Effects of upper airway pressure on abdominal muscle activity in conscious dogs.

We have examined arousal and abdominal muscle electromyogram (EMGabd) responses to upper airway pressure stimuli during physiological sleep in four dogs with permanent side-hole tracheal stomata. The dogs were trained to sleep with a tightly fitting snout mask, hermetically sealed in place, while breathing through a cuffed endotracheal tube inserted through the tracheostomy. Sleep stage was determined by behavioral and electroencephalographic criteria. EMGabd activity was measured using bipolar fine-wire electrodes inserted into the abdominal muscle layers. Static increases or decreases in upper airway pressure (+/- 6 cmH2O), when applied at the snout mask or larynx (upper trachea), caused an immediate decrease in EMGabd on the first two to three breaths; EMGabd usually returned to control levels within the 1-min test interval. In contrast, oscillatory pressure waves at 30 Hz and +/- 3 cmH2O amplitude (or -2 to -8 cmH2O amplitude) produced an immediate and sustained reduction in IMGabd in all sleep states. Inhibition of EMGabd could be maintained over many minutes when the oscillatory pressure stimulus was pulsed by using a cycle of 0.5 s on and 0.5 s off. Oscillatory upper airway pressures were also found to be powerful arousal-promoting stimuli, producing arousal in 94% of tests in drowsiness and 66% of tests in slowwave sleep. The results demonstrate the presence of breath-by-breath upper airway control of abdominal muscle activity.     

Effects of mean airway pressure on gas transport during high-frequency ventilation in dogs

In 10 anesthetized, paralyzed, supine dogs, arterial blood gases and CO2 production (VCO2) were measured after 10-min runs of high-frequency ventilation (HFV) at three levels of mean airway pressure (Paw) (0, 5, and 10 cmH2O). HFV was delivered at frequencies (f) of 3, 6, and 9 Hz with a ventilator that generated known tidal volumes (VT) independent of respiratory system impedance. At each f, VT was adjusted at Paw of 0 cmH2O to obtain a eucapnia. As Paw was increased to 5 and 10 cmH2O, arterial PCO2 (PaCO2) increased and arterial PO2 (PaO2) decreased monotonically and significantly. The effect of Paw on PaCO2 and PaO2 was the same at 3, 6, and 9 Hz. Alveolar ventilation (VA), calculated from VCO2 and PaCO2, significantly decreased by 22.7 +/- 2.6 and 40.1 +/- 2.6% after Paw was increased to 5 and 10 cmH2O, respectively. By taking into account the changes in anatomic dead space (VD) with lung volume, VA at different levels of Paw fits the gas transport relationship for HFV derived previously: VA = 0.13 (VT/VD)1.2 VTf (J. Appl. Physiol. 60: 1025-1030, 1986). We conclude that increasing Paw and lung volume significantly decreases gas transport during HFV and that this effect is due to the concomitant increase of the volume of conducting airways.     

Effects of continuous positive airway pressure on upper airway and respiratory muscle activity

To study the effects of continuous positive airway pressure (CPAP) on lung volume, and upper airway and respiratory muscle activity, we quantitated the CPAP-induced changes in diaphragmatic and genioglossal electromyograms, esophageal and transdiaphragmatic pressures (Pes and Pdi), and functional residual capacity (FRC) in six normal awake subjects in the supine position. CPAP resulted in increased FRC, increased peak and rate of rise of diaphragmatic activity (EMGdi and EMGdi/TI), decreased peak genioglossal activity (EMGge), decreased inspiratory time and inspiratory duty cycle (P less than 0.001 for all comparisons). Inspiratory changes in Pes and Pdi, as well as Pes/EMGdi and Pdi/EMGdi also decreased (P less than 0.001 for all comparisons), but mean inspiratory airflow for a given Pes increased (P less than 0.001) on CPAP. The increase in mean inspiratory airflow for a given Pes despite the decrease in upper airway muscle activity suggests that CPAP mechanically splints the upper airway. The changes in EMGge and EMGdi after CPAP application most likely reflect the effects of CPAP and the associated changes in respiratory system mechanics on the afferent input from receptors distributed throughout the intact respiratory system.     

Hemodynamic effects of pressures applied to the upper airway during sleep.

