Influence of airway pressure on genioglossus activity during sleep in normal children

RATIONALE: Most children with obstructive sleep apnea are able to sustain stable breathing during portions of sleep, despite an anatomic predisposition toward airway collapse. This suggests that additional determinants of airway patency are active, such as neuromuscular compensation. OBJECTIVES/METHODS: Using a custom intraoral surface electrode to record pharyngeal dilator muscle activity (the genioglossus [EMGgg]), we evaluated the muscle, ventilatory, and arousal responses to negative-pressure challenges during sleep in 19 healthy control children. MEASUREMENTS AND MAIN RESULTS: In response to these challenges, we observed (1) marked variability in individual EMGgg responsiveness (peak EMGgg [mean+/-SD], 214+/-101% baseline), which was consistent within subjects; (2) a relationship between EMGgg activity and inspiratory flow and airway collapsibility; (3) reflex increases in flow (peak flow increase from challenge breaths 1-5 [mean+/-SD], 49+/-41% baseline) and respiratory rate often sufficient to sustain minute ventilation near baseline levels, without arousal; and (4) arousal threshold to be highest in stage 4, intermediate in stage 2, and lowest in REM sleep. CONCLUSIONS: Healthy children have wide variation in upper airway neuromuscular compensatory responses and arousal thresholds that could represent intermediate phenotypes affecting the expression of sleep apnea. Children with robust upper airway neuromuscular responsiveness, or a very high arousal threshold, may be able to sustain minute ventilation when challenged with negative airway pressure.     

Role of airway mechanoreceptors in the inhibition of inspiration during mechanical ventilation in humans

The purpose of this study was to demonstrate a neuromechanical inhibitory effect on respiratory muscle activity during mechanical ventilation and to determine whether upper and lower airway receptors provide this inhibitory feedback. Several protocols were completed during mechanical ventilation: (1) positive and negative pressure changes in the upper airway, (2) airway anesthesia to examine the consequences of receptor blockade on respiratory muscle activity, (3) increasing FRC with positive end-expiratory pressure to study the effect of hyperinflation or stretch on respiratory muscle activity, and (4) use of heart-lung transplant patients to determine the effects of vagal denervation on respiratory muscle activity. All subjects were mechanically hyperventilated with positive pressure until inspiratory muscle activity was undetectable and the end-tidal PCO2 decreased to less than 30 mm Hg. End-tidal PCO2 (PETCO2) was increased by either adding CO2 to the inspired gas or decreasing tidal volume (50 ml/min). The PETCO2 where a change in inspiratory muscle activity occurred was taken as the recruitment threshold (PCO2RT). Neuromechanical feedback caused significant inspiratory muscle inhibition during mechanical ventilation, as evidenced by the difference between PCO2RT and PETCO2 during spontaneous eupnea (45 +/- 4 versus 39 +/- 4 mm Hg) and a lower PCO2RT when tidal volume was reduced with a constant frequency and fraction of inspired CO2. Recruitment threshold was unchanged during positive and negative pressure ventilation, during upper and lower airway anesthesia, and in vagally denervated lung transplant patients. These findings demonstrate that neuromechanical feedback causes highly significant inhibition of inspiratory muscle activity during mechanical ventilation; upper and lower airway receptors do not appear to mediate this effect.     

Local mechanisms drive genioglossus activation in obstructive sleep apnea

Individuals with obstructive sleep apnea (OSA) require increased pharyngeal muscle dilator activation during wakefulness to maintain upper airway patency. Negative pressure is one potential stimulus for this neuromuscular compensation. Individuals with OSA who have previously undergone tracheostomy provide an opportunity to study upper airway physiology in both the presence and absence of upper airway respiratory stimuli. If negative pressure (or another local airway stimulus) were important in driving pharyngeal dilator muscle activation, one would predict that during nasal breathing, the pharynx of a tracheostomized patient would be exposed to negative pressure, and that high levels of muscle activation would therefore be measured. Conversely, during breathing by the patient through the tracheal stoma, one would expect low levels of muscle activation in the absence of local stimuli. We measured a number of respiratory variables, including genioglossus activation under both nasal and tracheal stomal breathing conditions, in five patients. In all five patients there was a significant and substantial decrease in both peak phasic (100 +/- 0 to 53.4 +/- 9.2 arbitrary units [mean +/- SEM], p < 0.01) and tonic genioglossus activation (36.3 +/- 5.3 to 20.7 +/- 3.9 arbitrary units, p < 0.05) during stomal breathing as compared with nasal breathing. We conclude that local upper airway respiratory stimuli, possibly negative pressure, are important in mediating the increased pharyngeal dilator muscle activation seen in sleep apnea patients during wakefulness.     

