Upper airway response to electrical stimulation of the genioglossus in obstructive sleep apnea.

Contraction of the genioglossus (GG) has been shown to improve upper airway patency. In the present study, we evaluated responses in upper airway pressure-flow relationships during sleep to electrical stimulation (ES) of the GG in patients with obstructive sleep apnea. Five patients with chronically implanted hypoglossal nerve (HG) electrodes and nine patients with fine-wire electrodes inserted into the GG were studied. Airflow was measured at multiple levels of nasal pressure, and upper airway collapsibility was defined by the nasal pressure below which airflow ceased ["critical" pressure (Pcrit)]. ES shifted the pressure-flow relationships toward higher flow levels in all patients over the entire range of nasal pressure applied. Pcrit decreased similarly during both HG-ES and GG-ES (deltaPcrit was 3.98 +/- 2.31 and 3.18 +/- 1.70 cmH2O, respectively) without a significant change in upstream resistance. The site of collapse (velo- vs. oropharynx) did not influence the response to GG-ES. Moreover, ES-induced reductions in the apnea-hypopnea index of the HG-ES patients were associated with substantial decreases in Pcrit. Our findings imply that responses in apnea severity to HG-ES can be predicted by characterizing the patient's baseline pressure-flow relationships and response to GG-ES.     

Effect of age and weight on upper airway function in a mouse model

Defects in pharyngeal mechanical and neuromuscular control are required for the development of obstructive sleep apnea. Obesity and age are known sleep apnea risk factors, leading us to hypothesize that specific defects in upper airway neuromechanical control are associated with weight and age in a mouse model. In anesthetized, spontaneously breathing young and old wild-type C57BL/6J mice, genioglossus electromyographic activity (EMG(GG)) was monitored and upper airway pressure-flow dynamics were characterized during ramp decreases in nasal pressure (Pn, cmH?O). Specific body weights were targeted by controlling caloric intake. The passive critical pressure (Pcrit) was derived from pressure-flow relationships during expiration. The Pn threshold at which inspiratory flow limitation (IFL) developed and tonic and phasic EMG(GG) activity during IFL were quantified to assess the phasic modulation of pharyngeal patency. The passive Pcrit increased progressively with increasing body weight and increased more in the old than young mice. Tonic EMG(GG) decreased and phasic EMG(GG) increased significantly with obesity. During ramp decreases in Pn, IFL developed at a higher (less negative) Pn threshold in the obese than lean mice, although the frequency of IFL decreased with age and weight. The findings suggest that weight imposes mechanical loads on the upper airway that are greater in the old than young mice. The susceptibility to upper airway obstruction increases with age and weight as tonic neuromuscular activity falls. IFL can elicit phasic responses in normal mice that mitigate or eliminate the obstruction altogether.     

Effect of positive nasal pressure on upper airway pressure-flow relationships

To determine the influence of changes in nasal pressure (Pn) on airflow mechanics in the upper airway, we examined the effect of elevations in Pn on upper airway resistance and critical pressure (Pcrit) during stage I/II sleep in six patients with obstructive sleep apnea. When Pn was elevated above a Pcrit, periodic occlusions of the upper airway were eliminated and inspiratory airflow limitation was demonstrated by the finding that inspiratory airflow (VI) became maximal (VImax) and independent of fluctuations in hypopharyngeal pressure (Php) when Php fell below a specific Php (Php'). As Pn was elevated, VI vs. Php demonstrated 1) marked decreases in early and late inspiratory resistances from 75.9 +/- 34.7 and 54.6 +/- 19.0 to 8.0 +/- 1.7 and 7.6 +/- 1.6 cmH2O.l-1.s (P less than 0.05), respectively, and 2) increases in early and late inspiratory Php' to levels that exceeded Pcrit by 3.0 +/- 0.6 and 3.1 +/- 0.7 cmH2O, respectively, at the highest level of Pn applied (P less than 0.01). This latter finding suggests that elevations in Pn result in increases in Pcrit. We suggest that elevations in Pn produce distinct alterations in upper airway resistance and collapsibility, which may influence oppositely the level of airflow through the upper airway during sleep.     

