行脚趾捏来评估麻醉的充分性。 </li></ol></li><li>应用眼药膏角膜和（5毫克/千克）管理皮下注射术前卡布洛芬。 </li><li>将鼠标仰卧和利用快船从腹部取出的头发。 </li><li>用聚维酮碘的三个交替磨砂和70％异丙醇用无菌纱布垫施加准备手术区。 </li><li>在加热啮齿动物外科手术平台，脸鼻锥将鼠标仰卧和保护所有四肢并仔细鼠标的位置，使腹部与体视显微镜可见。 </li><li>放置无菌粘合剂敷料沿准备手术区域的各边缘。 </li><li>滴定异氟醚浓度在手术过程中保持足够的麻醉，同时保持自主呼吸。 </li></ol> 2.下腹主动脉阻断<ol><li>使3厘米的切口向下腹部中线使用手术刀，起始approximatelý0.5厘米劣于剑突。 </li><li>轻轻缩回用钳子皮肤和用细剪刀剪开精结缔组织腹壁皮肤解剖走。 </li><li>应用0.05-0.1毫升0.5％布比卡因对肌壁，使2厘米的切口插入腹壁，露出腹部器官。 <ol><li>如果沿腹壁发生出血，应用温和的压力用棉签。 </li></ol></li><li>轻轻抬起使用生理盐水浸湿棉签涂抹肠子。 注意:小心，以避免在一个温暖，无菌生理盐水纱布浸泡在腹腔外的海绵钝伤空肠回肠动脉和地点。 <ol><li>覆盖其他温暖，无菌生理盐水浸湿的纱布海绵肠子，以避免水分流失。 </li></ol></li><li>放置牵开lateralize直肠和暴露后腹膜。 </li><li>将小纱布垫所必需的retroperitone可视化嗯跟踪中使用的数。 </li><li>在右肾下极水平，用锋利的解剖钳做出retroperitonotomy横向到主动脉。 注:小心不要弄伤下腔静脉或周围血管。 <ol><li>说白了解剖腹膜后组织了主动脉 小心不要穿透下腔静脉或周围血管。 </li></ol></li><li>放置血管钳在主动脉至少1分钟，或其他指定的时间，并通过目视观察在远端主动脉缺乏搏动的验证闭塞。 </li><li>取出血管钳和验证止血。止血达到和当血液没有活性外渗看出确保。 <ol><li>通过加入0.5ml盐水腹腔并且如果盐水日益成为血液微染评估确认外渗。如果是这样的情况下，使用盐水浸泡敷料器1分钟，以确保施加轻柔的压力止血。 </li></ol></li><li>卸下放置在腹膜后的可视化，以帮助和替换原位肠到腹部的纱布垫。 </li><li>使用预温热的无菌盐水灌溉腹腔。 </li></ol> 3.剖腹手术及皮肤闭幕<ol><li>使用5-0编织，吸收单连续缝合关闭腹壁肌肉层。 </li><li>以聚合物粘合剂的1-3滴，然后随后用伤口夹关闭皮肤一旦粘合剂设置。 </li></ol> 4.恢复和术后评估<ol><li>鼠标的食物和水转移到恢复笼上一个加热垫在笼底。 </li><li>密切监视鼠标呼吸困难的症状。辖卡布洛芬（5毫克/千克），每日每术后指导机构48小时。 <ol><li>不要离开无人看管的动物，直到它已经恢复了足够的意识，以保持胸骨recumbency。 </li></ol></li><li>返回鼠标与食物和水的正常笼。 <ol><li>不要返回已动过手术，以公司的其他动物，直到完全康复的动物。 </li></ol></li><li>评估裂开每天伤口，术后14天删除片段。 </li></ol> 5.主动脉夹层和染色<ol><li>基于以下剥蚀损伤感兴趣的特定时间点为牺牲选择的小鼠。 </li><li> 通过异氟醚牺牲小鼠并立即与5毫克氯乙酰甲胆碱注射引起血管平滑肌松弛。 </li><li>经呼吸停止，缺乏角膜反射和缺乏运动的死亡的确认，灌注4％多聚甲醛的磷酸盐缓冲盐水在通过左侧心脏心室10分钟100毫米汞柱的灌注压。 </li><li>使用解剖立体显微镜仔细完整的腹主动脉分离开周围组织。 </li><li>横切主动脉喙肾动脉和尾至髂分叉，并通过沿背表面的纵行切口打开。 </li><li>针主动脉平35毫米的硅树脂涂层菜与腔侧为固定时间不少于2小时，但不超过12小时。随后，将组织既可以嵌入用于切片或在连接面整体贴装免疫细胞化学使用。 </li><li>山沾有鲁米那面朝上玻片的共聚焦显微镜盖玻片主动脉。 </li></ol>

