Dependence of pharyngeal resistance on genioglossal EMG activity, nasal resistance, and airflow J. C. LEITER, Department
S. L. KNUTH,
AND
of Physiology, Dartmouth
D. BARTLETT,
LEITERJ. C., S. L. KNUTH, AND D. BARTLETT, JR. Dependence of pharyngeal resistance on genioglossal EMG activity, nasal resistance, and airflow. J. Appl. Physiol. 73(Z): 584-590, 1992.-We investigated the quantitative relationships among pharyngeal resistance (Rph), genioglossalelectromyographic (EMGge) activity, nasal resistance (Rna), and airflow in 11 normal men aged19-50 while they were awake. We mademeasurementswith subjectsseatedwith the head erect, seatedwith the headflexed forward w40°, and supine.Each subject wore a face mask connected to a pneumotachograph to measureairflow. After topical anesthesia of the nose, two catheters for measuringnasaland pharyngeal airway pressureswere passed through one nostril: the nasalpressurecatheter waspositioned at the nasalchoanae,and the pharyngeal pressurecatheter was positionedjust abovethe epiglottis. We measuredEMGge activity with an intraoral surface electrode. The subjectsbreathed exclusively through the nose while inhaling room air or rebreathing CO,. We measuredRph, Rna, airflow, and EMGge activity at -90-ms intervals throughout each inspiration. Rph wasinvariant as headposition was changed.At any given head position, EMGge activity rose as airflow increased, and Rph remained constant. In contrast, Rna increased as airflow increased.BecauseRph was constant, EMGge activity was not correlated with Rph, but EMGge waspositively correlated with Rna and airflow. On the basisof the stability of Rph in the face of marked changesin collapsing forces, we conclude that the dynamic interplay of posture, head and jaw position, and upper airway muscleactivity quite effectively maintains pharyngeal patency, and interactions among these factors are subtle and complex. upper airway; electromyography; genioglossus;pharynx MAINTENANCEOFUPPERAIRWAY patencyduringinspira-
tion depends on the intrinsic stiffness of the upper airway (18) and on adequate activation of upper airway muscles to oppose the tendency of the extrathoracic airway to collapse (6, 24). Although the electromyographic (EMG) responses of upper airway muscles to a variety of chemical and mechanical stimuli have been described (19-21), few studies have quantitatively examined the mechanical effect of a given degree of EMG activity (2, 31). However, a significant mechanical effect of upper airway EMG activity on upper airway caliber, compliance, and patency has been implied by many studies (6, 18, 23, 24, 29). For example, the EMG response of the genioglossal muscle (EMGge) to elevated CO, has been described in humans (19), but the physical translation of EMGge activity into a mechanical effect on the upper airway has not been quantitatively described. In this report, we describe the effect of EMGge activity on inspiratory pharyngeal resistance (Rph) during CO, 584
0161-7567/92
$2.00
JR.
Medical School, Lebanon, New Hampshire 03756
rebreathing. We were not interested in the CO, response per se but used CO, to generate a wide range of inspiratory flow rates during which we could study the mechanical interactions among nasal resistance (Rna), Rph, and EMGge activity. It was our hypothesis that Rph should fall as EMGge activity increased. We studied the relationship between EMGge and Rph in subjects seated upright, seated with the head flexed forward, and supine. We chose the latter two conditions on the basis of reports that upper airway resistance increases when the head is flexed forward (14) or the subject is supine (l), during which EMGge activity also increases (26). In studying the interactions among posture, EMGge activity, and Rph, we hoped to assess the adequacy of EMG compensation when airway patency is compromised. At any given flow rate, we found an inverse relationship between EMGge activity and Rph. However, across flow rates, Rph was remarkably constant and invariant during postural changes. METHODS
We studied 11 normal men, ranging in age from 19 to 50 yr with a mean age of 35.4 t 9.9 (SD) yr. The average height was 177.4 t 26 (SD) cm, and the average weight was 76.6 t 26 (SD) kg. All the subjects were healthy, none was taking any medicines, and all gave informed consent. One nostril was anesthetized using an atomizer with a 3:2 mixture of 2% tetracaine HCl (Pontocaine HC1) and 0.05% naphazoline and a swab soaked with a 10% solution of cocaine. After the nose was satisfactorily anesthetized, two catheters (PE-260) of identical length were passed through the anesthetized nostril. The lateral wall of the tip of each catheter was perforated by multiple holes. The tip of the “nasal” catheter stopped at the nasal choanae, and the “pharyngeal” catheter stopped at the tip of the epiglottis. In the first series of studies, in which patients were studied upright, both nostrils were anesthetized, and the position of the catheters was confirmed by inspection with a fiber-optic laryngoscope passed through the contralateral nostril. Subsequently, we learned that the nasal catheter could be accurately placed blindly by using the anesthetic swab as a depth gauge: we passed the swab through the nose until it touched the posterior wall of the nasopharynx, noted the distance on the swab, and passed the nasal pressure catheter into the nostril 1 cm less than this distance. We also placed the pharyngeal catheter blindly by advancing the catheter as far as the subject could comfortably tolerate or 7 cm beyond the tip of the nasal catheter, which-
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Society
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ever came first. Once in position, the catheters were taped to the nose. The catheters were connected to pressure transducers (model MP 45, Validyne), and 50- to 100-ml/min bias airflow was directed through each catheter to keep it clear of secretions. Bias flow was introduced individually into each catheter through a 25-gauge needle inserted just proximal to the connection of the catheter to the pressure transducer. The frequency response of this system was flat up to 25 Hz. However, using a Validyne no. 28 diaphragm (56 cmH,O pressure range), we could not reliably resolve pressure differences less than ~0.04 cmH,O. At a flow rate of 0.1-0.2 l/s, this corresponds to a resistance of 0.4 cmH,O 1-l. s-within the range of pharyngeal resistances we were interested in studying. Therefore we restricted the analysis of pharyngeal resistances to flow rates >0.25 l/s. Subjects were studied while seated or lying in a dental chair and wearing a face mask connected to a pneumotachograph. The pneumotachograph was connected to a three-way stopcock through which the subject breathed room air or rebreathed CO, (93% O,-7% CO,) from a 6-liter reservoir (22). End-tidal CO, (PET~?J was analyzed by an infrared meter calibrated with gases of known CO, content. EMGge activity was measured using a mouthpiece surface electrode individually fitted to each subject (8). The electrode has been modified since its original description. For this study, the plastic molding material from which the mouthpiece is made was heated and fitted, under a vacuum, onto a plaster of Paris mold of the subject’s lower teeth and jaw. Mouthpieces made in this way fit better and were less cumbersome than the models described previously. The EMGge signal was band-pass filtered (l-10,000 Hz), amplified, rectified, and “integrated” by resistance-capacitance circuit with “on” and “off” time constants equal to 100 ms. To monitor head position, a video camera, lateral to the subject, recorded the image of the head and neck of each subject and displayed the image on a video monitor. The silhouette of the head and neck was traced on transparent plastic overlying the monitor screen in each experimental condition. The angular shift of the neck was measured from the rotation of a straight line, drawn along the back of the neck ?around a center point fixed at the base of the neck. The angulation of the head on the neck was measured from the rotation of a line, drawn from the corner of the eye through the external auditory meatus to the occiput, around a center of rotation fixed at the occiput. PETIT, pressure at the nasal choanae (Pna), I 0 flow, pressur&n the pharynx (Pph), and integrated EMGge activity were displayed on a strip chart recorder. Flow, Pna, Pph, and “raw” EMGge activity were recorded on VCR tape for subsequent analysis. Protocol. After insertion of the catheters, placement of the EMGge electrode, and application of the face mask, control measurements were made with the subject sitting upright. During control measurements, the subject breathed room air for 5-10 min, and this was followed by CO, rebreathing until the end-tidal concentration of CO, reached -8%. Measurements were made exclusively during nasal breathing. Five to 10 min after the control l
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flow insp 2
1 P na
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(Pna), FIG. 1_. Digitized records of flow, pressure at na sal choanae genioglossal EMG (Pph), and integrated P ressure at tip of epiglottis activity (EMGge). Subject was breathing room air; end-tidal PCO~ was 36 Torr. Nasal and pharyngeal resistances were calculated, and EMGge activity and airflow were measured at -9O-ms intervals during each inspiration. Thus, each resistance measurement was associated with a given flow rate and a particular level of EMGge activity. An example of data used for each determination is shown by dashed vertical lines spaced -90 ms apart. All measurements were made with mouth closed.
