Stimulation Induced Modulation of Sleep

刺激诱导的睡眠调节

• 批准号: 7748090
• 负责人: MATTHEW D. TARLER
• 金额: $ 29.39万
• 依托单位: CLEVELAND MEDICAL DEVICES, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-21 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7748090
• 关键词: Acclimatization; Acute; Adverse effects; Altitude; Altitude Sickness; Aortic Bodies; Automobile Driving; Baroreflex; Blood; Blood Pressure; Breathing; Carbon Dioxide; Carotid Body; Central Sleep Apnea; Chemoreceptors; Chronic; Chronic Obstructive Airway Disease; Chronic lung disease; Clinical; Clinical Medicine; Clinical Treatment; Complex; Congestive Heart Failure; Detection; Development; Devices; Disease; Dyspnea; Effectiveness; Environmental air flow; Esthesia; Exercise; Failure; Functional disorder; Generations; Goals; Gold; Health; Heart failure; Homeostasis; Hypercapnia; Hypercapnic respiratory failure; Hypertension; Hyperventilation; Hypesthesia; Hypocapnia; Hypoxemia; Hypoxia; Methods; Neck; Nerve Tissue; Neurologic; Neurology; Obesity; Obstructive Lung Diseases; Oxygen; Patients; Peripheral; Phase; Phenotype; Physiological; Population; Pregnancy; Recording of previous events; Reflex action; Research; Rest; Risk; Role; Safety; Severities; Sleep; Sleep Apnea Syndromes; Sleep Fragmentations; Small Business Innovation Research Grant; Therapeutic; Ventilator; airway obstruction; frontier; healthy volunteer; improved; innovation; mortality; neural stimulation; novel therapeutic intervention; pressure; public health relevance; relating to nervous system; respiratory; response; tool

DESCRIPTION (provided by applicant): The peripheral chemoreceptors (carotid primarily, and the aortic bodies) detect changes in arterial blood oxygen and carbon dioxide, and initiate reflexes that are important for maintaining homeostasis during hypoxemia. The response to changing carbon dioxide (CO2) levels produces major changes in respiratory drive, of special importance to the control of ventilation during sleep. The carotid bodies are critical for ventilatory acclimatization to high altitude, and contribute in part to exercise-induced hyperventilation, and are critical for the generation of periodic breathing during sleep. Augmented peripheral chemoreflexes can contribute to the severity of sleep apnea, and the development of hypertension in sleep apnea syndromes. In congestive heart failure, augmented carotid chemoreflexes contributes to the increased sympathetic drive so typical of the disease. Moreover, this increase in chemoreflex gain is associated with increased mortality and periodic breathing during sleep, during exercise or even while resting wake. The term "chemoreflex-modulated sleep apnea" captures the whole spectrum of influence of the chemoreflexes on sleep-breathing. There is an unmet clinical need for the development of new therapeutic approaches for patients with chemoreflex-dependent or modulated sleep apnea, a problem especially prevalent in the congestive heart failure (CHF) population. There is currently no method to safely modulate the carotid chemoreflexes. Direct current (DC) electrical neural stimulation has a long history in experimental neurology. The carotid bodies in the neck are accessible to DC stimulation, which can both suppress or enhance neural activity. Peripheral chemoreflex excitatory (anodal) modulation could offer new treatment options for obesity hypoventilation and several neurological illnesses with insufficient central neural respiratory drive, and chronic mountain sickness, while inhibitory (cathodal) modulation could have a central role in management of central and chemoreflex modulated sleep apnea, certain forms of hypertension, high-altitude sleep fragmentation from periodic breathing, and allow safe reductions in the pathologically enhanced carotid chemoreflexes and sympathetic drive in heart failure. Transcervical DC stimulation may also be able to modulate the sensation of dyspnea in chronic obstructive lung disease. The long-term goal of this research is to develop a wearable device to safely and effectively modulate the carotid chemoreflexes. The applicants have already developed innovative new methods for phenotyping sleep apnea, and to use CO2 as adjunctive therapy for chemoreflex-modulated sleep apnea. The goal of the current Phase I SBIR proposal is to assess the safety (including adverse effects on the baroreflexes), acute physiological effects of cathodal and anodal transcervical DC stimulation in healthy volunteers, and exploratory effects on chemoreflex-modulated sleep apnea. PUBLIC HEALTH RELEVANCE: Narrative The carotid body in the neck is critical for regulating the normal amounts of oxygen and carbon dioxide in the blood in health and several disease states. There is currently no method to safely modulate carotid body activity. Direct Current (DC) stimulation can suppress or enhance activity of nervous tissue and using excitatory (anodal) DC current modulation could offer new treatment options for obesity hypoventilation and several neurological illnesses with insufficient central neural respiratory drive, and chronic mountain sickness, while inhibitory (cathodal) modulation could have a central role in management of central sleep apnea, certain forms of hypertension, poor sleep at high altitude, and allow safe reductions in the pathologically enhanced carotid body activity in heart failure. Transcervical DC stimulation may also be able to reduce the sensation of breathlessness in patients with chronic lung disease. The long-term goal of this research is to develop a wearable device to safely and effectively modulate the carotid chemoreflexes. The goal of the current proposal is to assess tolerance, safety, effects on breathing, and explore effects on central forms of sleep apnea.

