INTERACTIONS IN VENTILATORY CONTROL DURING EXERCISE

这个项目的长期目标是了解基础知识 呼吸控制机制，特别是控制机制 轻度或中度体力活动时的通风。在这个项目中 期间，神经机制导致短期和长期的调制 将调查运动的呼吸反应。短期 调制会立即(在试验范围内)改变运动 换气反应而长期调节改变系统 在几个到多个试验的时间跨度上的特性和响应。 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。首先，假设 将测试短期调制与呼吸死亡的增加 太空需要改变脊髓呼吸神经元的兴奋性，通过 5-羟色胺能机制。有蛛网膜下腔导管的山羊 胸髓将被用来确定是否有药理作用 脊髓5-羟色胺受体的阻断阻止了短期的调节。 其次，这一假设将得到检验，即重复的、成对的化学感受器 刺激和运动改变了未来对运动的呼吸系统反应 单独的(即长期调制)。在正常山羊身上，重复 运动时出现低氧、增加死腔或受到启发 氦/氧混合物将改变正常的化学感受器反馈 锻炼20-30次，为期4天。长期调制将是 表示增大(缺氧、死角)或减弱 (氦/氧)在随后的运动试验中的通风反应。 第三，胸椎后根切断术(TDR)对选定脊髓的影响 将研究神经递质(5-羟色胺、TRH、P物质和降钙素基因相关肽) 使用免疫细胞化学技术。我们建议确定是否会发生变化 在上一个项目期内观察到的结果来自TDR本身，或者如果 它们与潜在的补偿机制有关 反复运动试验的换气功能。最后， 将使用呼吸肌激活的肌电分析 以确定TDR是否减少呼吸肌的激活或干扰 吸气肌和呼气肌之间的协调，从而 在最初的运动试验中考虑到呼吸衰竭 跟随TDR。肌肉利用的变化将在 功能恢复，一种长期调节的形式。短期和长期 运动呼吸反应的调节表明该系统 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帮助我们深入了解 正常的代偿过程和治疗的基本原理 疾病期间的干预。这些研究的结果还包括 对许多研究的设计和解释的影响 通风控制，因为这是一种通常假定为 不灵活或“硬连线”。

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".