Methacholine-induced volume dependence of respiratory resistance in preschool children.

Enhanced negative volume dependence of airway resistance is associated with bronchoconstriction in tracheostomized paralysed open-chest animals. Significant upper airways responses may be associated with bronchoconstriction and could thereby alter the pattern of volume dependence in spontaneously breathing subjects. The aim of the study was to test whether volume dependence of respiratory resistance (Rrs) could be demonstrated in preschool children undergoing routine methacholine challenge. The volume dependence of respiratory oscillation resistance at 12 and 20 Hz (Rrs,12 and Rrs,20) was examined in eight 4-5.5-yr-old children showing a positive response to methacholine. Multiple linear regression analysis was also used to account for flow dependence during tidal breathing (Rrs,12 or Rrs,20=K1+K2?V'?+K3V). Rrs,12 and Rrs,20 yielded similar results. Negative volume dependence was present at baseline and significantly enhanced by methacholine (p<0.01). For instance, the mean+/-SD inspiratory K3 at 20 Hz was 4.1+/-1.3 hPa x s x L(-2) at baseline and -15.0+/-4.3 hPa x s x L(-2) after methacholine, in which case it was also larger on expiration than on inspiration (p<0.05), possibly as a result of upper airway responses. A significant increase in the negative volume dependence of respiratory resistance may thus be shown in preschool children in response to methacholine. The volume dependence (K3) during inspiration may be particularly useful in detecting bronchoconstriction, because it is less likely to be affected by upper airway mechanisms than during expiration.     

Changes in inspiratory muscle electrical activity and upper airway resistance during periodic breathing induced by hypoxia during sleep

We hypothesized that: the balance of electrical activities between the upper airway and chest wall inspiratory muscles affects upper airway inspiratory caliber, and at low levels of central respiratory neural efferent activity, an imbalance between the electrical activities of these 2 inspiratory muscle groups exists that results in a decreased upper airway caliber. These hypotheses were tested during periodic breathing induced by mild hypoxemia in NREM sleep in 9 healthy male subjects. In 6 subjects during periodic breathing as central respiratory neural activity decreased, the tonic and phasic EMG activity of the upper airway inspiratory muscles decreased at a rate greater than that of the chest wall EMG activity. When the ratio of upper airway to chest wall EMG activity decreased below a critical level, which was reproducible across subjects, upper airway inspiratory resistance increased hyperbolically. Resistance at peak inspiratory flow increased from 4.10 +/- 0.97 (mean +/- SEM) to 48.70 +/- 21.00 cmH2O/L/s as tidal volume decreased from 0.79 +/- 0.12 to 0.20 +/- 0.02 L during periodic breathing in these subjects. In the 3 remaining subjects, the ratio of the upper airway to chest wall EMG activity did not decrease below the critical level as the activity of both muscle groups decreased during periodic breathing, and upper airway resistance did not increase. We conclude that within the confines of this study the nonlinear activation of upper airway and chest wall inspiratory muscles contributed to fluctuations in upper airway resistance observed during periodic breathing in sleep.(ABSTRACT TRUNCATED AT 250 WORDS)     

Randomized controlled trial of fluticasone in preschool children with intermittent wheeze

