Perfusion of Active Muscles: Metabolites and Nerves

活跃肌肉的灌注：代谢物和神经

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/7822178
• 关键词: Address; Adenosine; Blood flow; Catheters; Contracts; Data; Equilibrium; Exercise; Goals; Human; Hypoxia; Link; Literature; Measures; Metabolism; Muscle; Nature; Nerve; Oxygen; Perfusion; Physiological; Physiology; Publishing; Signal Transduction; Skeletal Muscle; Sympathetic Nervous System; System; Testing; Vasodilation; Vasodilator Agents; improved; innovation; novel; prevent; response; tool

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（由申请人提供）：HL-46493的长期目标是了解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动肌肉的血流。本次更新的重点是对肌肉血流、氧气输送和代谢之间“不匹配”的局部和全身反应，以探索人类a）肌肉灌注不足期间对节律性运动的升压反应是否改善了活动肌肉的血流; B）与活动肌肉灌注不足相关的潜在血管扩张剂“错误信号”; c）这些反应之间的相互作用;和d）缺氧与低灌注对骨骼肌O2输送的挑战引起类似代偿性调节的程度。在这种情况下，将解决以下具体目标：1）我们将使用小动脉内导管/球囊系统在有节奏的握力过程中产生分级的骨骼肌灌注不足，以评价对肌肉灌注不足的运动的升压反应是否改善了活动肌肉的血流量。我们假设，在血管收缩肌肉交感神经活动（MSNA）的结合节律性运动和低灌注引起的上升阻止升压反应，改善血液流向收缩肌肉。2)使用导管/球囊系统，我们将测量运动过程中肌肉灌注不足的局部血管舒张反应，并使用药理学工具来探索其性质。我们假设，局部血管舒张反应，以保持肌肉血流在轻度和中度，但不重的节奏时，手握MSNA可能会上升的低灌注的节律性运动。我们还假设腺苷（可能沿着NO）是代偿性扩张的主要因素。3)我们将测试在轻度缺氧的运动过程中维持O2输送到活动肌肉的代偿性血管扩张信号是否与在低灌注的常氧运动过程中引起代偿性血管扩张的信号相同或不同。我们假设腺苷（可能沿着NO）是两种情况下代偿性扩张的主要因素。总结及意义：肌肉血流量是运动能力的一个关键决定因素，目前尚不清楚全身交感神经兴奋和局部血管舒张反应的运动与灌注不足或缺氧相互作用，以调节血流量收缩人体骨骼肌。我们提出了新颖和创新的策略，以解决一些目前尚未解决的问题和争议，这些主题在人类。