INTERACTIONS IN VENTILATORY CONTROL DURING EXERCISE

运动期间通气控制的相互作用

• 批准号: 3352033
• 负责人: Gordon S. Mitchell
• 金额: $ 12.22万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3352033
• 关键词: afferent nerve; carotid body; catheterization; chemoreceptors; denervation; electromyography; exercise; goats; hyperoxia; hyperpnea; immunocytochemistry; neurosurgery; neurotransmitters; online computer; pulmonary respiration; respiratory gas analyzer; respiratory gas transport; respiratory hypoxia; respiratory muscles; respiratory pharmacology; serotonin receptor

The long range objective of this project is to understand fundamental mechanisms of ventilatory control, particularly mechanisms controlling ventilation during mild or moderate physical activity. In this project period, neural mechanisms causing short and long term modulation of the exercise ventilatory response will be investigated. Short term modulation causes immediate (within trial) changes in the exercise ventilatory response whereas long term modulation changes system properties and responses over a time span of several to many trials. Awake goats, trained to exercise on a treadmill, will be used as an experimental model. There are four primary aims. First, the hypothesis will be tested that short term modulation with increased respiratory dead space requires changes in spinal respiratory neuron excitability via serotonergic mechanisms. Goats with subarachnoid catheters in the thoracic spinal cord will be used to determine if pharmacological blockade of spinal serotonin receptors prevents short term modulation. Second, the hypothesis will be tested that repeated, paired chemoreceptor stimulation and exercise alter future ventilatory responses to exercise alone (ie. long term modulation). In normal goats, repeated presentations of exercise with hypoxia, increased dead space or inspired helium/oxygen mixtures will alter normal chemoreceptor feedback during exercise for 20-30 trials on four days. Long term modulation would be indicated by augmented (hypoxia, dead space) or attenuated (helium/oxygen) ventilatory responses during subsequent exercise trials. Third, the effects of thoracic dorsal rhizotomy (TDR) on selected spinal neurotransmitters (5-HT, TRH, Substance P and CGRP) will be investigated using immunocytochemical techniques. We propose to determine if changes observed during the previous project period result from TDR per se, or if they are associated with compensatory mechanisms underlying recovery of ventilatory function with repeated exercise trials. Finally, electromyographic analysis of respiratory muscle activation will be used to determine if TDR diminishes respiratory muscle activation or disrupts coordination between inspiratory and expiratory muscles, thereby accounting for ventilatory failure during initial exercise trials following TDR. Changes in muscle utilization will be observed during functional recovery, a form of long term modulation. Short and long term modulation of the exercise ventilatory response indicate that the system adapts to changing conditions (eg. pregnancy, onset of pulmonary disease, etc.). An understanding of these mechanisms may provide insight into normal compensatory processes, and the rationale for therapeutic intervention during disease. The results of these studies also have implications in the design and interpretation of many studies on ventilatory control, since this is a control system commonly assumed to be inflexible or "hard wired".

这个项目的长期目标是了解基本的 解释性控制机制，特别是控制 在轻度或中度体力活动期间进行通风。 在这个项目中 周期，神经机制引起的短期和长期的调制， 将研究运动诱发反应。 短期 调节会立即（在试验内）改变练习 长时程调制改变系统的解释性反应 在几次到多次试验的时间跨度上的性质和响应。 清醒的山羊，经过训练在跑步机上锻炼，将被用作 实验模型 有四个主要目标。 第一，假设 将测试呼吸死亡增加的短期调制 空间需要脊髓呼吸神经元兴奋性的变化， 能机制。 山羊与蛛网膜下腔导管在 将使用胸脊髓来确定是否具有药理学 脊髓5-羟色胺受体的阻断阻止了短期调节。 第二，假设将被测试，重复的，成对的化学感受器 刺激和锻炼改变了未来对锻炼的反应 独自一人（即长期调制）。 在正常山羊中，重复 介绍运动与缺氧，增加死腔或启发 氦/氧混合物将改变正常的化学感受器反馈， 练习20-30个试验四天。 长期调制将是 由增强（缺氧、死腔）或减弱指示 （氦/氧）在随后的运动试验中的解释性反应。 第三，胸背根切断术（TDR）对选择性脊髓损伤的影响。 神经递质（5-HT，TRH，P物质和CGRP）将被研究 用免疫细胞化学技术。 我们建议确定是否有变化 在上一个项目期间观察到的由TDR本身引起的，或者， 它们与恢复的补偿机制有关， 重复运动试验的排便功能。 最后， 将使用呼吸肌激活的肌电图分析 以确定TDR是否减少呼吸肌激活或干扰 吸气和呼气肌肉之间的协调，从而 解释在最初的运动试验中的解释性失败 在TDR之后。 肌肉利用率的变化将在 功能恢复，一种长期调节的形式。 短期和长期 运动诱发反应的调制表明， 适应不断变化的条件（例如，怀孕，肺部疾病发作， 等）。对这些机制的理解可以提供对以下方面的深入了解： 正常的代偿过程，以及治疗的基本原理 疾病期间的干预。 这些研究的结果也有 许多研究的设计和解释中的影响， 解释性控制，因为这是一个控制系统，通常假设， 不灵活或“硬连线”。