UPPER AIRWAY CONTROL OF TRANSTRACHEAL INSUFFLATION

经气管吹气的上呼吸道控制

• 批准号: 6537073
• 负责人: Alan R. Schwartz
• 金额: $ 35.74万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6537073
• 关键词: REM sleep; afferent nerve; biomechanics; carbon dioxide tension; clinical research; dogs; human subject; human therapy evaluation; hypercapnia; mathematical model; oral pharyngeal; oxygen tension; respiratory airflow disorder; respiratory airflow measurement; respiratory airway pressure; respiratory function; respiratory therapy; sleep apnea; tracheotomy

Obstructive sleep apnea is characterized by recurrent periods of pharyngeal occlusion during sleep with recognized cardiovascular, respiratory and neurocognitive dysfunction. Current treatment strategies have been designed to either relieve or bypass the site of upper airway obstruction, but are often ineffective or poorly tolerated. In this proposal, we outline a potentially novel approach for treating apneic patients with high flow transtracheal insufflation (hf-TTI), a method for delivering airflow to the trachea through a thin cannula. Based on current understanding of the pathogenesis of upper airway obstruction during sleep, we take advantage of the unique physiologic properties of the upper airways to regulate breathing patterns during hf-TTI administration. Utilizing a Starling resistor model of the upper airways, we will characterize the mechanical and reflex factors that control their properties, and build a conceptual framework for developing new strategies to support ventilation during sleep. In each of three Specific Aims, we explore airflow dynamics through the upper airway during hf-TTI administration and delineate the mechanisms which modulate upper airway collapsibility and outflow resistance. In Specific Aim 1, we will model the biomechanics of the upper airway under (a) steady-state and (b) dynamic hf-TTI conditions in apneic patients during sleep. In Specific Aim 2, we will explore why reflex responses to hf-TTI administration modulate upper airway collapsibility differently during (a) stable and (b) transitional sleep. In Specific Aim 3, we build upon insights gained from the earlier aims, and propose two novel hf-TTI strategies for ventilating (a) patients with severe upper airway obstruction and (b) animals with varying degrees of upper airway obstruction during sleep. Experiments are proposed initially to optimize upper airway function and ventilation in apneic patients during sleep. Complementary studies in animals are proposed to extend our insights to humans with lesser degrees of upper airway obstruction during sleep. Standard physiologic recording methods will be utilized to perform these experiments. The proposed experiments will serve to further our understanding of the underlying pathogenesis of upper airway obstruction as well as build the foundation for novel approaches to support ventilation in sleeping apneic patients.

阻塞性睡眠呼吸暂停的特点是在睡眠中反复出现咽部闭塞，并伴有公认的心血管、呼吸和神经认知功能障碍。目前的治疗策略被设计为要么缓解或绕过上呼吸道阻塞部位，但往往无效或耐受性差。在这项提案中，我们概述了一种潜在的新方法，用于治疗呼吸暂停患者的高流量经气管充气(HF-TTI)，一种通过细插管将气流输送到气管的方法。根据目前对睡眠中上呼吸道阻塞发病机制的认识，我们利用上呼吸道独特的生理特性来调节HF-TTI治疗期间的呼吸模式。利用上呼吸道的Starling电阻模型，我们将描述控制其特性的机械和反射因素，并建立一个概念性框架，以开发新的策略来支持睡眠期间的通风。在三个特定的目标中，我们探索了在HF-TTI给药期间通过上呼吸道的气流动力学，并描绘了调节上呼吸道塌陷性和流出阻力的机制。在特定的目标1中，我们将模拟睡眠中呼吸暂停患者在(A)稳态和(B)动态HF-TTI条件下上呼吸道的生物力学。在特定的目标2中，我们将探索为什么在(A)稳定睡眠和(B)过渡睡眠期间，对HF-TTI给药的反射反应对上呼吸道塌陷的调节不同。在具体目标3中，我们在早期目标的基础上提出了两种新的HF-TTI策略，用于治疗(A)患有严重上呼吸道阻塞的患者和(B)睡眠期间有不同程度上呼吸道阻塞的动物。最初提出的实验是为了优化呼吸暂停患者睡眠期间的上呼吸道功能和通风。在动物身上进行的补充研究被提议将我们的洞察力扩展到睡眠期间上呼吸道阻塞程度较轻的人类。将使用标准的生理记录方法来执行这些实验。建议的实验将有助于进一步了解上呼吸道阻塞的潜在发病机制，并为支持睡眠呼吸暂停患者呼吸支持的新方法奠定基础。