The Microcirculation in Claudication and Exercise Rehabilitation

描述(申请人提供)：外周动脉疾病(PAD)在美国是一种高度流行的疾病，大约有800万至1200万美国人受到影响。PAD主要被认为是一种以动脉粥样硬化为表现的大血管疾病。终末器官肌肉的微血管功能障碍对PAD症状的发生和进展的作用尚不确定。与冠状动脉血管疾病类似，大血管和微血管功能障碍可能共同参与了PAD进展的病理生理学过程。需要对PAD进展和症状来源的病理生理学有更深入的了解，以便为新的评估方法和新的治疗策略提供基础。目的：1)探讨中度PAD患者跛行极限运动耐量(PWT)与微血管血流量的关系。目的2)确定运动康复后PWT的变化是否与微血管血流的变化相关。目的：确定血管内皮细胞健康的生物标志物循环内皮祖细胞(EPC)和内皮衍生微粒(MPS)测量的血管健康状况是否在运动康复后有所改善，并与微血管血流量相关。设计与方法：对中度PAD的受试者进行平板运动试验。连续动脉自旋标记-灌注MRI将用于测量骨骼肌小腿微血管血流，流式细胞术将用于表征上述内皮血管健康状况。我们预计，有监督的运动康复计划将改善PWT、微血管血流和内皮血管健康状况。 公共卫生相关性：外周动脉疾病在美国是一种高度流行的疾病，影响到大约800万至1200万美国人。早期残疾源于跛行或缺血性肌肉疼痛，从而抑制行走。这种疾病的病理生理学被认为是由大血管引起的，然而微血管在这种疾病中的作用还不是很清楚，可能是重要的。提高对微血管系统在这种疾病中的作用的认识，以及通过相对非介入的成像和循环细胞生物标记物分析监测康复或其他治疗干预的影响的能力的改善，可能有助于这种疾病的治疗。

DESCRIPTION (provided by applicant): Peripheral arterial disease (PAD) is a highly prevalent condition in the United States, affecting approximately 8-12 million Americans. PAD is largely thought to be a macrovascular disease manifested by atherosclerosis. The contribution of microvascular dysfunction in the end-organ, muscle, to the incidence of symptoms and progression of PAD is uncertain. Similar to vascular disease in the coronary arteries, it is likely that a combination of macrovascular and microvascular dysfunction is involved in the pathophysiology of PAD progression. A more thorough understanding of the pathophysiology of PAD progression and symptom origin is required to provide the basis for new methods of evaluation and novel therapeutic strategies. Aims: Aim-1)To determine in a group of patients with moderate PAD, the relationship between claudication limited exercise tolerance (Peak Walking Time-PWT) and microvascular blood flow. Aim-2)To determine if changes in PWT with exercise rehabilitation correlate with changes in microvascular blood flow. Aim-3) To determine if the vascular health profile, as measured with circulating Endothelial Progenitor Cells (EPCs) and endothelially-derived microparticles (MPs), biomarkers of endothelial health, improves following exercise rehabilitation and correlate with microvascular blood flow. Design & Methods: Subjects with moderate PAD will undergo measurement of treadmill PWT. Continuous Arterial Spin Labeling-Perfusion MRI will be used to measure skeletal muscle calf microvascular blood flow and flow cytometry will be used to characterize the endothelial vascular health profile described above. We anticipate that a supervised exercise rehabilitation program will improve PWT, microvascular blood flow, and the endothelial vascular health profile. PUBLIC HEALTH RELEVANCE: Peripheral arterial disease is a highly prevalent condition in the United States, affecting approximately 8-12 million Americans. Early disability derives from claudication or ischemic muscle pain, inhibiting ambulation. The pathophysiology of this disorder is thought to be of macrovascular origin, however the contribution of the microvasculatrue to this disorder is not well understood and may be important. Improved knowledge of the contribution of the microvasculature to this disorder, and improvement in our ability to monitor, via relatively nonivasive imaging and circulating cellular biomarker assays, the impact of rehabilitation or other therpaeutic interventions, may assist in the treatment of this disorder.