A neuromuscular mechanism maintaining extrathoracic airway patency.

A neuromuscular mechanism extrathoracic airway patency

maintaining

ROBERT T. BROUILLETTE AND BRADLEY T. THACH Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine 63178 Division of Neonatology, St. Louis Children’s Hospital, St. Louis, Missouri

BROUILLETTE, ROBERT T., AND BRADLEY T. THACH. A neuromuscdar mechanism maintaining extrathoracic airway patency. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 46(4): 772-779, 1979.-The ability of the extrathoracic airway (ETA) to remain open when exposed to negative pressure was investigated in rabbits. Postmortem, the ETA collapsed at -6.3 t 0.6 cmH*O whereas, during airway occlusion maneuvers in lightly anesthetized animals, it remained patent at pressures as low as -80 cmH20. This discrepancy suggested that a neuromuscular mechanism maintains ETA patency. Four findings indicated that the genioglossus and geniohyoid muscles, which pull the tongue and hyoid bone anteriorly, help maintain ETA patency: I) anterior movement of the hyoid bone increased the negative pressure at which the ETA collapsed postmortem, 2) ETA closure during occluded inspirations occurred after 12th nerve section abolished electromyographic activity in these muscles and 3) after deep anesthesia depressed such activity, and 4) closing pressure was linearly related to peak integrated electromyograms of the two muscles. After 12th nerve section, ETA closing pressure became more negative with progressive asphyxia greatly exceeding postmortem closing pressure, which suggests that other muscles also help maintain ETA patency. Blood gas tensions, respiratory system mechanoreceptors, and depth of anesthesia appear to influence genioglossus and geniohyoid activity.

and

pharyngeal patency at negative transmural pressure. The negative pressure required to collapse the ETA in the absence and presence of neuromuscular activity was determined. The airway-maintenance function of the genioglossus (GG) and geniohyoid (GH) muscles was studied in three ways: by determining the effect of motor denervation of these muscles on in vivo airway closure; by investigating the relation of in vivo ETA closing pressure to GG and GH electromyograms (EMGs); and by mimicking GG and GH activity in the postmortem preparation. Furthermore, phasic respiratory activity of the GG and GH muscles during tidal breathing was documented and the immediate, as well as the progressive, recruitment of these muscles in response to airway occlusion maneuvers was studied. Finally, the effects of anesthesia on in vivo closing pressure and on GG and GH activity were examined. METHODS

Determination of postmortem closing pressure and site of closure. New Zealand White rabbits were used for all studies. Mean age was 27 t 4.5 (SD) days and mean weight was 568 t 206 (SD) g. Fourteen rabbits were rabbit; genioglossus; geniohyoid; pharynx; respiratory loading; anesthetized with ether and killed by exsanguination. respiratory control; anesthesia Secretions were removed from the airways, a mask was constructed of quick-drying epoxy glue, and a nasal catheter inserted 0.5 cm into one nostril (Fig. 1). The mouth TO FUNCTION AS A CONDUIT for air, the extrathoracic and other nostril were occluded by the mask. Another catheter was inserted and tied in the lower trachea and airway (ETA) must resist closure when intraluminal pressure decreases during inspiration. During maximal positioned to avoid traction on the trachea. The esophinspiratory efforts against nasal occlusion, pressures as agus was tied just below the cricoid cartilage isolating low as -80 to -100 cmH20 are transmitted to the nose the ETA as a closed system. The animals were studied without evidence of airway collapse (19). During normal supine with the head at a 90” angle to the spine. The tidal breathing in man, pharyngeal pressure rarely ex- airway was fast inflated, using a syringe, then slowly ceeds -1 cmHz0 (18), but in anesthetized subjects (16, deflated as nasal pressure and tracheal pressure were 21) and in certain individuals during sleep (12, 20, 29) measured with transducers (Statham PM-6 and PM-131) and recorded (Beckman R-61 1 polygraph). Postmortem intermittent airway obstruction occurs. This obstruction has been attributed to decreased muscle tone with re- closing pressure was defined as the negative intraluminal sultant passive pharyngeal closure (12). The only quan- pressure at which nasal pressure failed to decrease with titative evidence for a neuromuscular mechanism pre- tracheal pressure, i.e., the pressure at which the ETA venting pharyngeal collapse at negative transmural pres- collapsed (Fig. 2). Four to twenty-one determinations of sure comes from a recent study by Remmers and co- postmortem closing pressure were performed on each workers (20). Direct evidence for an airway-maintaining animal and means for each animal were averaged to obtain the group mean. All measurements were commechanism is still lacking. The present experiments were designed to investigate pleted by 60-90 min postmortem. To determine the segment of the ETA most susceptible the relation of airway pressure to airway closure in an animal model and to identify the muscles that maintain to closure when subjected to negative pressure, further