Previous studies have suggested that during non-rapid eye movement (NREM) sleep, neither large short-duration resistive loads nor sustained normoxic hypercapnia alone leads to increased genioglossus muscle activation. However, in normal individuals during stable NREM sleep, genioglossus activity rises above baseline as PCO2 rises and airway resistance increases. We therefore hypothesized that combinations of chemical (PCO2, PO2) and mechanical stimuli during NREM sleep would lead to increased genioglossal activation. We studied 15 normal subjects (9 males, 6 females) during stable NREM sleep, measuring genioglossus electromyogram, epiglottic/choanal pressure, and airflow under six conditions: (1) baseline, (2) inspiratory resistive loading (-5 to -15 cm H2O/ L/second), (3) increased PCO2 (5-10 mm Hg above baseline), (4) combined resistive loading and increased PCO2, (5 ) hypoxia (SaO2 80-85%), and (6 ) combined hypoxia/inspiratory resistive loading. Only the combined condition of hypercapnia and resistive loading led to significantly increased genioglossal activation, 3.91 +/- 0.77% to 9.64 +/- 1.96% of maximum. These data suggest that the genioglossus muscle is less responsive to either chemical stimuli (hypercapnia, hypoxia) or inspiratory resistive loading alone during NREM sleep at the degrees tested. When hypercapnia is combined with resistive loading, the muscle does respond. However, the possibility that higher levels of PCO2 or greater resistive loading alone could activate the muscle cannot be excluded.     

Electric stimulation of the upper airway muscle

In various studies, it has been postulated that pharyngeal collapse occurring during sleep in obstructive sleep apnea may be alleviated by stimulating the genioglossus muscle. Basic experiments have demonstrated that neuromuscular stimulation applied intraorally via electrodes or by direct neural stimulation of the hypoglossal nerve might improve upper airway and respiratory function. An increase of maximal inspiratory airflow, an improvement of upper airway collapsibility and a decrease in respiratory events during sleep were observed. An impairment of sleep quality during electric stimulation has been excluded simultaneously. Considering clinical aspects, anatomical properties and long-term experience in electric stimulation it might be possible to develop full implantable devices as an alternative treatment for patients with obstructive sleep apnea.     

Fade of pulmonary function during residual neuromuscular blockade

OBJECTIVES: A decrement in evoked muscle force with repetitive nerve stimulation (fade) suggests impaired neuromuscular transmission. We tested the hypothesis that fade of pulmonary function, ie, a decrease in values of FVC with the second spirometric maneuver compared to the first maneuver, occurs during impaired neuromuscular transmission. DESIGN: Prospective study. PARTICIPANTS: Six healthy male volunteers. INTERVENTIONS: A series of three consecutive spirometric maneuvers was performed every 5 min in six awake healthy volunteers before, during, and after partial paralysis evoked by rocuronium (0.01 mg/kg IV plus 2 to 8 microg/kg/min). MEASUREMENTS AND RESULTS: We measured FVC, FEV(1), forced inspiratory volume in 1 s (FIV(1)), peak expiratory flow (PEF), and peak inspiratory flow (PIF) by spirometry, and force of adductor pollicis muscle by mechanomyography (train-of-four [TOF] stimulation). A statistically significant fade (reduction of the second maneuver from the first maneuver) of FVC, FEV(1), FIV(1), PEF, and PIF was observed during neuromuscular blockade. With peak relaxation (TOF ratio, 0.5) fade amounted to medians of 10% (interquartile range [IQR], 9 to 23%), 7% (IQR, 2 to 16%), 31 (IQR, 19 to 47%), 9% (IQR, 3 to 24%), and 30% (IQR, 5 to 43%), respectively. A fade of >or= 10% was always associated with a clinically relevant (>or= 10%) FVC reduction from baseline (ie, FVC before rocuronium administration). However, FVC reduction from baseline was still present in 23% of measurements without a relevant FVC fade. CONCLUSIONS: A clinically relevant fall (fade) in FVC from the first to the second value during or after neuromuscular blockade suggests impaired pulmonary function and may be due to muscle paralysis. For this reason, the first (best) FVC value may overestimate pulmonary function and expose the patient to an unidentified risk.     

