Phasic mechanoreceptor stimuli can induce phasic activation of upper airway muscles in humans

Upper airway dilator muscles are phasically activated throughout breathing by respiratory pattern generator neurons. Studies have shown that non-physiological upper airway mechanoreceptive stimuli (e.g. rapidly imposed pulses of negative pressure) also activate these muscles. Such reflexes may become activated during conditions that alter airway resistance in order to stabilise airway patency. To determine the contribution of ongoing mechanoreceptive reflexes to phasic activity of airway dilators, we assessed genioglossal electromyogram (GG EMG: rectified with moving time average of 100 ms) during slow (physiological) oscillations in negative pressure generated spontaneously and passively (negative pressure ventilator). Nineteen healthy adults were studied while awake, during passive mechanical ventilation across normal physiological ranges of breathing rates (13–19 breaths min−1) and volumes (0.5–1.0 l) and during spontaneous breathing across the physiological range of end-tidal carbon dioxide (PET,CO2; 32–45 mmHg). Within-breath phasic changes in airway mechanoreceptor stimuli (negative pressure or flow) were highly correlated with within-breath phasic genioglossal activation, probably representing a robust mechanoreceptive reflex. These reflex relationships were largely unchanged by alterations in central drive to respiratory pump muscles or the rate of mechanical ventilation within the ranges studied. A multivariate model revealed that tonic GG EMG, PET,CO2 and breath duration provided no significant independent information in the prediction of inspiratory peak GG EMG beyond that provided by epiglottic pressure, which alone explained 93 % of the variation in peak GG EMG across all conditions. The overall relationship was: Peak GG EMG = 79.7 − (11.3 x Peak epiglottic pressure), where GG EMG is measured as percentage of baseline, and epiglottic pressure is in cmH2O. These data provide strong evidence that upper airway dilator muscles can be activated throughout inspiration via ongoing mechanoreceptor reflexes. Such a feedback mechanism is likely to be active on a within-breath basis to protect upper airway patency in awake humans. This mechanism could mediate the increased genioglossal activity observed in patients with obstructive sleep apnoea (i.e. reflex compensation for an anatomically smaller airway). Obstructive sleep apnoea (OSA) is a common disease characterised by repeated pharyngeal collapse during sleep. Upper airway patency depends on the balance between the dilating force of pharyngeal muscles and the collapsing force of intra-luminal negative pressure (generated during inspiration by respiratory ‘pump’ muscles) (Remmers et al. 1978). Many pharyngeal muscles are phasically active with breathing, yet we are uncertain whether the increased dilator muscle activation throughout inspiration spontaneously emanates from the respiratory pattern generator or is primarily a product of ongoing upper airway mechanoreceptor reflexes. If ongoing upper airway mechanoreceptor reflexes predominate, this would provide a feedback mechanism whereby local changes in the mechanical conditions of the upper airway could directly affect dilator muscle activity and protect upper airway patency within each breath. Numerous studies have demonstrated that imposing large, rapid pulses of negative pressure can activate pharyngeal dilator muscles (Horner et al. 1991a, b; Wheatley et al. 1993). The principal aim of this research was to determine whether or not this reflex is active during normal breathing. Our three specific aims were to determine: (i) the effects on pharyngeal muscle activation of upper airway pressure changes that are slow, phasic and within the physiological range (i.e. at normal breathing frequencies and tidal volumes), (ii) whether such physiological mechanoreceptive stimuli can induce phasic activation of upper airway muscles when the spontaneous central respiratory drive to the diaphragm is relatively quiescent, and (iii) whether increased spontaneous central respiratory drive affects the relationship between upper airway mechanoreceptor stimuli and pharyngeal muscle activation. For aim (i), a negative pressure ventilator was used to apply slow, physiological mechanoreceptor stimuli at a range of breathing frequencies. For aim (ii), to lessen the effects of central respiratory drive, subjects were studied during hypocapnia while being mechanically ventilated, as hypocapnia is associated with a reduction or cessation of spontaneous breathing (Shea, 1996). For aim (iii), hypercapnia was induced to increase spontaneous central respiratory drive. We chose to study the genioglossus (GG), as this is one of the principal upper airway dilator muscles (Remmers et al. 1978; Kobayashi et al. 1996). If upper airway mechanoreceptor reflexes are primarily responsible for phasic GG activation, we would expect phasic GG activation to persist throughout passive mechanical ventilation, that the magnitude of this phasic GG activity would be related to the level of passive mechanical ventilation, and that the relationship between upper airway mechanoreceptor stimuli and GG activity would be similar during passive mechanical ventilation and spontaneous breathing. On the other hand, if the spontaneous central respiratory drive to the diaphragm is primarily responsible for phasic GG activity, we would expect little phasic GG activation during passive mechanical ventilation and increased phasic GG activity when spontaneous breathing becomes stimulated during hypercapnia.