Influence of posture and breathing route on neural drive to upper airway dilator muscles during exercise

Transcription

1 J Appl Physiol 89: , Influence of posture and breathing route on neural drive to upper airway dilator muscles during exercise J. S. WILLIAMS, P. L. JANSSEN, D. D. FULLER, AND R. F. FREGOSI Respiratory Physiology Laboratory, Department of Physiology, The University of Arizona, Tucson, Arizona Received 14 May 1999; accepted in final form 3 April 2000 Williams, J. S., P. L. Janssen, D. D. Fuller, and R. F. Fregosi. Influence of posture and breathing route on neural drive to upper airway dilator muscles during exercise. J Appl Physiol 89: , Our purpose was to determine the influence of posture and breathing route on electromyographic (EMG) activities of nasal dilator (NDM) and genioglossus (GG) muscles during exercise. Nasal and oral airflow rates and EMG activities of the NDM and GG were recorded in 10 subjects at rest and during upright and supine incremental cycling exercise to exhaustion. EMG activities immediately before and after the switch from nasal to oronasal breathing were also determined for those subjects who demonstrated a clear switch point (n 7). NDM and GG EMG activities were significantly correlated with increases in nasal, oral, and total ventilatory rates during exercise, and these relationships were not altered by posture. In both upright and supine exercise, NDM activity rose more sharply as a function of nasal inspired ventilation compared with total or oral inspired ventilation (P 0.01), but GG activity showed no significant breathing-route dependence. Peak NDM integrated EMG activity decreased (P 0.008), and peak GG integrated EMG activity increased (P 0.032) coincident with the switch from nasal to oronasal breathing. In conclusion, 1) neural drive to NDM and GG increases as a function of exercise intensity, but the increase is unaltered by posture; 2) NDM activity is breathing-route dependent in steady-state exercise, but GG activity is not; and 3) drive to both muscles changes significantly at the switch point, but the change in GG activity is more variable and is often transient. This suggests that factors other than the breathing route dominate drive to the GG soon after the initial changes in the configuration of the oronasal airway are made. control of breathing; genioglossus muscle; hyperpnea; nasal dilator muscles THE DIAMETER OF THE NASAL and pharyngeal airways is regulated by the activity of several skeletal muscles (see Ref. 2 for review). Two upper airway muscles that have been studied in detail are the nasal dilator muscles (NDM), which dilate the external nares, and the genioglossus (GG), which protrudes and depresses the tongue. The NDM and GG are suitable models for studying upper airway motor control because they are amenable to electromyography (EMG) with minimally Address for reprint requests and other correspondence: R. F. Fregosi, Dept. of Physiology, Gittings Bldg., The Univ. of Arizona, Tucson, AZ ( fregosi@u.arizona.edu). invasive techniques, and they play a major role in controlling upper airway flow resistance (19, 26, 27). For example, voluntary flaring of the nostrils in humans (27) or evoked protrusion of the tongue in animals (17) is associated with reduced upper airway resistance. Recent studies have shown that NDM contract rhythmically during exercise, in phase with inspiration, and that NDM integrated EMG (iemg) activity changes in proportion to nasal airflow (5, 8, 33). However, data on GG activity during exercise are limited, and the available results are not clear cut. Recently, Shi et al. (25) demonstrated that GG iemg activity increases as a function of ventilation during progressive-intensity exercise in healthy human subjects, but the activity was the same whether or not the breathing route was nasal, oral, or oronasal. However, the breathing apparatus prevented the subjects from freely choosing their route of breathing in this study. Instead, the investigator controlled a valve that determined whether breathing was exclusively nasal, exclusively oral, or oronasal. Accordingly, one goal of the present experiments was to test the hypotheses that GG iemg activity increases with exercise intensity under conditions of unencumbered breathing and that the activity is more strongly correlated with oral ventilation than with either nasal or total ventilation. Posterior displacement of the tongue can result in increased pharyngeal airway resistance in supine, sleeping subjects (19). Posterior displacement of the tongue is a complex phenomenon that can be caused by a number of factors, including a sleep-induced decline in drive to the GG (19, 23), activation of tongue retractor muscles (9), changes in head position (12, 14), suction forces caused by negative airway pressure during inspiration (4), and the supine posture (23). Although the first four factors have been studied extensively, the influence of the supine posture on motor control of the tongue muscles has received little attention and remains poorly understood. If the supine position is a significant determinant of neural drive to the GG, then GG EMG activity should be higher in the supine compared with the upright posture at a given The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact /00 $5.00 Copyright 2000 the American Physiological Society

