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.     

Induction of airway collapse with subatmospheric pressure in awake patients with sleep apnea

To determine whether the pharyngeal airway is abnormal in awake patients with obstructive sleep apnea (OSA), we measured the ability of the pharyngeal airway to resist collapse from subatmospheric pressure applied to the nose in awake subjects, 12 with OSA and 12 controls. Subatmospheric pressure was applied to subjects placed in the supine position through a tightly fitting face mask. We measured airflow at the mask as well as mask, pharyngeal, and esophageal pressures. Ten patients developed airway obstruction when subatmospheric pressures between 17 and 40 cmH2O were applied. Obstruction did not occur in two patients with the least OSA. Obstruction did not occur in 10 controls; one obese control subject developed partial airway obstruction when -52 cmH2O was applied as did another with -41 cmH2O. We conclude that patients with significant OSA have an abnormal airway while they are awake and that application of subatmospheric pressure may be a useful screening test to detect OSA.     

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.     

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.     

Arousal responses to airway occlusion in sleeping dogs: comparison of nasal and tracheal occlusions

Previous studies have shown that the arousal threshold to hypoxia, hypercapnia, and tracheal occlusions is greatly depressed in rapid-eye-movement (REM) sleep compared with slow-wave sleep (SWS). The aim of this study was to compare the arousal thresholds in SWS and REM sleep in response to an upper airway pressure stimulus. We compared the waking responses to tracheal (T) vs. nasal (N) occlusion in four unanesthetized, naturally sleeping dogs. The dogs either breathed through a tracheal fistula or through the snout using a fiberglass mask. A total of 295 T and 160 N occlusion tests were performed in SWS and REM sleep. The mean time to arousal during N and T tests was variable in the same dog and among the dogs. The mean time to arousal in SWS-tracheal occlusion was longer than that in N tests in only two of the four dogs. The total number of tests inducing arousal within the first 15 s of SWS-nasal occlusion tests was significantly more than that of T tests (N: 47%; T: 27%). There was a marked depression of arousal within the initial 15 s of REM sleep in T tests compared with N tests (N: 21%; T: 0%). The frequency of early arousals in REM tests was less than that of SWS for both N and T tests. The early arousal in N occlusion is in sharp contrast to the well-described depressed arousal responses to hypoxia, hypercapnia, and asphyxia. This pattern of arousal suggests that the upper airway mechanoreceptors may play an important role in the induction of an early arousal from nasal occlusion.     

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.     

Waking and genioglossus muscle responses to upper airway pressure oscillation in sleeping dogs

We studied waking and genioglossus electromyographic (EMGgg) responses to oscillating pressure waves applied to the upper airways of three sleeping dogs. The dogs were previously prepared with a permanent side-hole tracheal stoma and were trained to sleep with a tight-fitting snout mask, hermetically sealed in place, while breathing through a cuffed endotracheal tube inserted through the tracheostomy. Sleep state was determined by behavioral, electroencephalographic, and electromyographic criteria, and EMGgg activity was measured using fine bipolar electrodes inserted directly into the muscle. Oscillatory pressure waves of 30 Hz and +/- 3 cmH2O (tested at atmospheric and subatmospheric upper airway pressures) were applied at the dog's nostrils or larynx, either constantly for a period of 1 min or in 0.5-s bursts. We found that the pressure stimulus had two major effects. First, it was a potentially powerful arousal-promoting stimulus. Arousal occurred in 78% of tests in slow-wave sleep (SWS) and 55% of tests in rapid-eye-movement (REM) sleep, with swallowing and sighing accompanying many of the arousals. Second, it produced an immediate and sustained augmentation of EMGgg, in wakefulness, SWS, and REM sleep. We conclude that oscillatory pressure waves in the upper airway, as found in snoring, produce reflex responses that help maintain upper airway patency during sleep. Loss of this type of reflex might contribute to the onset of obstructive sleep apnea in chronic snorers.     