Influence of negative pressure applied to the upper airway on the breathing pattern in unanesthetized awake dogs

We examined the influence of changes in upper airway pressure on the breathing pattern in 5 unanesthetized awake dogs. The dogs breathed through an endotracheal tube or through a comfortably fitting fiberglass snout mask. With matched resistances and volume of the dead space, the inspiratory duration, tidal volume, and minute ventilation were higher during nasal breathing compared to tracheal breathing. Nasal and tracheal occlusion produced prolongation of inspiration in the first occluded breathing attempt, but the prolongation was more marked in nasal occlusion tests. Augmentation of genioglossus muscle activity occurred on the first occluded breath in nasal but not tracheal occlusion. In another series of experiments, negative pressure was applied to the isolated upper airway while the dog breathed through a tracheostomy tube. Negative pressure caused a prolongation of inspiratory duration which was proportional to the level of the applied pressure. However, the prolongation of inspiratory duration was significantly more marked when application of negative pressure was timed simultaneously with tracheal occlusion. Our results demonstrate that the upper airway has a powerful effect on the control of breathing, which becomes more evident during tracheal occlusion.     

Changes in upper airway size during tidal breathing in children with obstructive sleep apnea syndrome

We performed respiratory-gated magnetic resonance imaging to evaluate airway dynamics during tidal breathing in 10 children with obstructive sleep apnea syndrome (OSAS; age, 4.3 +/- 2.3 years) and 10 matched control subjects (age, 5.0 +/- 2.0 years). We hypothesized that respiratory cycle fluctuations in upper airway cross-sectional area would be larger in children with OSAS. METHODS: Studies were performed under sedation. Respiratory gating was performed automatically at 10, 30, 50, 70, and 90% of inspiratory and expiratory volume. Airway cross-sectional area was measured at four ascending oropharyngeal levels at each increment of the respiratory cycle. RESULTS: We noted the following in subjects with OSAS compared with control subjects: (1) a smaller upper airway cross-sectional area, particularly during inspiration; (2) airway narrowing occurred during inspiration without evidence of complete airway collapse; (3) airway dilatation occurred during expiration, particularly early in the phase; and (4) magnitude of cross-sectional areas fluctuations during tidal breathing noted in OSAS at levels 1 through 4 were 317, 422, 785, and 922%, compared with 19, 15 17, and 24% in control subjects (p < 0.001, p < 0.005, p < 0.001, and p < 0.001, respectively). CONCLUSIONS: Fluctuations in airway area during tidal breathing are significantly greater in subjects with OSAS compared with control subjects. Resistive pressure loading is a probable explanation, although increased airway compliance may be a contributing factor.     

Respiratory responses to changes in airflow resistance in conscious man.

The time course and magnitude of adjustments in respiratory activity during the application and following the removal of inspiratory resistive loads were determined in conscious men. Changes in airflow resistance were made periodically during rebreathing of a gas mixture of carbon dioxide and oxygen. Ventilation, the ratio of tidal volume to inspiratory duration and the mouth pressure during airway occlusion, 100 ms after the onset of inspiration were used as measures of inspiratory neuromuscular activity. The occlusion pressure was measured during each breath using an electrically activated solenoid shutter which obstructed the airway for only the first 100 ms of each inspiration. During the second breath following the application of the resistive load, there was an increase in inspiratory output which occurred independently of changes in PCO2 and PO2. Further increases in inspiratory activity during successive loaded breaths, however, were due exclusively to changing chemical drive. The level of inspiratory neuromuscular activity remained elevated for a single breath following removal of the added resistance. Adjustments in respiratory activity were greater the more severe the load. The results suggest that non-chemically mediated respiratory compensation in conscious individuals develops rapidly and is important in maintaining ventilation when breathing is encumbered.     

Reversibility of airflow obstruction by hypoglossus nerve stimulation in anesthetized rabbits