2 CONTROL OF UPPER AIRWAY DILATOR MUSCLES DURING EXERCISE 591 level of total pulmonary ventilation. However, Leiter et al. (14) showed that changes in GG EMG activity during CO 2 rebreathing were the same in upright and supine postures. There are at least three possibilities that may have led to the negative results in the study of Leiter et al. First, their subjects were forced to breathe nasally. Because mouth opening alters the position of the tongue and jaw, drive to the GG may differ markedly in mouth-open vs. mouth-closed preparations. Second, total ventilatory output was changed with CO 2 rebreathing, and a more natural stimulus, such as exercise, is capable of increasing ventilation over a much wider range. Third, Leiter et al. used surface electrodes, which were attached to an athletic mouth guard. In addition to changing the configuration of the mouth and jaw with the mouth guard, surface electrodes have a lower sensitivity and selectivity than intramuscular wire electrodes (6). Accordingly, a second aim was to test the hypothesis that GG activity during exercise is higher in the supine compared with the upright posture. Our approach was to have subjects perform progressive-intensity exercise in both supine and upright postures, while we measured oral and nasal ventilation and GG and NDM EMG activities with intramuscular and surface electrodes, respectively. The switch from nasal to oronasal breathing (i.e., the switch point ) (16) during progressive-intensity exercise is associated with the onset of marked flow turbulence and resistance in the nasal airway (8). Moreover, both NDM EMG activity and nasal flow reach a plateau at the switch point, and further increases in exercise ventilation are primarily oral (8). Increased oral airflow may be mediated, in part, by increased drive to the GG, which would dilate the oropharynx and reduce overall pharyngeal flow resistance. Thus our third aim was to test the hypothesis that GG EMG activity increases sharply at the switch point and that the activity rises in proportion to oral ventilation as exercise intensity and total pulmonary ventilation continue to rise. METHODS Initially, 10 subjects (7 men and 3 women) were recruited for participation in the study, and at a later date an additional 11 subjects (6 men and 5 women) were screened for the presence of a clear switch point from nasal to oronasal breathing during exercise (see below). Three women from the screening subjects were subsequently included in the experimental study protocol. Study subjects (7 men and 6 women, mean age 29 8 yr, height cm, weight kg) were all active, healthy nonsmokers. None of the subjects reported recent upper airway infection or a past history of cardiovascular or pulmonary disease. All subjects demonstrated a forced vital capacity and forced expiratory volume in1sof 85% predicted ( and %, respectively) and a forced vital capacity-to-forced expiratory volume in 1 s ratio of 75% predicted (83 4). Informed consent was obtained from each subject, and the protocol was approved by the Human Subjects Committee of the University of Arizona. Resting and exercise measurements were obtained while the subject was either seated on an electronically braked cycle ergometer (Lode, Elema, Sweden) or lying on a platform behind the ergometer, which was custom-designed for supine exercise. Subjects wore a custom-made, partitioned face mask (Hans Rudolph), which allowed them to freely choose their own breathing route (i.e., nasal, oral, or oronasal). Inspiratory airflow was measured with two separate pneumotachographs (model 4700, Hans Rudolph, Kansas City, MO) attached directly to the nasal and oral ports of the face mask. The pressure drop across the pneumotachographs was measured with separate differential pressure transducers (model MP 45, Validyne). Calibration of the pneumotachographs was performed after each exercise test with a rotometer (Matheson). Bipolar EMG recordings of the right NDM were measured with 4-mm silver-silver chloride electrodes (Grass Instruments) placed 20 mm apart on the anterolateral aspect of the nose, as described previously (5, 8). The GG EMG was measured with a single fine-wire electrode (0.005 gauge, California Fine Wire) inserted into the GG muscle with a 27-gauge needle (23, 24) and referenced to a chin electrode. Heart rate was monitored at rest, during exercise, and for 6 min of recovery after exercise with a pulse oximeter (model 3700, Ohmeda). Protocol 1: EMG activities and airflow at rest and during incremental exercise (n 10). Subjects performed three maximal voluntary contractions (MVC) of each muscle before exercise began (flaring of the nostrils for the NDM and tongue protrusion against the teeth for the GG). Baseline ventilatory and EMG measurements were made for 3 min. The workload began at 50 W for male subjects and was increased by 50 W every 1.5 min up to 200 W and by 30 W every minute thereafter. Female subjects began exercise at 30 W, and the load was increased by 30 W every 1.5 min up to 120 W, with further increases of 20 W every minute. All subjects were instructed to maintain a pedal frequency of rpm. Ventilatory and EMG measurements were recorded continuously throughout the exercise test. Exercise was terminated at volitional fatigue or until pedal rate could not be maintained. MVC maneuvers of the NDM and GG were obtained 6 min after the end of exercise to ensure that the EMG electrodes remained stable. To determine the effects of posture on EMG activities at rest and during exercise, all 10 subjects returned to the laboratory 1 wk after the initial test and repeated protocol 1 in the supine position. Protocol 2: EMG activities and the switch from nasal to oronasal breathing during upright exercise (n 7). Four subjects from protocol 1 demonstrated a clear switch from nasal to oronasal breathing. An additional 11 subjects performed a submaximal upright exercise test while nasal and oral flow rates were measured, as described above, to identify additional subjects with a clear switch point. Three subjects were identified from these screening tests, and each of them subsequently performed an upright submaximal exercise test on a separate day, while both EMG activities and airflow were measured as described in protocol 1. Data analysis. EMG signals were amplified, band-pass filtered (0.1 5 khz), full-wave rectified, and moving-time averaged ( integrated ) with a time constant of 100 ms, as described previously (5, 8). iemg values were expressed as a percentage of the average peak activity obtained during the pre- and posttest MVC maneuvers (see protocol 1). Oral and nasal flow rates, as well as the iemg activities, were recorded on a strip chart recorder (model TA11, Gould). Unprocessed EMG activities and oral and nasal airflow were recorded on videotape (Vetter pulse code modulation system) for subsequent analysis. Oral and nasal flow signals were integrated utilizing a commercial waveform analysis package