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0 1979 the American

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FIG. 1. Diagram of extrathoracic airway of the rabbit used for postmortem studies. Nasal and tracheal pressures as airway is inflated, then slowly deflated, using a syringe tracheal catheter.

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and system are recorded attached to

PRESSURE

O POST MORTEM CLOSING PRESSURE -40

FIG. 2. Method of determining extrathoracic airway closing pressure in postmortem preparation. Tracing of an actual record is shown. Nasal (dotted line) and tracheal (solid line) pressures are superimposed for clarity. As tracheal pressure is slowly lowered, point at which nasal pressure fails to decrease with tracheal pressure (arrow) is termed postmortem closing pressure.

measurements were performed on five animals. To measure the resistance of the trachea to collapse, the nasal catheter was advanced until the tip had passed through the larynx and was just below the cricoid cartilage. Pressures in the upper and lower trachea were recorded as intraluminal pressure was slowly decreased. To measure the resistance of the nasal airway to collapse, the nasal catheter was withdrawn to its original position and the lower catheter advanced through the larynx until the tip was at the junction of the hard and soft palate. Pressures were again recorded as air was withdrawn from below. Catheter-tip placement was verified by dissection after measurements were completed. It proved technically impossible to separate the pharynx and larynx using this system. In two additional animals, the rate of decrease of tracheal pressure was varied from 5 to 300 cm/s and the effect on postmortem closing pressure determined. These observations were made to be sure that the quasi-static measurements of postmortem closing pressure were comparable to the dynamic measurements of in vivo closing pressure. The rates of decrease in tracheal pressure were

773 chosen to encompass the rates of decrease in tracheal pressure during occluded inspiratory efforts in the living 12th nerve-sectioned animals. Effect of simulating GG and GH contraction on postmortem closing pressure. To determine the effect of simulating GG and GH contraction on postmortem closing pressure, a midline suture was tied around the hyoid bone in five animals. Postmortem closing pressure was then determined with and without 2-3 mm anterior displacement of the hyoid bone by traction on the suture. This amount of displacement corresponded to that observed in vivo during airway occlusion maneuvers (see RESULTS). Each animal was used as its own control and results were compared by the two-tailed paired t test. Determination of in vivo closing pressure utilizing airway occlusion maneuvers: effect of GG and GH denervation. Six rabbits, 28-44 days old, were lightly anesthetized with ether and lo-30 mg/kg intraperitoneal pentobarbital. The animals were studied supine with the head at a 90” angle to the spine and breathing through a mask similar to that shown in Fig. 1. Under local lidocaine anesthesia, a midline incision was made through the skin and superficial fascia from chin to sternal notch to expose the anterior neck structures (9). A nonobstructing 18-gauge Teflon catheter was inserted in the trachea to measure tracheal pressure. Nasal pressure was measured from a sidearm on the nasal catheter. Statham PM-6 and PM-131 transducers were used. EMGs were recorded in the GG muscles of six animals using bipolar enamel-coated platinum 0.3-mm-diam needle electrodes with l-mm exposed tip. The electrodes were inserted 4-6-n-m deep through one mylohyoid muscle midway between chin and hyoid bone. Placement was confirmed by postmortem examination. EMG was recorded in the GH muscle of one animal using fine-wire electrodes placed directly in the muscle (3). In three animals EMGs were rectified and electrically integrated with an RC circuit with a time constant of 0.2 s (11). Such integrated electrical activity has been shown to be proportional to muscle tension for muscles contracting isometrically or at constant velocity (5). Nasal pressure, tracheal pressure, EMGs, and integrated EMGs were recorded on the polygraph during nasal airway occlusion maneuvers performed at end expiration. ETA patency was inferred if nasal pressure equaled tracheal pressure throughout occluded inspirations. ETA closure was inferred if nasal pressure failed to decrease with tracheal pressure on occluded inspirations. On such breaths, peak inspiratory nasal pressure was defined as in vivo closing pressure. Four to seven nasal occlusion maneuvers were recorded on lightly anesthetized animals with intact GG and GH function. Immediately after such base-line observations, the GG and GH muscles were deprived of motor innervation by sectioning the 12th cranial nerves bilaterally (4). The 12th nerve sections were performed distal to the ramus descendens, sparing the nerve supply to the infrahyoid musculature. Four to eight nasal occlusion maneuvers were then recorded on the lightly anesthetized animals deprived of GG and GH function. Effect of anesthesia on ETA patency and on GG and GH activity during airway occlusion maneuvers. Eleven


