The Effect of Ansa Cervicalis Neurostimulation on Airway Patency in Obstructive Sleep Apnea

颈衄神经刺激对阻塞性睡眠呼吸暂停患者气道通畅的影响

• 批准号: 10545762
• 负责人: David T. Kent
• 金额: $ 78.38万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-15 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10545762
• 关键词: Address; Air Movements; American; Anatomy; Area; Attenuated; Bilateral; Breathing; Cardiovascular system; Cervical; Characteristics; Contracts; Data; Defect; Development; Dilator; Disease; Distal; Eligibility Determination; Endoscopy; Health; Human; Hypoglossal nerve structure; Knowledge; Lateral; Legal patent; Literature; Maintenance; Mediating; Medical; Methods; Morbidity - disease rate; Muscle; Neck; Obstruction; Obstructive Sleep Apnea; Operative Surgical Procedures; Oropharyngeal; Patients; Pharmaceutical Preparations; Pharyngeal structure; Physiological; Physiology; Polysomnography; Publishing; REM Sleep; Research; Rest; Sedation procedure; Site; Sleep; Soft Palate; Source; Stretching; Structure; Techniques; Testing; Therapeutic; Thyroid cartilage structure; Tissues; Trachea; Traction; airway muscle; airway obstruction; analytical method; compliance behavior; genioglossus muscle; hypopharynx; insight; lung volume; mortality; neuromuscular; neurophysiology; non rapid eye movement; novel; novel strategies; novel therapeutics; personalized strategies; positive airway pressure; pressure; response; soft tissue; success; therapeutically effective; tongue root

Project Summary Obstructive sleep apnea (OSA) is a major source of cardiovascular morbidity and mortality where the first-line treatment, positive airway pressure, is often poorly tolerated. The development of effective alternative surgical therapies has been hindered by a fundamental lack of insight into the anatomic and neurophysiologic mechanisms responsible for airway patency. A substantial body of physiology literature documents that caudal pharyngeal stretch via tracheal traction is an important stabilizing mechanism of the upper airway, but forty years of surgical interventions for OSA have focused solely on destructive techniques or ventral displacement of pharyngeal soft tissue structures. Our proposal will address this knowledge and therapy gap by elucidating the distinct effects of caudal traction on upper airway patency in OSA patients. Our central hypothesis is the therapeutic stabilizing power of caudal tracheal traction can be harnessed via ansa cervicalis stimulation (ACS) of the sternothyroid muscle, which generates caudal traction on the pharynx by contracting the sternothyroid muscle, replicating many of the well-documented effects of caudal traction on pharyngeal patency. This hypothesis challenges the long-held concept that the genioglossus is the major pharyngeal dilator muscle responsible for the maintenance of pharyngeal patency during sleep. It rests instead on strong evidence that caudal pharyngeal traction, normally mediated by tracheal pull, increases pharyngeal patency during sleep through several distinct mechanisms. In SA1, we will elucidate the physiologic effects of unilateral and bilateral ACS on pharyngeal patency during drug-induced sleep endoscopy (DISE) with and without hypoglossal nerve stimulation (HNS), the current state-of-the-art neurostimulation therapy for the management of OSA (DISE, SA1). In SA2, we will determine the impact of ACS on the maintenance of airway patency in NREM and REM sleep. In both SAs, we will test the impact of anatomic constraints on stimulation responses. We hypothesize that ACS stretches the pharynx caudally, stiffening the soft palate and lateral pharyngeal walls. We additionally hypothesize that the combination of HNS and ACS creates synergistic effects through opposing forces that further stabilize the pharynx against collapse. Our aims challenge the primacy of the genioglossus in the maintenance of airway patency during sleep. This project outlines rigorous approaches for establishing synergistic mechanisms between the genioglossus and sternothyroid muscles based on our proven ability to activate these muscles independently. State-of-the-art physiologic methods will be deployed to probe the effects of muscle stimulation, sleep state, and anatomy on pharyngeal patency. Our findings will (1) transform our understanding of upper airway neuromuscular control during sleep, (2) establish relevant neuromotor targets for neurostimulation, and will (3) identify potential physiologic and anatomic predictors of therapeutic success.

项目摘要 阻塞性睡眠呼吸暂停（OSA）是心血管疾病发病率和死亡率的主要来源， 气道正压治疗通常耐受性差。有效替代手术的发展 由于缺乏对解剖学和神经生理学的基本了解， 负责气道通畅的机制。大量的生理学文献记录了尾侧 通过气管牵引的咽部牵拉是上气道的重要稳定机制，但40年来， 的OSA手术干预只集中在破坏性技术或腹侧移位， 咽部软组织结构我们的建议将通过阐明以下内容来解决这一知识和治疗差距： 尾部牵引对阻塞性睡眠呼吸暂停患者上气道通畅性的影响。我们的中心假设是 尾侧气管牵引的治疗稳定力可以通过颈袢刺激（ACS）来利用 胸骨甲状肌，通过收缩胸骨甲状肌在咽部产生尾牵引力 肌肉，复制了许多有据可查的尾部牵引对咽通畅性的影响。这 这一假说挑战了长期以来的概念，即颏舌肌是主要的咽扩张肌 负责在睡眠期间维持咽部开放。相反，它依赖于强有力的证据， 尾部咽牵引，通常由气管牵拉介导，在睡眠期间增加咽开放性 通过几种不同的机制在SA 1中，我们将阐明单侧和双侧的生理效应， ACS对有和无舌下神经的药物诱导睡眠内窥镜检查（DISE）期间咽部通畅性的影响 刺激（HNS），目前最先进的神经刺激疗法，用于治疗OSA（DISE，SA1）。 在SA2中，我们将确定ACS对NREM和REM睡眠中维持气道通畅的影响。在 我们将测试解剖约束对刺激反应的影响。我们假设ACS 向尾部伸展咽，使软腭和咽侧壁变硬。我们另外 假设HNS和ACS的组合通过相反的力量产生协同效应， 进一步稳定咽部防止塌陷。我们的目标是挑战颏舌肌在 睡眠期间维持气道通畅。该项目概述了建立 颏舌肌和胸骨甲状肌之间的协同机制，基于我们已证实的能力， 独立地激活这些肌肉。将采用最先进的生理学方法来探测其影响 肌肉刺激、睡眠状态和解剖结构对咽部通畅性的影响。我们的发现将（1）改变我们的 了解睡眠期间上呼吸道神经肌肉控制，（2）建立相关的神经运动目标， 神经刺激，并将（3）确定治疗成功的潜在生理和解剖预测因素。