3 592 CONTROL OF UPPER AIRWAY DILATOR MUSCLES DURING EXERCISE (Codas) to obtain both oral and nasal inspiratory tidal volume (VT) and ventilation (V I). Mean inspiratory flow (VT/TI, where TI is inspiratory time) was calculated as VT divided by the duration of inspiratory flow. Nasal and oral peak flow rates were determined from the chart recordings of the nasal and oral flow signals. Six-breath averages were derived for each variable during the last minute of rest and toward the end of each exercise work rate. To determine the average iemg activities at the switch from nasal to oronasal breathing, NDM and GG iemg activities were determined from a three-breath sample immediately preceding and immediately following the switch point. The nasal V I at the switch point was also determined as the average of a three-breath sample immediately before the switch. The switch point from nasal to oronasal breathing was identified for each subject via examination of the nasal and oral flow signals on the strip chart recordings (see Figs. 5 and 6). The switch point was defined when at least six consecutive oral breaths were recorded. iemg activities of the NDM and GG before and after the switch point are expressed as a percentage of maximal activity, as described above. Statistical analysis. ANOVA with repeated measures and the Student-Newman-Keuls post hoc procedure were used to determine the statistical significance of the changes in ventilation and EMG activities evoked by upright and supine exercise. To determine whether EMG activity depended on the breathing route, we used linear regression analysis to calculate the slopes and correlation coefficients of the relationship between iemg activities and nasal, oral, and total V I for each subject, under conditions of both upright and supine exercise. These data were then subjected to repeatedmeasures ANOVA. This allowed us to test the null hypothesis that the slopes and correlation coefficients of the EMG-V I relationships were the same whether the flow route was nasal, oral, or oronasal, and whether or not the exercise was done in the upright or supine posture. Differences between iemg activities before and after the switch point were determined with Student s t-test for paired comparisons. All average data are presented as means SE. An level of 0.05 was considered significant. RESULTS EMG activities and airflow at rest and during incremental exercise. EMG and ventilatory parameters at rest and during exercise are presented in Fig. 1. At rest in the upright position, NDM iemg activities were consistently observed in four of the subjects, and GG iemg activity was present in only one subject under these conditions. In supine rest, NDM iemg activity was present in seven of the subjects, and GG iemg activity was present in four subjects. Although the supine GG iemg activity tended to be higher compared with upright under resting conditions, no significant differences between upright and supine resting iemg activities for either NDM or GG were detected. Both NDM and GG EMG activities rose significantly as a function of exercise intensity, in both upright and supine positions, and the rise in EMG activities paralleled the changes in V I and VT/TI rates (Fig. 1). There were no significant differences in EMG activities, V I,or VT/TI between upright and supine exercise at any of the submaximal power outputs. Fig. 1. Changes (means SE) in nasal dilator muscle (NDM) and genioglossus (GG) integrated electromyogram (iemg) activities, mean inspiratory flow [ratio of tidal volume to inspiratory time (VT/TI)], and inspired pulmonary ventilation rate (V I) as a function of exercise power output during both upright exercise (A) and supine exercise (B). *Significantly different from resting control value (P 0.05). iemg activity at peak exercise power output for NDM averaged % maximum in upright exercise and % maximum in supine exercise (P 0.292). Corresponding values for the GG were % of maximum in upright exercise and 29 8% maximum in supine exercise (P 0.373). Peak NDM EMG activity was greater than peak GG EMG activity during peak upright exercise (P 0.047) but not during peak supine exercise (P 0.103). Peak power output averaged W during upright exercise and W in supine exercise. Breathing-route dependence of upper airway muscle activities during exercise. The results of the individual linear regression analyses of NDM and GG EMG activities on nasal, oral, and total V I are shown in Table 1. The raw data for all subjects under conditions of both upright and supine exercise are shown in Figs. 2 and 3. Although the average correlation coefficient for each of the EMG-flow relationships was significantly different than zero, repeated-measures ANOVA failed to detect any significant differences in the strength of the correlation coefficients between different flow routes or between upright and supine exercise in either muscle (Table 1). The average slopes of the relationship between EMG activities and nasal, oral, and total V I (i.e., the sensi-