Anatomic consequences of intrinsic tongue muscle activation.

We recently showed respiratory-related coactivation of both extrinsic and intrinsic tongue muscles in the rat. Here, we test the hypothesis that intrinsic tongue muscles contribute importantly to changes in velopharyngeal airway volume. Spontaneously breathing anesthetized rats were placed in a MRI scanner. A catheter was placed in the hypopharynx and connected to a pressure source. Axial and sagittal images of the velopharyngeal airway were obtained, and the volume of each image was computed at airway pressures ranging from +5.0 to -5.0 cm H2O. We obtained images in the hypoglossal intact animal (i.e., coactivation of intrinsic and extrinsic tongue muscles) and after selective denervation of the intrinsic tongue muscles, with and without electrical stimulation. Denervation of the intrinsic tongue muscles reduced velopharyngeal airway volume at atmospheric and positive airway pressures. Electrical stimulation of the intact hypoglossal nerve increased velopharyngeal airway volume; however, when stimulation was repeated after selective denervation of the intrinsic tongue muscles, the increase in velopharyngeal airway volume was significantly attenuated. These findings support our working hypothesis that intrinsic tongue muscles play a critical role in modulating upper airway patency.     

Neuromechanical control of the isolated upper airway of mice

We characterized the passive structural and active neuromuscular control of pharyngeal collapsibility in mice and hypothesized that pharyngeal collapsibility, which is elevated by anatomic loads, is reduced by active neuromuscular responses to airflow obstruction. To address this hypothesis, we examined the dynamic control of upper airway function in the isolated upper airway of anesthetized C57BL/6J mice. Pressures were lowered downstream and upstream to the upper airway to induce inspiratory airflow limitation and critical closure of the upper airway, respectively. After hyperventilating the mice to central apnea, we demonstrated a critical closing pressure (Pcrit) of -6.2 +/- 1.1 cmH(2)O under passive conditions that was unaltered by the state of lung inflation. After a period of central apnea, lower airway occlusion led to progressive increases in phasic genioglossal electromyographic activity (EMG(GG)), and in maximal inspiratory airflow (Vi(max)) through the isolated upper airway, particularly as the nasal pressure was lowered toward the passive Pcrit level. Moreover, the active Pcrit fell during inspiration by 8.2 +/- 1.4 cmH(2)O relative to the passive condition (P < 0.0005). We conclude that upper airway collapsibility (passive Pcrit) in the C57BL/6J mouse is similar to that in the anesthetized canine, feline, and sleeping human upper airway, and that collapsibility falls markedly under active conditions. Active EMG(GG) and Vi(max) responses dissociated at higher upstream pressure levels, suggesting a decrease in the mechanical efficiency of upper airway dilators. Our findings in mice imply that anatomic and neuromuscular factors interact dynamically to modulate upper airway function, and provide a novel approach to modeling the impact of genetic and environmental factors in inbred murine strains.     

Influences of NREM sleep on the activity of tonic vs. inspiratory phasic muscles in normal men.