Effect of positive nasal pressure on upper airway pressure-flow relationships

To determine the influence of changes in nasal pressure (Pn) on airflow mechanics in the upper airway, we examined the effect of elevations in Pn on upper airway resistance and critical pressure (Pcrit) during stage I/II sleep in six patients with obstructive sleep apnea. When Pn was elevated above a Pcrit, periodic occlusions of the upper airway were eliminated and inspiratory airflow limitation was demonstrated by the finding that inspiratory airflow (VI) became maximal (VImax) and independent of fluctuations in hypopharyngeal pressure (Php) when Php fell below a specific Php (Php'). As Pn was elevated, VI vs. Php demonstrated 1) marked decreases in early and late inspiratory resistances from 75.9 +/- 34.7 and 54.6 +/- 19.0 to 8.0 +/- 1.7 and 7.6 +/- 1.6 cmH2O.l-1.s (P less than 0.05), respectively, and 2) increases in early and late inspiratory Php' to levels that exceeded Pcrit by 3.0 +/- 0.6 and 3.1 +/- 0.7 cmH2O, respectively, at the highest level of Pn applied (P less than 0.01). This latter finding suggests that elevations in Pn result in increases in Pcrit. We suggest that elevations in Pn produce distinct alterations in upper airway resistance and collapsibility, which may influence oppositely the level of airflow through the upper airway during sleep.     

An induced blood pressure rise does not alter upper airway resistance in sleeping humans

Wilson, Christine R., Shalini Manchanda, David Crabtree,James B. Skatrud, and Jerome A. Dempsey. An induced blood pressurerise does not alter upper airway resistance in sleeping humans.J. Appl. Physiol. 84(1): 269-276, 1998.Sleep apnea is associated with episodic increases in systemicblood pressure. We investigated whether transient increases in arterialpressure altered upper airway resistance and/or breathingpattern in nine sleeping humans (snorers and nonsnorers). Apressure-tipped catheter was placed below the base of the tongue, andflow was measured from a nose or face mask. Duringnon-rapid-eye-movement sleep, we injected 40- to 200-µg iv boluses ofphenylephrine. Parasympathetic blockade was used if bradycardia wasexcessive. Mean arterial pressure (MAP) rose by 20 ± 5 (mean ± SD) mmHg (range 12-37 mmHg) within 12 s and remained elevated for105 s. There were no significant changes in inspiratory or expiratorypharyngeal resistance (measured at peak flow, peak pressure, 0.2 l/s orby evaluating the dynamic pressure-flow relationship). Atpeak MAP, end-tidal CO₂ pressure fell by 1.5 Torr and remained low for 20-25 s. At 26 s after peak MAP, tidal volume fell by 19%, consistent with hypocapnic ventilatory inhibition. We conclude that transient increases in MAP of a magnitude commonly observed during non-rapid-eye-movement sleep-disordered breathing do not increase upper airway resistance and, therefore, willnot perpetuate subsequent obstructive events.

     

Arousal response to upper airway obstruction in young lambs: comparison of nasal and tracheal occlusion

Experiments were done on seven lambs to determine if site of occlusion--nasal versus tracheal--influences the cardiopulmonary and arousal responses from sleep to upper airway obstruction. Each lamb was anesthetized and instrumented for sleep staging and measurements of heart rate and arterial hemoglobin oxygen saturation. A tracheostomy was also done and a fenestrated tracheostomy tube placed in the trachea. Prior to an experiment, A 5F balloon-tipped catheter was inserted through the decannulation cannula into the tracheostomy tube so that tracheal occlusions could be accomplished by inflating the balloon. In addition, a 5F balloon-tipped catheter was inserted into the inlet of a pre-formed silicone mask sealed to the animals snout with silicone rubber foam so that nasal occlusions could be accomplished by inflating the balloon. During an experiment, measurements were made in quiet sleep and in active sleep during control periods of tidal breathing and during experimental periods of nasal or tracheal occlusion. Upper airway obstruction was terminated by deflating the balloon once the animal aroused from sleep. Arousal occurred sooner following nasal occlusion than during tracheal occlusion in quiet sleep; 64 percent of arousals occurred within five seconds of nasal occlusion whereas only 14 percent of arousals occurred within five seconds of tracheal occlusion in quiet sleep. In addition, SaO2 and heart rate decreased more before arousal following tracheal occlusion than following nasal occlusion. However, there was not a significant effect of site of obstruction on time to arousal or the change in SaO2 before arousal in active sleep.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in lung volume and upper airway using MRI during application of nasal expiratory positive airway pressure in patients with sleep-disordered breathing