4 CONTROL OF UPPER AIRWAY DILATOR MUSCLES DURING EXERCISE 593 Table 1. Individual and group average correlation coefficients of the relationship between GG and NDM EMG activities and oral, nasal, and total V I for both upright and supine exercise Upright Exercise Supine Exercise Subject Nasal V I Oral V I Total V I Nasal V I Oral V I Total V I igg EMG DK DS PH RS AF DL CR RF JW PJ Mean SE indm EMG DK DS PH RS AF DL CR RF JW PJ Mean SE GG, genioglossus; NDM, nasal dilator muscle; EMG, electromyogram; V I, inspired ventilation; igg EMG, integrated EMG of the GG; indm EMG, integrated EMG of the NDM. tivity of the response) are shown in Fig. 4. The slope of the NDM iemg-nasal V I relationship was significantly greater than the corresponding slopes for oral and total V I (refer to Fig. 2), but there were no significant differences between upright and supine exercise. Although the slope of the GG iemg-nasal flow relationship in upright exercise tended to be higher than that for oral and total V I, none of the differences were significant. The supine posture had no significant influence on the GG iemg-flow relationships (Fig. 4). Upper airway muscle EMG activities and the switch from nasal to oronasal breathing during upright exercise. A switch from exclusively nasal to oronasal breathing during upright exercise occurred in 7 of the 21 subjects studied (33%); the remaining subjects breathed oronasally at rest. For male subjects, 3 of 13 demonstrated a switch point (23%), whereas 4 of the 8 female subjects tested demonstrated a switch from nasal to oronasal breathing during exercise (50%). The inspiratory ventilation rate at the switch point averaged l/min. Figure 5 demonstrates the iemg activities for NDM and GG immediately before and after the switch point in a representative subject. GG iemg activity was significantly increased after the switch to oronasal breathing, whereas NDM iemg activity was significantly decreased. Figure 6 shows an atypical response, inasmuch as this subject showed phasic activity in both the NDM and GG muscles during nasal breathing, but after the switch point GG activity became tonic, and the magnitude of the phasic NDM bursts declined (Fig. 6A). The subject eventually switched back to exclusive nasal breathing during recovery from exercise, and phasic GG activity returned at this time (Fig. 6B). Figure 7 shows the individual and group average responses of NDM and GG iemg activities before and after the switch from nasal to oronasal breathing during exercise. For the GG, five of the seven subjects demonstrated large increases in iemg activity after the switch to oronasal breathing, whereas two subjects showed no change. Six of the seven subjects demonstrated large reductions in NDM iemg after the switch to oronasal breathing, with only one subject showing a small increase. Although they were not analyzed quantitatively, we noted that, in a few cases, EMG activities tended to return to the preswitch point level within 1 min after the onset of oronasal breathing. However, these data were only rarely available because the exercise intensity was usually increased before a post-switch point steady state could be established. DISCUSSION The major findings of this study are as follows. 1) NDM and GG iemg activities increase monotonically with power output during both upright and supine incremental exercise. EMG activities during maximal exercise averaged and 50 60% of maximal activity for the GG and NDM, respectively. 2) Posture

5 594 CONTROL OF UPPER AIRWAY DILATOR MUSCLES DURING EXERCISE Fig. 2. Individual data showing the relationship between NDM iemg (indm EMG) activity and nasal (A), oral (B), and total (C) V I during upright incremental exercise to maximal levels of exertion. E, Upright exercise;, supine exercise. Solid lines are the result of the linear regression analysis for upright and supine exercise. has no significant effect on drive to the upper airway muscles during exercise. 3) Both NDM and GG EMG activities correlated equally well with nasal, oral, or total ventilation under conditions of both upright and supine exercise. 4) Analysis of EMG-ventilation slopes revealed that changes in NDM EMG activity were significantly more sensitive to changes in nasal V I than to changes in either oral or total V I during both upright and supine exercise. In contrast, the GG was equally sensitive to nasal, oral, and total V I. 5) The sudden switch from nasal to oronasal breathing is associated with increased GG iemg activity and a reduction in NDM iemg activity, although the changes are variable and transient in some subjects, especially in the GG. Given that two of our primary findings were negative (i.e., no route dependence for the GG and no influence of posture on the activity of either the GG or NDM), it is important to briefly address the statistical power of our analysis. The major analysis that was used to address these issues is summarized in Fig. 4, which represents the average EMG-V I slopes obtained during both upright and supine exercise. These data were obtained by computing the slope for each subject and subjecting the data to ANOVA. The statistical power coefficients were for the NDM data and 0.62 for Fig. 3. Individual data showing the relationship between GG iemg (igg EMG) activity and nasal (A), oral (B), and total (C) V I during upright incremental exercise to maximal levels of exertion. E, Upright exercise;, supine exercise. Solid lines are the result of the linear regression analysis for upright and supine exercise. Fig. 4. Average ( SE) slopes of the relationship between iemg activities and nasal, oral, and total V I during both upright and supine exercise, for the NDM (A) and GG (B). Data were obtained by computing the slope of these relationships for each of the subjects individually and then computing the average and SE. Statistical analysis was by repeated-measures ANOVA (see METHODS). * Significantly different from nasal V I slope (P 0.05).

