American Journal of Respiratory and Critical Care Medicine

Fiberoptic imaging in an isolated, sealed upper airway was performed in 10 decerebrate cats to determine the effect of pharyngeal muscle activation on airway pressure–area relationships. Bilateral cuff electrodes stimulated the distal cut ends of the following nerves: medial and lateral hypoglossus, glossopharyngeus, and pharyngeal branch of vagus. At given intraluminal pressures ranging from +6 to −6 cm H2O, cross-sectional area was measured in the rostral oropharynx, velopharynx, and caudal oropharynx, with and without nerve stimulation. A mixed model analysis of variance indicated a relatively constant increase in area across the pressure range with glossopharyngeal stimulation at any given level. Significant interactions between pressure and stimulation were present in the rostral oropharynx with medial hypoglossus stimulation and in the caudal oropharynx with independent and combined hypoglossal branch stimulation and pharyngeal branch of vagus stimulation. With stimulation of the hypoglossal nerves, greater increases in area in these regions occurred in the lower pressure ranges. Stimulation of the pharyngeal branch of the vagus caused a greater decrease in area at the higher pressure ranges in the caudal oropharynx and velopharynx. The results indicate that the mechanical effects of pharyngeal muscle activation depend not only on the region and muscles activated but also on the intraluminal pressure.

Pharyngeal muscles with phasic inspiratory activity dilate and stiffen the airway and are thought to play an important role in the pathogenesis of obstructive sleep apnea (OSA) (111). Suppression of motor output to these pharyngeal muscles during sleep promotes airway closure. On the basis of our current understanding of the pathogenesis of OSA, there has been persistent interest in developing treatments for this disorder that prevent suppression of pharyngeal muscle activity during sleep. Previous clinical studies report that selective activation of tongue muscles during inspiration increases maximum inspiratory airflow and prevents airway closure during sleep (12, 13). Pharyngeal airway closure in patients with OSA can occur in different segments of the pharynx, and the tongue muscles are only a few of the many skeletal muscles surrounding the pharyngeal airway (1416). A better understanding of the mechanical effects of selective pharyngeal muscle activation on airway function might help to promote further development of this potential treatment approach for OSA.

The pharyngeal airway muscles have complex anatomic relationships and receive their motor output from several different nerves (16). The hypoglossus (HG) nerve provides motor output to the intrinsic and extrinsic tongue muscles (17). The medial branch of the HG nerve innervates the genioglossus and geniohyoid muscles, both tongue protrudors. The lateral branch of the HG innervates the tongue retractors: the styloglossus and hyoglossus. Both branches carry motor output to the intrinsic tongue muscle fibers that play an important role in shaping the tongue. The pharyngeal branch of the vagus innervates the pharyngeal constrictor muscles, and the glossopharyngeal nerve provides motor output to the stylopharyngeus muscle (16). In addition, recent studies indicate that the glossopharyngeus also supplies the levator veli palatini, pharyngeal constrictors, and cricopharyngeus muscles via inputs to the pharyngeal plexus (18, 19).

Whereas the effects of generalized and selective pharyngeal muscle activation on overall pharyngeal airway mechanics have been extensively studied, far fewer studies have examined the effects of selective pharyngeal muscle activation on regional pharyngeal airway function. A previous fiberoptic study from this laboratory examined the regional effects of pharyngeal muscle activation on airway size in cats and found that the effects of selective pharyngeal muscle activation depend on the muscles being stimulated and the region of the pharyngeal airway being examined (20). During those experiments, measurements with and without stimulation were obtained at atmospheric intraluminal pressure. In the current study, fiberoptic imaging of the pharyngeal airway was performed in cats to determine the regional pressure–area relationships of the airway, with and without selective stimulation of nerves supplying motor output to various pharyngeal muscles. The study tested the hypothesis that the regional mechanical effects of selective pharyngeal muscle activation on airway function are dependent not only on airway region but also on intraluminal pressure and airway size. The experiments were designed to address the following specific questions. How did the cross-sectional area (CSA) versus pressure curves compare in different regions under passive (no-stimulation) conditions? What was the effect of a given nerve stimulation at a given region (rostral oropharynx, caudal oropharynx, velopharynx) on the pressure versus airway CSA curve? How did the CSA versus pressure curves compare for different nerve stimulations in the same region? How did stimulation of a given nerve affect the CSA versus pressure curve in different regions?