measurement, the subject repeated the room air-CO, rebreathing sequence in the upright posture, with the head flexed forward m40°, or supine. If the subject was willing and comfortable, a third test condition was sometimes tested; however, most experiments consisted of a control and single test condition. At the end of the experiment, the depth of each catheter was measured relative to the tip of the nose: the mean distance between nasal and pharyngeal catheters was 6.2 t 0.8 (SD) cm. Analysis. From the VCR recorder, flow, Pna, Pph, and the EMGge signal were played back and digitized at 128 Hz (Fig. 1). The EMGge signal was integrated before digitization. A minicomputer measured airflow, Pna, Pph, and integrated EMGge activity at -90-ms intervals throughout inspiration and calculated Rna and Rph at each point. Rna was calculated by dividing Pna by flow and subtracting the resistance of the pneumotachograph. Rph was calculated by dividing the difference between Pph and Pna by flow. EMGge activity was expressed as a percentage of the maximum value occurring in the first control CO, rebreathing test. This analysis resulted in lo-20 estimates (depending on inspiratory duration) of Rna, Rph, integrated EMGge activity, and airflow from each breath, and 50-100 breaths were analyzed in each condition in each subject. When airflow is turbulent, resistance increases with airflow if airway caliber is constant. To make inferences about airway caliber on the basis of resistance measurements, one must make the comparisons under isoflow conditions. Hence, all the data from a particular subject and condition were sorted by flow rate into equally spaced bins varying by 0.1 l/s: 0.1 t 0.05,0.2 t 0.05, . . . 2.0 t 0.05 l/s. Statistical comparisons were made using a two-way analysis of variance (ANOVA, posture by flow). When the ANOVA indicated significant differences, specific comparisons were made using the mean square error term from the ANOVA and t values adjusted by the Bonferroni method for multiple preplanned comparisons. RESULTS
Figure 2 shows the relationships of Rph, Rna, and integrated EMGge activity to inspiratory flow in one
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586
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upright seated subject The results are presented as function .s of flo w, with data from mu1 tiple breaths w ith various levels of PETcoo pooled and sorted by flow rate to emphasize the mechamcal relationship between EMGge activity and Rph. Rna increases as flow increases; this is consistent with turbulent airflow in the nose. In contrast, Rph is low and stable as flow increases, a pattern consistent with laminar flow in the pharynx. With increasing flow, EMGge activity increases, which tends to stabilize and dilate the pharyngeal airway. If increasing EMGge activity is responsible for the constancy of Rph as flow increases, then one might expect that as EMGge activity increases, Rph should fall at any given flow rate. The relationship between EMGge activity and Rph at a flow rate of 1.2 l/s in one subject is shown in Fig. 3. There is a clear inverse relationship between EMGge activity and Rph. The data shown here are representative, in that there was a consistent inverse relationship between EMGge activity and Rph, but the slope and shape of the response were variable across flow rates within a subject and among subjects. Because the relationship was variable, we did not attribute any significance to whether the relationship between EMGge activity and Rph was linear or curved. Furthermore, in some subjects, the range of EMGge activity at any particular flow rate was narrow, with most EMGge values clustered tightly around the mean value. During mea surements of pharyngeal resistance, the catheters may be irritating and stimulate upper airway secretions, which may increase Rph if the walls of the seairway are partially apposed (17, 23). Furthermore, cretions may foul the catheters and interfere with the measurements. To ensure that the measurements of Rph were stable over the period of this study, we made control measurements with the subjects seated upright, waited 10 min, and repea .ted the measurements. approximately Figure 4A shows the results of this experiment in six
AND
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subjects; the averages and standard errors of Rna, Rph, and integrated EMGge activity have been graphed as a function of flow. As the flow rate increased, Rna and EMGge activity rose significantly (P < 0.001 in both cases), whereas Rph was constant across flow rates. Rna and Rph did not change significantly between the first but the response profile of and second measurements, EMGge acti vity was elevated signific antly during the second measurement period (P = 0.004). We next tested the hypothesis that flexing the head forward would increase Rph (Fig. 4B). We studied five subjects, and three subjects were studied twice. The ANOVA was modified for this experiment to permit the analysis of five subjects with replications in three of the five subjects. After control measurements in the upright posture, each subject flexed his head forward. On the basis of measuremen ts of the lateral si .I.houettes of each subject recorded on V1 .deotape, flexion resulted in a compound forward angulation of the head and neck: the neck was pivoted forward 31.0 t 5.4' with the center of the axis of rotation at the base of the neck, and the head was bent a further 12.7 t LO0 forwa rd around an ax.is centered at the top of the neck. Thus th .e total change in angulati .on was 43.8 t 7.2O. Rph was invariant as flow increased and unchanged before and after flexion. Rna and EMGge activity both rose as airflow increased (P < 0.001 and P = 0.012, respectively), but Rna was significantly greater (P < 0.001) and EMGge activity was significantly less (P = 0.001) after flexion. In additional experiments with six subjects (each subject studied only once), we examined the effect of supine posture on Rna, Rph, and EMGge activity (Fig. 4C). As before, Rph did not change as the flow rate increased during both the upright and supine tests, but Rph was actually lower (P = 0.028) when the subjects were supine. Rna and EMGge activity increased significantly as airflow increased, but the changes in Rna and EMGge with respect to airflow were similar when subjects were upright and supine. In a post hoc analysis using data only from upright measurements from all the subjects (n = ll), we could not find any significant effect of age or body weight index on the relationships among Rna, Rph, and EMGge activity. For example, we did not find steeper inverse relation1.50
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FIG. 4. Nasal resistance (Rna), Rph, and integrated EMGge activity as a function of airflow. 0, Control; W, test condition. A: 2 seated upright measurements separated by - 10 min in 6 subjects. B: upright measurement followed by measurement made with neck flexed forward in 5 subjects, 3 of whom were studied twice. C: upright followed by supine measurement in 6 subjects. All data are means _t SE.
ships between EMGge activity and Rph in heavier or older subjects. It was our hypothesis that Rph varied as a function of both the flow rate and EMGge activity. To display the dual dependence of Rph on flow and EMGge activity, all the data from the control upright measurements on six subjects shown in Fig. 4A have been plotted on an orthographic three-dimensional projection in Fig. 5. Rph, the dependent variable (z-axis), has been plotted as a function of flow (x-axis) and EMGge activity (y-axis). The surface was obtained by a spline fit of the pooled raw data from all six subjects. The surface was smoothed with a low-pass filter and restricted to values within t2 SDS of the mean EMGge activity at each flow rate (there were too few points outside the 2-SD range to estimate the location of the surface accurately). The compound slope of the response surface reveals that, at any given flow rate, Rph is inversely related to EMGge activity, and at most levels of EMGge activity, Rph tends to increase as flow increases. The average values of EMGge activity and Rph at each flow rate have been plotted on the surface and follow a contour of relatively stable Rph. The surfaces were slightly flatter in both the control and the test conditions during the neck flexion and supination studies, but the basic relationships among Rph, EMGge activity, and airflow were similar.