6 CONTROL OF UPPER AIRWAY DILATOR MUSCLES DURING EXERCISE 595 Fig. 5. Representative record from 1 subject demonstrating increased GG EMG activity and decreased NDM EMG activity after the switch point from nasal to oronasal breathing during exercise. The response of this subject was common to the majority of the subjects that showed a switch point. Arrow indicates the switch point. On flow tracings, inspiration is represented as a downward deflection. The EMG recordings are uncalibrated. See text for further explanation. the GG, with a value of 1.0 being the highest possible. For values of 0.05, the recommended power value of our data set was Thus our NDM data are powerful enough to confidently exclude the possibility of a type II error, but the GG data should be interpreted with caution. It is possible that a larger sample size would have resulted in statistical significance. Nevertheless, the marked variability in GG activity during exercise, together with the poor relationship between GG activity and the flow route, indicates not only that the control of this particular upper airway muscle is complex but that it may play a relatively minor role compared with that played by the NDM during exercise. Drive to upper airway muscles during exercise. In the present study, NDM EMG activity averaged 50 60% of maximal activity at peak exercise power outputs. These data are in agreement with earlier studies from our laboratory showing values of 45 50% of maximal activity during exercise at 90% of the peak power output (8). During exercise sufficiently intense to raise the ventilation from 6 to 40 l/min, NDM activity averaged 70 and 30% of maximal activity during nasal and oral breathing, respectively, in a recent study by Shi et Fig. 6. Representative record from subject who had a highly atypical upper airway muscular response at the switch point. A: note that this subject had phasic activity in both GG and NDM before the switch point, but after the switch point GG activity tended to be largely tonic, whereas the NDM retained strong respiratory modulation. B: tracings show resumption of nasal breathing during recovery from exercise, with the return of strong respiratory modulation in the GG. Arrows indicate the switch point. The nasal V I tracing was saturated before the switch point (note the squaring off in the majority of the cycles in A). V, ventilation. See text for further explanation.

7 596 CONTROL OF UPPER AIRWAY DILATOR MUSCLES DURING EXERCISE Fig. 7. Individual ( ) and average responses (thick horizontal lines) of GG (A) and NDM (B) iemg activities before and after the switch from nasal to oronasal breathing in 7 subjects. * Significantly different from Before (P 0.05). al. (25). In the present study, peak ventilation rates exceeded 120 l/min, indicating that the exercise intensity was much more severe than that used by Shi and colleagues. That their EMG activities reached 70% of maximal activity during light exercise with nose breathing serves to emphasize the importance of the breathing route in modulating NDM activity (see below). We are unaware of any studies describing GG EMG activity during progressive-intensity exercise to maximal levels. Our data show an approximately linear relationship between GG iemg activity and power output during upright exercise to volitional fatigue, with peak activity reaching 40% maximal at exercise termination. Shi et al. reported GG iemg activities of 35 40% of the maximal activity during upright exercise at a VT/TI of 1.5 l/s, and the activity was the same whether the subjects breathed orally or nasally. These values are higher than those observed in the present study at similar levels of VT/TI (see Fig. 1), but this may reflect the fact that the subjects of Shi et al. were instructed to breathe either orally or nasally, as opposed to the present study wherein subjects freely chose their route of breathing. It is interesting to compare the peak drive to upper airway muscles during exercise with that to respiratory pump muscles. Abraham et al. (1) reported average peak EMG activities of 14 and 18% of maximal for external oblique and rectus abdominis muscles, respectively, at the point of maximal volitional exertion evoked by cycling exercise. Naus et al. (15) recorded the activity of external oblique, rectus abdominis, and expiratory intercostal muscle EMG activities during incremental cycling exercise and reported peak values ranging from 8 to 10% of maximal activity. Johnson et al. (13) measured transdiaphragmatic pressure (which serves as an index of muscle force) during peak exercise in human subjects and found that it averaged 46% of the value recorded during a maximal volitional effort. Given that force and EMG measurements are highly correlated, these data suggest that diaphragm EMG activity was close to 50% of the maximal level