Animal Experiments

The protocol was performed in 10 decerebrate, tracheotomized, spontaneously breathing adult cats, as approved by the Animal Care Committee. Anesthesia and general surgical preparation were described previously (20). The internal branch of the superior laryngeal nerve was severed bilaterally to remove laryngeal afferent feedback. The nose and mouth were sealed with a fast setting dental impression material (Frantz Design, Inc., Austin, TX). Cuff electrodes stimulated the bilateral, distal cut ends of the following nerves: medial HG, lateral HG, glossopharyngeus, and pharyngeal branch of vagus. The specific stimulation methods were the same as those detailed in a previous study (20).

A fiberoptic scope (Pentax, Orangeberg, NY) was advanced through the rostral trachea into the pharynx. As illustrated in our previous study, recordings were obtained at two levels of the airway: edge of soft palate and rostral oropharynx (20). The image at the edge of the soft palate revealed the orifices to the velopharynx and caudal oropharynx.

Video recordings of the fiberoptic images at a given airway level were obtained with and without bilateral stimulation of individual nerves and simultaneous bilateral stimulation of both medial and lateral HG branches (HG coactivation) over a pressure range of +6 to −6 cm H2O in 2 cm H2O increments. The specified pressures were produced by connecting the rostral trachea to adjustable positive (Respironics, Murrysville, PA) or negative pressure (Ametek, Kent, OH) sources. Throughout the recordings, pressure in the airway was monitored with a water manometer to ensure that the given pressure levels remained constant during passive and stimulated conditions.

Data Analysis

As previously detailed, video images were analyzed off-line to obtain metric unit measurements of CSA at each airway level and pressure, with and without nerve stimulation (20). Complete data sets were obtained in all 10 cats. A mixed model analysis of variance was used to assess how various factors influenced CSA measures. Ten subjects (n = 10 cats) were employed in a within-subjects factorial design that compared stimulation (two conditions: stimulation versus no-stimulation), region (three conditions: rostral oropharynx versus caudal oropharynx versus velopharynx), and nerve (five conditions: glossopharyngeus versus lateral HG versus medial HG versus medial + lateral HG versus pharyngeal branch of vagus). In this random coefficients model, slope and intercept were specified as random variables to describe the effect of pressure on CSA for each condition (stimulation, region, and nerve). Thus, the analysis of variance model included terms for stimulation, region, nerve, pressure, and subject, together with terms for higher-order interactions among the first three terms.

In further analyses, the predicted mean changes in CSA from the analysis of variance model were used to test the effect of stimulation among nerves within each of the three regions. Here, the baseline no-stimulation CSA score served as a covariant in a model with terms for stimulation, region, and pressure. In effect, these analyses modeled change scores (that is, change from the no-stimulation condition) and assessed the simple effect of nerve within a region or the effect of region on nerve. Post hoc tests were made using Tukey-adjusted contrasts for pairwise comparisons. Significance was assumed at p < 0.05.

The overall statistical results indicated a significant three-way interaction among the factors of stimulation, region, and nerve (F[1,2059] = 7.41; p = 0.007), such that the effect of stimulation was different for different nerves depending on region.

Comparison of Pressure–Area Curves in Different Regions Under No-Stimulation Conditions

Figure 1

compares the pressure–area relationships obtained in each of the three regions under unstimulated conditions. Pressure had a significant effect on CSA in each region (overall effect of pressure p < 0.0001). There were no statistically significant differences in the five pressure–area curves in a particular region. CSA in the rostral oropharynx was significantly larger than that in the caudal oropharynx or velopharynx across all pressure levels. No differences were detected between the caudal oropharynx and velopharynx. Over the pressure range of 0 to 6 cm H2O, the slope of the CSA–pressure relationship in the rostral oropharynx was greater than that at the more caudal levels. No differences in slopes across the three levels were present in the lower pressure range.