DISCUSSIUN
We have posed a simple mechanical question in this series of experiments: regardless of the level of ventilatory drive, what is the effect of EMGge activity on Rph as flow changes during inspiration? CO, rebreathing was used to generate a large range of flow rates over which we could study the interaction between EMGge activity and Rph. The essential finding of this set of studies was that, in awake normal humans breathing exclusively through the nose, Rph was low and remarkably constant as flow varied. We believe the constancy of Rph is, in part, related to augmented EMGge activity as flow increases. The stability of Rph is remarkable: in contrast, Rna rose consistently and steeply and, at a flow rate of 1.5 l/s, the average Rna was 3 cmH,O 1-l s, creating a collapsing transmural pressure in the pharynx of 24.5 cmH,O. Pharyngeal patency was maintained, however, and Rph remained low. Investigators have used a variety of techniques to measure upper airway resistances. Our method is similar to that described by Hudgel (11). The values of Rna and Rph are consistent with previous reports (7, 12, 28, 32), although many investigators reported resistances only at one flow (12, 32) or did not specify the flow rate and reported the peak resistance (11). Although our techl
l
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588
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FIG. 5. Rph (z-axis) from first upright measurement in 6 subjects in Fig. 4A, as a function of integrated EMGge activity (y-axis) and airflow between 0.3 and 2.0 l/s (x-axis) on 3-dimensional orthographic projection. Surface is smoothed spline fit of pooled data from all subjects. Surface has been restricted to k2 SDS from mean EMGge activity at each flow rate. Solid line through stippled area traverses contour of mean Rph at each EMGge activity level and flow rate, and stippled area defines region tl SD about mean Rph to indicate where on the surface Rph and EMGge values most frequently occurred.
nique is similar, there are a few points of difference worth emphasizing. Rna, as we measured it, reflects flow through both nostrils. In the flexed and supine studies, we used unilateral tetracaine, naphazoline, and cocaine anesthesia, and we tried to restrict anesthesia to the nose. Reflexes arising from airway distortion and airflow may have been reduced in the anesthetized nostril and nasopharynx, but not in the unanesthetized nostril and the more distal oropharynx. Hence, we believe that reflexes, which may modulate upper airway muscle activity, arising from airflow and airway distortion (4, 5, 13, 15) were present in these subjects. Lastly, the technique we used provided reproducible measurements over 245 min (Fig: 4A), and, in those subjects studied on more than one occasion, Rph, Rna, and EMGge activity were similar on the different days, although the latter two measurements were more variable across days. We were surprised that neck flexion did not increase Rph: Rph was constant during neck flexion despite a rise in Rna and a reduction in EMGge activity (Fig. 4B). In cadaver studies of neonates (23) and studies of anesthetized adults (16), neck flexion causes oropharyngeal collapse. Furthermore, Liistro et al. (14) found that supraglottic resistance (Rsg) increased during neck flexion of 19 and 39O in seated awake subjects. However, in awake upright adult subjects, neck flexion did not result in any radiographic evidence of pharyngeal collapse (27), and, on the basis of an analysis of lateral radiographs of the upper airway, the airway remained patent during neck flexion because the tongue moved forward, filling the oral cavity, and the hyoid moved anteriorly and superiorly, a change attributed to traction of the submandibularmuscles.-Our results are consistent with the previous radiographic studies in awake adults (27) in that Rph remained constant, the result one would expect if pharyngeal airway size did not diminish during neck flexion.
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The study of Liistro et al. is difficult to reconcile with the findings reported here, especially because the techniques used to measure upper airway resistance, the degree of neck flexion, and the age and weight of the subjects were similar in the studies. In addition to finding an increase in Rsg in upright subjects during neck flexion, Liistro et al. also described a reduction in oropharyngeal diameter, which they measured from sagittal magnetic resonance images of neck flexion in supine subjects. They attributed the increase in Rsg seen in upright subjects to oropharyngeal collapse analogous to the reduction in oropharyngeal diameter seen in supine subjects during neck flexion. It is possible that the results of supine neck flexion may not be applicable to upright neck flexion. However, Rubinstein et al. (25) described a significant reduction in pharyngeal area, measured by acoustic reflection, during neck flexion in seated subjects. Their subjects were instructed “to move their chin toward the sternal notch.” We gave less specific instructions, and it is apparent from the compound angulation we observed that our subjects may have dropped their heads down and anteriorly in addition to flexing the neck; the downward and anterior movement of the head may have preserved the pharyngeal area. None of this discussion is terribly satisfying in reconciling the conflicting findings; suffice it to say that upright radiographs tell a different story from upright acoustic reflection during neck flexion, and rather subtle differences in the way subjects choose to flex their necks probably have profound effects on pharyngeal caliber. If we take the sum of Rna and Rph to derive a measure similar to the Rsg reported by Liistro et al., we find that Rsg increased during neck flexion, but we have to attribute this change to an increase in Rna. However, we know of no reason why Rna should increase during neck flexion, and we know of no other reports of such a change. The results of the supine measurements are similar to those during neck flexion: we expected Rph to increase, but Rph actually decreased during the supine measurements. Furthermore the decline in Rph cannot be attributed to augmentation of EMGge activity, because EMGge activity was similar in supine and upright conditions. Anch et al. (1) studied Rsg in supine and upright normal subjects and patients with obstructive sleep apnea (OSA). They reported an increase in Rsg when subjects were supine. However, this was true only when they pooled results from normal subjects and patients with OSA. When only the normal subjects were analyzed, there was no significant difference between supine and upright resistance measurements. We have also made upright and supine measurements in patients with OSA and observed large increases in Rph in some of these subjects on changing from sitting to supine posture. Thus, our results are similar to those of Anch et al.: normal subjects maintain constant upper airway resistance during sitting and supine measurements, but Rph tends to increase in patients with OSA when they are supine. The response surface shown in Fig. 5 depicts the possible combinations of airflow and EMGge activity that we observed in six upright seated subjects. On average, subjects followed a contour of constant Rph on this surface. The consequence of deviating from this contour is elevated Rph or a level of EMGge activity that could be
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viewed as excessive if constancy of Rph is the sole determinant of EMGge activity. However, the consequences of under- or overactivating the genioglossus are not severe: Rph is low relative to other upper airway segmental resistances, and the slope of the EMGge-flow-Rph surface is fairly flat in these normal subjects. The flatness of the surface reflects the intrinsic compliance of the airway and the mechanical effectiveness of EMGge activity in changing Rph. Genioglossal activation clearly plays an important part in dilating and stabilizing the pharynx. EMGge activity was highly correlated with Rna under all conditions; this suggests appropriate compensation opposing airway collapse, because Rna determines in part the transmural pressures across the pharynx. Furthermore, Rph was inversely related to EMGge activity at any flow rate (Figs. 2 and 5) but a given level of EMGge activity was not invariably associated with the same Rph. In Fig. 4B, Rph remained constant in the face of greater transmural collapsing force within the pharynx (Rna increased) but lower EMGge activity, and in Fig. 4C, Rph fell without any increase in EMGge activity. These latter findings indicate that EMGge activity is not a unique determinant of Rph, and the genioglossus cannot be the sole muscle responsible for stiffening and dilating the pharynx. As others have suggested, the hyoid muscles (30), masseter (lo), and tensor veli palatini (2) may also dilate the upper airway. Furthermore, anterior displacement of the jaw by contraction of the lateral pterygoid, which protrudes the mandible (9) and moves the anterior pharyngeal wall forward, may be important. The VCR recordings of our subjects do not show any clear jaw displacement; however, the face mask and head strap holding the face mask partially obscured the subject’s jaws, and we cannot say with confidence that the jaw did not move forward during neck flexion. The constancy of Rph in the face of changing airflow and transmural pressure suggests the activity of feedback mechanisms controlling Rph. As outlined above, these mechanisms involve many muscles, but the genioglossus, by virtue of its location, has an important role. When one considers how EMGge activity might be controlled, it seems likely that a central command is modified by afferent signals from the upper airway, reflecting the adequacy of the initial central output at maintaining pharyngeal patency. Afferent information modulating EMGge activity arises, in part, from the upper airway, and receptors in the airway may detect airway distortion, consequent to the changes in airway transmural pressure, or the effect of airflow on the shearing force or temperature in the airway. Previous studies have pointed to the importance of both sources of information in modifying EMGge activity. Static negative pressure applied to the airway, which tends to collapse the airway, is associated with activation of the genioglossus (3, l3), and airflow through the upper airway activates the genioglossus (5). In our experiments, increasing CO, stimulated EMGge activity, and this effect was most apparent at higher flow rates. Higher flow rates may increase EMGge activity secondary to increased shear or increased airway cooling, and they are also associated with more negative transmural pressures, which generate afferent information by virtue of airway distortion if the airway collapses.
