Reflex effects and receptor responses to upper airway pressure and flow stimuli in developing puppies

We studied the changes in breathing pattern due to pressure and airflow stimuli applied to isolated upper airway in nine 1- to 14-day-old and six 29- to 35-day-old anesthetized puppies breathing through a tracheostomy. Negative-pressure and flow, both inspiratory and expiratory, altered the breathing pattern only in the 1- to 14-day-old puppies, whereas positive pressure was ineffective in both age groups. Negative pressure caused apnea in 12% of the trials, expiratory flow in 18%, and inspiratory flow in 21%. When apnea did not occur there was a significant prolongation of inspiratory and expiratory time and a decrease of tidal volume of the first breath following the application of negative pressures. Section of the superior laryngeal nerves abolished the responses to pressure and flow. In nine 1- to 14-day-old and four 29- to 35-day-old puppies we recorded the activity of single units of the superior laryngeal nerves. We identified specialized receptors responding to pressure (68.5%), flow (2.7%), and contraction of upper airway muscles (drive, 28.8%). All types of receptors had a prevalent inspiratory-related activity. In the younger age group the discharge rate of pressure receptors at comparable negative pressures was lower than in older puppies. The strong inhibitory influences originating from the upper airway in the early stages of development presumably reflect different integrative properties of the central nervous system.     

Upper airway cooling and l-menthol reduce ventilation in the guinea pig.

Cooling of the upper airway, which stimulates specific cold receptors and inhibits laryngeal mechanoreceptors, reduces respiratory activity in unanesthetized humans and anesthetized animals. This study shows that laryngeal cooling affects the pattern of breathing in the guinea pig and assesses the potential role of cold receptors in this response by using a specific stimulant of cold receptors (l-menthol). The response to airflows (30 ml/s, 10-s duration) through the isolated upper airway was studied in 23 anesthetized (urethan, 1 g/kg ip) guinea pigs breathing through a tracheostomy. Respiratory airflow, tidal volume, laryngeal temperature, and esophageal pressure were recorded before the challenges (control), during cold airflows (25 degrees C, 55% relative humidity), and during warm airflows (37 degrees C, saturated) with or without the addition of l-menthol. Whereas warm air trials had no effect, cold air trials, which lowered laryngeal but not nasal temperature, reduced ventilation (VE) to 85% of control, mainly by prolonging expiratory time (TE, 145% of control), an effect abolished by laryngeal anesthesia. Addition of l-menthol to the warm airflow caused a greater reduction in VE (41% of control) by prolonging TE (1,028% of control). Nasal anesthesia markedly reduced the apneogenic effect of l-menthol but did not affect the response to cold air trials. In conclusion, both cooling of the larynx and l-menthol in the laryngeal lumen reduce ventilation. Exposure of the nasal cavity to l-menthol markedly enhances this ventilatory inhibition; considering the stimulatory effect of l-menthol on cold receptors, these results suggest a predominant role of nasal cold receptors in this response.     

Reductions of neural activities to upper airway muscles after elevations in static lung volume.

We evaluated the hypothesis that the tonic discharge of pulmonary stretch receptors significantly influences the respiratory-modulated activities of cranial nerves. Decerebrate and paralyzed cats were ventilated with a servo-respirator, which produced changes in lung volume in parallel with integrated phrenic activity. Activities of the facial, hypoglossal, and recurrent laryngeal nerves and nerves to the thyroarytenoid muscle and triangularis sterni were recorded. After a stereotyped pattern of lung inflation, tracheal pressure was held at 1, 2, 4, or 6 cmH2O during the subsequent ventilatory cycle. Increases in tracheal pressure caused progressive reductions in both inspiratory and expiratory cranial nerve activities and progressive elevations in triangularis sterni discharge; peak levels of phrenic activity declined modestly. Similar changes were observed in normocapnia and hypercapnia. We conclude that the tonic discharge of pulmonary stretch receptors is an important determinant of the presence and magnitude of respiratory-modulated cranial nerve activity. This reflex mechanism may maintain upper airway patency and also regulate expiratory airflow.     