The increase in systemic blood pressure after an obstructive apnea is due, in part, to sympathetically mediated vasoconstriction. We questioned whether upper airway (UA) receptors could contribute reflexly to this vasoconstriction. Four unanesthetized dogs were studied during wakefulness and non-rapid-eye-movement (NREM) sleep. The dogs breathed via a fenestrated tracheostomy tube sealed around the tracheal stoma. The snout was sealed with an airtight mask, thereby isolating the UA when the fenestration was closed and exposing the UA to negative inspiratory intrathoracic pressure when it was open. The blood pressure response to three UA perturbations was studied: 1) square-wave negative pressures sufficient to cause UA collapse with the fenestration closed during a mechanical hyperventilation-induced central apnea; 2) tracheal occlusion with the fenestration open vs. closed; and 3) high-frequency pressure oscillations (HFPO) with the fenestration closed. During NREM sleep, 1) blood pressure response to tracheal occlusion was similar with the fenestration open or closed; 2) collapsing the UA with negative pressures failed to alter blood pressure during a central apnea; and 3) application of HFPO to the UA during eupnea and resistive-loaded breaths increased heart rate and blood pressure. However, these changes were likely to be secondary to the effects of HFPO-induced reflex changes on prolonging expiratory time. These findings suggest that activation of UA pressure-sensitive receptors does not contribute directly to the pressor response associated with sleep-disordered breathing events.     

Swallowing function and upper airway sensation in obstructive sleep apnea.

The objective of this study was to determine whether impaired upper airway (UA) mucosal sensation contributes to altered swallowing function in obstructive sleep apnea (OSA). We determined UA two-point discrimination threshold (2PDT) and vibratory sensation threshold (VST) in 15 men with untreated OSA and 9 nonapneic controls (CL). We then assessed swallowing responses to oropharyngeal fluid boluses delivered via a catheter. The threshold volume required to provoke swallowing and the mean latency to swallowing were determined, as was the phase of the respiratory cycle in which swallowing occurred [expressed as percentage of control cycle duration (%CCD)] and the extent of prolongation of the respiratory cycle after swallowing [inspiratory suppression time (IST)]. 2PDT and VST were significantly impaired in OSA patients compared with CL subjects. 2PDT was positively correlated with swallowing latency and threshold volume in CL subjects, but not in OSA patients. Threshold volume did not differ between the groups [median value = 0.1 ml (95% confidence interval = 0.1-0.2) for OSA and 0.15 ml (95% confidence interval = 0.1-0.16) for CL], whereas swallowing latency was shorter for OSA patients [3.3 (SD 0.7) vs. 3.9 (SD 0.8) s, P = 0.04]. %CCD and IST were similar for OSA patients and CL subjects. However, among OSA patients there was a significant inverse relation between VST and IST. These findings suggest that oropharyngeal sensory impairment in OSA is associated with an attenuation of inhibitory modulating inputs to reflex and central control of UA swallowing function.     

Effects of negative upper airway pressure on pattern of breathing in sleeping infants

Negative upper airway (UAW) pressure inhibits diaphragm inspiratory activity in animals, but there is no direct evidence of this reflex in humans. Also, little is known regarding reflex latency or effects of varying time of stimulation during the breathing cycle. We studied effects of UAW negative pressure on inspiratory airflow and respiratory timing in seven tracheostomized infants during quiet sleep with a face mask and syringe used to produce UAW suction without changing lower airway pressure. Suction trials lasted 2-3 s. During UAW suction, mean and peak inspiratory airflow as well as tidal volume was markedly reduced (16-68%) regardless of whether stimulation occurred in inspiration or expiration. Reflex latency was 42 +/- 3 ms. When suction was applied during inspiration or late expiration, the inspiration and the following expiration were shortened. In contrast, suction applied during midexpiration prolonged expiration and tended to prolong inspiration. The changes in flow, tidal volume, and timing indicate a marked inhibitory effect of UAW suction on thoracic inspiratory muscles. Such a reflex mechanism may function in preventing pharyngeal collapse by inspiratory suction pressure.     