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作者什么都没有透露。

动脉损伤剥蚀，由于经皮干预措施，例如气囊血管成形术和血管支架，导致早期和晚期血管栓塞和再狭窄，并有助于复发性缺血事件3,12。有趣的是，外科血管夹紧也被牵连作为动脉剥蚀的原因，扩大的问题，以进行任何血管过程的患者的范围内，无论是经皮或打开13。而受损的再内皮化是血栓形成和再狭窄的相当认可的起因，周围再内皮化的分子机制已难以澄清。动物模型已成为...

血栓形成和再狭窄的患者严重的早期和晚期并发症接受谁经皮血管介入，如血管内球囊成形术1,2。多种策略已经被用来解决这些并发症，尤其是双重抗血小板治疗和药物洗脱支架。然而，很少焦点一直放在血栓形成和再狭窄，内皮细胞覆盖率（剥蚀）即损失的潜在原因。剥蚀损伤是由于机械外伤到血管壁介入过程的必然结果。这种机械创伤可导致损坏和去除基底膜和血管平滑肌的保护内皮细胞层并且暴露于循环血液3。在这些领域中的内皮细胞的损失创建前血栓形成和促炎环境，不仅促进血小板粘附和随后的血栓形成，但LSO刺激迁移，并导致新内膜增厚和狭窄4血管平滑肌细胞的增殖。这些并发症，以及它们的相关的治疗，导致显著发病率，最值得注意的是复发性缺血性疾病和出血事件影响人类健康。 再内皮从伤口边缘的裸露损伤是非常重要的预防血栓形成和再狭窄5。尸检结果和动物模型已经证明有效的减少血栓的发生率与支架支柱覆盖6,7。药物洗脱支架，设计通过抑制平滑肌细胞增殖和内膜增生减少再狭窄率，导致动脉再内皮损伤显著和晚期血栓形成3率持续上升。不幸的是，对于认识再内皮化的机制一直是一个缓慢的过程，由于缺乏AP的主要限于propriate动物模型8。 几种动物模型对于理解下面的动脉损伤血管内皮细胞和血管平滑肌细胞的作用已创建7,9,10。大鼠颈动脉球囊损伤模型是最好的特点，并已用于研究在总量，细胞和分子水平11剥蚀损伤的作用。然而，具有优良的存活率动脉剥脱伤的高度重复性的小鼠模型的缺少和急需采取的提供给多个设置更好地阐明血管再生多个转基因株系的优势。 这份手稿介绍动脉剥脱伤是可重复的，简单执行的小鼠模型。该方法已经显示出最小的发病率和死亡率在几个转基因株系。因为转基因小鼠系的广泛数量的，该模型可以用于阐明剥蚀损伤后再内皮的分子机制。

<table><tbody><tr><td>Zeiss Discovery.V12 Stereomicroscope</td><td>Zeiss</td><td>495037-9904-000</td><td></td></tr><tr><td>Rodent Heated Surgical Platform</td><td>Protech International</td><td>RES4000</td><td>Heated platform for body temperature maintenance with nosecone for anesthestic maintenance and on which surgical procedure is performed</td></tr><tr><td>Isoflurane</td><td>Henry Schein</td><td>50033</td><td>4% Induction; 2.5% Maintenance</td></tr><tr><td>Isoflurane Vaporizer</td><td>Summit Medical Equipment</td><td>470062</td><td></td></tr><tr><td>Stryker T/Pump Warm Water Recirculator</td><td>Kent Scientific</td><td>TP-700</td><td></td></tr><tr><td>Artifical Tears Lubricant Opthalmic Ointment</td><td>Akorn Animal Health</td><td>17478-162-35</td><td></td></tr><tr><td>Carprieve (Carprofen)</td><td>Norbrook Laboratories</td><td>NDC 55529-131-01</td><td></td></tr><tr><td>Oster&amp;trade; A5 Professional Animal Clipper</td><td>M.Schneider &amp;amp; Sons Inc.</td><td>78005010</td><td>Use with animal clipper size 40</td></tr><tr><td>Adjustable Wire Retractor</td><td>Fine Science Tools</td><td>17004-05</td><td></td></tr><tr><td>Schwartz Micro Serrefines - Sharp Bend</td><td>Fine&amp;nbsp;Science Tools</td><td>18052-03</td><td></td></tr><tr><td>Surgical Instruments</td><td>Fine Science Tools</td><td></td><td>sharp dissecting forceps, blunt forceps, fine scissors, spring scissors, hemostat</td></tr><tr><td>0.5% Marcaine</td><td>Hospira</td><td>0409-1610-50</td><td></td></tr><tr><td>5-0 Suture, Vicryl</td><td>Fisher Scientific</td><td>NC0189890</td><td>tapered needle</td></tr><tr><td>Vetbond</td><td>Fisher Scientific</td><td>NC0304169</td><td></td></tr><tr><td>Falcon&amp;reg; 35 mm Not TC-Treated Easy-Grip Style Bacteriological Petri Dish</td><td>Corning</td><td>351008</td><td></td></tr><tr><td>Sylgard 184 Silicone Elastomer Kit</td><td>Dow Corning</td><td>3097358-1004</td><td></td></tr><tr><td>Dissecting pins</td><td>Fisher Scientific</td><td>NC9681411</td><td></td></tr></tbody></table>