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R. T. BROUILLETTE

rabbits, lo-84 days old, were studied. After ether and/or 30 mg/kg intraperitoneal pentobarbital, each animal was prepared as described above for measurement of nasal and tracheal pressures. GG and GH EMGs were measured in four and one animals, respectively. Four to fifteen airway occlusions were performed in the lightly anesthetized state. Successive doses of ether or lo-30 mg/kg intraperitoneal pentobarbital were then administered and four to seven airway occlusion maneuvers repeated when the animal was deeply anesthetized .. Depth of anesthesia was based on response to pinprick and on corneal reflexes. Two animals were allowed to recover from d.eep anesthesia and airway occlusion maneuvers were repeated on them to demonstrate that the anesthetic effect was reversible. Phasic inspiratory GG and GH activity during tidal breathing. To study the GG and GH muscles during tidal breathing, respiration was monitored in four lightly anesthetized animals using a miniature bellows pneumograph (Beckman) secured around the abdomen as GG and GH EMGs were recorded. No mask or tracheal catheter was attached to these animals. RESULTS

Determination of postmortem closing pressure and site of closure. A typical determination of postmortem closing pressure is shown in Fig. 2. As air was withdrawn from the airway, nasal pressure paralleled tracheal pressure until the point indicated by the arrow (Fig. 2). Thereafter, further decrease in tracheal pressure was not transmitted to the nose, indicating ETA closure. Postmortem closing pressure of 14 animals was -6.3 t 0.6 (SE) cmHn0 and was highly reproducible within each animal; standard deviation of replicate measurements on individual animals ranged from 0.5 to 1.5 cmHa0. Postmortem closing pressure did not vary with age over the

A

AND

B. T. THACH

limited age range studied. In each of the five animals in which site of closure was studied, both the trachea and the nasal airway remained patent at negative pressures of -40 cmH20. Since the ETA in these five animals collapsed at -6.0 t 0.8 (SE) cmH20, the site of ETA closure could be localized to either the pharynx or the larynx. In the two animals in which the rate of decrease of tracheal pressure was varied, only small changes of approximately 2 cmHzO in the postmortem closing pressure were seen. Effect of simulating GG and GH contraction onpostmortem cZosing pressure. Anterior displacement of the hyoid bone, simulating the action of the GG and GH muscles, decreased postmortem closing pressure from -6.0 t 0.8 to -14.2 t 1.4 (SE) cmHa0 (n = 5; P < 0.01, two-tailed paired t test). Determination of in vivo closing pressure utilizing airway occlusion maneuvers: effect of GG and GH denervation. Figure 3A shows a typical airway occlusion maneuver in a lightly anesthetized animal with intact GG and GH function. Nasal pressure equaled tracheal pressure throughout occluded breaths, indicating ETA patency. Progressively lower peak inspiratory pressures were generated as occlusion proceeded (30). In sharp contrast to postmortem ETA closure at pressures ap-6 cmHz0, the ETA of lightly anesthetized proximating animals remained patent at pressures as low as -80 cmHa0. GG and GH EMGs showed phasic inspiratory activity during airway occlusion maneuvers while the hyoid bone was observed to move 2-3 mm toward the chin during occluded inspirations. Figure 3B shows a typical airway occlusion maneuver in a lightly anesthetized animal after bilateral 12th cranial nerve section. Twelfth nerve section paralyzed the tongue and abolished GG and GH EMGs in each of the six animals. After 12th nerve section, midinspiratory