Upper airway muscle and diaphragm responses to hypoxia in the piglet

The neonatal ventilatory response to hypoxia is characterized by initial transient stimulation and subsequent respiratory depression. It is unknown, however, whether this response is also exhibited by the upper airway muscles that regulate nasal, laryngeal, and pharyngeal patency. We therefore compared electromyogram (EMG) amplitudes and minute EMGs for the diaphragm (DIA), alae nasi (AN), posterior cricoarytenoid (PCA), and genioglossus (GG) muscles in 12 anesthetized spontaneously breathing piglets during inhalation of 12% O2 over 10 min. Minute EMG for the DIA responded to hypoxia with an initial transient increase and subsequent return to prehypoxia levels by 10 min. Hypoxia also stimulated all three upper airway muscles. In contrast to the DIA EMG, however, AN, PCA, and GG EMGs all remained significantly above prehypoxia levels after 10 min of hypoxia. We have thus demonstrated that the initial stimulation and subsequent depression of the DIA EMG after 12% O2 inhalation contrast with the sustained increase in AN, PCA, and GG EMGs during hypoxia. We speculate that 1) central inhibition during neonatal hypoxia is primarily distributed to the motoneuron pools regulating DIA activation and 2) peripheral chemoreceptor stimulation and/or central disinhibition induced by hypoxia preferentially influence those motoneuron pools that regulate upper airway muscle activation, causing the different hypoxic responses of these muscle groups in the young piglet.     

Developmental changes in sequential activation of laryngeal abductor muscle and diaphragm in infants.

In animals and human adults, upper airway muscle activity usually precedes inspiratory diaphragm activity. We examined the interaction of the posterior cricoarytenoid muscle (PCA), which abducts the larynx, and the diaphragm (DIA) in the control of airflow in newborn infants to assess the effect of maturation on respiratory muscle sequence. We recorded tidal volume, airflow, and DIA and PCA electromyograms (EMG) in 12 full-term, 14 premature, and 10 premature infants with apnea treated with aminophylline. In most breaths, onset of PCA EMG activity preceded onset of DIA EMG activity (lead breaths). In all subjects, we also observed breaths (range 6-61%) in which PCA EMG onset followed DIA EMG onset (lag breaths). DIA neural inspiratory duration and the neuromechanical delay between DIA EMG onset and inspiratory flow were longer in lag than in lead breaths (P < 0.05 and P < 0.01, respectively). The frequency of lag breaths was greater in the premature infants [33 +/- 4% (SE)] than in either the full-term infants (21 +/- 3%, P < 0.03) or the premature infants with apnea treated with aminophylline (16 +/- 2%, P < 0.01). We conclude that the expected sequence of onset of PCA and DIA EMG activity is frequently disrupted in newborn infants. Both maturation and respiratory stimulation with aminophylline improve the coordination of the PCA and DIA.     

Response of genioglossus muscle activity to nasal airway occlusion in normal sleeping adults

To determine the combined effect of increased subatmospheric upper airway pressure and withdrawal of phasic volume feedback from the lung on genioglossus muscle activity, the response of this muscle to intermittent nasal airway occlusion was studied in 12 normal adult males during sleep. Nasal occlusion at end expiration was achieved by inflating balloon-tipped catheters located within the portals of a nose mask. No seal was placed over the mouth. During nose breathing in non-rapid-eye-movement (NREM) sleep, nasal airway occlusion resulted in multiple respiratory efforts before arousal. Mouth breathing was not initiated until arousal. Phasic inspiratory genioglossus activity was present in eight subjects during NREM sleep. In these subjects, comparison of peak genioglossus inspiratory activity on the first three occluded efforts to the value just before occlusion showed an increase of 4.7, 16.1, and 28.0%, respectively. The relative increases in peak genioglossus activity were very similar to respective increases in peak diaphragm activity. Arousal was associated with a large burst in genioglossus activity. During airway occlusion in rapid-eye-movement (REM) sleep, mouth breathing could occur without a change in sleep state. In general, genioglossus responses to airway occlusion in REM sleep were similar in pattern to those in NREM sleep. A relatively small reflex activation of upper airway muscles associated with a sudden increase in subatmospheric pressure in the potentially collapsible segment of the upper airway may help compromise upper airway patency during sleep.     

Neural control of airway pressures in rabbits

In twenty anaesthetized and spontaneously breathing rabbits airway pressures were measured above and below the larynx during tidal respiration through the larynx. Peak inspiratory and expiratory pressures at both sites were recorded in control conditions and then compared to values obtained in the course of progressive denervation of the airways. The two methods of denervation consisted of (1) bilateral section of superior and recurrent laryngeal nerves and of the midcervical vagotomy (horizontal method); (2) right-sided sections of the three nerves followed by left-sided sections (vertical method). Motor denervation of the larynx due to RLNs neurotomy (horizontal method) produced significant increases in intratracheal pressures in both phases of the respiratory cycle. Less prominent increments in pressures were achieved on RLNs neurotomy in the vertical method. SLNs section and vagotomy had little additional effect on airway pressures. Our results indicate that unilateral laryngeal palsy poses far smaller obstruction to breathing than simultaneous bilateral denervation, and that afferent denervation of the larynx has no effect on airway pressures.     