at peak exercise. Taken together, these data clearly show that neural drive to upper airway muscles can approach drive to the diaphragm during exercise and can far exceed drive to accessory muscles of the chest wall and abdomen. Influence of posture on upper airway muscle activities. The influence of posture on upper airway EMG activities may be clinically relevant because of the prevalence of airway obstruction during sleep. However, posture-induced changes in upper airway muscle activities are poorly understood (12, 21, 31). Sauerland and Mitchell (24) reported an augmentation of both tonic and phasic GG EMG activities in the resting, supine position compared with upright. To the contrary, Wasicko et al. (31) found that steady-state resting GG iemg activity was reduced in the supine compared with the head-up position. These authors attributed the findings to baroreceptor inhibition of hypoglossal motoneuronal activities. Leiter et al. (14) examined the effects of posture on nasal and pharyngeal resistance and GG iemg activities during CO 2 rebreathing. Both nasal resistance and GG iemg activity increased as a function of nasal airflow, but the changes were similar in the upright and supine positions. Our findings are in agreement with these results in that GG iemg activity was not significantly augmented in the supine compared with the upright position, as the ventilatory rate was increased by exercise (e.g., Figs. 1 and 3). The plateau in GG iemg activity that occurred at 60% of peak power output during supine exercise may be associated with recruitment of additional pharyngeal dilator muscles (2, 18). In other words, defense of the pharyngeal airway during exercise is very likely a shared task involving several pharyngeal muscles, as well as palatal and strap muscles. We also failed to demonstrate an effect of posture on NDM activities. However, the effect of posture on nasal resistance in normal subjects is modest (12, 21) and has been attributed to vascular changes in the nasal mucosa. Therefore, it is not surprising that NDM iemg activity was not augmented by supine exercise. Breathing-route dependence of drive to upper airway muscles during exercise. Shi et al. (25) conducted a detailed study of the influence of breathing route on drive to GG and NDM muscles during upright cycling exercise. By forcing their subjects to breathe via either the oral or nasal passage exclusively, they were able to demonstrate that NDM activity was much higher with nasal breathing, whereas GG EMG activity was independent of the breathing route. However, when sub-

8 CONTROL OF UPPER AIRWAY DILATOR MUSCLES DURING EXERCISE 597 jects are allowed to freely choose their breathing route during exercise, they generally breathe oronasally when the total pulmonary ventilation rate reaches 35 l/min. In the present study, this value corresponded to an exercise intensity of 60% of the peak power output (Fig. 1). Accordingly, studying the natural behavior of upper airway muscles and oronasal flow partitioning across a wide range of exercise intensities requires a paradigm that allows the subjects to freely choose their breathing route. Using this approach in the present study, we found that NDM activity was significantly more sensitive to nasal ventilation than to either oral or total ventilation in both upright and supine exercise. This route-dependent behavior of the NDM has been consistently demonstrated and is thought to reflect the role of these muscles in modulating resistance across the nasal valve, as discussed in detail previously (5, 8, 26, 33). In contrast to the NDM, GG activity showed no breathingroute dependence during exercise in either posture. Thus our findings obtained by examining changes in the relationship between muscle activity and flow route from the beginning to the end of an incremental exercise test are in complete agreement with those of Shi et al. (25), despite the use of very different techniques and exercise protocols. However, our experiments on the dynamic changes in drive to upper airway muscles at the switch point (Figs. 5 7) are entirely consistent with route-dependent control (see below). How, then, can we reconcile the very different conclusions drawn by these two unique analyses? First, many subjects in this and in our earlier studies breathed oronasally at rest and, therefore, did not show a clear switch point. Accordingly, the inclusion of their data in the correlation analysis reduced the power of the data set, because by definition their upper airway muscles showed less route-dependent modulation than those of the subjects who did have a clear switch point. In support of this idea, the data in Fig. 4 show a trend for route-dependent control of the GG, and this difference was significant only if subjects demonstrating a clear switch point were included in the