B FIG. 3. Tracheal pressure, nasal pressure, genioglossus EMG, and integrated genioglossus EMG in a lightly anesthetized animal before and after 12th nerve section. A: before nerve section. During airway occlusion maneuver (between arrows), nasal pressure equals tracheal pressure, indicating extrathoracic airway patency. Genioglossus EMG shows an increase in activity on first occluded inspiration and further increase on subsequent occluded inspirations. Genioglossus EMG on unoccluded inspirations is not seen due to reduced gain. B: after bilateral 12th nerve section. During airway occlusion maneuver (between arrows), nasal pressure fails to fully follow tracheal pressure with inspiration, indicating extrathoracic airway closure. Genioglossus activity is absent. Movement artifacts, phasic with respiratory efforts, are seen on genioglossus EMG channel.

i


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ETA closure at negative transmural pressure was seen on occluded inspirations. Note that nasal pressure failed to decrease to levels as low as tracheal pressure on occluded inspirations. In vivo closing pressure ranged from -4 to -40 cmH20 after 12th nerve section. Furthermore, in vivo closing pressure reached progressively lower levels on sequential occluded inspiratory efforts (Fig. 4). Effect of anesthesia on ETA patency and on GG and GH activity during airway occlusion maneuvers. During airway occlusion maneuvers in lightly anesthetized animals, ETA patency was maintained and increased phasic inspiratory GG and GH EMGs were observed (Fig. 5A). Figure 5B shows a typical airway occlusion maneuver in a deeply anesthetized animal. Midinspiratory ETA closure, similar to that seen after 12th nerve section, was observed in the deeply anesthetized animals. As is also shown in Fig. 5B, in vivo closing pressure reached progressively lower levels on sequential occluded inspirations. Deep anesthesia depressed the GG and GH EMG recruitment seen with airway occlusion maneuvers although an increase in EMG activity on sequential occluded inspirations was still observed. Figure 6 shows peak inspiratory tracheal pressure plotted against peak integrated GG EMG for occluded inspirations in light (33 mg/kg pentobarbital) and deep (66 mg/kg pentobarbital) anesthesia in one animal. Similar results were seen in three other animals. As airway occlusion proceeded in both lightly and deeply anesthetized animals, lower peak inspiratory tracheal pressures and increased peak integrated GG EMGs were observed. Thus sequential inspirations are upward and to the right in Fig. 6. Inspirations in light anesthesia, in which ETA patency was maintained, were characterized by relatively greater peak integrated GG EMG for a given peak tracheal pressure than inspirations in deep anesthesia, in which ETA closure occurred. Figure 7 shows in vivo closing pressure against peak integrated GG EMG for five nasal occlusions in a deeply anesthetized animal. In vivo closing pressure was linearly related to peak integrated GG EMG in this and in three other animals and to peak integrated GH EMG in one animal for which data was available. With backward extrapolation of the regression line to the yaxis, i.e., absent GG EMG, in vivo closing pressure (-7.8 cmHz0) closely approximated postmortem closing pressure (-6.3 cmHz0) in all animals. Phasic inspiratory GG and GH activity and recruitment during airway occlusion maneuvers. In four animals studied using the bellows pneumograph, GG and GH EMGs showed phasic inspiratory activity on unloaded inspirations (Fig. 8). Each of seven animals, studied with mask and tracheal catheter, showed similar phasic inspiratory EMG activity on unoccluded inspirations. GG and GH EMGs invariably increased following airway occlusion (Figs. 3A, 5, A and B). Phasic inspiratory GG and GH EMG activity on the first occluded inspiration was consistently increased compared to preceding unoccluded breaths. Furthermore, progressive recruitment of peak integrated GG and GH EMGs on subsequent inspirations was observed. When peak inspiratory tracheal pressure was plotted as a function of peak inte-