RATIONALE: Anesthesia-induced uncoupling of upper airway dilating and inspiratory pump muscles activation may cause inspiratory flow limitation, thereby mimicking obstructive sleep apnea/hypopnea. OBJECTIVES: Determine whether inspiratory flow limitation occurs in spontaneously breathing anesthetized rabbits and whether this can be reversed by direct hypoglossal nerve stimulation and by the application of continuous positive airway pressure. METHODS: Ten New Zealand White rabbits were anesthetized, instrumented, and studied supine while breathing spontaneously at ambient pressure or during the application of positive or negative airway pressure. Under each of these conditions, the effect of unilateral or bilateral hypoglossal nerve stimulation was investigated. MEASUREMENTS: Inspiratory flow and tidal volume were measured together with esophageal pressure and the electromyographic activity of diaphragm, alae nasi, and genioglossus muscles. MAIN RESULTS: Anesthesia caused a marked increase in inspiratory resistance, snoring, and in eight rabbits, inspiratory flow limitation. Hypoglossus nerve stimulation was as effective as continuous positive airway pressure in reversing inspiratory flow limitation and snoring. Its effectiveness increased progressively as airway opening pressure was lowered, reached a maximum at -5 cm H2O, but declined markedly at lower pressures. With negative airway opening pressure, airway collapse eventually occurred during inspiration that could be prevented by hypoglossus nerve stimulation. The recruitment characteristics of hypoglossus nerve fibers was steep, and significant upper airway dilating effects already obtained with stimulus intensities 36 to 60% of maximum. CONCLUSION: This study supports hypoglossus nerve stimulation as a treatment option for obstructive sleep apnea.     

Transmission fatigue of the rabbit diaphragm

This study evaluates the role of transmission fatigue of the diaphragm in rabbits subjected to inspiratory resistive loading (IRL) sufficiently severe to increase peak tidal airway pressure to about 50% of that elicited by 100 Hz phrenic nerve stimulation. After 58 +/- 14 min of IRL, the transdiaphragmatic pressure (Pdi) responses to phrenic nerve stimulation at 20, 60, and 100 Hz were reduced by approximately one third. In contrast, IRL induced no significant change in the response to direct diaphragm stimulation (in the presence of transient neuromuscular blockade). Although respiratory acidosis occurred during IRL (pH 7.04 +/- 0.04, PCO2 90 +/- 10, PO2 131 +/- 38), it was not sufficient to explain the reduced contractility. In a separate series of experiments, the diaphragm compound action potential elicited by unilateral phrenic nerve stimuli was recorded by implanted diaphragm electrodes and the Pdi elicited by contralateral phrenic nerve stimulation at 100 Hz was measured. Both action potential amplitude and Pdi declined during IRL and both improved after 10 min of recovery. These findings demonstrate that transmission fatigue plays a major role in rabbit diaphragm fatigue induced by spontaneous breathing against inspiratory resistance.     

The effects of breath-holds and Muller manoeuvres on upper airway carbon dioxide concentration in humans

BACKGROUND: Obstructive sleep apnoea is caused by collapse of the upper airway. The presence of CO(2) in the upper airway lumen evokes a number of reflexes which favour upper airway re-opening, and we have proposed previously that CO(2) would build up in the upper airway following airway collapse and that this would contribute to reflex airway re-opening. However, it is not known if CO(2) can transfer from the alveoli to the anatomical dead space of the upper airway during apnoea. OBJECTIVES: To determine if alveolar CO(2) can enter the upper airway during breath-holds and Muller manoeuvres. MATERIAL AND METHODS: With local ethics committee approval, 6 male volunteers (aged 22-48 years), following a quiet inspiration, carried out breath-holds and Muller manoeuvres until breaking point. CO(2) was measured continuously in samples obtained from the hypopharynx using an infrared analyser with a sample rate of 50 ml/min. Muller manoeuvres (forced inspirations against a closed upper airway) mimic the respiratory efforts which occur during obstructive apnoeas. RESULTS: In all cases, CO(2) increased progressively during apnoeas. There was a much larger increase in Muller manoeuvres (3.78 +/- 0.51%, mean +/- SEM at breaking point) compared to breath-holds. DISCUSSION: These results show that upper airway CO(2) concentration rises substantially during apnoeas and suggest that transfer of CO(2) from the lungs to the upper airway may evoke a number of reflex effects which could affect breathing and upper airway re-opening during obstructive apnoeas.     

