Modulation of laryngeal and respiratory pump muscle activities with upper airway pressure and flow.

The hypothesis that upper airway (UA) pressure and flow modulate respiratory muscle activity in a respiratory phase-specific fashion was assessed in anesthetized, tracheotomized, spontaneously breathing piglets. We generated negative pressure and inspiratory flow in phase with tracheal inspiration or positive pressure and expiratory flow in phase with tracheal expiration in the isolated UA. Stimulation of UA negative pressure receptors with body temperature air resulted in a 10--15% enhancement of phasic moving-time-averaged posterior cricoarytenoid electromyographic (EMG) activity above tonic levels obtained without pressure and flow in the UA (baseline). Stimulation of UA positive pressure receptors increased phasic moving-time-averaged thyroarytenoid EMG activity above tonic levels by 45% from baseline. The same enhancement of posterior cricoarytenoid or thyroarytenoid EMG activity was observed with the addition of flow receptor stimulation with room temperature air. Tidal volume and diaphragmatic and abdominal muscle activity were unaffected by UA flow and/or pressure, whereas respiratory timing was minimally affected. We conclude that laryngeal afferents, mainly from pressure receptors, are important in modulating the respiratory activity of laryngeal muscles.     

Stimulatory effect of CO2 on vagal bronchopulmonary C-fiber afferents during airway inflammation.

This study investigated 1) whether pulmonary C fibers are activated by a transient increase in the CO2 concentration of alveolar gas; and 2) if the CO2 sensitivity of these afferents is altered during airway inflammation. Single-unit pulmonary C-fiber activity was recorded in anesthetized, open-chest rats. Transient alveolar hypercapnia (HPC) was induced by administering a CO2-enriched gas mixture (25-30% CO2, 21% O2, balance N2) for five to eight breaths, which increased alveolar CO2 concentration progressively to near or above 13% for 3-5 s and lowered the arterial pH transiently to 7.10 +/- 0.05. Our results showed the following. 1) HPC evoked only a mild stimulation in a small fraction (4/47) of pulmonary C fibers, and there was no significant change in fiber activity (change in fiber activity = 0.22 +/- 0.16 imp/s; P > 0.1, n = 47). 2) In sharp contrast, after airway exposure to poly-L-lysine, a cationic protein known to induce mucosal injury, the same challenge of transient HPC activated 87.5% of the pulmonary C fibers tested and evoked a distinct stimulatory effect on these afferents (change in fiber activity = 6.59 +/- 1.78 imp/s; P < 0. 01, n = 8). 3) Similar potentiation of the C-fiber response to HPC was also observed after acute exposure to ozone (n = 6) and during a constant infusion of inflammatory mediators such as adenosine (n = 15) or prostaglandin E2 (n = 12). 4) The enhanced C-fiber sensitivity to CO2 after poly-L-lysine was completely abrogated by infusion of NaHCO3 (1.82 mmol.kg(-1).min(-1)) that prevented the reduction in pH during HPC (n = 6). In conclusion, only a small percentage (<10%) of the bronchopulmonary C fibers exhibit CO2 sensitivity under control conditions, but alveolar HPC exerts a consistent and pronounced stimulatory effect on the C-fiber endings during airway inflammation. This effect of CO2 is probably mediated through the action of hydrogen ions.     

Effect of upper airway negative pressure on proprioceptive afferents from the tongue.

We examined whether receptors in the tongue muscle respond to negative upper airway pressure (NUAP). In six cats, one hypoglossal nerve was cut and its distal end was prepared for single-fiber recording. Twelve afferent fibers were selected for study on the basis of their sensitivity to passive stretch (PS) of the tongue. Fiber discharge frequency was measured during PS of the tongue and after the rapid onset of constant NUAP. During PS of 1-3 cm, firing frequency increased from 17 +/- 7 to 40 +/- 11 (SE) Hz (P < 0.01). In addition, 8 of the 12 fibers responded to NUAP (-10 to -30 cmH2O), with firing frequency increasing from 23 +/- 9 to 41 +/- 9 Hz (P < 0.001). In two fibers tested, the increase in firing frequency in response to NUAP was not altered by topical anesthesia (10% lignocaine) applied liberally to the entire upper airway mucosa. Our results demonstrate that afferent discharges from the hypoglossal nerve are elicited by 1) stretching of the tongue and 2) NUAP before and after upper airway anesthesia. We speculate that activation of proprioceptive mechanoreceptors in the cat's tongue provides an additional pathway for the reflex activation of upper airway dilator muscles in response to NUAP, independent of superficially located mucosal mechanoreceptors.     