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ACTIVITY
589
However, the site of airway collapse may not be in the pharynx. Depending on the nature of airflow in the upper airway (laminar or turbulent), the stability of Rph as flow increases indicates that the pharyngeal cross-sectional area is at least constant and probably increases. Therefore, unless there is some change in pharyngeal shape giving rise to afferent information from the pharynx, the pharynx is not collapsed in a way that might reflexly activate the genioglossus. This is not to say that pharyngeal collapse could not activate the genioglossus, only that in these experiments it seems not to have contributed. In addition to airway distortion, nasal airflow itself may provide afferent information stimulating the genioglossus. In this context, it is interesting to note that EMGge activity was highly correlated with Rna, but not Rph, and Basner et al. (5) showed that nasal breathing, compared with oral breathing, activates the genioglossus. This suggests that receptors, sensing distortion or flow or temperature (4) in an upstream segment of the airway, the nose, may provide information that activates muscles in a more distal segment of the airway, the pharynx. To the extent that this speculation is true, it would mean that, during pharyngeal obstruction, those receptors most able to activate the genioglossus would not be stimulated, because there is no flow and no transmural pressure gradient in the nose during pharyngeal obstruction. Such a mechanism might contribute to the paucity of EMGge activation during pharyngeal obstruction before arousal occurs in patients with obstructive sleep apnea (24). In summary, Rph is normally a small component of total upper airway resistance and is held remarkably constant over a wide range of flow rates. The stability of Rph results, in part, from compensatory activation of the genioglossus as flow rates change. However, we have inferred the importance of other upper airway muscles from the absence of a unique relationship between Rph and EMGge activity. Hence, the subtle interplay of head and jaw position in concert with activation of upper airway muscles provides a variety of mechanisms whereby pharyngeal patency can be controlled. This work was supported in part by National Heart, Lung, and Blood Institute (NHLBI) Grant HL-19827, the Henry Hey1 Fund of the Hitchcock Foundation, and American Heart Association Grant NH87601. J. C. Leiter is the recipient of NHLBI Clinical Investigator Award HL-01998. Address reprint requests to J. C. Leiter. Received 16 July 1990; accepted in final form 2 March 1992. REFERENCES 1. ANCH, A. M., J. E. REMMERS, AND H. BUNCE III. Supraglottic airway resistance in normal subjects and patients with occlusive sleep apnea. J. Appl. physiol. 53: 1158-1163, 1982. 2. ANCH, A. M., J. E. REMMERS, E. K. SAUERLAND, AND W. J. DE GROOT. Oropharyngeal patency during waking and sleep in the Pickwickian syndrome: electromyographic activity of the tensor veli palatini. Electrocyogr. Clin. Neurophysiol. 2 1: 3 17-330, 1981. 3. ARONSON, R. M., E. ONAL, D. W. CARLEY, AND M. LOPATA. Upper airway and respiratory muscle responses to continuous negative airway pressure. J. Appl. Physiol. 66: 1373-1382, 1989. 4. BASNER, R. C., J. RINGLER, S. BERKOWITZ, R. M. SCHWARTZSTEIN, S. E. WEINBERGER, D. SPARROW, AND J. W. WEISS. Effect of inspired air temperature on genioglossus activity during nose breathing in awake humans. J. Appt. Physiol. 69: 1098~X03,1990. 5. BASNER, R. C., P. M. SIMON, R. M. SCHWARTZSTEIN, S. E. WEIN-
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590
PHARYNGEAL
RESISTANCE
AND EMGGE ACTIVITY
BERGER, AND J. W. WEISS. Breathing route influences upper airway muscle activity in awake normal adults. J. Appl. PhysioZ. 66: 1766-1771,1989. 6. BROUILLETTE,
R. T., AND B. T. THACH. Control of genioglossus muscle inspiratory activity. J. Appl. PhysioZ. 49: 801-808, 1980. 7. CRAIG, A. B., M. DVORAK, AND F. J. MCILREATH. Resistance to airflow through the nose. Ann. OtoZ. Rhinol. Laryngol. 74: 589-603, 1965. 8. DOBLE, E. A., J. C. LEITER, S. L. KNUTH, D. BARTLETT, JR. A noninvasive intraoral
J. A. DAUBENSPECK, AND electromyographic electrode for genioglossus muscle. J. AppZ. Physiol. 58: 1378-1382,
9.
20.
21.
22. 23.
1985. GRAY,
H. Anatomy of the Human Body (29th ed.), edited by C. M. Goss. Philadelphia, PA: Lea & Febiger, 1973, p. 389-390. 10. HOLLOWELL, D. E., AND P. M. SURATT. Activation of masseter muscles with inspiratory resistance loading. J. AppZ. Physiol. 67: 270-275,1989. 11. HUDGEL, D.
W. Variable site of airway narrowing among obstructive sleep apnea patients. J. AppZ. Physiol. 61: 1403-1409, 1986. 12. HYATT, R. E., AND R. E. WILCOX. Extrathoracic airway resistance in man. J. AppZ. Physiol. 16: 326-330, 1961. 13. LEITER, J. C., AND J. A. DAUBENSPECK. Selective reflex activation of the genioglossus in humans. J. AppZ. Physiol. 68: 2581-2587, 1990. 14. LIISTRO, VERITER.
G., D. STANESCU, G. DOOMS, D. RODENSTEIN, AND C. Head position modifies upper airway resistance in men. J. AppZ. Physiol. 64: 1285-1288, 1988. 15. MCBRIDE, B., AND W. A. WHITELAW. A physiological stimulus to upper airway receptors in humans. J. AppZ. Physiol. 51: 1189-1197, 1981. 16. MORIKAWA,
S., P. SAFAR, AND J. DECARLO. Influence of the headjaw position upon upper airway patency. Anesthesiology 22: 265-
270,196l. 17. OLSON,
L. G., AND K. P. STROHL. Airway secretions influence upper airway patency in the rabbit. Am. Rev. Respir. Dis. 137: 1379-
1381,1988. 18. OLSON, L.
G., AND K. P. STROHL. Non-muscular factors in upper airway patency in the rabbit. Respir. Physiol. 71: 147-155, 1988. 19. ONAL, E., M. LOPATA, AND T. D. O’CONNOR. Diaphragmatic and
24.
25.
26.
27. 28.
