Low-Energy Shockwave Treatment Distal To Peripheral Vascular Disease

低能量冲击波治疗远端周围血管疾病

• 批准号: 8617434
• 负责人: Lilach O Lerman
• 金额: $ 23.85万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8617434
• 关键词: Address; Attenuated; Biological; Blood Vessels; Bone Regeneration; Cardiovascular system; Cell membrane; Chronic; Clinical Medicine; Disease; Distal; Family suidae; Functional disorder; Human; Imaging Techniques; In Situ; Inflammation; Injury; Injury to Kidney; Intervention; Ischemia; Kidney; Magnetic Resonance Imaging; Mechanics; Mediating; Medicine; Microcirculation; Modeling; Musculoskeletal System; Myocardial Ischemia; Obstruction; Outcome; Oxidative Stress; Pathogenesis; Patients; Peripheral Vascular Diseases; Permeability; Process; Recovery; Renal function; Renovascular Hypertension; Shock; Stress; Structure; Techniques; Tendon structure; Testing; Therapeutic; Tissues; Vascular Patency; Western World; Work; aging population; artery occlusion; density; detector; hemodynamics; improved; improved functioning; innovation; neovascularization; novel; novel strategies; public health relevance; response; restoration; therapeutic target; tool; translational study

Peripheral vascular disease (PVD) is becoming increasingly common in the aging population of the Western world. Renovascular hypertension (RVH) associated with large vessel PVD induces remodeling and loss of downstream microvessels (MV), which are often irreversible after restoration of vascular patency. Alas, adequate strategies to restore the microcirculation and improve outcomes in RVH and PVD are yet to be identified and remain in dire need. Non-invasive low-energy extracorporeal shock wave treatment (SWT) is a novel experimental strategy, which generates mechanical forces that exert localized stress on cell membranes and elicit biological responses in the cardiovascular and musculoskeletal systems, including suppression of inflammation and stimulation of new MV formation. Remarkably, the potential of this novel approach to protect the microcirculation in chronic RVH and increase MV viability has not been explored. We have developed and characterized novel swine models of RVH that closely mimic human pathophysiology. Furthermore, we have developed and refined unique imaging techniques ideally suited for probing MV adaptive processes in PVD, as well as their potential contribution to MV injury and viability. These tools now provide a unique opportunity to assess the effects of low-energy extracorporeal SWT on pathophysiology and outcomes in RVH, and the feasibility of modifying them with novel interventions. The working hypothesis underlying this proposal is that SWT in RVH-PVD is safe, and would decrease MV injury, improve function and oxygenation, and thereby improve recovery upon restoration of upstream vascular patency. To test this hypothesis, we will study the effects of SWT utilizing a combination of cutting- edge multi-detector CT (MDCT), magnetic resonance imaging (MRI), and micro-CT using innovative tools. Furthermore, the ability of SWT to improve renal recovery prospects will be tested in PVD pigs undergoing revascularization and stenting. Two specific aims will be pursued: Specific Aim 1 will test the hypothesis that SWT is safe, and would improve function and structure distal to vascular obstruction 4 weeks later. Specific Aim 2 will test the hypothesis that SWT would restore the recovery potential of the kidney in response to revascularization of PVD. The proposed studies will advance our understanding of the pathogenesis of MV injury distal to PVD, and may establish a novel, clinically feasible therapeutic strategy. Improvement of the MV network is a promising technique in cardiovascular medicine, but this cutting edge approach is yet to be applied in RVH-PVD. Thus, these studies will likely contribute significantly towards management of PVD.

外周血管疾病(PVD)在西方老龄化人口中越来越常见 世界。大血管PVD相关的肾血管性高血压(RVH)导致血管重构和血管功能丧失 下游微血管(MV)，血管通畅后往往不可逆。唉， 恢复微循环和改善RVH和PVD预后的适当策略尚未到位 被确认并仍处于迫切需要的情况下。 无创低能量体外冲击波治疗(SWT)是一种新的实验策略，它 产生机械力，在细胞膜上施加局部应力，并在 心血管和肌肉骨骼系统，包括抑制炎症和刺激新的 MV地层。值得注意的是，这种新方法在保护慢性RVH微循环方面的潜力 而提高MV的存活率还没有得到探索。 我们开发了新的猪RVH模型，并对其进行了表征，这种模型非常接近人类的病理生理学。 此外，我们还开发和改进了独特的成像技术，非常适合探测自适应MV。 PVD的过程，以及它们对MV损伤和存活的潜在贡献。这些工具现在提供了 评估低能量体外SWT对病理生理学和预后影响的独特机会 以及用新的干预措施对其进行修改的可行性。 支持这一建议的工作假设是，RVH-PVD的SWT是安全的，并将减少MV 损伤，改善功能和氧合，从而提高上游恢复后的恢复 血管通畅。为了验证这一假设，我们将研究SWT的效果，使用切割- 使用创新工具的边缘多探测器CT(MDCT)、磁共振成像(MRI)和微型CT。 此外，SWT改善肾脏恢复前景的能力将在接受PVD治疗的猪身上进行测试。 血运重建和支架置入术。 将追求两个具体目标：具体目标1将检验SWT是安全的并将得到改善的假设 4周后观察血管梗阻远端的功能和结构。《特定目标2》将检验这一假设 SWT可恢复PVD血运重建后肾脏的恢复潜能。 建议的研究将促进我们对PVD远端MV损伤的发病机制的理解，并可能 建立一种新的、临床上可行的治疗策略。MV网络的改进是一个很有前途的 这是心血管医学中的一项前沿技术，但这种尖端方法尚未应用于RVH-PVD。因此， 这些研究可能会对PVD的管理有很大的帮助。