Long-term facilitation of upper airway muscle activities in vagotomized and vagally intact cats

Mateika, J. H., and R. F. Fregosi. Long-termfacilitation of upper airway muscle activities in vagotomized andvagally intact cats. J. Appl. Physiol.82(2): 419-425, 1997.The primary purpose of the presentinvestigation was to determine whether long-term facilitation (LTF) ofupper airway muscle activities occurs in vagotomized and vagally intactcats. Tidal volume and diaphragm, genioglossus, and nasal dilatormuscle activities were recorded before, during, and after one carotidsinus nerve was stimulated five times with 2-min trains of constantcurrent. Sixty minutes after stimulation, nasal dilator andgenioglossus muscle activities were significantly greater than controlin the vagotomized cats but not in the vagally intact cats. Tidalvolume recorded from the vagotomized and vagally intact cats wassignificantly greater than control during the poststimulation period.In contrast, diaphragm activities were not significantly elevated inthe poststimulation period in either group of animals. We conclude that1) LTF of genioglossus and nasaldilator muscle activities can be evoked in vagotomized cats;2) vagal mechanisms inhibit LTF inupper airway muscles; and 3) LTF canbe evoked in accessory inspiratory muscles because LTF of inspiredtidal volume was greater than LTF of diaphragm activity.

     

Vagal afferents and active upper airway closure during pulmonary edema in lambs.

The present study was undertaken to gain further insight into the mechanisms responsible for the sustained active expiratory upper airway closure previously observed during high-permeability pulmonary edema in lambs. The experiments were conducted in nonsedated lambs, in which airflow and thyroarytenoid and inferior pharyngeal constrictor muscle electromyographic activity were recorded. We first studied the consequences of hemodynamic pulmonary edema (induced by impeding pulmonary venous return) on upper airway dynamics in five lambs; under this condition, a sustained expiratory upper airway closure consistently appeared. We then tested whether expiratory upper airway closure was related to vagal afferent activity from bronchopulmonary receptors. Five bivagotomized lambs underwent high-permeability pulmonary edema: no sustained expiratory upper airway closure was observed. Finally, we studied whether a sustained decrease in lung volume induced a sustained expiratory upper airway closure. Five lambs underwent a 250-ml pleural infusion: no sustained expiratory upper airway closure was observed. We conclude that 1) the sustained expiratory upper airway closure observed during pulmonary edema in nonsedated lambs is related to stimulation of vagal afferents by an increase in lung water and 2) a decrease in lung volume does not seem to be the causal factor.     

Termination of upper limb movement by cutaneous afferents.

We tested whether cutaneous afferents from the skin field close to an upper limb muscular region would carry information to spinal neurons at the onset or at the offset of a voluntary elbow extension movement lasting 1 s. We detected a depression of EMG activity both at onset and at the offset of the reaching movement but in the latter case depression was significantly larger and immediate. The marked depression of EMG activity suggests an inhibition, via spinal neurons, of the descending excitation to the motoneurones supplying the triceps brachii. This spinal control might be a very efficient mechanism for the termination of voluntary movement.     

Superior laryngeal and hypoglossal afferents tonically influence upper airway motor excitability in anesthetized rats.

Upper airway (UA) muscle activity is stimulated by changes in UA transmural pressure and by asphyxia. These responses are reduced by muscle relaxation. We hypothesized that this is due to a change in afferent feedback in the ansa hypoglossi and/or superior laryngeal nerve (SLN). We examined 1) the glossopharyngeal motor responses to UA transmural pressure and asphyxia and 2) how these responses were changed by muscle relaxation in animals where one or both of these afferent pathways had been sectioned bilaterally. Experiments were performed in 24 anesthetized, thoracotomized, artificially ventilated rats. Baseline glossopharyngeal activity and its response to UA transmural pressure and asphyxia were moderately reduced after bilateral section of the ansa hypoglossi (P < 0.05). Conversely, bilateral SLN section increased baseline glossopharyngeal activity, augmented the response to asphyxia, and abolished the response to UA transmural pressure. Muscle relaxation reduced resting glossopharyngeal activity and the response to asphyxia (P < 0.001). This occurred whether or not the ansa hypoglossi, the SLN, or both afferent pathways had been interrupted. We conclude that ansa hypoglossi afferents tonically excite and SLN afferents tonically inhibit UA motor activity. Muscle relaxation depressed UA motor activity after section of the ansa hypoglossi and SLN. This suggests that some or all of the response to muscle relaxation is mediated by alterations in the activity of afferent fibers other than those in the ansa hypoglossi or SLN.     