Influence of upper airway negative pressure reflex on response to airway occlusion in sleeping infants

Artificially produced upper airway suction inhibits the diaphragm in animals and infants; however, the effects of spontaneously generated suction in humans are unknown. We studied nine tracheostomized infants because separation of the upper from the lower airway allowed us to channel suction created by an occluded inspiratory effort to both upper and lower airways (upper + lower airway occlusions) or to the lower airway only (lower airway occlusion). The tracheostomy airway was briefly occluded at end expiration during quiet sleep. In upper + lower airway occlusions, peak airway pressure of the first occluded breath was less negative and rate of pressure decrease slower than that of lower airway occlusions, indicating that upper airway suction inhibits thoracic inspiratory muscles. The threshold for this response was less than or equal to 4 cmH2O suction pressure. The effect on inspiratory time was variable. A decrease in slope of the inspiratory pressure waveform occurring at approximately 0.12 s after inspiration onset was more marked in upper + lower airway occlusions. We conclude that infants have an upper airway reflex response to inspiratory pressure that alters not only the peak and slope but also the shape of the inspiratory pressure waveform.     

Developmental changes in response to subatmospheric pressure loading of the upper airway.

Children snore less than adults and have fewer obstructive apneas, suggesting a less collapsible upper airway. We therefore hypothesized that the compensatory upper airway responses to subatmospheric pressure loading decrease with age because of changes in upper airway structure and ventilatory drive. We measured upper airway upstream pressure-flow relationships during sleep in 20 nonsnoring, nonobese children and adults. Measurements were made by correlating maximal inspiratory airflow with the level of nasal pressure applied via a mask. The slope of the upstream pressure-flow curve (S(PF)) was used to characterize upper airway function. We found that S(PF) was flatter in children than in adults (8 +/- 5 vs. 30 +/- 18 ml x s(-1). cmH(2)O(-1), P < 0.002) and that S(PF) correlated with age (r = 0.62, P < 0.01) and body mass index (r = 0. 63, P < 0.01). The occlusion pressure in 100 ms during sleep was measured in six children and two adults; it correlated inversely with S(PF) (r = -0.80, P < 0.02). We conclude that the upper airway compensatory responses to subatmospheric pressure loading decrease with age. This is associated with increased body mass index, even in nonsnoring, nonobese subjects. Ventilatory drive during sleep plays a role in modulating upper airway responses.     

Effect of topical upper airway anesthesia on apnea duration through the night in obstructive sleep apnea

Cala, S. J., P. Sliwinski, M. G. Cosio, and R. J. Kimoff.Effect of topical upper airway anesthesia on apnea duration through the night in obstructive sleep apnea. J. Appl.Physiol. 81(6): 2618-2626, 1996.It haspreviously been reported that the duration of obstructive apneasincreases from the beginning to the end of the night (M. Charbonneau,J. M. Marin, A. Olha, R. J. Kimoff, R. D. Levy, and M. Cosio.Chest 106: 1695-1701, 1994). The purpose of this study wasto test the hypothesis that stimulation of upper airway (UA) sensoryreceptors during obstructed inspiratory efforts contributes to arousaland apnea termination and that a progressive attenuation of thismechanism through the night contributes to apnea lengthening. Westudied seven patients (six men, one woman) with severe obstructivesleep apnea (apnea-hypopnea index = 93 ± 26 events/h) during twoconsecutive nights of polysomnographic monitoring. On one night (randomorder), we performed topical UA anesthesia with 0.2% tetracaine and onthe control night, sham anesthesia. We measured apnea duration,esophageal pressure (Pes) during apneas, and apneicO₂ desaturation. Consistent withprevious findings, apnea duration, number of efforts per apnea, andpeak Pes at end apnea increased from the beginning to the end of the control nights. UA anesthesia produced a significant increase in apneaduration at the beginning of the night but no change in apnea length atthe end of the night. Peak Pes and the rate of increase in Pes duringthe anesthesia nights were greater than during control nights, but therate of increase in Pes was similar for the beginning and end of thecontrol and anesthesia nights. These findings suggest that UA sensoryreceptors play a role in mediating apnea termination at the beginningof the night but that the contribution of these receptors diminishes asthe night progresses such that greater inspiratory efforts arerequired to trigger arousal, leading to apnea prolongation.

     

Upper airway muscle paralysis reduces reflex upper airway motor response to negative transmural pressure in rat.

