STOCHASTIC FACTORS IN IRREGULAR AND PERIODIC BREATHING

这一提议检验了这一假设，即不规律的和周期性的 呼吸可能是由随机干扰与 呼吸作用(即，相对于呼吸的随机干扰 呼吸周期)和非线性确定性性质 呼吸神经化学和神经机械反馈系统。是这样的 干扰可能起源于呼吸系统(例如，在 受体或神经元放电，在血气波动中)或外部 (例如，来自更高的大脑活动)。初步实验和 数学模型研究表明，在各种正态和非正态情况下 病理条件下“嘈杂”的呼吸到呼吸紊乱 呼吸模式、通风或血气可引起额外的刺激 呼吸行为模式，包括自我维持的呼吸与呼吸 呼吸周期参数的变化，不规则呼吸暂停，以及 通风中的周期性振荡。拟议的研究将审查 首先，化学驱动和睡眠状态对 自发性干扰的特征，以及由此产生的呼吸 呼吸、呼吸参数和呼吸肌电信号的变化 人类受试者。这些干扰因素对地震灾害发生的影响 周期性呼吸和呼吸暂停将通过数学预测 进行了模拟和实验验证。协调研究涉及 清醒和睡眠的人类和麻醉的大鼠将评估 几种生理机制，包括中枢和外周 化学感受器和机械感受器在促进振荡中的作用 以及潮气量、呼吸时间的自我维持变化，以及 通风。这些机制的贡献将由第一次评估 降低，然后增强，每种机制的生理活性。 这些研究将利用新技术来优化血液控制。 人体内气体及反馈系统白噪声识别 属性。这些发现对患者群体的适用性将是 使用数学模拟进行了探索。这些研究将评估一个 理解不规则和周期性原因的新框架 呼吸，这可能对发展早期治疗很重要 对患者的干预，并将开发新的敏感技术 评估通风稳定性。

This proposal tests the hypothesis that both irregular and periodic breathing can result from interactions between stochastic disturbances to respiration (i.e., disturbances that are random relative to the respiratory cycle) and the nonlinear deterministic properties of respiratory neurochemical and neuromechanical feedback systems. Such disturbances may originate within the respiratory system (e.g., in receptor or neuronal discharges, in blood gas fluctuations) or external to it (e.g., from higher brain activities). Preliminary experimental and mathematical modelling studies demonstrate that under various normal and pathological conditions "noisy" breath to breath disturbances to respiratory pattern, ventilation, or blood gases can excite additional modes of respiratory behavior, including self-sustaining breath to breath variations in respiratory cycle parameters, irregular apneas, and periodic oscillations in ventilation. Proposed studies will examine first the effects of chemical drive and sleep state on the characteristics of spontaneous disturbances to, and the resulting breath to breath variations in, ventilatory parameters and respiratory EMGs in human subjects. The influence of these disturbances on the occurrence of periodic breathing and apneas will be predicted through mathematical simulations and tested experimentally. Coordinated studies involving awake and asleep humans and anesthetized rats will assess the roles of several physiological mechanisms, including central and peripheral chemoreceptors and pulmonary mechanoreceptors, in promoting oscillations and self-sustaining variations in tidal volume, breath timing, and ventilation. Contributions of these mechanisms will be assessed by first reducing, then enhancing, the physiological activity of each mechanism. These studies will utilize new techniques for optimal control of blood gases in humans and for white-noise identification of feedback system properties. Applicability of the findings to patient populations will be explored using mathematical simulations. These studies will evaluate a new framework for understanding the causes of irregular and periodic breathing, which may be important for developing early therapeutic interventions in patients, and will develop new sensitive techniques for assessing ventilatory stability.