Upper airway muscle activity and the thoracic volume dependence of upper airway resistance

Although a thoracic volume dependence of upper airway resistance and caliber is known to exist in seated subjects, the mechanisms mediating this phenomenon are unknown. To test the hypothesis that actively altered end-expiratory lung volume (EELV) affects upper airway resistance in the supine position and to explore the mechanisms of any EELV-induced resistance changes, we studied five normal males during wakefulness. Supraglottic upper airway resistance (Ruaw) was calculated at an inspiratory flow of 0.1 l/s. The genioglossal electromyogram was obtained with indwelling wire electrodes and processed as moving time average. End-tidal CO2 was monitored by infrared analyzer. Observations were made during four 20-breath voluntary maneuvers: two at high and two at low EELV in each subject. Each maneuver was preceded by a control period at functional residual capacity. At high lung volume the EELV was increased by 2.23 +/- 0.54 (SD) liters; Ruaw decreased to 67.8 +/- 35.1% of control, while tonic and phasic genioglossal activities declined to 79.0 +/- 23.1 and 72.4 +/- 29.8%, respectively. At low lung volume the EELV was decreased by 0.86 +/- 0.23 liters. Ruaw increased to 178.2 +/- 186.8%, while tonic and phasic genioglossal activities increased to 243.0 +/- 139.3 and 249.1 +/- 146.3%, respectively (P less than 0.0001 for all). The findings were not explained by CO2 perturbations or respiratory pattern. Multiple linear regression analysis indicated that the genioglossal responses blunted the EELV-induced changes in upper airway patency.(ABSTRACT TRUNCATED AT 250 WORDS)     

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

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

Effects of continuous positive airway pressure on upper airway and respiratory muscle activity

To study the effects of continuous positive airway pressure (CPAP) on lung volume, and upper airway and respiratory muscle activity, we quantitated the CPAP-induced changes in diaphragmatic and genioglossal electromyograms, esophageal and transdiaphragmatic pressures (Pes and Pdi), and functional residual capacity (FRC) in six normal awake subjects in the supine position. CPAP resulted in increased FRC, increased peak and rate of rise of diaphragmatic activity (EMGdi and EMGdi/TI), decreased peak genioglossal activity (EMGge), decreased inspiratory time and inspiratory duty cycle (P less than 0.001 for all comparisons). Inspiratory changes in Pes and Pdi, as well as Pes/EMGdi and Pdi/EMGdi also decreased (P less than 0.001 for all comparisons), but mean inspiratory airflow for a given Pes increased (P less than 0.001) on CPAP. The increase in mean inspiratory airflow for a given Pes despite the decrease in upper airway muscle activity suggests that CPAP mechanically splints the upper airway. The changes in EMGge and EMGdi after CPAP application most likely reflect the effects of CPAP and the associated changes in respiratory system mechanics on the afferent input from receptors distributed throughout the intact respiratory system.     

Effects of cricothyroid muscle contraction on upper airway flow dynamics in dogs.

We studied the effects of cricothyroid muscle (CT) contraction on upper airway flow dynamics in eight prone open-mouth anesthetized dogs. Animals were mechanically ventilated via a tracheostomy while a constant airflow (Vuaw) passed through the isolated upper airway. Nasal airflow (Vn) was monitored using a nasal mask and pneumotachograph. Bilateral CT contraction was induced by electrical stimulation of the external branches of the superior laryngeal nerves. During CT contraction with Vuaw of 100-443 ml/s in the inspiratory direction, total upper airway resistance (Ruaw) fell by 49.1 +/- 5.4% (SE) while supraglottic resistance fell by 63.6 +/- 3.6%; simultaneously Vn fell by 55.3 +/- 3.8% and Vuaw increased by 7.2 +/- 1.7%. Similar results were obtained when Vuaw was in the expiratory direction. In three dogs in which the attachments of the CT to either the thyroid or cricoid cartilage were severed, superior laryngeal nerve stimulation had no systematic effect on Ruaw. Because visual assessment during CT contraction consistently revealed dilation of the piriform recesses, we suggest that CT contraction is associated with pharyngeal dilation, which in open-mouth dogs (with overlapping soft palate and epiglottis) redistributes flow to the oral route with a net reduction in Ruaw. Thus the CT may have a respiratory role as a pharyngeal dilator.     

Effects of upper airway pressure on abdominal muscle activity in conscious dogs.