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vivo closing pressures for 4 animals after 12th nerve section for the first 6-8 occluded inspirations. Animals were lightly anesthetized and had not demonstrated extrathoracic airway closure before 12th nerve section. In each case, in vivo closing pressure reaches progressively more negative levels on sequential occluded inspirations. Values shown are means & SE for 4-6 airway occlusion maneuvers. FIG.

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grated GG EMG or peak integrated GH EMG, a curvilinear relationship was obtained in both lightly and deeply anesthetized animals (Fig. 6). DISCUSSION

Evidence for neuromuscular maintenance of ETA patency at negative intraluminal pressure and identification of the muscles involved. During occluded inspirations in lightly anesthetized rabbits, the ETA remained patent at pressures as low as -80 cmHa0 but in postmortem animals, the ETA collapsed when subjected to relatively slight negative pressures. This discrepancy suggests that a neuromuscular mechanism maintains ETA patency in the face of negative intraluminal pressure. The observatio n that d.eeply a.nestheti .zed animals show midinspiratory closur be during airway occlusion maneuvers provides further evidence for such a mechanism. In addition, anatomical considerations suggest that this mechanism operates at the pharyngeal level. Our postmortem study of the ETA placed the site of closure in either the pharynx or larynx and, in anesthetized human subjects, the pharynx appears to be the site of passive closure (16, 21). Furthermore, anterior displacement of the hyoid bone, located in the anterior pharyngeal wall, decreased postmortem closing pressure. Thus, muscles that displace the tongue and hyoid anteriorly, such as the GG and GH muscles, might function to prevent pharyngeal closure in vivo. ETA closure at negative intraluminal pressure following motor denervation of the GG and GH muscles more directly established the airway ,-maintaining func tion of these muscles. Two findings in the 12th nerve-sectioned animals suggest that other muscles, not innervated by the 12th cranial nerve, act as accessory muscles to maintain ETA patency at negative intraluminal pressure. First, in vivo closing pressure in these animals usually exceeded postmortem closing pressure. Second, in vivo closing pressure of 12th nerve-sectioned animals reached progressively lower levels on sequential occluded inspirations (Fig. 4)


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AND

B. T. THACH

FIG. 5. Tracheal pressure, nasal pressure, genioglossus EMG, and integrated genioglossus EMG at two levels of anesthesia. A: lightly anesthetized animal (33 mg/kg pentobarbital). During airway occlusion maneuver (between arrou~) nasal pressure equals tracheal pressure indicating extrathoracic airway patency. Genioglossus EMG is phasic with inspiration. Phasic activity prior to occlusion is not apparent due to low gain. Increased genioglossus EMG on the first occluded inspiration and further increase on subsequent occluded inspirations can be appreciated. Motion artifact is seen during first occluded inspiration; motion artifacts after the sixth occluded breath indicate arousal. B: same animal, now deeply anesthetized (66 mg/kg pentobarbital). During airway occlusion maneuver (between arrows), nasal pressure fails to fully follow tracheal pressure with inspiration, indicating midinspiratory extrathoracic airway closure. In vivo closing pressure, i.e., peak nasal pressure of inspirations showing extrathoracic airway closure, reaches progressively lower levels on sequential occluded inspirations. Genioglossus EMG is still phasic with inspiration but increase with airway occlusion is less than when animal was lightly anesthetized.