reproducible arterial denudation injury by infrarenal abdominal aortic clamping in a murine model

经皮血管介入均匀导致动脉剥脱伤了随后导致血栓形成和再狭窄。这些并发症可在伤口边缘内再内皮归因于损伤。然而，再内皮的细胞和分子机制仍有待确定。虽然一些动物模型动脉剥脱术后学习再内皮可用，很少在鼠标由于局限性手术来执行。这破坏的机会，以利用转基因小鼠系，并调查特定基因的至再内皮过程中的贡献。在这里，我们提出了一个一步一步的协议中使用外部钳位血管下腹腹主动脉动脉创造剥蚀损伤的高度重复性的小鼠模型。纤维蛋白原和β-catenin的受伤主动脉的免疫细胞化学染色表现出亲血栓表面的暴露ð内皮完整的边界，分别。这里介绍的方法具有速度，优良的整体存活率，和相关技术容易的优点，创造了在转基因小鼠模型强加动脉剥蚀损伤一个唯一实用工具。使用这种方法，调查人员可能阐明正常或病理状态下重新内皮化的机制。

八十五只经历了本报告下腹主动脉阻断中描述的生存手术技术。总的生存率为85.9％。手术并发症包括肠道出血及大血管穿孔，导致5.9％和3.5％的死亡率分别为（ 见表1）。从麻醉中苏醒后，小鼠正常走路，且没有缺血性损伤的迹象下四肢。没有体重减轻或食欲不振指出。 继立体显微镜下剖腹探查术及腹膜后解剖无...

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

理解再内皮的细胞和分子机制下列动脉剥蚀损伤是至关重要的在防止血栓形成和动脉的再狭窄。在这里，我们描述了肾腹主动脉动脉可重复性损伤剥蚀的协议。该程序的开发研究，规范使用小鼠模型内皮细胞再生的基本机制。

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 ...

reproducible-arterial-denudation-injury-infrarenal-abdominal-aortic

Research

JoVE Journal

Medicine

9.2K 次观看.  University of California, Los Angeles. 理解再内皮的细胞和分子机制下列动脉剥蚀损伤是至关重要的在防止血栓形成和动脉的再狭窄。在这里，我们描述了肾腹主动脉动脉可重复性损伤剥蚀的协议。该程序的开发研究，规范使用小鼠模型内皮细胞再生的基本机制。 

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

Use of a Hanging-weight System for Isolated Renal Artery Occlusion

In hospitalized patients, over 50% of cases of acute kidney injury (AKI) are caused by renal ischemia 1-3. A recent study of hospitalized patients revealed that only a mild increase in serum creatinine levels (0.3 to 0.4 mg/dl) is associated with a 70% greater risk of death than in persons without any increase 1. Along these lines, surgical procedures requiring cross-clamping of the aorta and renal vessels are associated with a renal failure rates of up to 30% 4. Similarly, AKI after cardiac surgery occurs in over 10% of patients under normal circumstances and is associated with dramatic increases in mortality. AKI are also common complications after liver transplantation. At least 8-17% of patients end up requiring renal replacement therapy 5. Moreover, delayed graft function due to tubule cell injury during kidney transplantation is frequently related to ischemia-associated AKI 6. Moreover, AKI occurs in approximately 20% of patients suffering from sepsis 6.The occurrence of AKI is associated with dramatic increases of morbidity and mortality 1. Therapeutic approaches are very limited and the majority of interventional trials in AKI have failed in humans. Therefore, additional therapeutic modalities to prevent renal injury from ischemia are urgently needed 3, 7-9. 
To elucidate mechanisms of renal injury due to ischemia and possible therapeutic strategies murine models are intensively required 7-13. Mouse models provide the possibility of utilizing different genetic models including gene-targeted mice and tissue specific gene-targeted mice (cre-flox system). However, murine renal ischemia is technically challenging and experimental details significantly influence results. We performed a systematic evaluation of a novel model for isolated renal artery occlusion in mice, which specifically avoids the use of clamping or suturing the renal pedicle 14. This model requires a nephrectomy of the right kidney since ischemia can be only performed in one kidney due to the experimental setting. In fact, by using a hanging-weight system, the renal artery is only instrumented once throughout the surgical procedure. In addition, no venous or urethral obstruction occurs with this technique. We could demonstrate time-dose-dependent and highly reproducible renal injury with ischemia by measuring serum creatinine. Moreover, when comparing this new model with conventional clamping of the whole pedicle, renal protection by ischemic preconditioning is more profound and more reliable. Therefore his new technique might be useful for other researchers who are working in the field of acute kidney injury.