29. 30.
genioglossal electromyogram responses to CO, rebreathing in humans. J. AppZ. Physiol. 50: 1052-1055, 1981. ONAL, E., M. LOPATA, AND T. D. O’CONNOR. Diaphragmatic and genioglossal electromyogram responses to isocapnic hypoxia in humans. Am. Rev. Respir. Dis. 124: 215-217, 1981. PATRICK, G. B., K. P. STROHL, S. B. RUBIN, AND M. D. ALTOSE. Upper airway and diaphragm muscle responses to chemical stimulation and loading. J. AppZ. Physiol. 53: 1133-1137, 1982. REBUCK, A. S. Measurement of ventilatory response to CO, by rebreathing. Chest 70s: 118-121, 1976. REED, W. R., J. L. ROBERTS, AND B. T. THACH. Factors influencing regional patency and configuration of the human infant upper airway. J. AppZ. Physiol. 58: 635-644, 1985. REMMERS, 3. E., W. J. DEGROOT, E. K. SAUERLAND, AND A. M. ANCH. Pathogenesis of upper airway occlusion during sleep. J. AppZ. Physiol. 44: 931-938, 1978. RUBINSTEIN, I., P. A. MCCLEAN, R. BOUCHER, N. ZAMEL, J. J. FREDBERG, AND V. HOFFSTEIN. Effect of mouthpiece, noseclips, and head position on airway area measured by acoustic reflections. J. AppZ. Physiol. 63: 1469-1474, 1987. SAUERLAND, E. K., AND S. MITCHELL. Electromyographic activity of intrinsic and extrinsic muscles of the human tongue. Tex. Rep. BioZ. Med. 33: 445-455, 1975. SHELTON, R. L., JR., AND J. F. BOSMA. Maintenance of the pharyngeal airway. J. AppZ. Physiol. 17: 209-214, 1962. SPANN, R. W., AND R. E. HYATT. Factors affecting upper airway resistance in conscious man. J. AppZ. PhysioZ. 31: 708-712, 1971. STROHL, K. P., AND J. M. FOUKE. Dilating forces on the upper airway of anesthetized dogs. J. AppZ. Physiol. 58: 452-458, 1985. VAN DE GRAAF, W. B., S. B. GOTTFRIED, J. MITRA, E. VAN LUNTEREN, N. S. CHERNIACK, AND K. P. STROHL. Respiratory function of hyoid muscles and hyoid arch. J. AppZ. Physiol. 57: 197-204,
1984. 31. WEINER, D., CHERNIACK.
J. MITRA, J. SALAMONE, M. NOCHOMOVITZ, AND N. S. Effect of chemical drive on the electrical activity and force of contraction of the tongue and chest wall muscles (Abstract). Am. Rev. Respir. Dis. 121: 418, 1980. 32. WHITE, D. P., R. M. LOMBARD, R. J. CADIEUX, AND C. W. ZWILLICH. l Pharyngeal resistance in normal humans: influence of gender, age, and obesity. J. AppZ. Physiol. 58: 365-371, 1985.
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S. L. KNUTH,
AND
of Physiology, Dartmouth
D. BARTLETT,
LEITERJ. C., S. L. KNUTH, AND D. BARTLETT, JR. Dependence of pharyngeal resistance on genioglossal EMG activity, nasal resistance, and airflow. J. Appl. Physiol. 73(Z): 584-590, 1992.-We investigated the quantitative relationships among pharyngeal resistance (Rph), genioglossalelectromyographic (EMGge) activity, nasal resistance (Rna), and airflow in 11 normal men aged19-50 while they were awake. We mademeasurementswith subjectsseatedwith the head erect, seatedwith the headflexed forward w40°, and supine.Each subject wore a face mask connected to a pneumotachograph to measureairflow. After topical anesthesia of the nose, two catheters for measuringnasaland pharyngeal airway pressureswere passed through one nostril: the nasalpressurecatheter waspositioned at the nasalchoanae,and the pharyngeal pressurecatheter was positionedjust abovethe epiglottis. We measuredEMGge activity with an intraoral surface electrode. The subjectsbreathed exclusively through the nose while inhaling room air or rebreathing CO,. We measuredRph, Rna, airflow, and EMGge activity at -90-ms intervals throughout each inspiration. Rph wasinvariant as headposition was changed.At any given head position, EMGge activity rose as airflow increased, and Rph remained constant. In contrast, Rna increased as airflow increased.BecauseRph was constant, EMGge activity was not correlated with Rph, but EMGge waspositively correlated with Rna and airflow. On the basisof the stability of Rph in the face of marked changesin collapsing forces, we conclude that the dynamic interplay of posture, head and jaw position, and upper airway muscleactivity quite effectively maintains pharyngeal patency, and interactions among these factors are subtle and complex. upper airway; electromyography; genioglossus;pharynx MAINTENANCEOFUPPERAIRWAY patencyduringinspira-
tion depends on the intrinsic stiffness of the upper airway (18) and on adequate activation of upper airway muscles to oppose the tendency of the extrathoracic airway to collapse (6, 24). Although the electromyographic (EMG) responses of upper airway muscles to a variety of chemical and mechanical stimuli have been described (19-21), few studies have quantitatively examined the mechanical effect of a given degree of EMG activity (2, 31). However, a significant mechanical effect of upper airway EMG activity on upper airway caliber, compliance, and patency has been implied by many studies (6, 18, 23, 24, 29). For example, the EMG response of the genioglossal muscle (EMGge) to elevated CO, has been described in humans (19), but the physical translation of EMGge activity into a mechanical effect on the upper airway has not been quantitatively described. In this report, we describe the effect of EMGge activity on inspiratory pharyngeal resistance (Rph) during CO, 584
0161-7567/92
$2.00
JR.
Medical School, Lebanon, New Hampshire 03756
rebreathing. We were not interested in the CO, response per se but used CO, to generate a wide range of inspiratory flow rates during which we could study the mechanical interactions among nasal resistance (Rna), Rph, and EMGge activity. It was our hypothesis that Rph should fall as EMGge activity increased. We studied the relationship between EMGge and Rph in subjects seated upright, seated with the head flexed forward, and supine. We chose the latter two conditions on the basis of reports that upper airway resistance increases when the head is flexed forward (14) or the subject is supine (l), during which EMGge activity also increases (26). In studying the interactions among posture, EMGge activity, and Rph, we hoped to assess the adequacy of EMG compensation when airway patency is compromised. At any given flow rate, we found an inverse relationship between EMGge activity and Rph. However, across flow rates, Rph was remarkably constant and invariant during postural changes. METHODS
We studied 11 normal men, ranging in age from 19 to 50 yr with a mean age of 35.4 t 9.9 (SD) yr. The average height was 177.4 t 26 (SD) cm, and the average weight was 76.6 t 26 (SD) kg. All the subjects were healthy, none was taking any medicines, and all gave informed consent. One nostril was anesthetized using an atomizer with a 3:2 mixture of 2% tetracaine HCl (Pontocaine HC1) and 0.05% naphazoline and a swab soaked with a 10% solution of cocaine. After the nose was satisfactorily anesthetized, two catheters (PE-260) of identical length were passed through the anesthetized nostril. The lateral wall of the tip of each catheter was perforated by multiple holes. The tip of the “nasal” catheter stopped at the nasal choanae, and the “pharyngeal” catheter stopped at the tip of the epiglottis. In the first series of studies, in which patients were studied upright, both nostrils were anesthetized, and the position of the catheters was confirmed by inspection with a fiber-optic laryngoscope passed through the contralateral nostril. Subsequently, we learned that the nasal catheter could be accurately placed blindly by using the anesthetic swab as a depth gauge: we passed the swab through the nose until it touched the posterior wall of the nasopharynx, noted the distance on the swab, and passed the nasal pressure catheter into the nostril 1 cm less than this distance. We also placed the pharyngeal catheter blindly by advancing the catheter as far as the subject could comfortably tolerate or 7 cm beyond the tip of the nasal catheter, which-