suggesting asphyxial recruitment of other airway-maintaining muscles. Comparison of postmortem closing pressure, a quasi-static measurement, and in vivo closing pressure, a dynamic measurement, might not be valid if pharyngeal closure was delayed as transpharyngeal pressure decreased during occluded inspirations. However, in the two animals in which the rate of decrease of tracheal pressure was varied, relatively smaIl changes in postmortem closing pressure were seen. The present experiments do not indicate which additional muscles contribute to the maintenance of ETA patency. The posterior cricoarytenoid muscle, the abductor of the larynx, has been shown to be an accessory muscle of inspiration (2, 17). However, it acts in series with the GG and GH muscles and thus should not influence pharyngeal closure. Therefore, palatal, cervical extensor (26), or pharyngeal muscles not innervated by the 12th cranial nerve (digastric or mylohyoid muscles), which presumably act in parallel with the GG and GH muscles, may also oppose pharyngeal collapse at negative transmural pressure.

Phasic inspiratory GG and GH activity and recruitment during airway occlusion maneuvers. The GG and GH muscles

have not generally

been regarded

as acces-

sory muscles of respiration (6). However, an increase in the anterior-posterior diameter of the human pharynx and anterior displacement of the hyoid bone and tongue on maximal inspiratory efforts lead Mitchinson and Yoffey (15) to speculate that the GG and GH muscles could function as accessory muscles of inspiration in man. Phasic inspiratory genioglossus (1, 14)) geniohyoid (27, 28), and efferent 12th cranial nerve activity (13, 27, 28) has been repeatedly demonstrated in animals. Furthermore, phasic inspiratory GG activity during tidal breathing has been demonstrated by Sauerland and co-workers (23-25) in man. The present study demonstrates similar phasic GG and GH EMG activity during tidal breathing in rabbits. Thus, ample evidence presently exists to consider the GG and GH muscles as accessory muscles of inspiration. In man, loss or diminution of GG activity during sleep (12, 20) and during anesthesia (16, 21) has been associated with pharyngeal obstruction. However, in the present studies, removal of GG and GH activity in the 12th nerve-sectioned rabbits did not result in ETA obstruction during tidal breathing. Thus, there may be species variation in the physiological function of the GG and GH muscles and their full range of function as


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accessory muscles of respiration has yet to be defined. The consistent increase in GG and GH EMGs on the first breath following airway occlusion occurred before change in arterial blood gases could influence respiratory activity. Similar increases in diaphragmatic (22) and laryngeal abductor (8) activity are eliminated by midcervical vagotomy. In contrast, inspiratory intercostal EMG recruitment on the fllrst occluded inspiratory effort depends both on airway stretch receptors and on intercostal muscle spindles (22). However, lingual muscle

0

spindles are believed to be absent in rabbits (7). By analogy to other inspiratory muscles, increased GG and GH activity on the first occluded inspiratory effort likely results from decrease in inhibitory input from lower airway stretch receptors. However, the contribution of afferent inputs from as yet unidentified lingual muscle spindles or mechanoreceptors in the ETA or chest wall cannot be excluded by the present observations. Increases in GG and GH EMGs on occluded inspirations, after the fast, are most likely accounted for by decrease in arterial oxygen tension and/or by increase in arterial carbon dioxide tension. Previous work has shown that mechanoreceptor reflexes influencing peak inspiratory tracheal pressure during airway occlusion are com-

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6. Peak inspiratory tracheal pressure vs. peak integrated genioglossus EMG for the animal shown in Fig. 5. Values during 6 occlusions in light (33 mg/kg pentobarbital) and 15 occlusions in deep anesthesia (66 mg/kg) are shown. First occluded inspirations are closest to the origin and sequential occluded inspirations are upward and to right. Inspirations in deep anesthesia are characterized by ETA obstruction and lower peak integrated genioglossus EMG for a given tracheal pressure than inspirations in light anesthesia in which ETA obstruction did not occur. Note curvilinear relation of points for both light and deep anesthesia, indicating that with asphyxia, genioglossus EMG increases more than occlusion pressure. FIG.

