A Tool for Neurotheraputic Therapy for Sleep Disordered Breathing

睡眠呼吸障碍的神经治疗工具

基本信息

批准号：
9054568
负责人：
KINGMAN PERKINS STROHL
金额：
$ 28.51万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-30 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9054568
关键词：
Address Adverse effects Affect Alternative Therapies Anatomy Anesthesia procedures Animal Model Apnea Behavior Behavioral Bilateral Biological Assay Biomedical Engineering Bionics Blood Pressure Brain Stem Carotid Body Central Sleep Apnea Chronic Clinical Continuous Positive Airway Pressure Crowding Custom Devices Dilator Disease Disease remission Effectiveness Electrodes Environmental air flow Evoked Potentials Fiber Filler Frequencies Grant Heart Diseases Heart Rate Human Human Pathology Hypoglossal nerve structure Implant Individual Injection of therapeutic agent Measures Mechanics Medical Modeling Motor Cortex Muscle Nerve Obstruction Obstructive Sleep Apnea Operative Surgical Procedures Oral Oropharyngeal Oryctolagus cuniculus Outcome Pathway interactions Patients Pharmaceutical Preparations Pharyngeal structure Physiology Polysomnography Population Production Recurrence Reflex action Research Personnel Resistance Respiration Respiratory Diaphragm Respiratory Muscles Respiratory physiology Scientist Silicones Site Sleep Sleep Apnea Syndromes Sleep Disorders Soft Palate Staging Stimulus Surveys System Technology Temperament Testing Therapeutic Therapeutic Intervention Variant Work airway obstruction autonomic reflex base cardiovascular risk factor carotid sinus cost heart rate variability improved mortality pre-clinical pressure prevent public health relevance relating to nervous system respiratory sensory cortex success therapy outcome tongue root tool tool development treatment effect

项目摘要

DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) is a serious sleep disorder affecting 2-9% of the US population. It is caused by recurrent obstruction of the upper airway (velopharynx and oropharynx) during sleep and produces daytime sleepiness, and increases cardiovascular risk and mortality. Treatment with continuous positive airway pressure (CPAP) is effective and reduces behavioral and cardiovascular risk, but 40% of patients with moderate to severe disease cannot or will not tolerate this first line therapy, and alternatives no very predictable as long-term treatment. A barrier to testing neurostimulation approaches for OSA is the lack of a reliable tool for development and testing of technology, effectiveness, and off-target effects. The proposal is to develop and verify clinical correlates of OSA in a rabbit model of OSA, based on it having general anatomic similarity to the human upper airway, and its size, cost, and temperament. We will produce recurrent obstruction during sleep by partial nasopharyngeal obstruction, airway crowding produced by injection of a silicone filler in the base of the tongue, and verify the endpoints present in human OSA, including sympathetic excitation (increasing heart rate and blood pressure) and sleep instability. We will characterize site(s) of obstruction and the upstream-pressure-flow behavior of the airway. The model will be tested by unilateral hypoglossal nerve stimulation (HNS), and compared to carotid sinus nerve stimulation (CNS) which has an ability to activate and coordinate bilateral upper airway muscle activation through brainstem mechanisms. Aim 1 is to develop, verify, and examine the production of upper airway obstruction acutely under anesthesia and Aim 2 is to record selected consequences during sleep and its stages, intermediate endpoints in the pathology of human OSA. In addition, electrodes will survey cortical state-related evoked potentials and respiratory muscle activation, and blood pressure and heart rate variability will assay autonomic efferent effects. We will mitigate OSA by HNS and CNS. Cuff electrodes will provide selective stimulation. Stimulus parameters will initially be classically-based, and move towards non-traditional paradigms using varying frequency and amplitude, to activate appropriate efferent vs. the afferent fibers. The deliverables in Aim 1 are to demonstrate feasibility and functions, using stimulation approaches to alter upper airway stiffness and resistance and examine respiratory control during drug-induced surgical anesthesia. In Aim 2, we verify the stability and fidelity of the model to human OSA, monitoring sleep (in)stability and autonomic outcomes. We will use HNS to immediately reverse OSA, and study its effects on on-target velopharyngeal and oropharyngeal sites for therapeutic intent, mitigation of sympathetic excitation, and off-target effects on the sensory or motor cortex and autonomic reflex actions. This application creates a tool where scientists in respiratory control, upper airway physiology, and biomedical engineering can address model neurotherapeutic efficacy and side effects as treatment for a common sleep disorder.

描述（由申请人证明）：阻塞性睡眠呼吸暂停（OSA）是一种严重的睡眠，在睡眠期间，上呼吸道的2-9％（速咽和口咽）的ur骨阻塞，并产生白天的嗜睡，并增加心血管风险和死亡率。 ND心血管风险，但中度的40％不能或无法作为长期治疗的渴求。 OSA在OSA的兔子模型中，它与人类上呼吸道具有一般的解剖相似性，其大小，成本和气质在睡眠期间通过部分鼻腔肠道阻塞，气道拥挤，通过注射硅胶填充剂在舌头和人类OSA中存在的终点，我们将表征obstraction的位点，并通过单侧神经刺激（HNS）测试，并将其上游压力。颈神经刺激（CNS）和通过脑干机制进行双侧呼吸道肌肉激活将调查皮质状态相关的电位和呼吸肌肉，血压和心率将测定我们将通过HNS和CNS来减轻OSA。振幅，激活适当的offerte vs.情感纤维。刺激方法可以改变气道刚度并检查药物 - 亚洲人的呼吸控制。人类OSA的模型，监测睡眠（IN）稳定性和自主性结果。该应用在呼吸道上创建了敬酒的科学家。