Effects of a Given Nerve Stimulation at a Given Region on the Pressure–Area Curve

For any given nerve or nerve combination, the effect of stimulation on CSA varied according to region. Stimulation of the medial HG caused the largest average increase in CSA across pressure levels in the rostral oropharynx (p < 0.0001). A significant interaction of pressure and CSA with medial HG stimulation (p = 0.049) was present in the rostral oropharynx (Figure 2)

. In this region, increases in CSA with medial HG stimulation were reduced at the higher pressure levels of 2, 4, and 6 cm H2O. The same trend occurred in the caudal oropharynx, where medial HG stimulation increased CSA at lower pressures. The increase in CSA was attenuated at 2 cm H2O, and CSA slightly decreased with stimulation at higher pressures (p = 0.0005). In the velopharynx, there was no significant interaction of medial HG stimulation with pressure, although there was a small, relatively constant increase in CSA across all pressure levels (p < 0.0008).

The fiberoptic imaging revealed that stimulation of the lateral HG not only retracted the tongue but also displaced it in a ventral direction. As with medial HG stimulation, the average increase in CSA across pressure levels with lateral HG stimulation was greatest in the rostral oropharynx (p ⩽ 0.0002). Although CSA increases in the rostral oropharynx appeared to be slightly attenuated at the highest pressure levels of 4 and 6 cm H2O, testing for an interaction between pressure and stimulation was not significant. However, interaction of pressure and CSA with lateral HG stimulation was present in the caudal oropharynx, where stimulation increased CSA for only the lower pressure levels of −2, −4, and −6 cm H2O (p = 0.001). In the velopharynx, lateral HG stimulation resulted in a modest but significant increase in CSA across the pressure range (p = 0.012). However, there appeared to be no difference at the highest pressure level (6 cm H2O), and there was no interaction between pressure and stimulation in this region.

HG coactivation resulted in a relatively constant increase in CSA across all pressure levels in both the rostral oropharynx and velopharynx. The greatest average increase in CSA during HG coactivation occurred in the rostral oropharynx (p < 0.001), and this was consistent with the results obtained by adding the effects on CSA of individual stimulation of the medial and lateral HG branches. In the caudal oropharynx, HG coactivation showed a significant interaction with pressure (p < 0.0001), such that CSA was significantly increased only in the lower pressure range of −2 through −6 cm H2O.

Figure 3

shows the effect of glossopharyngeal nerve stimulation on velopharyngeal CSA. The increase in CSA with glossopharyngeal nerve stimulation was relatively constant over the various pressure levels in each region (p < 0.0007). However, the average change in CSA due to glossopharyngeal stimulation was greater in the caudal oropharynx than in the velopharynx (p < 0.05) or in the rostral oropharynx (p < 0.022). There were no significant interactions between pressure and stimulation on CSA in any region during glossopharyngeal stimulation.

Unlike stimulation of other nerves, stimulation of the pharyngeal branch of the vagus decreased CSA in the caudal oropharynx and velopharynx (p < 0.0002) but had no significant effect in the rostral oropharynx (p = 0.19). The effects of stimulation on CSA in the velopharynx are shown in Figure 4

. There was a significant interaction between pressure and stimulation in the caudal oropharynx (p = 0.001) and velopharynx (p < 0.0001) due to the pronounced reduction of CSA during stimulation at and above atmospheric pressure.

Effects of Stimulating the Different Nerves on the Pressure–Area Curve in a Given Region

Table 1

TABLE 1. Mean ± se cross-sectional area changes (mm2) with stimulation of the different nerves across pressure levels*


Nerve

Rostral Oropharynx

Caudal Oropharynx

Velopharynx
Glossopharyngeal25.0 ± 5.042.5 ± 3.325.5 ± 4.1
Medial HG68.8 ± 6.3, 3.6 ± 1.9§11.9 ± 2.4
Lateral HG35.3 ± 7.3 4.4 ± 2.0§6.4 ± 2.0
Medial + lateral HG78.7 ± 7.4 8.2 ± 1.6§18.7 ± 3.3
Pharyngeal branch of the vagus
−7.8 ± 5.5
−10.1 ± 2.3§
−28.7 ± 2.6,

*Significant difference in change in CSA across regions for given nerve stimulation indicating the region in which stimulation of a given nerve had the greatest effect.

p values < 0.03.

Significant interaction of pressure and stimulation of a given nerve in a given region indicating that the pressure–area relationships with and without muscle stimulation were not parallel to each other.

p < 0.05.