analysis. Second, even if significant route-dependent control were revealed in our analysis, we found that the GG was more sensitive to nasal than to oral flow (Fig. 4). This latter observation was opposite to our expectations but is consistent with the findings of Basner et al. (3), who clearly documented higher GG activities in subjects who were asked to voluntarily breathe either orally or nasally. Taken together, these data indicate that GG activity is more strongly modulated by factors that are independent of the flow route. For example, our laboratory previously showed that NDM activity was significantly higher during exercise than during CO 2 rebreathing when comparisons were made at equivalent levels of total pulmonary ventilation in subjects who were confined to nasal breathing (see Fig. 7 in Ref. 28). These data demonstrated that central command is a powerful drive to the NDM during exercise, and it is possible that the GG is even more profoundly influenced by central motor command under these conditions. Drive to upper airway muscles at the switch point. The airflow rate at the switch point ranges from 22 to 44 l/min (8, 16, 22, 32, 33), and our estimate of 30 l/min is within this range, demonstrating that our methodology was sound and did not alter the normal ventilatory response to exercise. Although our finding of a reduced NDM iemg activity at the switch point is in agreement with previous reports (25, 33), there are no prior data on GG activity at the switch point. Although the physiological significance of the change in muscle activities at the switch point is not known, the reduction in NDM iemg activity that occurs after the switch may be related to reduced nasal flow resistance after mouth opening and the switch to oronasal breathing (8). However, the augmentation of GG iemg activity after the switch point is unlikely to be explained on the basis of flow resistance, because pharyngeal resistance should decline after mouth opening. It is possible that mouth opening and caudal movement of the jaw shortens the GG muscle fibers so that greater neural drive (i.e., increased EMG activity) is needed for the same degree of force production. Nevertheless, we found that changes in EMG activities at the switch point were often transient and that the between-subject variability in the pattern of drive to the GG was variable (compare Figs. 5 and 6). It is possible that the increase in drive to the GG at the switch point diminishes shortly after the initial adjustments of airway configuration are made. This may explain why route-dependent control is not observed under steady-state conditions or when the data from several respiratory cycles are averaged (see above). It is also important to note that oronasal breathing depends on the position of the soft palate (20), and a breathing-route-dependent pattern of activation has been previously reported for palatal muscles (29, 30). Oronasal breathing is initiated when the soft palate is moved to the midposition of the pharynx, as shown by Rodenstein and Stanescu (20). However, because the soft palate and the base of the tongue are in close communication, the tongue must either move forward or depress and stiffen, so that the velopharynx is wide and/or rigid enough to promote adequate oral airflow. It is likely that the tongue and palatal muscles are driven in a highly coordinated fashion at the switch point, with the relative magnitude of activation governed by lingual and pharyngeal anatomy and mobility. Finally, recent studies in rats prepared with an isolated upper airway showed that activation of the GG with the mouth sealed ( nose breathing ) increased flow and caused stiffening of the pharynx (10). In contrast, when both nose and mouth were open ( oronasal breathing ), GG activation increased flow even further but did not stiffen the airway. These data clearly demonstrate that the functional significance of GG activation depends on the breathing route and that GG activation can contribute to pharyngeal flow control, whether the breathing route is nasal or oronasal. This observation is consistent with the notion that the