Role of upper airway in ventilatory control in awake and sleeping dogs

We examined the role of the upper airway in the regulation of the pattern of breathing in six adult dogs during wakefulness and sleep. The dogs breathed through a fenestrated endotracheal tube inserted through a tracheostomy. The tube was modified to allow airflow to be directed either through the nose or through the tracheostomy. When airflow was diverted from nose to tracheostomy there was an abrupt increase in the rate of expiratory airflow, resulting in prolongation of the end-expiratory pause but no change in overall expiratory duration or respiratory frequency. Furthermore, electromyogram recordings from implanted diaphragmatic and laryngeal muscle electrodes did not show any changes that could be interpreted as an attempt to delay expiratory airflow or increase end-expiratory lung volume. The effects of switching from nose to tracheostomy breathing could be reversed by adding a resistance to the endotracheal tube so as to approximate upper airway resistance. The findings indicate that under normal conditions in the adult dog upper airway receptors play little role in regulation of respiratory pattern and that the upper airway exerts little influence on the maintenance of end-expiratory lung volume.     

Influence of posterior cricoarytenoid muscle activity on pressure-flow relationship of the larynx

We examined the effect of posterior cricoarytenoid (PCA) muscle activity on the pressure-flow (PV) relationship of the larynx in five anesthetized tracheostomized dogs. The PCA activity was recorded using bipolar fine-wire electrodes, expressed as a percentage of the quiet breathing level and altered by mechanical ventilation, changes in lung volume, and chest wall compression. Subglottic pressure was recorded while a constant flow of air was passed through the upper airway. In the absence of PCA activity the PV relationship was alinear and could be described by a power function (P = K0Va, where K0 and a are constants). The slope of the log P-log V plots in the absence of PCA and thyroarytenoid activity was 1.83 +/- 0.02 (SD), whereas with increasing PCA activity it was 1.88 +/- 0.11. An effective hydraulic diameter (DH) was calculated for 20% increments of PCA activity, and in two dogs glottic diameter (Dg) was calculated from glottic area measurements obtained by fiber-optic laryngoscopy. Both DH and Dg increased linearly with increasing PCA activity. Denervation of the cricothyroid muscle had no systematic effect on laryngeal resistance. The results indicate that the PV relationship of the larynx may be described by a power function with a single exponent, the magnitude of which is independent of glottic dilator muscle activity and consistent with orifice flow. However, laryngeal diameter increases linearly with PCA activity in the range studied.     

Time of application of negative pressure pulses and upper airway muscle activity

Effect of upper airway pressure changes on thoracic inspiratory muscles has been shown to depend on the time of application during the breathing cycle. The present study was designed to investigate the importance of the time of application of upper airway negative pressure pulses on upper airway muscles. The upper airway was functionally isolated into a closed system in 24 anesthetized spontaneously breathing rabbits. Negative pressure pulses were applied in early (within the first 200 ms) and late (greater than or equal to 200 ms) inspiration, while electromyograms (EMG) of the diaphragm (Dia), genioglossus (GG), alae nasi (AN), and/or posterior cricoarytenoid (PCA) muscles were simultaneously monitored. When negative pressure pulse was applied in early inspiration, the increase in GG activity was greater [0.49 +/- 0.37 to 4.24 +/- 3.71 arbitrary units (AU)] than when negative pressure was applied in late inspiration (0.44 +/- 0.29 to 2.64 +/- 3.05 AU). Similarly, increased activation of AN (2.63 +/- 1.01 to 4.26 +/- 1.69 AU) and PCA (3.46 +/- 1.16 to 6.18 +/- 2.93 AU) was also observed with early inspiratory application of negative pressure pulses; minimal effects were seen in these muscles with late application. An inhibitory effect on respiratory timing consisting of a prolongation in inspiration (TI) and a decrease in peak Dia EMG/TI was observed as previously reported. These results indicate that the time of application of negative pressure during the breathing cycle is an important variable in determining the magnitude of the response of upper airway muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute effect of cigarette smoke on laryngeal receptors