We have examined arousal and abdominal muscle electromyogram (EMGabd) responses to upper airway pressure stimuli during physiological sleep in four dogs with permanent side-hole tracheal stomata. The dogs were trained to sleep with a tightly fitting snout mask, hermetically sealed in place, while breathing through a cuffed endotracheal tube inserted through the tracheostomy. Sleep stage was determined by behavioral and electroencephalographic criteria. EMGabd activity was measured using bipolar fine-wire electrodes inserted into the abdominal muscle layers. Static increases or decreases in upper airway pressure (+/- 6 cmH2O), when applied at the snout mask or larynx (upper trachea), caused an immediate decrease in EMGabd on the first two to three breaths; EMGabd usually returned to control levels within the 1-min test interval. In contrast, oscillatory pressure waves at 30 Hz and +/- 3 cmH2O amplitude (or -2 to -8 cmH2O amplitude) produced an immediate and sustained reduction in IMGabd in all sleep states. Inhibition of EMGabd could be maintained over many minutes when the oscillatory pressure stimulus was pulsed by using a cycle of 0.5 s on and 0.5 s off. Oscillatory upper airway pressures were also found to be powerful arousal-promoting stimuli, producing arousal in 94% of tests in drowsiness and 66% of tests in slowwave sleep. The results demonstrate the presence of breath-by-breath upper airway control of abdominal muscle activity.     

Modulation of the masseteric reflex by gastric vagal afferents

Several investigations have shown that the vagal nerve can affect the reflex responses of the masticatory muscles acting at level either of trigeminal motoneurons or of the mesencephalic trigeminal nucleus (MTN). The present experiments have been devoted to establish the origin of the vagal afferent fibres involved in modulating the masseteric reflex. In particular, the gastric vagal afferents were taken into consideration and selective stimulations of such fibres were performed in rabbit. Conditioning electrical stimulation of truncus vagalis ventralis (TVV) reduced the excitability of the MTN cells as shown by a decrease of the antidromic response recorded from the semilunar ganglion and elicited by MTN single-shock electrical stimulation. Sympathetic and cardiovascular influences were not involved in these responses. Mechanical stimulation of gastric receptors, by means of gastric distension, clearly diminished the amplitude of twitch tension of masseteric reflex and inhibited the discharge frequency of proprioceptive MTN units. The effect was phasic and depended upon the velocity of distension. Thus the sensory volleys originating from rapid adapting receptors reach the brain stem through vagal afferents and by means of a polysynaptic connection inhibits the masseteric reflex at level of MTN cells.     

Relation between upper airway volume and hyoid muscle length

Previous studies have suggested that the geniohyoid and sternohyoid muscles act to enlarge the upper airway. If correct, there should be an inverse relation between upper airway volume and the length of hyoid muscles. To test this, known volumes of air were injected into or removed from the isolated sealed upper airway of eight pentobarbital sodium-anesthetized cats, and the resultant changes in geniohyoid and sternohyoid length were measured using sonomicrometry. Increases in upper airway volume shortened the geniohyoid in all cats (P less than 0.001) and shortened the sternohyoid in seven of eight cats (P less than 0.01); mean geniohyoid shortening (as a % of resting length) exceeded that of the sternohyoid. Decreases in upper airway volume lengthened the geniohyoid in all cats (P less than 0.001) but caused variable changes in sternohyoid length. Extension of the neck increased the resting lengths of both the geniohyoid (P less than 0.001) and sternohyoid (P less than 0.002). Neck flexion shortened the resting length of both hyoid muscles (P less than 0.001 for both), with the geniohyoid shortening more (as a % of resting length) than the sternohyoid (P less than 0.005). Progressive flexion of the neck from 180 to 90 degrees caused progressive increases in the ratio of changes in muscle length to changes in upper airway volume during airway inflation but did not affect this relation during airway deflation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Upper airway muscle paralysis reduces reflex upper airway motor response to negative transmural pressure in rat.