The reflex upper airway (UA) motor response to UA negative pressure (UANP) is attenuated by neuromuscular blockade. We hypothesized that this is due to a reduction in the sensitivity of laryngeal mechanoreceptors to changes in UA pressure. We examined the effect of neuromuscular blockade on hypoglossal motor responses to UANP and to asphyxia in 15 anesthetized, thoracotomized, artificially ventilated rats. The activity of laryngeal mechanoreceptors is influenced by contractions of laryngeal and tongue muscles, so we studied the effect of selective denervation of these muscle groups on the UA motor response to UANP and to asphyxia, recording from the pharyngeal branch of the glossopharyngeal nerve (n = 11). We also examined the effect of tongue and laryngeal muscle denervation on superior laryngeal nerve (SLN) afferent activity at different airway transmural pressures (n = 6). Neuromuscular blockade and denervation of laryngeal and tongue muscles significantly reduced baseline UA motor nerve activity (P < 0.05), caused a small but significant attenuation of the motor response to asphyxia, and markedly attenuated the response to UANP. Motor denervation of tongue and laryngeal muscles significantly decreased SLN afferent activity and altered the response to UANP. We conclude that skeletal muscle relaxation reduces the reflex UA motor response to UANP, and this may be due to a reduction in the excitability of UA motor systems as well as a decrease of the response of SLN afferents to UANP.     

Relationship between surface tension of upper airway lining liquid and upper airway collapsibility during sleep in obstructive sleep apnea hypopnea syndrome.

Lowering surface tension (gamma) of upper airway lining liquid (UAL) reduces upper airway opening (anesthetized humans) and closing (anesthetized rabbits) pressures. We now hypothesize that in sleeping obstructive sleep apnea hypopnea syndrome (OSAHS) patients lowering gamma of UAL will enhance upper airway stability and decrease the severity of sleep-disordered breathing. Nine OSAHS patients [respiratory disturbance index (RDI): 49 +/- 8 (SE) events/h, diagnostic night] participated in a two-part, one-night, polysomnography study. In the first part, upper airway closing pressures (during non-rapid eye movement sleep, Pcrit) were measured and samples of UAL (awake) were obtained before and after 2.5 ml of surfactant (Exosurf, Glaxo Smith Kline) was instilled into the posterior pharynx. The gamma of UAL was determined with the use of the "pull-off" force technique. In the second part, subjects received a second application of 2.5 ml of surfactant and then slept the remainder of the night (205 +/- 30 min). Instillation of surfactant decreased the gamma of UAL from 60.9 +/- 3.1 mN/m (control) to 45.2 +/- 2.5 mN/m (surfactant group) (n = 9, P < 0.001). Pcrit decreased from 1.19 +/- 1.14 cmH2O (control) to -0.56 +/- 1.15 cmH2O (surfactant group) (n = 7, P < 0.02). Compared with the second half of diagnostic night, surfactant decreased RDI from 51 +/- 8 to 35 +/- 8 events/h (n = 9, P < 0.03). The fall in RDI (deltaRDI) correlated with the fall in gamma of UAL (deltagamma) (deltaRDI = 1.8 x deltagamma, r = 0.68, P = 0.04). Hypopneas decreased approximately 50% from 42 +/- 8 to 20 +/- 5 events/h (n = 9, P < 0.03, paired t-test). The gamma of UAL measured the next morning remained low at 49.5 +/- 2.7 mN/m (n = 9, P < 0.001, ANOVA, compared with control). In conclusion, instillation of surfactant reduced the gamma of UAL in OSAHS patients and decreased Pcrit and the occurrence of hypopneas. Therapeutic manipulation of gamma of UAL may be beneficial in reducing the severity of sleep-disordered breathing in OSAHS patients.     

Soft palate muscle responses to negative upper airway pressure

The afferentpathways and upper airway receptor locations involved in negative upperairway pressure (NUAP) augmentation of soft palate muscle activity havenot been defined. We studied the electromyographic (EMG) response toNUAP for the palatinus, tensor veli palatini, and levator veli palatinimuscles in 11 adult, supine, tracheostomized, anesthetized dogs. NUAPwas applied to the nasal or laryngeal end of the isolated upper airwayin six dogs and to four to six serial upper airway sites from the nasalcavity to the subglottis in five dogs. When NUAP was applied at thelarynx, peak inspiratory EMG activity for the palatinus and tensorincreased significantly (P < 0.05) and plateaued at a NUAP of 10cmH₂O. Laryngeal NUAP failed toincrease levator activity consistently. Nasal NUAP did not increase EMGactivity for any muscle. Consistent NUAP reflex recruitment of softpalate muscle activity only occurred when the larynx was exposed to the stimulus and, furthermore, was abolished by bilateral section of theinternal branches of the superior laryngeal nerves. We conclude thatsoft palate muscle activity may be selectively modulated by afferentactivity originating in the laryngeal and hypopharyngeal airway.     

