Hypoglossal nerve stimulation in a rabbit model of obstructive sleep apnea reduces apneas and improves oxygenation.

Based on a prior anesthetized model, we developed an unanesthetized model to evaluate the effects of hypoglossal nerve stimulation (HNS) during sleep. We prepared three rabbits with injections of hyaluronic acid in the base of tongue to produce upper airway obstruction followed by HNS implant. Two rabbits were saline controls, and one, a passive control. Measures were sleep, airflow, effort, oxygen saturation, and heart rate. HNS with electrodes around the right hypoglossal nerve were adjusted to a level without behaviorally disturbing the animal. During HNS stimulation in the tongue-base injected rabbits, obstructive apneas and hypopneas of intermediate (3 to 7 cycles of respiratory effort) or longer (≥8 cycles) duration were largely eliminated while less clinically relevant shorter events (<3) were unaffected, and oxygen saturation was improved. Control animals exhibited no intermediate or long events. In this model HNS can relieve induced sleep apnea, without disturbing the animal: however, despite being non-canine and of substantial size, the model has its challenges.NEW & NOTEWORTHY This report describes a rabbit model for testing the impact of hypoglossal nerve stimulation (HNS) on obstructive apneas. Obstructive sleep apnea (OSA) is induced by injecting hyaluronic acid (as a filler) into the base of the tongue. HNS reduced the length and rate of obstructions and improved oxygenation during sleep. Our efforts with this model advanced understanding of the complexities of this OSA preclinical model for neurostimulation reversal of sleep-disordered breathing.

Sciatic nerve stimulation and its effects on upper airway resistance in the anesthetized rabbit model relevant to sleep apnea.

Obstructive sleep apnea (OSA) is a disorder characterized by collapse of the velopharynx and/or oropharynx during sleep when drive to the upper airway is reduced. Here, we explore an indirect approach for activation of upper airway muscles that might affect airway dynamics, namely, unilateral electrical stimulation of the afferent fibers of the sciatic nerve, in an anesthetized rabbit model. A nerve cuff electrode was placed around the sciatic and hypoglossal nerves to deliver stimulus while airflow, air pressure, and alae nasi electromyogram (EMG) were monitored both before and after sciatic transection. Sciatic nerve stimulation increased respiratory effort, rate, and alae nasi EMG, which persisted for seconds after stimulation; however, upper airway resistance was unchanged. Hypoglossal stimulation reduced resistance without altering drive. Although sciatic nerve stimulation is not ideal for treating OSA, it remains a target for altering respiratory drive. NEW & NOTEWORTHY Previously, sciatic nerve stimulation has been shown to activate upper airway and chest wall muscles. The supposition that resistance through the upper airway would be reduced with this afferent reflex was disproven. Findings were in contrast with the effect of hypoglossal nerve stimulation, which was shown to decrease resistance without changing muscle activation or ventilatory drive.

Hypoglossal nerve stimulation in a pre-clinical anesthetized rabbit model relevant to OSA.

We tested the functional effects of hypoglossal (CNXII) stimulation in the anesthetized rabbit before and after injections of saline into the tongue base to obstruct the airway. Data (n = 6) show little or no effect of CN XII trunk stimulation; however, medial branch stimulation (20-100 Hz; 50-500 µs pulse width, and incremental increases from 10 µA) reduced upper airway resistance. Medial branch stimulation was less effective in reducing resistance than anterior advancement of the hyoid. Endoscopic viewing (n-3) of the retropalate showed this region as the narrowest and dynamically changed by anterior hyoid displacement, with less evident effects than CNXII stimulation. We conclude that under these conditions CNXII medial branch stimulation reduces airway resistance, especially after induced obstruction.