NEUROMUSCULAR CHANGES IN ENGLISH BULLDOGS

英国斗牛犬是睡眠呼吸障碍（SDB）的动物模型。 在这些狗中，睡眠呼吸暂停在快速眼动期比非快速眼动期发生得更频繁 睡吧该实验室最近表明，SDB与 呼吸肌的正常阶段性REM睡眠相关变化： 驱动力中的分馏、离心和间歇性递减。 此外，呼吸驱动到上气道扩张肌肉， 非REM，当SDB在斗牛犬中不存在时，与驱动相比， 正常犬（Beagles）。因此，清醒时的气道塌陷 而非快速眼动睡眠只能通过增加神经驱动来阻止， 气道扩张器我们认为，这种神经活动的增加是一种 对上呼吸道解剖学狭窄的反应。中的协议 该提案旨在建立这一机制和后果， 上呼吸道扩张肌的长期、近持续的过度活动。 一组方案（A）将研究生理学、药理学 （特别是血清素）和动态解剖（通过电影CT测量 成像）的上气道及其扩张肌， 不受约束的、长期使用器械的斗牛犬和对照犬。在 此外，计划中的研究将确定是否慢性增加 活动具有永久性后果，特别是使用依赖性神经 可塑性（方案B）以及肌肉形态和功能的变化 （C号议定书）。这将通过比较狗与慢性 气管切开术给那些通过自然上呼吸道呼吸的人。 这项工作将使用先进的技术进行动态 影像学、神经解剖学和肌肉生物学，以及睡眠研究 以及来自不受限制、未麻醉动物的慢性记录 准备工作它代表了一种新颖的综合方法， 最基本的问题在该领域：神经肌肉适应慢性 障碍和最终失败的可能机制 这些适应性反应。

English bulldogs are an animal model for sleep-disordered breathing (SDB). In these dogs, SDB occurs much more frequently in REM than in non-REM sleep. This laboratory has recently shown that SDB was associated with normal phasic REM sleep-related changes in respiratory muscles: fractionations, asynchrony, and intermittent decrements in drive. Furthermore, respiratory drive to an upper airway dilating muscle during non-REM, when SDB is absent in bulldogs, was increased compared to drive in normal dogs (beagles). It thus appears that airway collapse in waking and non-REM sleep is prevented only by increased neural drive to upper airway dilators. We propose that this increase in neural activity is a response to the anatomic narrowing of the upper airways. The protocols in this proposal aim to establish the mechanisms and consequences of this long-term, near-continuous hyperactivity of upper airway dilating muscles. A group of protocols (A) will investigate the physiology, pharmacology (especially serotonin), and dynamic anatomy (as measured by cine CT imaging) of the upper airway and its dilator muscles in unanesthetized, unrestrained, chronically instrumented bulldogs and control dogs. In addition, the planned studies will establish whether the chronic increased activity has permanent consequences, specifically use-dependent neural plasticity (Protocol B) and changes in muscle morphology and function (Protocol C). This will be accomplished by comparing dogs with chronic tracheostomies to those breathing through their natural upper airways. This work will be conducted using sophisticated techniques for dynamic imaging, neuroanatomy, and muscle biology, in addition to sleep studies and chronic recording from unrestrained, unanesthetized animal preparations. It represents a novel and integrated approach to some of the most basic questions in the field: neuromuscular adaptations to chronic obstruction and possible mechanisms underlying the eventual failure of these adaptive responses.