Copyright 0 1992 the American Physiological
Society
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PHARYNGEAL
RESISTANCE
ever came first. Once in position, the catheters were taped to the nose. The catheters were connected to pressure transducers (model MP 45, Validyne), and 50- to 100-ml/min bias airflow was directed through each catheter to keep it clear of secretions. Bias flow was introduced individually into each catheter through a 25-gauge needle inserted just proximal to the connection of the catheter to the pressure transducer. The frequency response of this system was flat up to 25 Hz. However, using a Validyne no. 28 diaphragm (56 cmH,O pressure range), we could not reliably resolve pressure differences less than ~0.04 cmH,O. At a flow rate of 0.1-0.2 l/s, this corresponds to a resistance of 0.4 cmH,O 1-l. s-within the range of pharyngeal resistances we were interested in studying. Therefore we restricted the analysis of pharyngeal resistances to flow rates >0.25 l/s. Subjects were studied while seated or lying in a dental chair and wearing a face mask connected to a pneumotachograph. The pneumotachograph was connected to a three-way stopcock through which the subject breathed room air or rebreathed CO, (93% O,-7% CO,) from a 6-liter reservoir (22). End-tidal CO, (PET~?J was analyzed by an infrared meter calibrated with gases of known CO, content. EMGge activity was measured using a mouthpiece surface electrode individually fitted to each subject (8). The electrode has been modified since its original description. For this study, the plastic molding material from which the mouthpiece is made was heated and fitted, under a vacuum, onto a plaster of Paris mold of the subject’s lower teeth and jaw. Mouthpieces made in this way fit better and were less cumbersome than the models described previously. The EMGge signal was band-pass filtered (l-10,000 Hz), amplified, rectified, and “integrated” by resistance-capacitance circuit with “on” and “off” time constants equal to 100 ms. To monitor head position, a video camera, lateral to the subject, recorded the image of the head and neck of each subject and displayed the image on a video monitor. The silhouette of the head and neck was traced on transparent plastic overlying the monitor screen in each experimental condition. The angular shift of the neck was measured from the rotation of a straight line, drawn along the back of the neck ?around a center point fixed at the base of the neck. The angulation of the head on the neck was measured from the rotation of a line, drawn from the corner of the eye through the external auditory meatus to the occiput, around a center of rotation fixed at the occiput. PETIT, pressure at the nasal choanae (Pna), I 0 flow, pressur&n the pharynx (Pph), and integrated EMGge activity were displayed on a strip chart recorder. Flow, Pna, Pph, and “raw” EMGge activity were recorded on VCR tape for subsequent analysis. Protocol. After insertion of the catheters, placement of the EMGge electrode, and application of the face mask, control measurements were made with the subject sitting upright. During control measurements, the subject breathed room air for 5-10 min, and this was followed by CO, rebreathing until the end-tidal concentration of CO, reached -8%. Measurements were made exclusively during nasal breathing. Five to 10 min after the control l
AND
EMGGE
585
ACTIVITY
flow insp 2
1 P na
cm
H20
cm
H2Cl
0
L I
’ PPh
0
(Pna), FIG. 1_. Digitized records of flow, pressure at na sal choanae genioglossal EMG (Pph), and integrated P ressure at tip of epiglottis activity (EMGge). Subject was breathing room air; end-tidal PCO~ was 36 Torr. Nasal and pharyngeal resistances were calculated, and EMGge activity and airflow were measured at -9O-ms intervals during each inspiration. Thus, each resistance measurement was associated with a given flow rate and a particular level of EMGge activity. An example of data used for each determination is shown by dashed vertical lines spaced -90 ms apart. All measurements were made with mouth closed.
measurement, the subject repeated the room air-CO, rebreathing sequence in the upright posture, with the head flexed forward m40°, or supine. If the subject was willing and comfortable, a third test condition was sometimes tested; however, most experiments consisted of a control and single test condition. At the end of the experiment, the depth of each catheter was measured relative to the tip of the nose: the mean distance between nasal and pharyngeal catheters was 6.2 t 0.8 (SD) cm. Analysis. From the VCR recorder, flow, Pna, Pph, and the EMGge signal were played back and digitized at 128 Hz (Fig. 1). The EMGge signal was integrated before digitization. A minicomputer measured airflow, Pna, Pph, and integrated EMGge activity at -90-ms intervals throughout inspiration and calculated Rna and Rph at each point. Rna was calculated by dividing Pna by flow and subtracting the resistance of the pneumotachograph. Rph was calculated by dividing the difference between Pph and Pna by flow. EMGge activity was expressed as a percentage of the maximum value occurring in the first control CO, rebreathing test. This analysis resulted in lo-20 estimates (depending on inspiratory duration) of Rna, Rph, integrated EMGge activity, and airflow from each breath, and 50-100 breaths were analyzed in each condition in each subject. When airflow is turbulent, resistance increases with airflow if airway caliber is constant. To make inferences about airway caliber on the basis of resistance measurements, one must make the comparisons under isoflow conditions. Hence, all the data from a particular subject and condition were sorted by flow rate into equally spaced bins varying by 0.1 l/s: 0.1 t 0.05,0.2 t 0.05, . . . 2.0 t 0.05 l/s. Statistical comparisons were made using a two-way analysis of variance (ANOVA, posture by flow). When the ANOVA indicated significant differences, specific comparisons were made using the mean square error term from the ANOVA and t values adjusted by the Bonferroni method for multiple preplanned comparisons. RESULTS
Figure 2 shows the relationships of Rph, Rna, and integrated EMGge activity to inspiratory flow in one
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586
PHARYNGEAL
7.OT 0 -0 6.0 t l -
RESISTANCE
EMG activity
0
nasal
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resistance
O-0-0’
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FIG. 2. Mean values of integrated EMGge activity and nasal and pharyngeal resistances within 0.1-1/s sequential ranges of airflow as functions of flow. Data are from first seated upright measurement from a single subject.
