R01HL161635

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

Vanderbilt University Medical Center

THE NATIONAL CENTER ON SLEEP DISORDERS RESEARCH (NCSDR) SUPPORTS RESEARCH AND RESEARCH TRAINING RELATED TO SLEEP DISORDERED BREATHING, AND THE FUNDAMENTAL FUNCTIONS OF SLEEP AND CIRCADIAN RHYTHMS. THE CENTER ALSO STEWARDS SEVERAL FORUMS THAT FACILITATE THE COORDINATION OF SLEEP RESEARCH ACROSS NIH, OTHER FEDERAL AGENCIES AND OUTSIDE ORGANIZATIONS, INCLUDING THE SLEEP DISORDERS RESEARCH ADVISORY BOARD AND AN NIH-WIDE SLEEP RESEARCH COORDINATING COMMITTEE. THE CENTER ALSO PARTICIPATES IN THE TRANSLATION OF NEW SLEEP RESEARCH FINDINGS FOR DISSEMINATION TO HEALTH CARE PROFESSIONALS AND THE PUBLIC. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

Nashville, Tennessee 37203 United States

Single Zip Code

Research Project Grant (Parent R01 Clinical Trial Required) (PA-20-183)

Amendment Since initial award the total obligations have increased 287% from $806,359 to $3,120,041.