§p ⩽ 0.001.

Definition of abbreviations: CSA = cross-sectional area; HG = hypoglossus.

summarizes the average changes in regional CSA with given nerve stimulation across pressure levels. These results used the predicted mean changes in CSA from the analysis of variance model to assess the simple effect of nerve within a region or the effect of region on a nerve. The greatest variability in CSA in relation to stimulation of different nerves occurred in the rostral oropharynx where the only nerve pairs that were not significantly different were glossopharyngeal versus lateral HG and HG coactivation versus only medial HG stimulation. Across pressures in the caudal oropharynx, the increase in CSA was significantly greater with stimulation of the glossopharyngeal nerve than with any of the other nerves. The only other significant difference among the remaining four nerves in the caudal oropharynx was between HG coactivation versus the pharyngeal branch of the vagus (p = 0.028). Within the velopharynx, the change in CSA versus pressure curve with pharyngeal branch of the vagus stimulation was significantly different from each of the other nerves, but there were no other significant differences among the remaining four nerves.

Effects of Stimulation of a Given Nerve on the Pressure–Area Curves Across Regions

The predicted mean values from the analysis of variance model were used to test the effect of stimulating a given nerve across regions. For the glossopharyngeal nerve the increase in CSA in the caudal oropharynx was greater than that in both the rostral oropharynx (p < 0.022) and the velopharynx (p < 0.05), but CSA changes in the rostral oropharynx and velopharynx were not significantly different (p = 1.0). For all HG nerve conditions (lateral HG, medial HG, and HG coactivation) the predicted CSA versus pressure curves were significantly greater in the rostral oropharynx compared with both caudal oropharynx and velopharynx (all cases p ⩽ 0.002), with no significant differences between the caudal oropharynx and velopharynx. Reduction in CSA with stimulation of the pharyngeal branch of the vagus was most effective in the velopharynx, and this effect was significantly different in this region than that in the caudal oropharynx (p < 0.016) and rostral oropharynx (p < 0.024), whereas there were no differences between the latter two regions (p = 1.0).

The results of the current study extend our previous findings by demonstrating that regional mechanical effects of selective pharyngeal muscle activation are dependent on intraluminal airway pressure. HG coactivation and individual stimulation of the medial and lateral HG resulted in greater increases in CSA in the caudal oropharynx when intraluminal pressure was subatmospheric. A similar effect of pressure on change in CSA was present with stimulation of the medial HG in the rostral oropharynx. Whereas stimulation of the glossopharyngeal nerve increased airway CSA in all three regions examined, the changes in CSA in a given region were uniform across the pressure range. In contrast to the other nerves, stimulation of the pharyngeal branch of the vagus decreased CSA in the caudal oropharynx and velopharynx, and greater decreases in CSA occurred as airway pressure was increased in these regions.

Over the pressure range studied, airway CSA without nerve stimulation, i.e., under passive conditions, progressively increased with increasing pressure in all three regions. Similar results have been reported in cats by Brennick and colleagues (21) using magnetic resonance imaging to study regional variations of pharyngeal airway volume and compliance. Therefore, activation of the pharyngeal muscles over the pressure range tested occurred not only at different intraluminal pressures but also at different airway sizes. Both intraluminal pressure and airway size may have influenced the mechanical effects of muscle activation. When intraluminal pressure is subatmospheric, activation of pharyngeal dilator muscles must act against this negative transmural pressure, and this may limit an increase in airway CSA. This effect would become progressively less important as intraluminal pressure increased. In addition to altering transmural pressure at the time of muscle activation, application of different intraluminal pressures changed the size of the compliant pharyngeal airway. These changes in airway size may have changed the intrinsic properties of the pharyngeal muscles (e.g., length–tension relationships), thus altering their mechanical effects on the airway. Changes in airway size might also change the orientation of the pharyngeal muscles through the movement of their points of attachment, e.g., the hyoid bone. Thus, changes in pharyngeal pressure may alter a number of variables that may be combined in a complex way to determine how pharyngeal muscles operate to change CSA.

