Endovascular device and treatment for stabilizing aortic aneurysms

稳定主动脉瘤的血管内装置和治疗

• 批准号: 7924478
• 负责人: Matthew Frank Ogle
• 金额: $ 19.43万
• 依托单位: VATRIX MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-05 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7924478
• 关键词: Abdominal Aortic Aneurysm; Adult; Aneurysm; Animal Model; Aorta; Aortic Aneurysm; Aortic Injury; Architecture; Area; Arteries; Binding; Blood Vessels; Blood flow; Bypass; Catheters; Cause of Death; Cells; Characteristics; Degenerative Disorder; Development; Device Designs; Devices; Diagnosis; Dilatation - action; Disease; Disease Progression; Effectiveness; Elastin; Elements; Evaluation; Extracellular Matrix Degradation; Extracellular Matrix Proteins; Family suidae; Frequencies; Goals; Growth; Growth and Development function; Health; In Vitro; Inferior; Inflammatory Infiltrate; Lead; Life; Liquid substance; Location; Longevity; Matrix Metalloproteinases; Methods; Modeling; Monitor; Operative Surgical Procedures; Patients; Pentas; Procedures; Property; Rattus; Research; Research Design; Resistance; Risk; Rupture; Series; Silicon; Site; Stabilizing Agents; Staging; Stents; Tannic Acid; Technology; Testing; Tissues; Vascular Graft; Work; abdominal aorta; aging population; base; design; effective therapy; glucogallin; in vitro testing; in vivo; minimally invasive; novel; novel therapeutic intervention; older men; prototype; public health relevance; repaired; seal; tool

DESCRIPTION (provided by applicant): Abdominal aortic aneurysms (AAAs) are associated with impaired arterial wall integrity, leading to abnormal ballooning and eventual fatal rupture. Currently the sole treatment for such aneurysms is surgical intervention. Surgical procedures entail either endovascular stent graft repair or complete replacement of the diseased arterial segment with an artificial vascular graft. Although often effective, endovascular stents are anatomically appropriate for only 30% to 60% of AAA patients at the outset and present the risk of endoleaks and graft displacement. Moreover, open surgery for full size graft insertion is highly invasive, making it inappropriate for patients with high operative risk. The drawbacks associated with these procedures are significant enough that they are only applied to those patients with late-stage, critical aneurysms. Treatment options are particularly limited (virtually non-existent) for patients with small or moderate aneurysms, which comprise the largest percentage of all aneurysm patients. Consequently, novel therapeutic approaches targeted at hindering the progression of aneurysms promptly after diagnosis would be extremely beneficial. By halting the aneurysm-related expansion or growth, the risk of rupture could be significantly decreased. In addition to arterial dilatation, the onset and progression of AAAs are associated with enzymatic degradation of extracellular matrix components such as elastin. Phenolic tannins, such as penta-galloylglucose (PGG), bind to vascular elastin, and in doing so, render elastin highly resistant to enzymatic degeneration while also making the tissue mechanically stronger. These unique properties provide a platform for the potential development of novel, safe, and effective treatments for all AAAs. In previous studies, we have shown that PGG binds to aortic tissue, protects extracellular matrix proteins such as elastin, mechanically strengthens the tissue, and is effective in stopping aneurysm growth/development in a widely accepted animal model. This proposal describes the development of endovascular tools to deliver this treatment locally to the site of aneurysm (from inside the blood vessel). For the work proposed here, we will evaluate the ability of our devices to deliver the aforementioned stabilizing agents to an isolated area of aortic aneurysmal disease. The tools and delivery procedure will be carried out in an endovascular and minimally invasive fashion. Evaluation of three distinct device prototypes will initially be performed in vitro with physiologically relevant silicon models. Upon selection of the superior device prototype, this particular design will also be evaluated in vivo. For these studies, the device will be deployed to isolate a region of porcine infrarenal abdominal aorta, allowing PGG to be delivered to this specific region. Subsequent analysis will evaluate the binding of PGG to the local aortic wall, and its effect on this tissue. PUBLIC HEALTH RELEVANCE: Abdominal aortic aneurysms (AAAs) progressively grow over a period of years and pose great health risks as a result of the potential to rupture, which can be fatal in >80% of cases. AAAs are apparently increasing in frequency and are a serious health concern for the aging population, among the top 10 causes of death for older men. The goal is to develop a minimally invasive treatment for AAAs which would hinder the progression or growth of this life-threatening disease, subsequently reducing the risk of rupture and positively impacting thousands of patients.

描述（由申请人提供）：腹主动脉瘤（AAA）与动脉壁完整性受损有关，导致异常膨胀并最终致命的破裂。目前，此类动脉瘤的唯一治疗方法是手术干预。外科手术需要血管内覆膜支架修复或用人工血管移植物完全替换患病动脉段。尽管血管内支架通常有效，但在解剖学上仅适合 30% 至 60% 的 AAA 患者，并且存在内漏和移植物移位的风险。此外，全尺寸移植物插入的开放手术具有高度侵入性，因此不适合手术风险高的患者。与这些手术相关的缺点非常明显，以至于它们仅适用于患有晚期、危重动脉瘤的患者。对于小或中度动脉瘤患者来说，治疗选择尤其有限（几乎不存在），这些患者占所有动脉瘤患者的比例最大。因此，在诊断后立即阻止动脉瘤进展的新治疗方法将非常有益。通过停止与动脉瘤相关的扩张或生长，可以显着降低破裂的风险。除了动脉扩张之外，AAA 的发生和进展还与细胞外基质成分（如弹性蛋白）的酶降解有关。酚类单宁，例如五没食子酰葡萄糖 (PGG)，与血管弹性蛋白结合，从而使弹性蛋白对酶促变性具有高度抵抗力，同时也使组织具有更强的机械强度。这些独特的特性为潜在开发针对所有 AAA 的新型、安全且有效的治疗方法提供了平台。在之前的研究中，我们已经表明，PGG 与主动脉组织结合，保护弹性蛋白等细胞外基质蛋白，机械强化组织，并在广泛接受的动物模型中有效阻止动脉瘤生长/发展。该提案描述了血管内工具的开发，以将这种治疗局部递送到动脉瘤部位（从血管内部）。对于这里提出的工作，我们将评估我们的设备将上述稳定剂输送到主动脉瘤疾病的孤立区域的能力。工具和输送程序将以血管内微创方式进行。首先将使用生理相关的硅模型在体外对三种不同的设备原型进行评估。在选择了优质的设备原型后，这种特殊的设计也将在体内进行评估。在这些研究中，该装置将用于隔离猪肾下腹主动脉的一个区域，从而将 PGG 输送到该特定区域。随后的分析将评估 PGG 与局部主动脉壁的结合及其对该组织的影响。 公众健康相关性：腹主动脉瘤 (AAA) 在数年内逐渐生长，由于可能破裂而带来巨大的健康风险，超过 80% 的病例可能致命。 AAA 的发生频率明显增加，对老龄化人口来说是一个严重的健康问题，是导致老年男性死亡的十大原因之一。我们的目标是开发一种针对 AAA 的微创治疗方法，阻止这种危及生命的疾病的进展或生长，从而降低破裂的风险，并对数千名患者产生积极影响。