STOCHASTIC FACTORS IN IRREGULAR AND PERIODIC BREATHING

这一提议验证了一个假设，即不规则和周期性 呼吸可以由随机干扰之间的相互作用引起， 呼吸（即，随机干扰相对于 呼吸循环）和非线性确定性的性质， 呼吸神经化学和神经机械反馈系统。 等 干扰可能起源于呼吸系统内（例如，在 受体或神经元放电，在血气波动）或外部 对于它（例如，大脑的活动）。 初步实验和 数学模型研究表明，在各种正常和 病理条件“嘈杂的”呼吸到呼吸干扰， 呼吸模式、通气或血气可激发额外的 呼吸行为模式，包括自我维持的呼吸 呼吸周期参数变化、不规则呼吸暂停，以及 通气的周期性振荡。 拟议的研究将审查 首先，化学驱力和睡眠状态对 自发干扰的特征，以及由此产生的呼吸 呼吸变化，呼吸参数和呼吸肌电图， 人类实验对象 这些干扰对发生的影响 将通过数学方法预测周期性呼吸和呼吸暂停 模拟和实验测试。 协调研究，包括 清醒和睡眠的人类和麻醉大鼠将评估的作用， 几种生理机制，包括中枢和外周 化学感受器和肺机械感受器，促进振荡 以及潮气量、呼吸定时和 通风. 这些机制的捐款将首先由 减少，然后增强，每种机制的生理活动。 这些研究将利用新技术来优化血液控制， 人体内的气体和反馈系统的白噪声识别 特性. 研究结果对患者人群的适用性将 用数学模拟来探索。 这些研究将评估 了解不定期和定期报告原因的新框架 呼吸，这可能是重要的发展早期治疗 对患者进行干预，并将开发新的敏感技术， 评估蒸发稳定性。

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.