Aerobic Training to Improve Energy Utilization and Antioxidant Capacity in Stroke

描述 15%至30%的中风幸存者是永久性残疾，这通常导致中风后久坐不动的生活方式和功能依赖。虽然已知轻偏瘫步态使步行活动的能量消耗增加1.5- 2倍，但慢性卒中如何影响每日总能量消耗（TDEE）和饮食摄入目前尚不清楚。改变能量平衡（消耗`摄入）可能导致底物氧化受损和骨骼肌氧化应激。骨骼肌中氧化应激的升高与疲劳以及心血管和肌肉耐力的降低有关。在老年非中风人群中进行跑步机运动训练可改善家庭步行活动、身体功能和代谢状况，并对骨骼肌具有抗氧化作用。此外，确保能量和大量营养素的摄入量满足个人的能量和燃料需求可能会导致氧化损伤的减少。这项随机对照研究测试了跑步机康复加营养调整的假设，（“心脏健康”饮食加充足蛋白质）（TM+N）与拉伸加营养改良（ST+N）（营养控制）将1）改善能量平衡和底物氧化，2）减少全身和组织水平的氧化应激，和3）这些干预措施（TM+N和ST+N）的各自比较跑步机（TM）和拉伸（ST）控制从她的导师的当前R 01将支持营养调整在中风的康复作用。我们提出以下目标：目标1：评估6个月TM+N与ST+N对慢性卒中幸存者TDEE和底物氧化的影响。 目标二：研究6个月TM+N与ST+N对慢性卒中幸存者全身和组织氧化应激和抗氧化能力的影响。 目标3：比较TM+N和ST+N分别与TM和ST单独治疗对慢性卒中幸存者能量平衡以及全身和组织氧化应激的影响。 将招募具有稳定神经功能缺损的老年（55-75岁）慢性卒中（卒中后至少6个月）男性和绝经后女性（n=50）。受试者将被随机分配参加六个月的饮食调整（<30%的卡路里为脂肪，<10%为饱和脂肪，<2,400 mg钠，25 g/d的纤维和1.0-1.2 g/kg/d的瘦蛋白）加有氧运动训练或饮食调整加全身拉伸。七天的加速度计和饮食记录将用于确定能量平衡。将使用间接量热法测定空腹以及峰值和次极量运动期间的底物氧化。将进行抽血和轻瘫和非轻瘫股外侧肌骨骼肌活检，以确定运动康复或拉伸（有或无营养调整）后全身和组织水平氧化应激含量（硝酸盐/亚硝酸盐和硫代巴比妥酸反应物质）和抗氧化能力（超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶）的变化 在慢性中风幸存者中。 本CDA-2申请中描述的指导和培训将大大提高被提名人成为独立调查员的能力，同时确定有氧运动康复与营养调整可以改善TDEE并减少氧化应激的机制。我们假设，这项研究将提供证据，以改善中风治疗，底物利用，血液和骨骼肌的抗氧化能力，并减少退伍军人中风幸存者的身体活动，可能导致与慢性中风残疾退伍军人护理相关的临床成本降低。

DESCRIPTION Fifteen to 30% of stroke survivors are permanently disabled, which usually leads to a sedentary lifestyle and functional dependence following stroke. While it is known that hemiparetic gait elevates the energy cost of ambulatory activity by 1.5- 2 fold, how chronic stroke affects total daily energy expenditure (TDEE) and dietary intake is currently unknown. Altered energy balance (expenditure ` intake) may result in impaired substrate oxidation and skeletal muscle oxidative stress. Elevated oxidative stress in skeletal muscle is associated with fatigue and decreased cardiovascular and muscular endurance. Treadmill exercise training in older, non-stroke populations improves home ambulatory activity, physical function, and metabolic profiles and has antioxidant effects in skeletal muscle. Additionally, ensuring that energy and macronutrient intake meets an individual's energy and fuel needs may result in decreases in oxidative damage. This randomized control study tests the hypothesis that treadmill rehabilitation plus nutritional modification ("heart healthy" diet plus adequate protein) (TM+N) versus stretching plus nutritional modification (ST+N) (nutrition control) will 1) improve energy balance and substrate oxidation, 2) reduce systemic and tissue level oxidative stress, and 3) that the respective comparison of these interventions (TM+N and ST+N) to treadmill (TM) and stretching (ST) controls from her mentor's current R01 will support the rehabilitative role of nutritional modification in stroke. We propose the following aims: Aim 1: To assess the effects of six months of TM+N versus ST+N on TDEE and substrate oxidation in chronic stroke survivors. Aim 2: To examine the effects of six months of TM+N versus ST+N on systemic and tissue oxidative stress and antioxidant capacity in chronic stroke survivors. Aim 3: To compare the effects of TM+N and ST+N versus TM and ST alone, respectively, on energy balance and systemic and tissue oxidative stress, in chronic stroke survivors. Older (55-75 years), men and postmenopausal women (n=50) with chronic stroke (at least 6 months post stroke) with stable neurological deficits will be recruited. Subjects will be randomized to participate in six months o dietary modification (<30% of calories as fat, <10% as saturated fat, <2,400 mg sodium, 25 g/d of fiber, and 1.0-1.2 g/kg/d of lean protein) plus aerobic exercise training or dietary modificatio plus whole body stretching. Seven-day accelerometry and dietary records will be used to determine energy balance. Indirect calorimetry will be used to determine substrate oxidation during fasting and a peak and submaximal exercise bout. Blood draws and paretic and non-paretic vastus lateralis skeletal muscle biopsies will be performed to determine changes in systemic and tissue level oxidative stress content (nitrate/nitrite and thiobarbituric acid reactiv substances) and antioxidant capacity (superoxide dismutase, glutathione peroxidase, and catalase) following exercise rehabilitation or stretching with and without nutritional modification in chronic stroke survivors. The mentoring and training described in this CDA-2 application will greatly enhance the nominee's development into an independent investigator, while simultaneously identifying mechanisms by which aerobic exercise rehabilitation with nutritional modification can improve TDEE and reduce oxidative stress. We postulate that this study will provide evidence to improve stroke treatment, substrate utilization, and the antioxidant capacity of blood and skeletal muscle and reduce physical inactivity in Veteran stroke survivors, potentially leading to a reduction in clinical costs related to the care of Veterans with disabilit from chronic stroke.