The results indicate a complex relationship between changes in pharyngeal airway size and compliance, depending on which nerve is stimulated. For the sake of this discussion, the slope of the pressure–area curve is used to indicate the compliance of the airway under passive and stimulated conditions, although compliance is normally defined only under passive conditions. In this context, changes in airway size with stimulation of a given nerve were not uniformly associated with predictable changes in compliance. For example, the similar slopes of the pressure–area relationships, with and without glossopharyngeal stimulation at any airway level examined, indicate that stimulation of this nerve over the pressure range tested caused significant airway enlargement without a change in airway compliance. In contrast, in those conditions that were associated with a significant interaction between stimulation and pressure, stimulation caused significant changes in both CSA and compliance. For example, stimulation of the medial HG, lateral HG, and hypoglossal coactivation increased airway area while decreasing compliance in the caudal oropharynx, and similar results were obtained with medial HG stimulation in the rostral oropharynx. Stimulation of the pharyngeal branch of the vagus also stiffened the more distal pharyngeal airway regions but did so while decreasing airway size.

Modeling the upper airway as a Starling resistor, previous investigators have studied the effects of selective pharyngeal muscle activation on airway collapsibility in cats and rats by measuring critical airway pressure (Pcrit) in an isolated upper airway (510). In a study in cats, similar reductions in Pcrit were found with stimulation of the whole HG nerve or its medial branch (9). The decrease in Pcrit with stimulation of the lateral HG was not statistically significant (9). Using similar techniques, Fuller and colleagues (10) reported that whole HG nerve stimulation decreased airway collapsibility in rats. Independent stimulation of the medial and lateral branches did not alter Pcrit, although medial HG stimulation was felt to dilate the airway (10).

In addition to the species differences between the current study and that of Fuller and colleagues (10), a comparison of the current results with those of the previous animal studies is limited by differences in technique. Pcrit, by the nature of the technique, assesses airway collapsibility under dynamic rather than static conditions. In addition, the Pcrit technique is limited in its ability to localize the flow-limitation effect to a particular region of the pharyngeal airway and provides a more global assessment of pharyngeal airway collapsibility. Unlike the Pcrit studies in cats, the mouth in the rats studied by Fuller and colleagues (10) was not sealed, and flow measurements could have included flow through the oral airway. Changes in flow through the oropharynx, with and without muscle stimulation, could have affected the measurements of maximum inspiratory flow, Pcrit, and upstream resistance. Indeed, the few experiments (n = 3) performed to assess this possibility suggested that medial HG stimulation decreased Pcrit when the mouth was sealed (10). It is noteworthy that in the current studies, the largest increase in airway area, with whole and medial HG stimulation, occurred in the rostral oropharynx, suggesting that flow might occur through the oral airway during muscle stimulation under dynamic conditions.

Across the pressure range examined, HG coactivation and selective stimulation of the medial branch had similar effects on CSA, regardless of region. Some previous studies, including one from this laboratory, have reported a synergistic effect of whole nerve HG stimulation, compared with selective stimulation or stimulation of either the medial or lateral branches (10, 20). In agreement with the current study, Brennick and colleagues (27) used magnetic resonance imaging of the isolated pharyngeal airway to examine the regional effects of selective HG nerve stimulations under static conditions at atmospheric pressure in anesthetized, tracheotomized rats. Whole HG and selective medial branch stimulation caused similar increases in total nasopharyngeal volume, but medial branch stimulation enlarged oropharyngeal airway volume significantly more than did whole nerve stimulation.

Figure 5

shows a schematic model proposed by Isono and Remmers (22) to explain the mechanical effects of pharyngeal muscle activation on airway function. The model predicts that contraction of pharyngeal dilators shifts the passive pressure–area relationship up and to the left, i.e., pharyngeal muscle contraction dilates and stiffens the pharyngeal airway. According to this model, greater changes in airway area occur when muscle activation occurs at lower transmural airway pressures. The results of the current study support the model under active conditions. As predicted by the model, at any pharyngeal airway level examined, absolute CSA during stimulation of nerves innervating pharyngeal dilators, i.e., the hypoglossal and glossopharyngeal nerves, was reduced at lower pressures compared with that at higher pressures. However, stimulation of certain nerves in certain regions (Table 1) resulted in greater change in CSA at lower pressures. The enhanced dilating effects at lower pressures would be advantageous in helping to restore airway patency when airway size is narrowed or closed.