Airway pressures during crying: an index of respiratory muscle strength in infants with neuromuscular disease

The purpose of this study was to assess the strength of the respiratory muscles in 12 infants with neuromuscular disease (age range: 0.17-2.08 years) by measuring the maximal inspiratory and expiratory airway pressures (Pimax and PEmax) during crying efforts. Infants were divided into two groups according to their respiratory history. Group A included six infants in stable condition without clinical evidence of respiratory abnormalities, and Group B included six infants with severe generalized muscle weakness and previous respiratory failure. The infants in Group B had been weaned from mechanical ventilation 6 to 14 days before being studied. For infants of Group A, Pimax and PEmax values were 77 +/- 28 cmH2O and 62 +/- 18 cmH2O, respectively; for infants of Group B, they were 38 +/- 8 cmH2O and 34 +/- 8 cmH2O, respectively. A positive correlation was found between PEmax and body mass percentile. No infant had hypercapnia at the time of the study, and Pao2 values in infants of Group B were significantly lower than those of Group A. These results suggest that measurements of airway pressures during crying may provide an index of respiratory muscle strength in infants with generalized muscle weakness.     

Upper airway resistance during progressive hypercapnia and progressive hypoxia in normal awake subjects

Ventilatory motor output is known to influence the upper airway. Although inspiratory upper airway resistance decreases during progressive hypoxia or hypercapnia, the effects of hypoxia and hypercapnia on expiratory upper airway resistance remain unknown. In the present study, we attempted to examine whether the expiratory and the inspiratory upper airway resistances were modified in the same way by progressive hyperoxic hypercapnia or by progressive normocapnic hypoxia. Nine healthy subjects (five males, four females, 33+/-9 years) participated in the study. Inspiratory upper airway (iUAR) and expiratory upper airway resistances (eUAR) were calculated at flow 300 ml x s(-1). Both resistances were obtained during a baseline period and during progressive hyperoxic hypercapnia or progressive normocapnic hypoxia. In all subjects, iUAR and eUAR decreased significantly during hypercapnic or hypoxic challenge (P<0.05). eUAR was always lower than iUAR during hypercapnic challenge (P<0.0001) and during hypoxic challenge (P<0.0001). The authors conclude that expiratory upper airway resistance, as with inspiratory resistance, decreases during progressive hypercapnia or during progressive hypoxia. Pharyngeal dilator or constrictor muscle activities may be implicated.     

Influence of respiratory behavior on ventilation,respiratory work and intrinsic PEEP during noninvasive nasal pressure support ventilation in normal subjects

BACKGROUND: In clinical practice, patients have different inspiratory behaviors during noninvasive pressure support ventilation (PSV): some breathe quietly, others actively help PSV by an additional effort, and others even resist the inspiratory pressure of PSV. OBJECTIVE: What is the influence of patient collaboration (inspiratory behavior) on the efficiency of PSV? METHODS: We ventilated 10 normal subjects with nasal PSV (inspiratory/expiratory: 10/0 and 15/5 cm H(2)O) and measured their flow and volume with a pneumotachograph and their esophageal and gastric pressures during three different respiratory voluntary behaviors: relaxed inspiration, active inspiratory work and resisted inspiration. RESULTS: When compared with relaxed inspiration with 10/0 cm H(2)O PSV: (1) an active inspiratory effort increased tidal volume (from 789 +/- 356 to 1,046 +/- 586 ml; p = 0.006), minute ventilation (from 10.40 +/- 4.45 to 15.77 +/- 7.69 liters/min; p < 0.001), transdiaphragmatic work per cycle (from 0.55 +/- 0.33 to 1.72 +/- 1.40 J/cycle; p = 0.002) and inspiratory work per cycle (from 0.14 +/- 0.20 to 1.26 +/- 1.01 J/cycle; p = 0.003); intrinsic positive end-expiratory pressure (PEEP(i)) increased from 1.23 +/- 1.02 to 3.17 +/- 2.30 cm H(2)O; p = 0.002); (2) a resisted inspiration decreased tidal volume (to 457 +/- 230 ml; p = 0.007), minute ventilation (to 6.93 +/- 3.04 liters/min; p = 0.028) along with a decrease in transdiaphragmatic work but no change in PEEP(i). Data obtained during a bilevel PSV of 15/5 cm H(2)O were similar to those obtained with the 10/0 cm H(2)O settings. CONCLUSIONS: Active inspiratory effort increases ventilation during PSV at the expense of an increased breathing work and PEEP(i). Resisted inspiration inversely decreases inspiratory work and ventilation with no air trapping. These differences between inspiratory behaviors could affect the expected beneficial effects of PSV in acutely ill patients.     