An upper airway resonator model of high-frequency inspiratory sounds in children with sleep-disordered breathing.

The goal of this study was to determine how high-frequency inspiratory sounds (HFIS) are generated by sleeping children with obstructive sleep-disordered breathing (OSDB). We hypothesized that HFIS are generated when a high-velocity jet of air, generated by a narrowed upper airway, induces the upper airway to act as a resonating chamber. We tested two predictions of this hypothesis: 1) the upper airway is narrowed in children who make HFIS and 2) the length of the upper airway, calculated from HFIS harmonic intervals, is similar to that calculated from magnetic resonance imaging (MRI) scans. The study was conducted in the setting of a sleep laboratory. Participants included 29 children between 6 and 12 yr of age with adenotonsillar hypertrophy suspected of having OSDB. Minimum cross-sectional airway area and airway long dimensions (lips to larynx or soft palate) were measured in awake children with MRIs. Later that night, sound was recorded with a microphone suspended above their bed while the children underwent polysomnography. Sounds were later analyzed with fast Fourier transforms. We found that sleeping children who generated HFIS had significantly narrower upper airways compared with children who did not make HFIS [minimum airway area 20.5 +/- 4.4 vs. 70.9 +/- 22.5 mm(2) (mean +/- SE), respectively; P = 0.02]. There was a significant inverse correlation between the log(10) of the narrowest airway area and the number of HFIS recorded per hour (r(2) = 0.55, P < 0.00001). The harmonics characteristics of HFIS predicted that they were generated by sound resonating in chamber whose length was 12.0 +/- 0.9 cm, which is similar to the MRI measured distance from the lips to the larynx of 12.8 +/- 0.4 cm. In conclusion, these data suggest that children generate HFIS when 1) they have a narrowed upper airway and 2) their upper airway acts as a resonating chamber.     

Oscillatory pressure wave transmission from the upper airway to the carotid artery.

Snoring-associated vibration energy transmission from the upper airway to the carotid artery has been hypothesized as a potential atherosclerotic plaque initiating/rupturing event that may provide a pathogenic mechanism linking snoring and embolic stroke. We examined transmission of oscillatory pressure waves from the pharyngeal lumen to the common carotid artery wall and lumen in seven male, anesthetized, spontaneously breathing New Zealand White rabbits. Airflow was monitored via a pneumotachograph inserted in series in the intact trachea. Fifteen 20-s runs of, separately, 40-, 60-, and 90-Hz oscillatory pressure waves [pressure amplitude in the trachea (Ptr(amp)), amplitude 2-20 cmH(2)O] were generated by a loudspeaker driven by a sine wave generator and amplifier and superimposed on tidal breathing via the cranial tracheal connector. Pressure transducer-tipped catheters measured pressure amplitudes in the tissues adjacent to the common carotid artery bifurcation (Pcti(amp)) and within the lumen (carotid sinus; Pcs(amp)). Data were analyzed using power spectrum analysis and linear mixed-effects statistical modeling. Both the frequency (f) and amplitude of the injected pressure wave influenced Pcti(amp) and Pcs(amp), in that ln Pcti(amp) = 1.2(Ptr(amp)) + 0.02(f) - 5.2, and ln Pcs(amp) = 0.6(Ptr(amp)) + 0.02(f) - 4.9 (both P < 0.05). Across all frequencies tested, transfer of oscillatory pressure across the carotid artery wall was associated with an amplitude gain, as expressed by a Pcs(amp)-to-Pcti(amp) ratio of 1.8 +/- 0.3 (n = 6). Our findings confirm transmission of oscillatory pressure waves from the upper airway lumen to the peripharyngeal tissues and across the carotid artery wall to the lumen. Further studies are required to establish the role of this incident energy in the pathogenesis of carotid artery vascular disease.