A previous study of the sealed, isolated cat upper airway from this laboratory revealed that stimulation of the pharyngeal branch of the vagus constricted the airway at relatively high pressures but dilated the airway at relatively low subatmospheric pressures (23). In the current study, airway dilating effects were not demonstrated with stimulation of the pharyngeal branch of the vagus in the lower range of pressures, despite testing over a pressure range similar to that in the previous study. The lack of agreement between the two studies may be due to technical differences in how airway size was assessed. Whereas the former study examined pressure–volume relationships to determine the overall effects of nerve stimulation on the upper airway, the current study used fiberoptic imaging to obtain pressure–area relationships at specific pharyngeal airway levels. It is possible that results in a particular region(s) of the pharyngeal airway may not reflect the overall effects of stimulation. Limitations inherent in fiberoptic imaging and how they were addressed are presented in a previous publication using this technique (20).

Previous investigators have attempted to use selective tongue muscle stimulation during sleep to treat patients with OSA (12, 13). Eisele and colleagues (12) report an increase in maximum inspiratory airflow with stimulation of the whole HG (n = 3) or medial branch (n = 2). Schwartz and colleagues (13) also found that maximum inspiratory airflow increased with intramuscular stimulation of the genioglossus muscle but decreased when tongue retractor muscles were stimulated. The latter investigators also found that stimulation prevented airway closure during sleep. Using techniques similar to those in the current study, Isono and colleagues (24) studied the effects of tongue electrical stimulation on pharyngeal mechanics in anesthetized patients with OSA. Tongue electrical stimulation dilated and stiffened the oropharyngeal airway at lower airway pressures but had no effect on velopharyngeal area.

Although cats do not exhibit OSA, the anatomy of the cat pharyngeal airway is similar to that in humans, and it is likely that in humans the regional mechanical effects of pharyngeal muscle activation also have regional mechanical effects on airway function. Therefore, our results may be of potential clinical importance because they relate to the treatment of OSA. Clinical studies have shown that the site of airway closure in patients with OSA is variable (14, 15). The primary site of airway closure differs across patients, and complex patterns of closure involving multiple pharyngeal segments are known to occur. Of the nerves tested in the current study, stimulation of the glossopharyngeal and HG nerves exhibited dilating effects not only in the rostral but also in the caudal pharyngeal airway. However, the regional differences seen in the current study suggest that stimulation of one nerve or muscle may not be uniformly effective in preventing upper airway closure in patients with OSA. If possible, development of a pharmacologic intervention that activates overall motor output to pharyngeal muscle dilators might be a preferable therapeutic approach compared with selective activation of a particular pharyngeal muscle or muscle group.

In conclusion, the results of the current study support our previous findings that stimulation of pharyngeal airway muscles has different regional effects on airway size. The study extends these findings by demonstrating that the effect of muscle stimulation is also dependent on the conditions of the airway at the time of activation. The results indicate that some muscles are more effective dilators, i.e., cause greater increases in airway area, when the size of the compliant airway is decreased by subatmospheric intraluminal pressure. A better understanding of the regional pharyngeal airway mechanics may help to develop novel therapeutic approaches to OSA that use selective pharyngeal muscle stimulation to prevent airway closure during sleep.

Allison McCormick and Sharif Branham provided technical assistance. Jacqueline Cater provided statistical assistance.

