Blood Flow Regulation and Neuromuscular Function Post-Stroke

中风后的血流调节和神经肌肉功能

• 批准号: 10751266
• 负责人: Matthew Durand
• 金额: $ 67.31万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10751266
• 关键词: Acetylcholine; Activities of Daily Living; Acute; Affect; Age; Area; Beds; Biological Availability; Blood Vessels; Blood flow; Clinical; Clinical Trials; Complex; Data; Double-Blind Method; Equilibrium; Exercise; Exposure to; Fatigue; Hyperemia; Impairment; Individual; Intervention; Ischemia; Leg; Lower Extremity; Mediating; Metabolic; Modality; Motor; Motor Neurons; Muscle; Muscle Contraction; Muscle Fatigue; Muscle Weakness; Nerve; Neural Inhibition; Neurologic; Nitric Oxide; Norepinephrine; Oxygen; Paresis; Performance; Perfusion; Persons; Play; Process; Randomized; Regulation; Rehabilitation therapy; Resistance; Rest; Role; Skeletal Muscle; Stimulus; Stroke; Sympathetic Nervous System; Testing; Tissues; Training; Vascular Endothelium; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents; Walking; Work; chronic stroke; functional disability; functional gain; improved; interest; ischemic conditioning; leg paresis; motor deficit; negative affect; neural; neuromuscular; neuromuscular function; post stroke; rehabilitation strategy; response; sex; stroke survivor; vasoconstriction

Increased neuromuscular fatigability (the acute, exercise induced reduction in force) is an understudied consequence of stroke. This is a clinically meaningful area of study because increased neuromuscular fatigability can negatively affect task endurance for activities like walking, and successful rehabilitation strategies require repeated levels of muscle activation and overload to cause functional gains in motor performance. In addition to decreased neural drive to motorneuron pools, recent data indicate that reduced blood flow to exercising paretic muscle may play a significant role in increased neuromuscular fatigability. Exercising muscles require adequate blood flow to match the increase in metabolic demand, and we have shown that stroke survivors have reduced blood flow to the leg muscles during exercise. During exercise, sympathetic nervous system activity increases in an activity-dependent manner, causing vasoconstriction in inactive muscle beds. In the active muscle, the release of local vasodilatory factors counteracts sympathetic vasoconstriction to maintain vascular tone. This process, called functional sympatholysis, has been postulated to be critical to muscle perfusion during exercise. Our central hypothesis is that in people with stroke functional sympatholysis is impaired and results in dysregulated blood flow during exercise, which exacerbates neuromuscular fatigability and limits motor function. We propose three specific aims. In Aim 1 we will establish impaired functional sympatholysis in chronic stroke survivors and determine the relationship with metrics of neuromuscular fatigue. We will test two hypotheses in Aim 1: 1) that functional sympatholysis during exercise is impaired in the paretic leg of chronic stroke survivors compared to the non-paretic leg and age- and sex-matched controls, and 2) stroke survivors with the highest degree of functional sympatholysis impairment will have greater paretic leg muscle fatigability, and both impaired modulation of motor unit firing rates and increased metabolite buildup in the muscle during exercise. In Aim 2 we will interrogate microvascular (dys)function in the lower extremity of chronic stroke survivors. We will test two hypotheses in Aim 2: 1) that compared age- and sex-matched controls, chronic stroke survivors will have reduced nitric oxide-mediated vasodilation to acetylcholine and an enhanced vasoconstrictor response to locally infused norepinephrine, and 2) that maximum dilation to acetylcholine in the affected leg will be positively associated with lower paretic muscle fatigability. Finally, in Aim 3 we will determine if a non-invasive intervention called ischemic conditioning (IC), which is known to improve muscle performance and vascular endothelial function, can improve functional sympatholysis, and if improvements in functional sympatholysis are associated with reduced paretic muscle fatigability. We will test two hypotheses in Aim 3: 1) that IC causes immediate and sustainable improvements in functional sympatholysis, and 2) that IC-induced improvements in functional sympatholysis are associated with improved muscle fatigue resistance, and both greater modulation of motor unit firing rates and less muscle metabolite buildup during fatiguing contractions.

神经肌肉疲劳增加（急性，运动引起的力量减少）是一个未充分研究的问题