Neuromuscular rehabilitation to improve function in older adults with PAD

外周动脉疾病（PAD）及其相关的身体功能和血糖下降 新陈代谢影响近20%的老年人，并导致大量的医疗保健费用。现行标准 PAD患者的护理仅包括医疗管理或手术血运重建，但这并不 充分解决与受损血管生成和毛细血管 稀疏化有氧运动训练（AEX）可使PAD患者的功能得到适度改善，但 并不能恢复健康老年人的功能状态。这可能部分归因于有限的 PAD患者对AEX的血管生成反应。辅助治疗，如神经肌肉电刺激 （NMES）可以增强骨骼肌血管生成，以改善这些患者的功能和代谢。 本研究将检验AEX+NMES可改善血管生成生长因子表达、内皮细胞增殖和血管生成的假设。 祖细胞（EPC）动员，骨骼肌毛细血管密度和肌肉灌注超过AEX或 仅NMES，这些机制的改善将转化为流动人口的更大增加， 糖耐量受损（IGT）老年PAD患者的容量和糖代谢。这将是 通过两个目标进行测试。目的1：确定AEX+NMES、仅AEX和仅NMES与 骨骼肌毛细血管密度的调控及相关的血管生成机制。目标2：确定 干预对血管生成的影响是否转化为肌肉灌注的改善， 行走能力和葡萄糖代谢。我们将研究48名患有PAD和IGT的老年男性和女性（60- 75岁，方丹I-II期PAD），按性别和人种分层，随机分配至4组之一 (AEX+NMES、仅AEX、仅NMES或对照; n=12/组）。在3个月干预前后， 参与者将完成研究测试，包括：a）标准化跑步机测试，以评估步行能力 B）通过对比增强超声评估运动功能; 改良的体能测试和6分钟步行; c）口服葡萄糖耐量测试; d）腓肠肌 肌肉取样以测量毛细血管密度和血管生成生长因子表达;和e）急性发作 的AEX或NMES，以评估对循环血管生成生长因子水平和EPC动员的影响。 重复测量ANCOVA将用于确定EX+NMES、仅NMES和仅AEX的影响 与对照组相比。这将是第一项使用NMES作为AEX辅助手段的研究，目标是 改善伴有IGT的老年PAD患者的肌肉灌注、身体功能和代谢。而且这 研究设计将评估AEX和NMES对血管生成机制的独立和联合作用 与功能和新陈代谢的任何改善有关。这可能导致更大规模的审判， 改善老年PAD患者的治疗，以减少功能独立性的丧失， 手术干预、发病率和死亡率。

Peripheral artery disease (PAD) and its associated declines in physical function and glucose metabolism affect nearly 20% of older adults and result in substantial health care costs. The current standard of care for PAD patients includes only medical management or surgical revascularization, but this does not sufficiently address functional and metabolic impairments related to impaired angiogenesis and capillary rarefaction. Aerobic exercise training (AEX) results in modest functional improvements in PAD patients, but does not restore functional status to that of healthy older adults. This may be attributable, in part, to a limited angiogenic response to AEX in PAD patients. Adjunct therapies such as neuromuscular electrical stimulation (NMES) may enhance skeletal muscle angiogenesis to improve function and metabolism in these patients. This study will test the hypothesis that AEX+NMES improves angiogenic growth factor expression, endothelial progenitor cell (EPC) mobilization, skeletal muscle capillary density, and muscle perfusion more than AEX or NMES alone, and that improvements in these mechanisms will translate to greater increases in ambulatory capacity and glucose metabolism in older PAD patients with impaired glucose tolerance (IGT). This will be tested through two aims. Aim 1: Determine the effects of AEX+NMES, AEX-only, and NMES-only compared to Control on skeletal muscle capillary density and associated angiogenic mechanisms. Aim 2: Determine whether the effects of the interventions on angiogenesis translate to improvements in muscle perfusion, ambulatory capacity, and glucose metabolism. We will study 48 older men and women with PAD and IGT (60- 75yrs, Fontaine Stage I-II PAD) randomized, with stratification by sex and race, to one of four groups (AEX+NMES, AEX-only, NMES-only, or Control; n=12/group). Before and after the 3-month interventions, participants will complete research testing consisting of: a) A standardized treadmill test to assess ambulatory capacity and calf muscle perfusion by contrast-enhanced ultrasound; b) Assessment of mobility function by modified physical performance test and 6-minute walk; c) Oral glucose tolerance test; d) Gastrocnemius muscle sampling to measure capillary density and angiogenic growth factor expression; and e) An acute bout of AEX or NMES to assess effects on circulating angiogenic growth factor levels and EPC mobilization. Repeated measures ANCOVA will be used to determine the effects of EX+NMES, NMES-only, and AEX-only compared to Control. This would be the first study to use NMES as an adjunct to AEX with the goal of improving muscle perfusion, physical function, and metabolism in older PAD patients with IGT. Moreover, this study design will assess the independent and combined effects of AEX and NMES on angiogenic mechanisms associated with any improvements in function and metabolism. This could lead to larger trials intended to improve the treatment of older PAD patients in order to reduce the loss of functional independence, rates of surgical intervention, morbidity and mortality.