upright seated subject The results are presented as function .s of flo w, with data from mu1 tiple breaths w ith various levels of PETcoo pooled and sorted by flow rate to emphasize the mechamcal relationship between EMGge activity and Rph. Rna increases as flow increases; this is consistent with turbulent airflow in the nose. In contrast, Rph is low and stable as flow increases, a pattern consistent with laminar flow in the pharynx. With increasing flow, EMGge activity increases, which tends to stabilize and dilate the pharyngeal airway. If increasing EMGge activity is responsible for the constancy of Rph as flow increases, then one might expect that as EMGge activity increases, Rph should fall at any given flow rate. The relationship between EMGge activity and Rph at a flow rate of 1.2 l/s in one subject is shown in Fig. 3. There is a clear inverse relationship between EMGge activity and Rph. The data shown here are representative, in that there was a consistent inverse relationship between EMGge activity and Rph, but the slope and shape of the response were variable across flow rates within a subject and among subjects. Because the relationship was variable, we did not attribute any significance to whether the relationship between EMGge activity and Rph was linear or curved. Furthermore, in some subjects, the range of EMGge activity at any particular flow rate was narrow, with most EMGge values clustered tightly around the mean value. During mea surements of pharyngeal resistance, the catheters may be irritating and stimulate upper airway secretions, which may increase Rph if the walls of the seairway are partially apposed (17, 23). Furthermore, cretions may foul the catheters and interfere with the measurements. To ensure that the measurements of Rph were stable over the period of this study, we made control measurements with the subjects seated upright, waited 10 min, and repea .ted the measurements. approximately Figure 4A shows the results of this experiment in six
AND
EMGGE
ACTIVITY
subjects; the averages and standard errors of Rna, Rph, and integrated EMGge activity have been graphed as a function of flow. As the flow rate increased, Rna and EMGge activity rose significantly (P < 0.001 in both cases), whereas Rph was constant across flow rates. Rna and Rph did not change significantly between the first but the response profile of and second measurements, EMGge acti vity was elevated signific antly during the second measurement period (P = 0.004). We next tested the hypothesis that flexing the head forward would increase Rph (Fig. 4B). We studied five subjects, and three subjects were studied twice. The ANOVA was modified for this experiment to permit the analysis of five subjects with replications in three of the five subjects. After control measurements in the upright posture, each subject flexed his head forward. On the basis of measuremen ts of the lateral si .I.houettes of each subject recorded on V1 .deotape, flexion resulted in a compound forward angulation of the head and neck: the neck was pivoted forward 31.0 t 5.4' with the center of the axis of rotation at the base of the neck, and the head was bent a further 12.7 t LO0 forwa rd around an ax.is centered at the top of the neck. Thus th .e total change in angulati .on was 43.8 t 7.2O. Rph was invariant as flow increased and unchanged before and after flexion. Rna and EMGge activity both rose as airflow increased (P < 0.001 and P = 0.012, respectively), but Rna was significantly greater (P < 0.001) and EMGge activity was significantly less (P = 0.001) after flexion. In additional experiments with six subjects (each subject studied only once), we examined the effect of supine posture on Rna, Rph, and EMGge activity (Fig. 4C). As before, Rph did not change as the flow rate increased during both the upright and supine tests, but Rph was actually lower (P = 0.028) when the subjects were supine. Rna and EMGge activity increased significantly as airflow increased, but the changes in Rna and EMGge with respect to airflow were similar when subjects were upright and supine. In a post hoc analysis using data only from upright measurements from all the subjects (n = ll), we could not find any significant effect of age or body weight index on the relationships among Rna, Rph, and EMGge activity. For example, we did not find steeper inverse relation1.50
T
0.00 0
flow
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PHARYNGEAL
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(L/s%)
FIG. 4. Nasal resistance (Rna), Rph, and integrated EMGge activity as a function of airflow. 0, Control; W, test condition. A: 2 seated upright measurements separated by - 10 min in 6 subjects. B: upright measurement followed by measurement made with neck flexed forward in 5 subjects, 3 of whom were studied twice. C: upright followed by supine measurement in 6 subjects. All data are means _t SE.
ships between EMGge activity and Rph in heavier or older subjects. It was our hypothesis that Rph varied as a function of both the flow rate and EMGge activity. To display the dual dependence of Rph on flow and EMGge activity, all the data from the control upright measurements on six subjects shown in Fig. 4A have been plotted on an orthographic three-dimensional projection in Fig. 5. Rph, the dependent variable (z-axis), has been plotted as a function of flow (x-axis) and EMGge activity (y-axis). The surface was obtained by a spline fit of the pooled raw data from all six subjects. The surface was smoothed with a low-pass filter and restricted to values within t2 SDS of the mean EMGge activity at each flow rate (there were too few points outside the 2-SD range to estimate the location of the surface accurately). The compound slope of the response surface reveals that, at any given flow rate, Rph is inversely related to EMGge activity, and at most levels of EMGge activity, Rph tends to increase as flow increases. The average values of EMGge activity and Rph at each flow rate have been plotted on the surface and follow a contour of relatively stable Rph. The surfaces were slightly flatter in both the control and the test conditions during the neck flexion and supination studies, but the basic relationships among Rph, EMGge activity, and airflow were similar.
DISCUSSIUN
We have posed a simple mechanical question in this series of experiments: regardless of the level of ventilatory drive, what is the effect of EMGge activity on Rph as flow changes during inspiration? CO, rebreathing was used to generate a large range of flow rates over which we could study the interaction between EMGge activity and Rph. The essential finding of this set of studies was that, in awake normal humans breathing exclusively through the nose, Rph was low and remarkably constant as flow varied. We believe the constancy of Rph is, in part, related to augmented EMGge activity as flow increases. The stability of Rph is remarkable: in contrast, Rna rose consistently and steeply and, at a flow rate of 1.5 l/s, the average Rna was 3 cmH,O 1-l s, creating a collapsing transmural pressure in the pharynx of 24.5 cmH,O. Pharyngeal patency was maintained, however, and Rph remained low. Investigators have used a variety of techniques to measure upper airway resistances. Our method is similar to that described by Hudgel (11). The values of Rna and Rph are consistent with previous reports (7, 12, 28, 32), although many investigators reported resistances only at one flow (12, 32) or did not specify the flow rate and reported the peak resistance (11). Although our techl
l
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FIG. 5. Rph (z-axis) from first upright measurement in 6 subjects in Fig. 4A, as a function of integrated EMGge activity (y-axis) and airflow between 0.3 and 2.0 l/s (x-axis) on 3-dimensional orthographic projection. Surface is smoothed spline fit of pooled data from all subjects. Surface has been restricted to k2 SDS from mean EMGge activity at each flow rate. Solid line through stippled area traverses contour of mean Rph at each EMGge activity level and flow rate, and stippled area defines region tl SD about mean Rph to indicate where on the surface Rph and EMGge values most frequently occurred.
nique is similar, there are a few points of difference worth emphasizing. Rna, as we measured it, reflects flow through both nostrils. In the flexed and supine studies, we used unilateral tetracaine, naphazoline, and cocaine anesthesia, and we tried to restrict anesthesia to the nose. Reflexes arising from airway distortion and airflow may have been reduced in the anesthetized nostril and nasopharynx, but not in the unanesthetized nostril and the more distal oropharynx. Hence, we believe that reflexes, which may modulate upper airway muscle activity, arising from airflow and airway distortion (4, 5, 13, 15) were present in these subjects. Lastly, the technique we used provided reproducible measurements over 245 min (Fig: 4A), and, in those subjects studied on more than one occasion, Rph, Rna, and EMGge activity were similar on the different days, although the latter two measurements were more variable across days. We were surprised that neck flexion did not increase Rph: Rph was constant during neck flexion despite a rise in Rna and a reduction in EMGge activity (Fig. 4B). In cadaver studies of neonates (23) and studies of anesthetized adults (16), neck flexion causes oropharyngeal collapse. Furthermore, Liistro et al. (14) found that supraglottic resistance (Rsg) increased during neck flexion of 19 and 39O in seated awake subjects. However, in awake upright adult subjects, neck flexion did not result in any radiographic evidence of pharyngeal collapse (27), and, on the basis of an analysis of lateral radiographs of the upper airway, the airway remained patent during neck flexion because the tongue moved forward, filling the oral cavity, and the hyoid moved anteriorly and superiorly, a change attributed to traction of the submandibularmuscles.-Our results are consistent with the previous radiographic studies in awake adults (27) in that Rph remained constant, the result one would expect if pharyngeal airway size did not diminish during neck flexion.
