UNIT CONTROL OF MUSCLE BLOOD FLOW

肌肉血流的单位控制

• 批准号: 6183754
• 负责人: STEVEN S SEGAL
• 金额: $ 27.92万
• 依托单位: JOHN B. PIERCE LABORATORY, INC.
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6183754
• 关键词: acetylcholine; arterioles; capillary; curare; electrostimulus; fluorescence microscopy; hamsters; innervation; microcirculation; microelectrodes; motor neurons; muscle; muscle contraction; neuromuscular junction; neuropharmacology; perfusion; vascular smooth muscle nervous control; vasodilation; video microscopy

DESCRIPTION (Applicant's abstract): The goal of this research is to elucidate the anatomical and physiological interactions among muscle fibers, motor nerves, and the local control of capillary perfusion. The thin, parallel-fibered hamster retractor muscle has been developed as a model system for studying these interactions using video microscopy and image analysis. When muscle fibers are active, oxygen requirements increase along their entire length, which encompasses many microvascular units (MVUs) of capillary flow control. However, the anatomical correspondence among MVUs which supply a fiber or fiber bundle is not understood. Therefore, AIM I is to define the organization and perfusion of MVUs with respect to muscle fiber position and contractile activity. Through imaging microvessels and muscle fibers, we will test the hypotheses that (i) MVUs align with muscle fibers; and that (ii) MVUs supplying a fiber (bundle) originate from common parent arterioles. Stimulation with microelectrodes will be used to test the hypothesis that (iii) muscle fiber contraction results in perfusion of MVUs along the active fibers. Acetylcholine (ACh) triggers vasodilation that is conducted rapidly along the arteriolar wall to increase MVU perfusion. Because neuromuscular junctions (NMJs) are the source of ACh in muscle, AIM II is to define the spatial and functional relationships among NMJs and MVUs. By labeling and imaging NMJs and MVUs, we will test the hypothesis that (i) motor innervation corresponds with microvascular topology. Stimulating NMJs while observing blood flow in microvessels will be used to test the hypotheses that perfusion of MVUs is coordinated with muscle fiber activation via ACh release at NMJs. The influence of motor unit recruitment on MVU perfusion is unknown. By defining the functional properties of motor units in the retractor muscle and observing MVU perfusion in response to motor unit stimulation, we will test the hypotheses that (i) each motor unit has fibers distributed throughout the muscle, that (ii) fibers within a given MVU derive from different motor units, and that (iii) motor unit recruitment is accompanied by MVU recruitment. Our long term goal is to elucidate physiological and pathophysiological interaction(s) among muscle fibers, motor nerves, and the local control of blood flow at the cellular level in vivo. We envision a new foundation from which to test hypotheses concerning the determinants of physical performance in healthy individuals as well as the mechanisms responsible for changes in work capacity with training, disuse or disease, and during the normal course of aging.

描述（申请人的摘要）：本研究的目标是 阐明肌纤维之间的解剖学和生理学相互作用， 运动神经和毛细血管灌注的局部控制。 薄薄的， 平行纤维仓鼠牵开肌已被开发为模型 使用视频显微镜和图像研究这些相互作用的系统 分析。 当肌肉纤维活跃时，氧气需求量随之增加 它们的整个长度，包含许多微血管单元（MVU） 毛细管流量控制。 然而，MVU 之间的解剖学对应关系 供应纤维或纤维束的情况尚不清楚。 因此，AIM I 是 定义与肌肉相关的 MVU 的组织和灌注 纤维位置和收缩活动。 通过微血管成像和 肌肉纤维，我们将测试以下假设：(i) MVU 与肌肉对齐 纤维； (ii) 提供光纤（束）的 MVU 来自共同的 母小动脉。 微电极刺激将用于测试 (iii) 肌纤维收缩导致灌注的假设 沿活性纤维的 MVU。 乙酰胆碱 (ACh) 引发血管舒张 沿着小动脉壁快速传导以增加 MVU 灌注。 因为神经肌肉接头 (NMJ) 是 ACh 的来源 肌肉，AIM II 是定义肌肉之间的空间和功能关系 NMJ 和 MVU。 通过对 NMJ 和 MVU 进行标记和成像，我们将测试 假设 (i) 运动神经支配与微血管相对应 拓扑。 在观察微血管血流的同时刺激 NMJ 将 用于检验 MVU 的灌注与 通过 NMJ 释放 ACh 激活肌纤维。 电机的影响 MVU 灌注的单位募集情况未知。 通过定义泛函 牵开肌运动单位的特性和观察 MVU 灌注响应运动单位刺激，我们将测试假设 (i) 每个运动单位都有分布在整个肌肉中的纤维，即 (ii) 给定 MVU 内的纤维源自不同的运动单位，并且 (iii) 运动单位募集伴随着 MVU 募集。 我们的长 术语目标是阐明生理和病理生理学 肌纤维、运动神经和局部控制之间的相互作用 体内细胞水平的血流。 我们设想一个新的基础 用于检验有关身体表现决定因素的假设 健康个体以及导致变化的机制 训练、废用或疾病以及正常过程中的工作能力 的老化。