The reflex upper airway (UA) motor response to UA negative pressure (UANP) is attenuated by neuromuscular blockade. We hypothesized that this is due to a reduction in the sensitivity of laryngeal mechanoreceptors to changes in UA pressure. We examined the effect of neuromuscular blockade on hypoglossal motor responses to UANP and to asphyxia in 15 anesthetized, thoracotomized, artificially ventilated rats. The activity of laryngeal mechanoreceptors is influenced by contractions of laryngeal and tongue muscles, so we studied the effect of selective denervation of these muscle groups on the UA motor response to UANP and to asphyxia, recording from the pharyngeal branch of the glossopharyngeal nerve (n = 11). We also examined the effect of tongue and laryngeal muscle denervation on superior laryngeal nerve (SLN) afferent activity at different airway transmural pressures (n = 6). Neuromuscular blockade and denervation of laryngeal and tongue muscles significantly reduced baseline UA motor nerve activity (P < 0.05), caused a small but significant attenuation of the motor response to asphyxia, and markedly attenuated the response to UANP. Motor denervation of tongue and laryngeal muscles significantly decreased SLN afferent activity and altered the response to UANP. We conclude that skeletal muscle relaxation reduces the reflex UA motor response to UANP, and this may be due to a reduction in the excitability of UA motor systems as well as a decrease of the response of SLN afferents to UANP.     

Soft palate muscle responses to negative upper airway pressure

The afferentpathways and upper airway receptor locations involved in negative upperairway pressure (NUAP) augmentation of soft palate muscle activity havenot been defined. We studied the electromyographic (EMG) response toNUAP for the palatinus, tensor veli palatini, and levator veli palatinimuscles in 11 adult, supine, tracheostomized, anesthetized dogs. NUAPwas applied to the nasal or laryngeal end of the isolated upper airwayin six dogs and to four to six serial upper airway sites from the nasalcavity to the subglottis in five dogs. When NUAP was applied at thelarynx, peak inspiratory EMG activity for the palatinus and tensorincreased significantly (P < 0.05) and plateaued at a NUAP of 10cmH₂O. Laryngeal NUAP failed toincrease levator activity consistently. Nasal NUAP did not increase EMGactivity for any muscle. Consistent NUAP reflex recruitment of softpalate muscle activity only occurred when the larynx was exposed to the stimulus and, furthermore, was abolished by bilateral section of theinternal branches of the superior laryngeal nerves. We conclude thatsoft palate muscle activity may be selectively modulated by afferentactivity originating in the laryngeal and hypopharyngeal airway.     

Upper airway muscle activity and upper airway resistance in young adults during sleep

Henke, Kathe G. Upper airway muscle activity and upperairway resistance in young adults during sleep. J. Appl. Physiol. 84(2): 486-491, 1998.To determinethe relationship between upper airway muscle activity and upper airwayresistance in nonsnoring and snoring young adults, 17 subjects werestudied during sleep. Genioglossus and alae nasi electromyogramactivity were recorded. Inspiratory and expiratory supraglotticresistance (Rinsp and Rexp, respectively) were measured at peak flow,and the coefficients of resistance(K_insp andK_exp,respectively) were calculated. Data were recorded during control,with continuous positive airway pressure (CPAP), and on the breathimmediately after termination of CPAP. Rinsp during control averaged 7 ± 1 and 10 ± 2 cmH₂O · l¹ · sand K_inspaveraged 26 ± 5 and 80 ± 27 cmH₂O · l¹ · s²in the nonsnorers and snorers, respectively(P = not significant). Onthe breath immediately after CPAP,K_insp did notincrease over control in snorers (80 ± 27 for control vs. 46 ± 6 cmH₂O · l¹ · s²for the breath after CPAP) or nonsnorers (26 ± 5 vs. 29 ± 6 cmH₂O · l¹ · s²).These findings held true for Rinsp.K_exp did notincrease in either group on the breath immediately after termination ofCPAP. Therefore, 1) increases inupper airway resistance do not occur, despite reductions inelectromyogram activity in young snorers and nonsnorers, and2) increases in Rexp and expiratoryflow limitation are not observed in young snorers.

     

Modulation by corticospinal volleys of presynaptic inhibition to Ia afferents in man.

New methods have been recently developed to explore selectively presynaptic inhibition of Ia afferents in humans. They have allowed us to describe a highly specialized organisation in these pathways. A differential control has been disclosed during voluntary movements among various motoneuronal pools: at the onset of a selective voluntary contraction presynaptic inhibition of Ia afferents projecting to the 'contracting' motoneurons is strongly decreased whereas presynaptic inhibition of Ia afferents to antagonistic or synergistic motoneuronal pools, not involved in the contraction, is increased. Indirect arguments suggested that these modulations are centrally patterned. A differential control has been also disclosed between upper and lower limb pathways. Using transcranial magnetic stimulation to induce a descending corticospinal volley, we have shown that a corticospinal volley inhibits preferentially 'presynaptic interneurons'at the lumbar spinal level, an effect which is strengthened by a cutaneous input whereas it preferentially activates 'presynaptic interneurons' at the cervical spinal level, an effect which is inverted by a cutaneous input.