Studies of sleep influences on human pharyngeal and other respiratory muscles suggest that the activity of these muscles may be affected by non-rapid-eye-movement (NREM) sleep in a nonuniform manner. This variable sleep response may relate to the pattern of activation of the muscle (inspiratory phasic vs. tonic) and peripheral events occurring in the airway. Furthermore, the ability of these muscles to respond to respiratory stimuli during NREM sleep may also differ. To systematically investigate the effect of NREM sleep on respiratory muscle activity, we studied two tonic muscles [tensor palatini (TP), masseter (M)] and two inspiratory phasic ones [genioglossus (GG), diaphragm (D)], also measuring the response of these muscles to inspiratory resistive loading (12 cmH2O.l-1.s) during wakefulness and NREM sleep. Seven normal male subjects were studied on a single night with intramuscular electrodes placed in the TP and GG and surface electrodes placed over the D and M. Sleep stage, inspiratory airflow, and moving time average electromyograph (EMG) of the above four muscles were continuously recorded. The EMG of both tonic muscles fell significantly (P less than 0.05) during NREM sleep [TP awake, 4.3 +/- 0.05 (SE) arbitrary units, stage 2, 1.1 +/- 0.2; stage 3/4, 1.0 +/- 0.2. Masseter awake, 4.8 +/- 0.6; stage 2, 3.3 +/- 0.5; stage 3/4, 3.1 +/- 0.5]. On the other hand, the peak phasic EMG of both inspiratory phasic muscles (GG and D) was well maintained.(ABSTRACT TRUNCATED AT 250 WORDS)     

Contribution of male sex, age, and obesity to mechanical instability of the upper airway during sleep.

Male sex, obesity, and age are risk factors for obstructive sleep apnea, although the mechanisms by which these factors increase sleep apnea susceptibility are not entirely understood. This study examined the interrelationships between sleep apnea risk factors, upper airway mechanics, and sleep apnea susceptibility. In 164 (86 men, 78 women) participants with and without sleep apnea, upper airway pressure-flow relationships were characterized to determine their mechanical properties [pharyngeal critical pressure under hypotonic conditions (passive Pcrit)] during non-rapid eye movement sleep. In multiple linear regression analyses, the effects of body mass index and age on passive Pcrit were determined in each sex. A subset of men and women matched by body mass index, age, and disease severity was used to determine the sex effect on passive Pcrit. The passive Pcrit was 1.9 cmH(2)O [95% confidence interval (CI): 0.1-3.6 cmH(2)O] lower in women than men after matching for body mass index, age, and disease severity. The relationship between passive Pcrit and sleep apnea status and severity was examined. Sleep apnea was largely absent in those individuals with a passive Pcrit less than -5 cmH(2)O and increased markedly in severity when passive Pcrit rose above -5 cmH(2)O. Passive Pcrit had a predictive power of 0.73 (95% CI: 0.65-0.82) in predicting sleep apnea status. Upper airway mechanics are differentially controlled by sex, obesity, and age, and partly mediate the relationship between these sleep apnea risk factors and obstructive sleep apnea.     

Influence of tongue muscle contraction and dynamic airway pressure on velopharyngeal volume in the rat.

The mammalian pharynx is a collapsible tube that narrows during inspiration as transmural pressure becomes negative. The velopharynx (VP), which lies posterior to the soft palate, is considered to be one of the most collapsible pharyngeal regions. I tested the hypothesis that negative transmural pressure would narrow the VP, and that electrical stimulation of extrinsic tongue muscles would reverse this effect. Pressure (-6, -3, 3, and 6 cmH2O) was applied to the isolated pharyngeal airway of anesthetized rats that were positioned in a 4.7-T MRI scanner. The volume of eight axial slices encompassing the length of the VP was computed at each level of pressure, with and without bilateral hypoglossal nerve stimulation (0.1-ms pulse, one-third maximum force, 80 Hz). Negative pressure narrowed the VP, and either whole hypoglossal nerve stimulation (coactivation of protrudor and retractor muscles) or medial nerve branch stimulation (independent activation of tongue protrudor muscles) reversed this effect, with the greatest impact in the caudal one-third of the VP. The dilating effects of medial branch stimulation were slightly larger than whole nerve stimulation. Positive pressure dilated the VP, but tongue muscle contraction did not cause further dilation under these conditions. I conclude that the narrowest and most collapsible segment of the rat pharynx is in the caudal VP, posterior to the tip of the soft palate. Either coactivation of protrudor and retractor muscles or independent contraction of protrudor muscles caused dilation of this region, but the latter was slightly more effective.     