AND EMGGE ACTIVITY
The study of Liistro et al. is difficult to reconcile with the findings reported here, especially because the techniques used to measure upper airway resistance, the degree of neck flexion, and the age and weight of the subjects were similar in the studies. In addition to finding an increase in Rsg in upright subjects during neck flexion, Liistro et al. also described a reduction in oropharyngeal diameter, which they measured from sagittal magnetic resonance images of neck flexion in supine subjects. They attributed the increase in Rsg seen in upright subjects to oropharyngeal collapse analogous to the reduction in oropharyngeal diameter seen in supine subjects during neck flexion. It is possible that the results of supine neck flexion may not be applicable to upright neck flexion. However, Rubinstein et al. (25) described a significant reduction in pharyngeal area, measured by acoustic reflection, during neck flexion in seated subjects. Their subjects were instructed “to move their chin toward the sternal notch.” We gave less specific instructions, and it is apparent from the compound angulation we observed that our subjects may have dropped their heads down and anteriorly in addition to flexing the neck; the downward and anterior movement of the head may have preserved the pharyngeal area. None of this discussion is terribly satisfying in reconciling the conflicting findings; suffice it to say that upright radiographs tell a different story from upright acoustic reflection during neck flexion, and rather subtle differences in the way subjects choose to flex their necks probably have profound effects on pharyngeal caliber. If we take the sum of Rna and Rph to derive a measure similar to the Rsg reported by Liistro et al., we find that Rsg increased during neck flexion, but we have to attribute this change to an increase in Rna. However, we know of no reason why Rna should increase during neck flexion, and we know of no other reports of such a change. The results of the supine measurements are similar to those during neck flexion: we expected Rph to increase, but Rph actually decreased during the supine measurements. Furthermore the decline in Rph cannot be attributed to augmentation of EMGge activity, because EMGge activity was similar in supine and upright conditions. Anch et al. (1) studied Rsg in supine and upright normal subjects and patients with obstructive sleep apnea (OSA). They reported an increase in Rsg when subjects were supine. However, this was true only when they pooled results from normal subjects and patients with OSA. When only the normal subjects were analyzed, there was no significant difference between supine and upright resistance measurements. We have also made upright and supine measurements in patients with OSA and observed large increases in Rph in some of these subjects on changing from sitting to supine posture. Thus, our results are similar to those of Anch et al.: normal subjects maintain constant upper airway resistance during sitting and supine measurements, but Rph tends to increase in patients with OSA when they are supine. The response surface shown in Fig. 5 depicts the possible combinations of airflow and EMGge activity that we observed in six upright seated subjects. On average, subjects followed a contour of constant Rph on this surface. The consequence of deviating from this contour is elevated Rph or a level of EMGge activity that could be
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viewed as excessive if constancy of Rph is the sole determinant of EMGge activity. However, the consequences of under- or overactivating the genioglossus are not severe: Rph is low relative to other upper airway segmental resistances, and the slope of the EMGge-flow-Rph surface is fairly flat in these normal subjects. The flatness of the surface reflects the intrinsic compliance of the airway and the mechanical effectiveness of EMGge activity in changing Rph. Genioglossal activation clearly plays an important part in dilating and stabilizing the pharynx. EMGge activity was highly correlated with Rna under all conditions; this suggests appropriate compensation opposing airway collapse, because Rna determines in part the transmural pressures across the pharynx. Furthermore, Rph was inversely related to EMGge activity at any flow rate (Figs. 2 and 5) but a given level of EMGge activity was not invariably associated with the same Rph. In Fig. 4B, Rph remained constant in the face of greater transmural collapsing force within the pharynx (Rna increased) but lower EMGge activity, and in Fig. 4C, Rph fell without any increase in EMGge activity. These latter findings indicate that EMGge activity is not a unique determinant of Rph, and the genioglossus cannot be the sole muscle responsible for stiffening and dilating the pharynx. As others have suggested, the hyoid muscles (30), masseter (lo), and tensor veli palatini (2) may also dilate the upper airway. Furthermore, anterior displacement of the jaw by contraction of the lateral pterygoid, which protrudes the mandible (9) and moves the anterior pharyngeal wall forward, may be important. The VCR recordings of our subjects do not show any clear jaw displacement; however, the face mask and head strap holding the face mask partially obscured the subject’s jaws, and we cannot say with confidence that the jaw did not move forward during neck flexion. The constancy of Rph in the face of changing airflow and transmural pressure suggests the activity of feedback mechanisms controlling Rph. As outlined above, these mechanisms involve many muscles, but the genioglossus, by virtue of its location, has an important role. When one considers how EMGge activity might be controlled, it seems likely that a central command is modified by afferent signals from the upper airway, reflecting the adequacy of the initial central output at maintaining pharyngeal patency. Afferent information modulating EMGge activity arises, in part, from the upper airway, and receptors in the airway may detect airway distortion, consequent to the changes in airway transmural pressure, or the effect of airflow on the shearing force or temperature in the airway. Previous studies have pointed to the importance of both sources of information in modifying EMGge activity. Static negative pressure applied to the airway, which tends to collapse the airway, is associated with activation of the genioglossus (3, l3), and airflow through the upper airway activates the genioglossus (5). In our experiments, increasing CO, stimulated EMGge activity, and this effect was most apparent at higher flow rates. Higher flow rates may increase EMGge activity secondary to increased shear or increased airway cooling, and they are also associated with more negative transmural pressures, which generate afferent information by virtue of airway distortion if the airway collapses.
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However, the site of airway collapse may not be in the pharynx. Depending on the nature of airflow in the upper airway (laminar or turbulent), the stability of Rph as flow increases indicates that the pharyngeal cross-sectional area is at least constant and probably increases. Therefore, unless there is some change in pharyngeal shape giving rise to afferent information from the pharynx, the pharynx is not collapsed in a way that might reflexly activate the genioglossus. This is not to say that pharyngeal collapse could not activate the genioglossus, only that in these experiments it seems not to have contributed. In addition to airway distortion, nasal airflow itself may provide afferent information stimulating the genioglossus. In this context, it is interesting to note that EMGge activity was highly correlated with Rna, but not Rph, and Basner et al. (5) showed that nasal breathing, compared with oral breathing, activates the genioglossus. This suggests that receptors, sensing distortion or flow or temperature (4) in an upstream segment of the airway, the nose, may provide information that activates muscles in a more distal segment of the airway, the pharynx. To the extent that this speculation is true, it would mean that, during pharyngeal obstruction, those receptors most able to activate the genioglossus would not be stimulated, because there is no flow and no transmural pressure gradient in the nose during pharyngeal obstruction. Such a mechanism might contribute to the paucity of EMGge activation during pharyngeal obstruction before arousal occurs in patients with obstructive sleep apnea (24). In summary, Rph is normally a small component of total upper airway resistance and is held remarkably constant over a wide range of flow rates. The stability of Rph results, in part, from compensatory activation of the genioglossus as flow rates change. However, we have inferred the importance of other upper airway muscles from the absence of a unique relationship between Rph and EMGge activity. Hence, the subtle interplay of head and jaw position in concert with activation of upper airway muscles provides a variety of mechanisms whereby pharyngeal patency can be controlled. This work was supported in part by National Heart, Lung, and Blood Institute (NHLBI) Grant HL-19827, the Henry Hey1 Fund of the Hitchcock Foundation, and American Heart Association Grant NH87601. J. C. Leiter is the recipient of NHLBI Clinical Investigator Award HL-01998. Address reprint requests to J. C. Leiter. Received 16 July 1990; accepted in final form 2 March 1992. REFERENCES 1. ANCH, A. M., J. E. REMMERS, AND H. BUNCE III. Supraglottic airway resistance in normal subjects and patients with occlusive sleep apnea. J. Appl. physiol. 53: 1158-1163, 1982. 2. ANCH, A. M., J. E. REMMERS, E. K. SAUERLAND, AND W. J. DE GROOT. Oropharyngeal patency during waking and sleep in the Pickwickian syndrome: electromyographic activity of the tensor veli palatini. Electrocyogr. Clin. Neurophysiol. 2 1: 3 17-330, 1981. 3. ARONSON, R. M., E. ONAL, D. W. CARLEY, AND M. LOPATA. Upper airway and respiratory muscle responses to continuous negative airway pressure. J. Appl. Physiol. 66: 1373-1382, 1989. 4. BASNER, R. C., J. RINGLER, S. BERKOWITZ, R. M. SCHWARTZSTEIN, S. E. WEINBERGER, D. SPARROW, AND J. W. WEISS. Effect of inspired air temperature on genioglossus activity during nose breathing in awake humans. J. Appt. Physiol. 69: 1098~X03,1990. 5. BASNER, R. C., P. M. SIMON, R. M. SCHWARTZSTEIN, S. E. WEIN-
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