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 border="0" cellpadding="0" cellspacing="0" width="762">
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			<td align="right">351008</td>
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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...

Watch this Scientific Journal Video about Reproducible Arterial Denudation Injury by Infrarenal Abdominal Aortic Clamping in a Murine Model at JoVE.com

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

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 ...

科研

医学

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 ...

A Murine Model of Arterial Restenosis: Technical Aspects of Femoral Wire Injury

Cardiovascular disease caused by atherosclerosis is the leading cause of death in the developed world. Narrowing of the vessel lumen, due to atherosclerotic plaque development or the rupturing of established plaques, interrupts normal blood flow leading to various morbidities such as myocardial infarction and stroke. In the clinic endovascular procedures such as angioplasty are commonly performed to reopen the lumen. However, these treatments inevitably damage the vessel wall as well as the vascular endothelium, triggering an excessive healing response and the development of a neointimal plaque that extends into the lumen causing vessel restenosis (re-narrowing). Restenosis remains a major cause of failure of endovascular treatments for atherosclerosis. Thus, preclinical animal models of restenosis are vitally important for investigating the pathophysiological mechanisms as well as translational approaches to vascular interventions. Among several murine experimental models, femoral artery wire injury is widely accepted as the most suitable for studies of post-angioplasty restenosis because it closely resembles the angioplasty procedure that injures both endothelium and vessel wall. However, many researchers have difficulty utilizing this model due to its high degree of technical difficulty. This is primarily because a metal wire needs to be inserted into the femoral artery, which is approximately three times thinner than the wire, to generate sufficient injury to induce prominent neointima. Here, we describe the essential surgical details to effectively overcome the major technical difficulties of this model. By following the presented procedures, performing the mouse femoral artery wire injury becomes easier. Once familiarized, the whole procedure can be completed within 20 min.

The mouse femoral artery wire injury model of restenosis is technically challenging. In this protocol we show the key technical details essential for successfully performing wire injury to induce consistent&#160;neointima for studies of restenosis.

动脉再狭窄小鼠模型:股导线损伤的技术方面

Cardiovascular disease caused by atherosclerosis is the leading cause of death in the developed world. Narrowing of the vessel lumen, due to ...

Murine Model of Intestinal Ischemia-reperfusion Injury

Intestinal ischemia is a life-threatening condition associated with a broad range of clinical conditions including atherosclerosis, thrombosis, hypotension, necrotizing enterocolitis, bowel transplantation, trauma and chronic inflammation. Intestinal ischemia-reperfusion (IR) injury is a consequence of acute mesenteric ischemia, caused by inadequate blood flow through the mesenteric vessels, resulting in intestinal damage. Reperfusion following ischemia can further exacerbate damage of the intestine. The mechanisms of IR injury are complex and poorly understood. Therefore, experimental small animal models are critical for understanding the pathophysiology of IR injury and the development of novel therapies.
Here we describe a mouse model of acute intestinal IR injury that provides reproducible injury of the small intestine without mortality. This is achieved by inducing ischemia in the region of the distal ileum by temporally occluding the peripheral and terminal collateral branches of the superior mesenteric artery for 60 min using microvascular clips. Reperfusion for 1 hr, or 2 hr after injury results in reproducible injury of the intestine examined by histological analysis. Proper position of the microvascular clips is critical for the procedure. Therefore the video clip provides a detailed visual step-by-step description of this technique. This model of intestinal IR injury can be utilized to study the cellular and molecular mechanisms of injury and regeneration.

Here we describe the detailed procedure of intestinal ischemia-reperfusion in mice which results in reproducible injury without mortality to encourage the standardization of this technique across the field. This model of intestinal ischemia-reperfusion injury can be utilized to study the cellular and molecular mechanisms of injury and regeneration.

肠缺血再灌注损伤的小鼠模型

Intestinal ischemia is a life-threatening condition associated with a broad range of clinical conditions including atherosclerosis, thrombosis, ...

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 ...

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 ...

Intravital Microscopy of Monocyte Homing and Tumor-Related Angiogenesis in a Murine Model of Peripheral Arterial Disease

The therapeutic goal for peripheral arterial disease and ischemic heart disease is to increase blood flow to ischemic areas caused by hemodynamic stenosis. Vascular surgery is a viable option in selected cases, but for patients without indications for surgery such as progression to rest pain, critical limb ischemia, or major disruptions to life or work, there are few possibilities for mitigating their disease. Cell therapy via monocyte-enhanced perfusion through the stimulation of collateral formation is one of a few non-invasive options.
Our group examines arteriogenesis after monocyte transplantation into mice using the hindlimb ischemia model. Previously, we have demonstrated improvement in hindlimb perfusion using tetanus-stimulated syngeneic monocyte transplantation. In addition to the effects on the collateral formation, tumor growth could be affected by this therapy as well. To investigate these effects, we use a basement membrane-like matrix mouse model by injecting the extracellular matrix of the Engelbreth-Holm-Swarm sarcoma into the flank of the mouse, after occlusion of the femoral artery.
After the artificial tumor studies, we use intravital microscopy to study in vivo tumor-angiogenesis and monocyte homing within collateral arteries. Previous studies have described the histological examination of animal models, which presupposes subsequent analysis to post-mortem artifacts. Our approach visualizes monocyte homing to areas of collateralization in real time sequences, is easy to perform, and investigates the process of arteriogenesis and tumor angiogenesis in vivo.

Monocytes are important mediators of arteriogenesis in the context of peripheral arterial disease. Using a basement membrane-like matrix and intravital microscopy, this protocol investigates monocyte homing and tumor-related angiogenesis after monocyte injection in the femoral artery ligation murine model.

小鼠外周动脉疾病模型中单核细胞归巢和肿瘤相关血管生成的活体显微镜观察

The therapeutic goal for peripheral arterial disease and ischemic heart disease is to increase blood flow to ischemic areas caused by hemodynamic ...

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. ...

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 ...