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。

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.