Nasal expiratory positive airway pressure (nEPAP) delivered with a disposable device (Provent, Ventus Medical) has been shown to improve sleep-disordered breathing (SDB) in some subjects. Possible mechanisms of action are 1) increased functional residual capacity (FRC), producing tracheal traction and reducing upper airway (UA) collapsibility, and 2) passive dilatation of the airway by the expiratory pressure, carrying over into inspiration. Using MRI, we estimated change in FRC and ventilation, as well as UA cross-sectional area (CSA), in awake patients breathing on and off the nEPAP device. Ten patients with SDB underwent nocturnal polysomnography and MRI with and without nEPAP. Simultaneous images of the lung and UA were obtained at 6 images/s. Image sequences were obtained during mouth and nose breathing with and without the nEPAP device. The nEPAP device produced an end-expiratory pressure of 4-17 cmH(2)O. End-tidal Pco(2) rose from 39.7 ± 5.3 to 47.1 ± 6.0 Torr (P < 0.01). Lung volume changes were estimated from sagittal MRI of the right lung. Changes in UA CSA were calculated from transverse MRI at the level of the pharynx above the epiglottis. FRC determined by MRI was well correlated to FRC determined by N(2) washout (r = 0.76, P = 0.03). nEPAP resulted in a consistent increase in FRC (46 ± 29%, P < 0.001) and decrease in ventilation (50 ± 15%, P < 0.001), with no change in respiratory frequency. UA CSA at end expiration showed a trend to increase. During wakefulness, nEPAP caused significant hyperinflation, consistent with an increase in tracheal traction and a decrease in UA collapsibility. Direct imaging effects on the UA were less consistent, but there was a trend to dilatation. Finally, we showed significant hypoventilation and rise in Pco(2) during use of the nEPAP device during wakefulness and sleep. Thus, at least three mechanisms of action have the potential to contribute to the therapeutic effect of nEPAP on SDB.     

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.     

Changes in upper airway resistance with lung inflation and positive airway pressure

The influence of pulmonary inflation and positive airway pressure on nasal and pharyngeal resistance were studied in 10 normal subjects lying in an iron lung. Upper airway pressures were measured with two low-bias flow catheters while the subjects breathed by the nose through a Fleish no. 3 pneumotachograph into a spirometer. Resistances were calculated at isoflow rates in four different conditions: exclusive pulmonary inflation, achieved by applying a negative extra-thoracic pressure (NEP); expiratory positive airway pressure (EPAP), which was created by immersion of the expiratory line; continuous positive airway pressure (CPAP), realized by loading the bell of the spirometer; and CPAP without pulmonary inflation by simultaneously applying the same positive extrathoracic pressure (CPAP + PEP). Resistance measurements were obtained at 5- and 10-cmH2O pressure levels. Pharyngeal resistance (Rph) significantly decreased during each measurement; the decreases in nasal resistance were only significant with CPAP and CPAP + PEP; the deepest fall in Rph occurred with CPAP. It reached 70.8 +/- 5.5 and 54.8 +/- 6.5% (SE) of base-line values at 5 and 10 cmH2O, respectively. The changes in lung volume recorded with CPAP + PEP ranged from -180 to 120 ml at 5 cmH2O and from -240 to 120 ml at 10 cmH2O. Resistances tended to increase with CPAP + PEP compared with CPAP values, but these changes were not significant (Rph = 75.9 +/- 6.1 and 59.9 +/- 6.6% at 5 and 10 cmH2O of CPAP + PEP). We conclude that 1) the upper airway patency increases during pulmonary inflation, 2) the main effect of CPAP is related to pneumatic splinting, and 3) pulmonary inflation contributes little to the decrease in upper airways resistance observed with CPAP.     