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7. In vivo closing pressure vs. peak integrated genioglossus EMG for the animal shown in Figs. 5 and 6. Values for five occlusions in deep anesthesia (66 mg/kg pentobarbital) are shown. First occluded inspirations are closest to the origin and subsequent occluded inspirations are upward and to right. Linear regression equation is given. FIG.

INSPIRATION

FIG. 8. Abdominal movement, integrated genioglossus and geniohyoid electromyograms (EMGs) during unloaded tidal breathing in a 945-g lightly anesthetized rabbit. Abdominal movement is monitored by a bellows pneumograph. EMGs are phasic with inspiration.


778 plete within the fast occluded breath and that further decreases in tracheal pressure on subsequent occluded inspirations are completely accounted for by changes in arterial blood gas tensions (30). It has been previously shown that peak integrated phrenic electroneurogram and peak integrated inspiratory intercostal EMG are directly proportional to peak inspiratory tracheal pressure during progressive asphyxia from airway occlusion (10). The curvilinear relation between peak inspiratory tracheal pressure and peak integrated GG and GH EMGs during progressive asphyxia is therefore of considerable interest (Fig. 6). This relation suggests that asphyxia activates the airway-maintaining GG and GH muscles more than inspiratory pressure-generating muscles. Effect of anesthesia on maintenance of ETA patency and on GG and GH EMG. Airway obstruction i n anesthetized patients is well known and radiographic studies have demonstrated retrusion of the tongue against the posterior oropharyngeal wall (16,X). However, the present observations appear to be the first to demonstrate the effect of anesthesia on GG and GH EMG activity. Midinspiratory ETA closure during airway occlusion was seen in-deeply but not lightly anesthetized animals. Furthermore, the obstructed inspirations of deeply anesthetized animals were characterized by relatively less GG and GH activity for a given tracheal pressure than the unobstructed inspirations of lightly anesthetized animals (Fig. 6). In deeply anesthetized animals, the negative pressure at which the ETA closed, i.e., in vivo closing pressure, was directly proportional to peak integrated GG and GH EMGs (Fig. 7). In as much as peak inspiratory tracheal pressure correlates well with peak integrated phrenic electroneurogram (lo), these findings suggest that deep anesthesia depresses the airway-maintain-

R. T. BROUILLETTE

AND

B. T. THACH

ing GG and GH muscles more than the diaphragm and, furthermore, that peak integrated GG and GH EMGs predict the level at which the ETA will close when subjected to negative pressure in vivo. Because other muscles also appear to be involved in airway maintenance, deep anesthesia may well depress these muscles as well as the GG and GH muscles. Relevance to studies in man. The present findings indicate that the GG and GH muscles are accessory muscles of respiration that phasically increase pharyngeal rigidity thereby preventing inspiratory airway obstruction. Remmers et al. (20) have recently drawn similar conclusions from studies on “Pickwickian” patients with repetitive episodes of airway obstruction during sleep. In these patients sleep depresses GG muscle activity and promotes airway closure in a manner analogous to deep anesthesia in th .e present studies. However, in the present studies, airway closure was not observed during unloaded tidal breathing even in deeply anesthetized animals. In contrast, airway obstruction in anesthetized humans (16, 21) occurs during unloaded tidal breathing. Thus, the human ETA deprived of neuromuscular support may be even more susceptible to collapse than that of the rabbit. The authors acknowledge Drs. R. K. Deuel, P. R. Dodge, R. E. Marshall, and C. M. Rovainen for review of the manuscript and Ms. Lois Price for assistance in its preparation. This research was supported by National Institutes of Health Grant 56545A, National Institute of Child Health and Human Development Grant HD-10993-02, and a grant from The Life Seekers. R. T. Brouillette is the recipient of an American Lung Association Training Fellowship . Received

11 August

1978; accepted

in final

form

1 December

1978.

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