Determinants of respiratory muscle weakness in stable chronic neuromuscular disorders

In neuromuscular disease, the precise relationship between general and respiratory muscle weakness is at present unclear. That relationship and the influence on respiratory muscle strength of such factors as type and duration of neuromuscular disease, distribution of general muscle weakness, and nutritional status were studied in 30 patients with stable chronic neuromuscular disease not presenting with respiratory symptoms. The degree of general muscle weakness was assessed by clinical examination of the strength of 17 muscle groups, yielding a general muscle strength index. The degree of respiratory muscle weakness was assessed by measuring maximal static inspiratory and expiratory mouth pressures. Maximal inspiratory (mean +/- SD: 68 +/- 28 percent predicted) and expiratory (66 +/- 29 percent predicted) mouth pressures were frequently reduced, but did not correlate with general muscle strength. The ability to estimate the degree of respiratory muscle weakness improved to some extent when the type of neuromuscular disease and the distribution of general muscle weakness were taken into account: thus, maximal expiratory mouth pressure was significantly lower (p less than 0.05) in myopathy than in polyneuropathy, and in proximal than in distal muscle weakness. Duration of neuromuscular disease and nutritional status did not influence respiratory muscle strength. It is concluded that in stable chronic neuromuscular disease, respiratory muscle involvement depends on a complexity of factors, in particular the type of neuromuscular disease and the distribution, rather than the degree, of general muscle weakness. In the individual patient, however, only direct measurement of maximal inspiratory and expiratory mouth pressures allows accurate assessment of respiratory muscle strength. These tests ought to complement neurologic examination.     

Respiratory activity in the superior laryngeal nerve of the rabbit

We studied the respiratory modulation of laryngeal afferents and their response to transmural pressure in 24 anesthetized, spontaneously breathing rabbits. Laryngeal afferent activity has a predominant inspiratory augmentation during tracheal breathing or tracheal occlusion that can be accounted for by the respiratory movement transmitted to the larynx through the trachea. During upper airway breathing or upper airway occlusion SLN afferent activity increases in expiration and decreases in inspiration. This respiratory modulation is due to changes in upper airway pressure (Pua). In fact, positive pressure stimulates SLN afferent activity, while negative pressure inhibits it. Mechanical restriction of epiglottal movement reduced the response to Pua changes during upper airway occlusion and application of maintained positive (0.1-0.5 kPa) and negative (-0.1 to -0.5 kPa) pressures (P less than 0.005). Furthermore, surgical removal of epiglottis decreased the baseline activity of SLN to 16.5% of control. These experiments suggest that in the rabbit the epiglottis is the main source of SLN afferent activity and that its displacement, due to changes in Pua, is the most important factor for modulating SLN activity. Most of the laryngeal receptors showed an inspiratory augmentation with tracheal breathing and occlusion, were stimulated by positive pressure and inhibited by negative pressure, reflecting the behavior observed in the whole nerve.     

Effect of salicylate on upper airway dilating muscles in anesthetized dogs

It is well documented that salicylate given in large doses stimulates ventilation. As increased ventilatory drive is often associated with augmented upper airway dilating muscle activity, we evaluated in anesthetized dogs the effect of salicylate on the electrical activity of three upper airway muscles, the alae nasi, the genioglossus, and the posterior cricoarytenoid. The electromyograms of these muscles were compared with those of the diaphragm before and at 15-min intervals after intravenous salicylate administration (250 mg/kg). Salicylate induced a gradual increase in ventilation and in the electrical activity of all muscles examined (p less than 0.001). Compared to baseline activity, salicylate increased the electrical activity of the genioglossus more than that of the diaphragm (p less than 0.01). The increase in upper airway muscle activity was observed also in vagotomized dogs, and was not accounted for by changes in arterial blood gases or pH. Increases in upper airway muscle electrical activity were associated with a significant decrease in upper airway resistance to airflow (mean reduction of 62 +/- 7% SE, p less than 0.01). The preferential increase in genioglossus electrical activity and the decrease in upper airway resistance observed in this study with salicylate suggest that salicylate, and possibly other pharmacologic agents that stimulate ventilation, may improve upper airway patency.