Upper airway exposure to cigarette smoke elicits reflex changes in breathing pattern. To examine whether laryngeal afferents are affected by cigarette smoke, neural activity was recorded from the peripheral cut end of superior laryngeal nerve in anesthetized dogs. A box-balloon system, connected to the breathing circuit, allowed smoke to be inhaled spontaneously through the isolated upper airway while preserving its normal respiratory flow and pressure. Our results showed the following. Inhalation of cigarette smoke (25-50% concentration, 300-400 ml) caused a marked increase in activity of laryngeal irritant receptors which were either silent or randomly discharging during control breathing [their activity increased from a control value of 1.67 +/- 0.50 (mean +/- SE; n = 21) to a peak of 5.03 +/- 0.85 impulses/s in 11-15 s]. The activity of laryngeal cold receptors was reduced to 77.3 and 63.8% of control (n = 9) during the two breaths of smoke inhalation, respectively. After returning toward the base-line activity, a more pronounced inhibition (26.3% of control) occurred at three to nine breaths after the smoke inhalation. A small but significant decrease (88.5% of control) in the inspiratory discharge of laryngeal mechanoreceptors was observed during the first test breath. These effects were independent of the CO2 content of the smoke. Furthermore, there was no difference between the responses of these laryngeal afferents to high- and low-nicotine cigarette smoke.     

Differential response of respiratory muscles to airway occlusion in infants

The effect of end-expiratory occlusion on respiratory muscle activity was studied in 10 unsedated preterm infants during sleep. Electromyograms (EMG) of the upper airway were recorded from surface electrodes placed over the submental (SM) area; diaphragm (DIA) EMGs were obtained with identical electrodes over the right subcostal margin. Phasic SM EMG accompanied 56 +/- 36% of breaths during spontaneous breathing and increased to 80 +/- 26% (P less than 0.05) on the first inspiratory effort after occlusion. Occlusion increased peak amplitude (P less than 0.001) and total duration (P less than 0.005) of the SM EMG without significant changes in its initial rate of rise. In contrast, only the total duration of the DIA EMG increased (P less than 0.005) during occlusion. Inspiratory time increased from 470 +/- 120 to 720 +/- 210 ms (P less than 0.001) during the first occluded effort, but expiratory time did not change. With sustained occlusion, peak amplitude of the SM EMG progressively increased, but DIA EMG only significantly increased by the third occluded effort. Pharyngeal patency was invariably maintained throughout the induced airway occlusions. Sharp bursts of SM EMG activity coincided with resolution of spontaneous obstructive apneic episodes in four infants. The immediate increase in SM EMG associated with airway occlusion may be a mechanism that prevents the development of obstructive apnea.     

Effects of HCl-pepsin laryngeal instillations on upper airway patency-maintaining mechanisms

Gastroesophageal reflux has been indicated as anetiopathological factor in disorders of the upper airway. Upper airwaycollapsing pressure stimulates pressure-responsive laryngeal receptorsthat reflexly increase the activity of upper airway abductor muscles. We studied, in anesthetized dogs, the effects of repeated laryngeal instillations of HCl-pepsin (HCl-P; pH = 2) on the response of laryngeal afferent endings and the posterior cricoarytenoid muscle (PCA) to negative pressure. The effect of negative pressure on receptordischarge or PCA activity was evaluated by comparing their response toupper airway (UAO) and tracheal occlusions (TO). It is only during UAO,but not during TO, that the larynx is subjected to negative transmuralpressure. HCl-P instillation decreased the rate of discharge during UAOof the 10 laryngeal receptors studied from 56.4 ± 10.9 (SE) to 38.2 ± 9.2 impulses/s (P < 0.05). With UAO, the peak PCA moving time average, normalized by dividing itby the peak values of esophageal pressure, decreased after six HCl-Ptrials from 4.29 ± 0.31 to 2.23 ± 0.18 (n = 6;P < 0.05). The responses to TO ofeither receptors or PCA remained unaltered. We conclude that exposureof the laryngeal mucosa to HCl-P solutions, as it may occur withgastroesophageal reflux, impairs the patency-maintaining mechanismsprovided by laryngeal sensory feedback. Inflammatory and necroticalterations of the laryngeal mucosa are likely responsible for theseeffects.

