Designer Receptors Exclusively Activated by Designer Drugs Approach to Treatment of Sleep-disordered Breathing.

Obstructive sleep apnea is recurrent upper airway obstruction caused by a loss of upper airway muscle tone during sleep. The main goal of our study was to determine if designer receptors exclusively activated by designer drugs (DREADD) could be used to activate the genioglossus muscle as a potential novel treatment strategy for sleep apnea. We have previously shown that the prototypical DREADD ligand clozapine-N-oxide increased pharyngeal diameter in mice expressing DREADD in the hypoglossal nucleus.

Chemogenetic stimulation of the hypoglossal neurons improves upper airway patency.

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep. OSA leads to high cardiovascular morbidity and mortality. The pathogenesis of OSA has been linked to a defect in neuromuscular control of the pharynx.

Tongue fat infiltration in obese versus lean Zucker rats.

Study Objectives: Obesity is the most important risk factor for obstructive sleep apnea (OSA), and the effects of obesity may be mediated by tongue fat. Our objective was to examine the effects of obesity on upper airway structures in obese (OBZ) and non-obese (NBZ) Zucker rats.

Design: Animal study.

Respiratory modulation of the pharyngeal airway in lean and obese mice.

Unlabelled: Obesity is an important risk factor for pharyngeal airway collapse in obstructive sleep apnea (OSA). To examine the effect of obesity on pharyngeal airway size on inspiration and expiration, respiratory-gated MRI of the pharynx was compared in New Zealand obese (NZO) and New Zealand white (NZW) mice (weights: 50.4g vs.

Modeling upper airway collapse by a finite element model with regional tissue properties.

This study presents a new computational system for modeling the upper airway in rats that combines tagged magnetic resonance imaging (MRI) with tissue material properties to predict three-dimensional (3D) airway motion. The model is capable of predicting airway wall and tissue deformation under airway pressure loading up to airway collapse. The model demonstrates that oropharynx collapse pressure depends primarily on ventral wall (tongue muscle) elastic modulus and airway architecture.

Altered upper airway and soft tissue structures in the New Zealand Obese mouse.

Rationale: The effect of obesity on upper airway soft tissue structure and size was examined in the New Zealand Obese (NZO) mouse and in a control lean mouse, the New Zealand White (NZW).

Objectives: We hypothesized that the NZO mouse has increased volume of neck fat and upper airway soft tissues and decreased pharyngeal airway caliber.

Methods: Pharyngeal airway size, volume of the upper airway soft tissue structures, and distribution of fat in the neck and body were measured using magnetic resonance imaging (MRI).

Mechanical effects of genioglossus muscle stimulation on the pharyngeal airway by MRI in cats.

To examine the regional mechanical effects of selective genioglossus muscle activation on pharyngeal airway size and function, magnetic resonance images of the pharyngeal airway were obtained in five paralyzed, anesthetized cats over a range of positive and negative pressures in an isolated, sealed upper airway. When all results across pressure levels and pharyngeal regions were analyzed, genioglossus stimulation significantly increased the cross-sectional area (CSA) of the nasopharyngeal airway. Within specific regions, stimulation tended toward significantly increasing cross-sectional airway area in the mid-nasopharynx.

Phasic respiratory pharyngeal mechanics by magnetic resonance imaging in lean and obese zucker rats.

Rationale: Although obstructive sleep apnea is strongly associated with obesity, we have little understanding of how obesity may alter the mechanical properties of the pharynx and the role of obesity in the pathogenesis of sleep apnea.

Objectives: The overall objective of this study was to determine the effect of obesity on pharyngeal airway size and pharyngeal wall tissue strain in lean and obese Zucker rats.

Methods: Respiratory-gated magnetic resonance imaging with noninvasive tissue tagging was performed in anesthetized, spontaneously breathing lean (n = 9) and obese (n = 9) Zucker rats.

Pharyngeal airway wall mechanics using tagged magnetic resonance imaging during medial hypoglossal nerve stimulation in rats.

To better understand pharyngeal airway mechanics as it relates to the pathogenesis and treatment of obstructive sleep apnoea, we have developed a novel application of magnetic resonance imaging (MRI) with non-invasive tissue tagging to measure pharyngeal wall tissue motion during active dilatation of the airway. Eleven anaesthetized Sprague-Dawley rats were surgically prepared with platinum electrodes for bilateral stimulation of the medial branch of the hypoglossus nerve that supplies motor output to the protrudor and intrinsic tongue muscles. Images of the pharyngeal airway were acquired before and during stimulation using a gated multislice, spoiled gradient recalled (SPGR) imaging protocol in a 4.

Effects of pharyngeal muscle activation on airway pressure-area relationships.

Fiberoptic imaging in an isolated, sealed upper airway was performed in 10 decerebrate cats to determine the effect of pharyngeal muscle activation on airway pressure-area relationships. Bilateral cuff electrodes stimulated the distal cut ends of the following nerves: medial and lateral hypoglossus, glossopharyngeus, and pharyngeal branch of vagus. At given intraluminal pressures ranging from +6 to -6 cm H2O, cross-sectional area was measured in the rostral oropharynx, velopharynx, and caudal oropharynx, with and without nerve stimulation.