9 598 CONTROL OF UPPER AIRWAY DILATOR MUSCLES DURING EXERCISE GG muscle fails to show route-dependent control because its major mechanical influence is on the retroglossal airspace, which is caudal to the junction of the oral and nasopharyngeal airways (25). Accordingly, activation of the GG during hyperpnea will depend primarily on the need for retroglossal dilation and/or stiffness, irrespective of the breathing route. We thank James Waisley for technical assistance. These studies were supported in part by National Institutes of Health Grants HL-56876, HL-51056, and T32NS0730. Present addresses: J. S. Williams, Department of Exercise Science, The University of Mississippi, Jackson, MS ( D. D. Fuller, Department of Comparative Biosciences, The University of Wisconsin School of Veterinary Medicine, Madison, WI ( P. L. Janssen, Department of Animal Biology, The University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA ( REFERENCES 1. Abraham KA, Feingold H, Fuller DD, Mateika JH, and Fregosi RF. Pattern of expiratory muscle recruitment during incremental exercise (Abstract). Med Sci Sports Exerc 29: S288, Bartlett DJ. Upper airway motor systems. In: Handbook of Physiology. The Respiratory System. Control of Breathing. Bethesda, MD: Am. Physiol. Soc., 1986, sect. 3, vol. II, pt. 1, chapt. 8, p Basner RC, Simon PM, Schwartzstein RM, Weinberger SE, and Weiss JW. Breathing route influences upper airway muscle activity in awake normal humans. J Appl Physiol 66: , Brennick MJ, Parisi RA, and England SJ. Influence of preload and afterload on genioglossus muscle length in awake goats. Am J Respir Crit Care Med 155: , Connel D and Fregosi RF. Influence of nasal airflow and resistance on nasal dilator muscle activities during exercise. J Appl Physiol 74: , DeLuca CJ. Physiology and mathematics of myoelectric signals. IEEE Trans Biomed Eng 26: , Eisele DW, Smith PL, Alam DS, and Schwartz AR. Direct hypoglossal nerve stimulation in obstructive sleep apnea. Arch Otolaryngol Head Neck Surg 123: 57 61, Fregosi RF and Lansing RW. Neural drive to nasal dilator muscles: influence of exercise intensity and oronasal flow partitioning. J Appl Physiol 79: , Fuller DD, Mateika JH, and Fregosi RF. Co-activation of tongue protrudor and retractor muscles during chemoreceptor stimulation in the rat. J Physiol (Lond) 507: , Fuller DD, Williams JS, Janssen PL, and Fregosi RF. Effect of co-activation of tongue protrudor and retractor muscles on tongue movements and pharyngeal airflow mechanics in the rat. J Physiol (Lond) 519: , Glantz SA. Primer of Biostatistics (3rd ed.). New York: McGraw- Hill, Hassegawa M and Saito Y. Postural variations in nasal resistance and symptomatology in allergic rhinitis. Acta Otolaryngol (Stockh) 88: , Johnson BD, Babcock MA, Suman OE, and Dempsey JA. Exercise-induced diaphragmatic fatigue in healthy humans. J Physiol (Lond) 460: , Leiter JC, Knuth SL, and Bartlett D Jr. Dependence of pharyngeal resistance on genioglossal EMG activity, nasal resistance, and airflow. J Appl Physiol 73: , Naus F, Sharratt M, McGill S, and Hughson R. An EMG confirmation of active expiration (Abstract). FASEB J 4: A292, Niinimaa V, Cole P, Mintz S, and Shepard RJ. The switching point from nasal to oro-nasal breathing. Respir Physiol 42: 61 71, Odeh M, Schnall R, Gavriely N, and Oliven A. Dependency of upper airway patency on head position: the effect of muscle contraction. Respir Physiol 100: , Okabe S, Chonan T, Hida W, Satoh M, Kikuchi Y, and Takishima T. Role of chemical drive in recruiting upper airway and inspiratory intercostal muscles in patients with obstructive sleep apnea. Am Rev Respir Dis 147: , Remmers JE, DeGroot WJ, Sauerland EK, and Anch AM. Pathogenesis of upper airway occlusion during sleep. J Appl Physiol 44: , Rodenstein DO and Stanescu DC. Soft palate and oronasal breathing in humans. J Appl Physiol 57: , Rundcrantz H. Postural variations of nasal patency. Acta Otolaryngol (Stockh) 68: , Saibene FP, Mognoni P, Lafortuna CL, and Mostardi R. Oronasal breathing during exercise. Pflügers Arch 378: 65 69, Sauerland EK and Harper RM. The human tongue during sleep: electromyographic activity of the genioglossus muscle. Exp Neurol 51: , Sauerland EK and Mitchell S. Electromyographic activity of intrinsic and extrinsic muscles of the human tongue. Tex Rep Biol Med 33: , Shi Y-X, Seto-Poon M, and Wheatley JR. Breathing route dependence of upper airway activity during hyperpnea. J Appl Physiol 84: , Shi Y-X, Seto-Poon M, and Wheatley JR. Alae nasi activation decreases nasal resistance during hyperoxic hypercapnia. J Appl Physiol 85: , Strohl KP, O Cain CF, and Slutsky AS. Alae nasi activation and nasal resistance in healthy subjects. J Appl Physiol 52: , Sullivan J, Fuller D, and Fregosi RF. Control of nasal dilator muscle activities during exercise: role of nasopharyngeal afferents. J Appl Physiol 80: , Tangel DJ, Mezzanotte WS, Sandberg EJ, and White DP. Influences of NREM sleep on the activity of tonic vs. inspiratory phasic muscles in men. J Appl Physiol 73: , Tangel DJ, Mezzanotte WS, and White DP. Respiratoryrelated control of palatoglossus and levator palitini muscle activity. J Appl Physiol 78: , Wasicko MJ, Knuth SL, and Leiter JC. Response of genioglossus EMG activity to passive tilt in men. J Appl Physiol 74: 73 81, Wheatley JR, Amis TC, and Engel LA. Oronasal partitioning of ventilation during exercise. J Appl Physiol 71: , Wheatley JR, Amis TC, and Engel LA. Influence of airflow temperature and pressure on alae nasi electrical activity. J Appl Physiol 71: , 1991.