     

Blood flow in respiratory muscles during maximal exertion in ponies with laryngeal hemiplegia

The interactive effects of upper airway negative pressure and hypercapnia on the pattern of breathing were assessed in pentobarbital-anesthetized cats. At any given level of pressure in the upper airway, hypercapnia increased respiratory rate, reduced inspiratory time, and augmented tidal volume, inspiratory airflow, and the peak and rate of rise of diaphragm electrical activity. Conversely, at any given level of CO2, upper airway negative pressure decreased respiratory rate, prolonged inspiratory time, and depressed inspiratory airflow and diaphragm electromyogram (EMG) rate of rise. Application of negative pressure to the upper airway shifted the relationship between tidal volume and inspiratory time upward and rightward. The relationship between inspiratory and expiratory times, however, was linearly correlated over a wide range of chemical drives and levels of upper airway pressure. These results suggest that in the anesthetized cat upper airway negative pressure afferent inputs 1) interact in an additive fashion with hypercapnia to alter the pattern of breathing, 2) interact multiplicatively with CO2 to influence mean inspiratory airflow and diaphragm EMG rate of rise, 3) depress the generation of central inspiratory activity, 4) increase the time-dependent volume threshold for inspiratory termination, and 5) affect the ratio between inspiratory and expiratory times in a similar manner as alterations in PCO2.     

Interaction between upper airway negative pressure pulses and CO2 on breathing pattern

The interaction between CO2 and negative pressure pulses on breathing pattern was investigated in 10 anesthetized, spontaneously breathing rabbits. The upper airway was functionally isolated into a closed system. A servo-respirator triggered by the inspiratory activity of the diaphragm was used to apply pressure pulses of -15 cmH2O to the isolated upper airway in early inspiration while the animal was breathing room air, 100% O2, 6% CO2 in O2, or 9% CO2 in O2. The negative pressure pulses produced a reversible inhibition of inspiration in most trials with resultant increase in inspiratory duration (TI); no change was observed in peak diaphragmatic electromyogram (Dia EMG) or expiratory duration, whereas a decrease was seen in mean inspiratory drive (peak Dia EMG/TI). This prolongation of inspiratory duration and decrease in mean inspiratory drive with negative pressure pulses persisted at higher levels of CO2; the slopes of the test breaths were not significantly different from that of control breaths. These results suggest that upper airway negative pressure pulses are equally effective in altering the breathing pattern at all levels of CO2.     

Upper airway negative-pressure effects on respiratory activity of upper airway muscles

Influence of upper airway negative-pressure change on the respiratory activity of various upper airway muscles was investigated in 13 anesthetized rabbits. Phasic inspiratory activity increased or appeared during virtually all negative-pressure trials in nasolabial, cricothyroid, and posterior cricoarytenoid muscles. No phasic inspiratory activity was seen in the sternothyroid (ST) and sternohyoid (SH) muscles before negative-pressure applications but appeared during 80% of trials in ST and 62% of trials in SH. During maintained negative pressure, a gradual decline in activity was often observed in the nasolabial and laryngeal muscles, whereas a rapid decline in activity was seen in the cervical strap muscles. Reflex effects of negative pressure was markedly reduced or abolished by sectioning the internal branch of the superior laryngeal nerve bilaterally. Reflex augmentation of upper airway muscle activity reported here may have functional significance in the maintenance of upper airway patency. It could prevent upper airway collapse when negative pressure swings in the upper airway increase or facilitate recovery when large negative pressure swings are produced by obstructed inspiratory efforts.     

Response of laryngeal mechanoreceptors to high-frequency pressure oscillation.

High-frequency pressure oscillations (HFPO) in the upper airway induce arousal, activation of genioglossus muscle, and bronchoconstriction. The present study was designed to determine the response of superior laryngeal nerve afferent fibers to HFPO. In 10 anesthetized dogs spontaneously breathing through a tracheal cannula, the upper airway was converted to a closed system. The activity of thin bundles separated from the peripheral cut end of the superior laryngeal nerve was monitored. Of 104 mechanoreceptors identified, 87 were classified as respiratory modulated and 17 as non-respiratory modulated on the basis of their response to transmural pressure change and muscle activity. The responses of these fibers to HFPO of +/- 2.5 cmH2O at 10, 20, and 30 Hz were determined. Among the respiratory-modulated receptors, 86 of 87 increased their activity in response to HFPO. Of the 17 non-respiratory-modulated receptors, 12 receptors showing a random or tonic activity did not respond to HFPO, whereas the 5 that were silent during control condition responded exclusively to HFPO. Our results show that HFPO of similar frequency but much less magnitude than snoring is capable of activating the vast majority of laryngeal mechanoreceptors. Pressure-sensitive respiratory-modulated endings appear to mediate the arousal and genioglossal response, whereas non-respiratory-modulated receptors responding to HFPO presumably mediate the bronchoconstrictive response.     