1. Remmers JE, deGroot WJ, Sauerland EK, Anch AM. Pathogenesis of upper airway occlusion during sleep. J Appl Physiol 1978;44:931–938.
2. Brouillette RT, Thach BT. A neuromuscular mechanism maintaining extrathoracic airway patency. J Appl Physiol 1979;46:772–779.
3. Fouke JM, Teeter JP, Strohl KP. Pressure–volume behavior of the upper airway. J Appl Physiol 1986;61:912–918.
4. Strohl KP, Fouke JM. Dilating forces on the upper airway in anaesthetized dogs. J Appl Physiol 1985;58:452–458.
5. Hida W, Kurosawa H, Okabe S, Kikuchi Y, Midorikawa J, Chung Y, Takishima T, Shirato K. Hypoglossal nerve stimulation affects the pressure–volume behavior of the upper airway. Am J Respir Crit Care Med 1995;151:455–460.
6. Schwartz AR, Thut DC, Tuss B, Seelagy M, Yuan N, Brower RG, Permutt S, Wise RA, Smith PL. Effect of electrical stimulation of the hypoglossal nerve on airflow mechanics in the isolated upper airway. Am Rev Respir Dis 1993;147:1144–1150.
7. Brennick MJ, Trouard TP, Gmitro AF, Fregosi RF. MRI study of pharyngeal airway changes during stimulation of the hypoglossal nerve branches in rats. J Appl Physiol 2000;90:1373–1384.
8. McWhorter AJ, Rowley JA, Eisele DW, Smith PL, Schwartz AR. The effect of tensor veli palatini stimulation on upper airway patency. Arch Otolaryngol Head Neck Surg 1999;125:937–940.
9. Eisele DW, Schwartz AR, Hari A, Thut DC, Smith PL. The effects of selective nerve stimulation on upper airway airflow mechanics. Arch Otolaryngol Head Neck Surg 1995;121:1361–1364.
10. Fuller DD, Williams PL, Janssen PL, Fregosi RF. Effect of co-activation of tongue protrudor and retractor muscles on tongue movements and pharyngeal airflow mechanics in the rat. J Physiol 1999;519:601–613.
11. Oliven A, Odeh M, Schnall RP. Improved upper airway patency elicited by electrical stimulation of the hypoglossal nerves. Respiration 1996;63:213–216.
12. Eisele DW, Smith PL, Alam DS, Schwartz AR. Direct hypoglossal nerve stimulation in obstructive sleep apnea. Arch Otolaryngol Head Neck Surg 1997;123:57–61.
13. Schwartz AR, Eisele DW, Hari A, Testerman R, Erickson D, Smith PL. Electrical stimulation of the lingual musculature in obstructive sleep apnea. J Appl Physiol 1996;81:643–652.
14. Morrison DL, Launois SH, Isono S, Feroah TR, Whitelaw WA, Remmers JE. Pharyngeal narrowing and closing pressures in patients with obstructive sleep apnea. Am Rev Respir Dis 1993;148:606–611.
15. Hudgel DW. Variable site of airway narrowing among obstructive sleep apnea patients. J Appl Physiol 1986;61:1403–1409.
16. Williams PL. Alimentary system: tongue and pharynx. In: Bannister LH, editor. Gray's anatomy. New York: Churchill Livingstone; 1995. p. 1721–1733.
17. O'Reilly PMR, Fitzgerald MJT. Fibre composition of the hypoglossal nerve in the rat. J Anat 1990;172:227–243.
18. Furusawa K, Yamaoka M, Kogo M, Matsuya T. The innervation of the levator veli palatini muscle by the glossopharyngeal nerve. Brain Res Bull 1991;26:599–604.
19. Nishio J, Matsuya T, Machida J, Miyazaki T. The motor nerve supply of the velopharyngeal muscles. Cleft Palate J 1976;13:20–30.
20. Kuna ST. Effects of pharyngeal muscle activation on airway size and configuration. Am J Respir Crit Care Med 2001;164:1236–1241.
21. Brennick MJ, Ogilvie MD, Margulies SS, Hiller L, Gefter WB, Pack AI. MRI study of regional variations of pharyngeal wall compliance in cats. J Appl Physiol 1998;85:1884–1897.
22. Isono S, Remmers JE. Anatomy and physiology of upper airway obstruction. In: Kryger MH, Roth T, Dement WC, editors. Principles and practice of sleep medicine. Philadelphia: W.B. Saunders; 1994. p. 642–656.
23. Kuna ST, Vanoye CR. Mechanical effects of pharyngeal constrictor activation on pharyngeal airway function. J Appl Physiol 1999;86:411–417.
24. Isono S, Tanaka A, Nishino T. Effects of tongue electrical stimulation on pharyngeal mechanics in anaesthetized patients with obstructive sleep apnoea. Eur Respir J 1999;14:1258–1265.
Correspondence and requests for reprints should be addressed to Samuel T. Kuna, M.D., Philadelphia Veterans Affairs Medical Center (111P), University and Woodland Avenue, Philadelphia, PA 19104. E-mail:

Related

No related items
American Journal of Respiratory and Critical Care Medicine
166
7

Click to see any corrections or updates and to confirm this is the authentic version of record