Electrical Stimulation of the Upper Airway

1

Introduction

Sleep-disordered breathing results from a combination of factors affecting upper airway patency and the control of ventilation. Although the mechanisms underlying upper airway collapse are incompletely understood, a decline in pharyngeal neuromuscular activity during sleep appears to play a critical role. This knowledge has supported the notion that stimulation of upper airway muscles may represent a specific approach to the treatment of obstructive sleep apnea (OSA).

Although multiple upper airway dilator muscles play a role in maintaining upper airway patency during sleep, it has been widely accepted that the genioglossus (GG) muscle is one of the most important because activation advances the tongue. Investigators have considered tensor veli palatini function in animals and humans, but the majority of research related to electrical stimulation of upper airway musculature has described the tonic and reflexive activation of the GG muscle during wake and sleep. Consequently, methods have been explored to selectively stimulate upper airway dilator muscles, particularly the GG. This chapter will describe the foundation of research conducted in animals and humans that paved the way to provide upper airway stimulation as a treatment for OSA in adults.

2

Animal Studies

Miki et al. conducted the first animal experiments in this area and inserted needle electrodes periorally into the GG of spontaneously breathing dogs. A decrease in upper airway resistance was observed with progressively increasing stimulation frequencies up to 50 Hz. Schwartz et al. investigated the influence of bilateral supramaximal hypoglossal nerve (HGN) stimulation on upper airway mechanics. A graded increase in maximal inspiratory airflow (V _I max) was observed with increasing stimulation frequency. The improvement in V _I max could be attributed to a fall in upper airway collapsibility (reflected by a decrease in the critical closing pressure, or P _crit ), but the result was partially offset by a concomitant increase in upstream resistance. Interestingly, the observed fall in P _crit was of similar magnitude to that required for elimination of OSA in humans. In these experiments, the placement of the electrodes on the HGN was such that recruitment of different muscles (GG, styloglossus, hyoglossus, and intrinsic tongue muscles) could be obtained; stimulation of any or all of these might have contributed to the observed improvement in upper airway collapsibility.

Oliven et al. studied pressure–flow relationships of the upper airway during selective stimulation of the HGN in anesthetized dogs. Stimulation resulted in a significant decrease of upper airway resistance and an increase in P _crit and V _I max compared with controls. Eisele et al. conducted studies in the isolated feline upper airway to investigate how upper airway mechanics were altered by differential electrode placement along the HGN and the ansa cervicalis. From these data, it was concluded that a major decrease in upper airway collapsibility by HGN stimulation is dependent upon the activation of the GG and that electrode placement on the proximal segment of the HGN results in the largest improvement in V _I max. The importance of electrode placement and stimulation of specific upper airway muscles was also emphasized by Bishara et al. ; in spontaneously breathing dogs, selective stimulation of the GG with fine wire electrodes inserted into the muscle effectively reduced upper airway resistance and eliminated upper airway obstruction.

Goding et al. reported data on chronic stimulation of the HGN in dogs using bilateral cuff electrodes placed around the HGN. Stimulation started at 4 weeks after implantation and lasted for a period of 8 weeks at a ratio of 8 hours a day, 7 days a week. A major finding of this study, besides the improvement in peak upper airway flow during stimulation, was the absence of any damage to the nerve secondary to chronic stimulation. These results first suggested that long-term HGN stimulation in humans might be safe.