Low-Energy Shockwave Treatment Distal To Peripheral Vascular Disease

描述（由申请人提供）：外周血管疾病（PVD）在西方世界的老龄化人口中变得越来越普遍。肾血管性高血压（RVH）与大血管PVD相关，可诱导下游微血管（MV）的重塑和损失，这些在血管通畅恢复后往往是不可逆的。遗憾的是，恢复微循环和改善RVH和PVD预后的适当策略尚未确定，并且仍然迫切需要。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，引发心血管和肌肉骨骼系统的生物反应，包括抑制炎症和刺激新MV的形成。值得注意的是，这种新方法在保护慢性RVH微循环和增加MV活力方面的潜力尚未得到探索。我们已经开发和表征了新的猪RVH模型，密切模仿人类病理生理。此外，我们已经开发和完善了独特的成像技术，非常适合探测PVD中的MV自适应过程，以及它们对MV损伤和生存能力的潜在贡献。这些工具现在提供了一个独特的机会来评估低能量体外SWT对RVH病理生理和结果的影响，以及用新的干预措施修改它们的可行性。该建议的工作假设是，在RVH-PVD中，SWT是安全的，可以减少中压损伤，改善功能和氧合，从而在恢复上游血管通畅后促进恢复。为了验证这一假设，我们将利用尖端的多探测器CT （MDCT）、磁共振成像（MRI）和使用创新工具的微型CT的组合来研究SWT的影响。此外，SWT改善肾脏恢复前景的能力将在接受血管重建术和支架置入的PVD猪中进行测试。具体目标1将验证SWT是安全的假设，并在4周后改善血管梗阻远端功能和结构。特异性目的2将检验SWT在PVD血运重建后恢复肾脏恢复潜力的假设。本研究将促进我们对PVD远端MV损伤的发病机制的理解，并可能建立一种新的、临床可行的治疗策略。改进中压网络在心血管医学中是一种很有前途的技术，但这种前沿技术尚未应用于RVH-PVD。因此，这些研究可能会对PVD的管理做出重大贡献。

DESCRIPTION (provided by applicant): 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.