Upper airway muscle activity during nasal occlusion in newborn babies

Submental electromyorgams (SM EMG) were recorded from 20 preterm babies (gestational age 30 +/- 2 wk, postmenstrual age at study 35 +/- 2 wk) (mean +/- SD) and 3 full-term infants (7-14 days old). SM EMG was evaluated during eupnea and brief experimental airway occlusion. Phasic inspiratory SM EMG was rarely seen during eupnea. SM EMG tended to increase on the first occluded effort, although this increase was not statistically significant in most babies. All infants showed progressive breath-by-breath augmentation of phasic SM EMG during occlusions in rapid-eye-movement (REM) as well as quiet (QS) sleep; phasic increases in SM EMG were similar during REM and QS occlusions in the majority (16/22) of babies. Periods of airway closure were detected during 24 occlusions in 5 infants; phasic SM EMG was reduced on these occasions. The results are consistent with the idea that recruitment of upper airway muscles contributes to the stability of the airway of the preterm human.     

Superior laryngeal nerve section alters responses to upper airway distortion in sleeping dogs

Curran, Aidan K., Peter R. Eastwood, Craig A. Harms, CurtisA. Smith, and Jerome A. Dempsey. Superior laryngeal nerve sectionalters responses to upper airway distortion in sleeping dogs.J. Appl. Physiol. 83(3): 768-775, 1997.We investigated the effect of superior laryngeal nerve (SLN)section on expiratory time(TE) and genioglossuselectromyogram (EMGgg) responses to upper airway (UA) negative pressure(UANP) in sleeping dogs. The same dogs used in a similar intact study(C. A. Harms, C. A., Y.-J. Zeng, C. A. Smith, E. H. Vidruk, and J. A. Dempsey. J. Appl. Physiol. 80:1528-1539, 1996) were bilaterally SLN sectioned. After recovery,the UA was isolated while the animal breathed through a tracheostomy.Square waves of negative pressure were applied to the UA from below thelarynx or from the mask (nares) at end expiration and held until thenext inspiratory effort. Section of the SLN increased eupneicrespiratory frequency and minute ventilation. Relative to the same dogsbefore SLN section, sublaryngeal UANP caused lessTE prolongation while activation of the genioglossus required less negative pressures. Mask UANP had noeffect on TE or EMGgg activity.We conclude that the SLN 1) is notobligatory for the reflex prolongation ofTE and activation of EMGggactivity produced by UANP and 2)plays an important role in the maintenance of UA stability and thepattern of breathing in sleeping dogs.

     

Effects of tracheal airway occlusion on hyoid muscle length and upper airway volume

Complex relationships exist among electromyograms (EMGs) of the upper airway muscles, respective changes in muscle length, and upper airway volume. To test the effects of preventing lung inflation on these relationships, recordings were made of EMGs and length changes of the geniohyoid (GH) and sternohyoid (SH) muscles as well as of tidal changes in upper airway volume in eight anesthetized cats. During resting breathing, tracheal airway occlusion tended to increase the inspiratory lengthening of GH and SH. In response to progressive hypercapnia, the GH eventually shortened during inspiration in all animals; the extent of muscle shortening was minimally augmented by airway occlusion despite substantial increases in EMGs. SH lengthened during inspiration in six of eight animals under hypercapnic conditions, and in these cats lengthening was greater during airway occlusion even though EMGs increased. Despite the above effects on SH and GH length, upper airway tidal volume was increased significantly by tracheal occlusion under hypercapnic conditions. These data suggest that the thoracic and upper airway muscle reflex effects of preventing lung inflation during inspiration act antagonistically on hyoid muscle length, but, because of the mechanical arrangement of the hyoid muscles relative to the airway and thorax, they act agonistically to augment tidal changes in upper airway volume. The augmentation of upper airway tidal volume may occur in part as a result of the effects of thoracic movements being passively transmitted through the hyoid muscles.