Lung mechanics and neuromuscular output during CO2 inhalation after airway anesthesia

Airway anesthesia with aerosolized lidocaine has been associated with an increase in minute ventilation (VE) during CO2 inhalation. The increase in VE may be due to increased neuromuscular output or decreased mechanical load on breathing. To evaluate this we measured VE, breathing pattern, mouth occlusion pressure, and lung mechanics in 20 normal subjects during room-air breathing and then inhalation of 6% CO2-94% O2, before and after airway anesthesia. Measurements of lung mechanics included whole-lung resistance, dynamic and static compliance, and functional residual capacity. Airway anesthesia had no detectable effect on any measurements during room-air breathing. During CO2 inhalation, airway anesthesia produced increases in VE and mean inspiratory flow rate (VT/TI) and more negative inspiratory pleural pressure but had no detectable effect on lung mechanics or mouth occlusion pressure. Pleural pressure was more negative during the latter 25% of inspiration. We concluded that airway receptors accessible to airway anesthesia play a role in determining neuromuscular output during CO2 inhalation.     

Genioglossus and breathing responses to airway occlusion: effect of sleep and route of occlusion

We examined the effect of sleep state on the response of genioglossus muscle (EMGgg) activity to total airway occlusion applied at 1) nasal (N) airway [and thus exposing the upper airway (UAW) to pressure changes] and 2) tracheal (T) airway (thus excluding UAW from pressure changes). A total of 233 tests were performed during wakefulness (W), 98 tests in slow-wave sleep (SWS), and 72 tests in rapid-eye-movement (REM) sleep. Prolongation of inspiratory time (TI) of the first occluded effort occurred in all tests irrespective of behavioral state, with the greatest increase seen in awake N tests. Nasal tests augmented EMGgg activity in the first occluded breath and produced a linear increase in EMGgg during occlusion. The EMGgg activity at any given time during nasal occlusion in SWS was less than that recorded during W tests. There was a marked reduction in EMGgg response to N occlusion during REM sleep. The EMGgg activity during awake T tests was significantly less than that of N tests at any given time during occlusion. There was no relationship between the level of EMGgg activity and asphyxia in T tests performed during SWS and REM sleep. Nasal tests decreased the force generated by the inspiratory pump muscles and the central drive to breathing compared with T tests. These results confirm the important role of the UAW in regulating breathing pattern and indicate that both immediate and progressive load-compensating responses during nasal occlusion are influenced by information arising from the UAW.     

Control of respiratory activity of the genioglossus muscle in micrognathic infants

The genioglossus (GG) muscle activity of four infants with micrognathia and obstructive sleep apnea was recorded to assess the role of this tongue muscle in upper airway maintenance. Respiratory air flow, esophageal pressure, and intramuscular GG electromyograms (EMG) were recorded during wakefulness and sleep. Both tonic and phasic inspiratory GG-EMG activity was recorded in each of the infants. On occasion, no phasic GG activity could be recorded; these silent periods were unassociated with respiratory embarrassment. GG activity increased during sigh breaths. GG activity also increased when the infants spontaneously changed from oral to nasal breathing and, in two infants, with neck flexion associated with complete upper airway obstruction, suggesting that GG-EMG activity is influenced by sudden changes in upper airway resistance. During sleep, the GG-EMG activity significantly increased with 5% CO2 breathing (P less than or equal to 0.001). With nasal airway occlusion during sleep, the GG-EMG activity increased with the first occluded breath and progressively increased during the subsequent occluded breaths, indicating mechanoreceptor and suggesting chemoreceptor modulation. During nasal occlusion trials, there was a progressive increase in phasic inspiratory activity of the GG-EMG that was greater than that of the diaphragm activity (as reflected by esophageal pressure excursions). When pharyngeal airway closure occurred during a nasal occlusion trial, the negative pressure at which the pharyngeal airway closed (upper airway closing pressure) correlated with the GG-EMG activity at the time of closure, suggesting that the GG muscle contributes to maintaining pharyngeal airway patency in the micrognathic infant.