Perfusion of Active Muscles: Metabolites and Nerves

活跃肌肉的灌注：代谢物和神经

基本信息

批准号：
7822178
负责人：
MICHAEL J JOYNER
金额：
$ 1.12万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-01 至 2010-10-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The long-term goal of HL-46493 is to understand how substances released by contracting skeletal muscles and sympathetic nerves interact and regulate blood flow to the active muscles. This renewal focuses on local and systemic responses to "mismatches" between muscle blood flow, O2 delivery and metabolism to explore in humans a) whether the pressor response to rhythmic exercise during muscle hypoperfusion improves blood flow to active muscles; b) the potential vasodilator "error signals" associated with hypoperfusion in active muscles; c) the interactions between these responses; and d) the extent to which challenges to skeletal muscle O2 delivery with hypoxia vs. hypoperfusion evoke similar compensatory adjustments. In this context, the following specific aims will be addressed: 1) We will use a small intra- arterial catheter/balloon system to create graded skeletal muscle hypoperfusion during rhythmic handgripping to evaluate whether the pressor response to exercise with muscle hypoperfusion improves blood flow to the active muscles. We hypothesize that the rise in vasoconstricting muscle sympathetic nerve activity (MSNA) evoked by the combination of rhythmic exercise and hypoperfusion prevents the pressor response from improving blood flow to the contracting muscles. 2) Using the catheter/balloon system, we will measure the local vasodilator responses to muscle hypoperfusion during exercise and use pharmacological tools to explore their nature. We hypothesize that local vasodilator responses to rhythmic exercise with hypoperfusion serve to maintain muscle blood flow during mild and moderate but not heavy rhythmic handgripping when MSNA is likely to rise. We also hypothesize that adenosine (perhaps along with NO) will be the main factor responsible for the compensatory dilation. 3) We will test whether the compensatory vasodilator signals that maintain O2 delivery to active muscles during exercise with mild hypoxia are the same or different than those that cause compensatory vasodilation during normoxic exercise with hypoperfusion. We hypothesize that adenosine (perhaps along with NO) will be the main factor responsible for the compensatory dilation under both circumstances. Summary and Significance: Muscle blood flow is a key determinant of exercise capacity, and it is unknown how systemic sympathoexcitation and local vasodilator responses to exercise with either hypoperfusion or hypoxia interact to regulate blood flow to contracting human skeletal muscles. We propose novel and innovative strategies to address a number of currently unresolved issues and controversies related to these topics in humans.

描述（申请人提供）：HL-46493的长期目标是了解通过收缩骨骼肌和交感神经释放的物质如何相互作用并调节流向活性肌肉的血液流动。这种更新着重于对人类肌肉血流，O2递送和代谢之间“不匹配”的局部和全身反应，以探索人类a）施加对肌肉下灌注期间节奏运动的反应是否可以改善血液流向活跃肌肉的血液； b）潜在的血管扩张剂与活性肌肉中的灌注不足有关的“误差信号”； c）这些响应之间的相互作用； d）在骨骼肌O2递送与低氧灌注相对于下灌注方面的挑战在多大程度上引起了类似的补偿性调整。在这种情况下，将解决以下具体目标：1）我们将使用小的动脉内导管/气球系统在节奏手工剪辑过程中创建分级的骨骼肌灌注不足，以评估施加肌肉下灌注的压力反应是否可以改善运动肌肉的血液流动。我们假设血管收缩的肌肉交感神经活动（MSNA）的升高是通过节奏运动和灌注不足的组合所引起的，这阻止了压迫反应改善血液流向收缩肌肉。 2）使用导管/气球系统，我们将在运动过程中测量局部血管扩张器对肌肉灌注不足的反应，并使用药理学工具探索其性质。我们假设局部血管舒张者对节奏灌注的节奏运动的反应可在轻度和中度和中度但不重的节奏手工夹下在MSNA上升时保持肌肉血流。我们还假设腺苷（也许与否一起）将是负责补偿性扩张的主要因素。 3）我们将测试轻度低氧运动过程中维持O2递送到活性肌肉的补偿性血管扩张器信号是否与在低灌注液中进行正常氧性运动过程中导致补偿性血管舒张的补偿性血管扩张器信号相同或不同。我们假设腺苷（也许与否一起）将是两种情况下弥补补偿性扩张的主要因素。摘要和意义：肌肉血流是运动能力的关键决定因素，尚不清楚系统性交感神经和局部血管扩张剂对运动的反应如何通过灌注不足或缺氧相互作用，以调节血液流动以缩短人类骨骼肌的血液。我们提出了新颖的创新策略，以解决与人类中这些主题有关的许多目前未解决的问题和争议。