Mechanisms used to restore ventilation after partial upper airway collapse during sleep in humans

Abstract

Background: Most patients with obstructive sleep apnoea (OSA) can restore airflow after an obstructive respiratory event without arousal at least some of the time. The mechanisms that enable this ventilatory recovery are unclear but probably include increased upper airway dilator muscle activity and/or changes in respiratory timing. The aims of this study were to compare the ability to recover ventilation and the mechanisms of compensation following a sudden reduction of continuous positive airway pressure (CPAP) in subjects with and without OSA. Methods: Ten obese patients with OSA (mean (SD) apnoea-hypopnoea index 62.6 (12.4) events/h) and 15 healthy non-obese non-snorers were instrumented with intramuscular genioglossus electrodes and a mask/ pneumotachograph which was connected to a modified CPAP device that could deliver either continuous positive or negative pressure. During stable non-rapid eye movement sleep the CPAP was repeatedly reduced 2-10 cm H 2 O below the level required to eliminate flow limitation and was held at this level for 5 min or until arousal from sleep occurred. Results: During reduced CPAP the increases in genioglossus activity (311.5 (49.4)% of baseline in subjects with OSA and 315.4 (76.2)% of baseline in non-snorers, p = 0.9) and duty cycle (123.8 (3.9)% of baseline in subjects with OSA and 118.2 (2.8)% of baseline in non-snorers, p = 0.4) were similar in both groups, yet patients with OSA could restore ventilation without cortical arousal less often than non-snorers (54.1% vs 65.7% of pressure drops, p = 0.04). When ventilatory recovery did not occur, genioglossus muscle and respiratory timing changes still occurred but these did not yield adequate pharyngeal patency/ventilation. Conclusions: Compensatory mechanisms (increased genioglossus muscle activity and/or duty cycle) often restore ventilation during sleep but may be less effective in obese patients with OSA than in non-snorers.

Pathophysiology of Adult Obstructive Sleep Apnea

“…These compensatory responses were similar between patients with OSA and healthy individuals. However, patients with OSA were less able to restore ventilation without cortical arousal than were healthy individuals given stimuli of similar magnitude (32).…”

“…Nonetheless, although genioglossus muscle responsiveness may be impaired during sleep compared with wakefulness, it is clear that the muscle does respond to sustained negative pressure ( Figure 1) and potentially hypercapnia, particularly when combinations of stimuli are provided (31)(32)(33). However, there appears to be substantial interindividual variability in the effectiveness of these compensatory responses to restore airflow during respiratory loading in sleep (32).…”

“…In studying the response to experimentally induced transient continuous positive airway pressure (CPAP) reductions in patients with OSA, Younes noted that inspiratory flow increased in 22% of instances before arousal and was restored in 17% of trials in the absence of arousal (41). More recently, Jordan and colleagues conducted a study to examine the mechanisms underlying these arousal-free restorations of airflow (32). Transient pressure reductions for up to 5 minutes resulted in increases in genioglossus muscle activity and changes in duty cycle.…”

“…Indeed, advances in our understanding of the neuroanatomy of the genioglossus negative pressure reflex and hypoglossal motor nucleus inputs from rat studies have highlighted the extensive presence of inhibitory inputs to the genioglossus muscle (28)(29)(30). Nonetheless, although genioglossus muscle responsiveness may be impaired during sleep compared with wakefulness, it is clear that the muscle does respond to sustained negative pressure ( Figure 1) and potentially hypercapnia, particularly when combinations of stimuli are provided (31)(32)(33). However, there appears to be substantial interindividual variability in the effectiveness of these compensatory responses to restore airflow during respiratory loading in sleep (32).…”

Parameters affecting pharyngeal response to genioglossus stimulation in sleep apnoea

“…The main treatment modality for OSA is the application of CPAP, a remedy that is poorly tolerated, leading to low compliance or frank refusal by many patients. Considering the obvious role of neuromuscular mechanisms in the pathogenesis of OSA, since apnoeas occur only during sleep in association with a decline in GG activity [38], it is reasonable to assume that adequately applied electrical activation of this muscle may prevent pharyngeal collapse. Therefore, attempts to stimulate the GG in OSA patients for therapeutic purposes have been undertaken ever since the physiological importance of this muscles' action was appreciated, with variable results [2,36,39,40].…”