描述（由申请人提供）：外周化学感受器（主要是颈动脉和主动脉体）检测动脉血氧和二氧化碳的变化，并启动对于低氧血症期间维持体内平衡很重要的反射。对二氧化碳 (CO2) 水平变化的反应会导致呼吸驱动发生重大变化，这对于睡眠期间的通气控制特别重要。颈动脉体对于适应高海拔的通气至关重要，并且在一定程度上导致运动引起的过度通气，并且对于睡眠期间周期性呼吸的产生也至关重要。外周化学反射增强可能导致睡眠呼吸暂停的严重程度以及睡眠呼吸暂停综合征中高血压的发生。在充血性心力衰竭中，颈动脉化学反射的增强有助于增强交感神经驱动，这是该疾病的典型特征。此外，化学反射增益的增加与死亡率增加以及睡眠期间、运动期间甚至休息清醒时的周期性呼吸有关。术语“化学反射调节的睡眠呼吸暂停”涵盖了化学反射对睡眠呼吸的整个影响范围。对于化学反射依赖性或调节性睡眠呼吸暂停患者开发新的治疗方法的临床需求尚未得到满足，这一问题在充血性心力衰竭 (CHF) 人群中尤其普遍。目前尚无安全调节颈动脉化学反射的方法。直流（DC）电神经刺激在实验神经学领域有着悠久的历史。颈部的颈动脉体可以接受直流电刺激，这既可以抑制也可以增强神经活动。外周化学反射兴奋性（阳极）调节可以为肥胖、通气不足和几种中枢神经呼吸驱动不足的神经系统疾病以及慢性高山病提供新的治疗选择，而抑制性（阴极）调节可以在中枢和化学反射调节的睡眠呼吸暂停、某些形式的高血压、周期性呼吸引起的高原睡眠碎片的治疗中发挥核心作用，并允许安全 心力衰竭时病理性增强的颈动脉化学反射和交感神经驱动减少。经宫颈直流电刺激也可能能够调节慢性阻塞性肺病的呼吸困难的感觉。这项研究的长期目标是开发一种可穿戴设备来安全有效地调节颈动脉化学反射。申请人已经开发出用于对睡眠呼吸暂停进行表型分析的创新方法，并使用二氧化碳作为化学反射调节睡眠呼吸暂停的辅助疗法。当前第一阶段 SBIR 提案的目标是评估健康志愿者的安全性（包括对压力反射的不利影响）、阴极和阳极经宫颈直流电刺激的急性生理效应，以及对化学反射调节的睡眠呼吸暂停的探索性影响。公共卫生相关性：叙述 颈部的颈动脉体对于在健康和多种疾病状态下调节血液中的正常氧气和二氧化碳量至关重要。目前尚无安全调节颈动脉体活动的方法。直流（DC）刺激可以抑制或增强神经组织的活动，使用兴奋性（阳极）直流电流调制可以为肥胖、通气不足和中枢神经呼吸驱动不足的几种神经系统疾病以及慢性高山病提供新的治疗选择，而抑制（阴极）调制可以在中枢性睡眠呼吸暂停、某些形式的高血压、高海拔睡眠不良的治疗中发挥核心作用，并允许安全 心力衰竭时病理性增强的颈动脉体活动减少。经宫颈直流电刺激也可能能够减轻慢性肺病患者的呼吸困难感。这项研究的长期目标是开发一种可穿戴设备来安全有效地调节颈动脉化学反射。当前提案的目标是评估耐受性、安全性、对呼吸的影响，并探索对中枢性睡眠呼吸暂停的影响。