A precise murine model for acute kidney injury (AKI) due to ischemia is an important tool to investigate acute kidney injury and possibly find therapeutic tools to treat renal injury. The hanging weight system offers a tool for immediate and reliable renal artery occlusion and reperfusion without causing renal congestion.

一个悬重系统使用隔离肾动脉闭塞

In hospitalized patients, over 50% of cases of acute kidney injury (AKI) are caused by renal ischemia 1-3. A recent study of hospitalized patients ...

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 ...

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 ...

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 ...

Reproducible Motor Deficit Following Aortic Occlusion in a Rat Model Of Spinal Cord Ischemia

Spinal cord ischemia is a fatal complication following thoracoabdominal aortic aneurysm surgery. Researchers can investigate the strategies for preventing and treating this complication using experimental models of spinal cord ischemia. The model described here demonstrates varying degrees of paraplegia that relate to the length of occlusion following thoracic aortic occlusion in a rat spinal cord ischemia model.
A 2-Fr. balloon-tipped catheter was advanced through the femoral artery into the descending thoracic aorta until the catheter tip was placed at the left subclavian artery in anesthetized male Sprague-Dawley rats. Spinal cord ischemia was induced by inflating the catheter balloon. After a set period of occlusion (9, 10, or 11 min), the balloon was deflated. Neurologic assessment was performed using the motor deficit index at 24 h after surgery, and the spinal cord was harvested for histopathological examination.
Rats that underwent 9 min of aortic occlusion showed mild and reversible motor impairment in the hind limb. Rats subjected to 10 min of aortic occlusion presented with moderate but reversible motor impairment. Rats subjected to 11 min of aortic occlusion displayed complete and persistent paralysis. The motor neurons in the spinal cord sections were more preserved in rats subjected to shorter duration of aortic occlusion.
Researchers can achieve a reproducible hind limb motor deficit following thoracic aortic occlusion using this spinal cord ischemia model.

This study demonstrates the technique to make a minimally invasive and easily reproducible model of spinal cord ischemia in rats. Various degrees of hind limb motor deficit can be produced by controlling the aortic occlusion time.

主动脉阻塞后脊髓缺血大鼠模型中的可再生电机缺陷

Spinal cord ischemia is a fatal complication following thoracoabdominal aortic aneurysm surgery. Researchers can investigate the strategies for preventing ...

Balloon-based Injury to Induce Myointimal Hyperplasia in the Mouse Abdominal Aorta

The use of animal models is essential for a better understanding of MH, one major cause for arterial stenosis.In this article, we demonstrate a murine balloon denudation model, which is comparable with established vessel injury models in large animals. The aorta denudation model with balloon catheters mimics the clinical setting and leads to comparable pathobiological and physiological changes. Briefly, after performing a horizontal incision in the aorta abdominalis, a balloon catheter will be inserted into the vessel, inflated, and introduced retrogradely. Inflation of the balloon will lead to intima injury and overdistension of the vessel. After removing the catheter, the aortic incision will be closed with single stiches. The model shown in this article is reproducible, easy to perform, and can be established quickly and reliably. It is especially suitable for evaluating expensive experimental therapeutic agents, which can be applied in an economical fashion. By using different knockout-mouse strains, the impact of different genes on MH development can be assessed.

This article demonstrates a murine model to study the development of myointimal hyperplasia (MH) after aortic balloon injury.

球囊损伤诱发小鼠腹主动脉 Myointimal 增生的研究

The use of animal models is essential for a better understanding of MH, one major cause for arterial stenosis.In this article, we demonstrate a murine ...

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.

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 ...