Phasic respiratory modulation of pharyngeal collapsibility via neuromuscular mechanisms in rats

Obstructive sleep apnea patients experience recurrent upper airway (UA) collapse due to decreases in the UA dilator muscle activity during sleep. In contrast, activation of UA dilators reduces pharyngeal critical pressure (Pcrit, an index of pharyngeal collapsibility), suggesting an inverse relationship between pharyngeal collapsibility and dilator activity. Since most UA muscles display phasic respiratory activity, we hypothesized that pharyngeal collapsibility is modulated by respiratory drive via neuromuscular mechanisms. Adult male Sprague-Dawley rats were anesthetized, vagotomized, and ventilated (normocapnia). In one group, integrated genioglossal activity, Pcrit, and maximal airflow (V(max)) were measured at three expiration and five inspiration time points within the breathing cycle. Pcrit was closely and inversely related to phasic genioglossal activity, with the value measured at peak inspiration being the lowest. In other groups, the variables were measured during expiration and peak inspiration, before and after each of five manipulations. Pcrit was 26% more negative (-15.0 ± 1.0 cmH(2)O, -18.9 ± 1.2 cmH(2)O; n = 23), V(max) was 7% larger (31.0 ± 1.0 ml/s, 33.2 ± 1.1 ml/s), nasal resistance was 12% bigger [0.49 ± 0.05 cmH(2)O/(ml/s), 0.59 ± 0.05 cmH(2)O/(ml/s)], and latency to induced UA closure was 14% longer (55 ± 4 ms, 63 ± 5 ms) during peak inspiration vs. expiration (all P < 0.005). The expiration-inspiration difference in Pcrit was abolished with neuromuscular blockade, hypocapnic apnea, or death but was not reduced by the superior laryngeal nerve transection or altered by tracheal displacement. Collectively, these results suggest that pharyngeal collapsibility is moment-by-moment modulated by respiratory drive and this phasic modulation requires neuromuscular mechanisms, but not the UA negative pressure reflex or tracheal displacement by phasic lung inflation.     

Lung volume and collapsibility of the passive pharynx in patients with sleep-disordered breathing.

Lung volume dependence of pharyngeal airway patency suggests involvement of lung volume in pathogenesis of obstructive sleep apnea. We examined the structural interaction between passive pharyngeal airway and lung volume independent of neuromuscular factors. Static mechanical properties of the passive pharynx were compared before and during lung inflation in eight anesthetized and paralyzed patients with sleep-disordered breathing. The respiratory system volume was increased by applying negative extrathoracic pressure, thereby leaving the transpharyngeal pressure unchanged. Application of -50-cmH(2)O negative extrathoracic pressure produced an increase in lung volume of 0.72 (0.63-0.91) liter [median (25-75 percentile)], resulting in a significant reduction of velopharyngeal closing pressure of 1.22 (0.14-2.03) cmH(2)O without significantly changing collapsibility of the oropharyngeal airway. Improvement of the velopharyngeal closing pressure was directly associated with body mass index. We conclude that increase in lung volume structurally improves velopharyngeal collapsibility particularly in obese patients with sleep-disordered breathing.     

Influence of gender on upper airway mechanics: upper airway resistance and Pcrit.

It has been proposed that the difference in sleep apnea prevalence is related to gender differences in upper airway anatomy and physiology. To explain the prevalence difference, we hypothesized that men would have an increased upper airway resistance and increased critical closing pressure (Pcrit) compared with women. In protocol 1, resistance at two points, fixed flow of 0.2 l/s (RL) and peak flow (Rpk), was measured in 33 men and 27 women without significant sleep-disordered breathing. We found no difference in either RL (-6.9 +/- 5.9 vs. -8.6 +/- 8.2 cmH2O) or Rpk (-9.3 +/- 6.8 vs. -10.0 +/- 11.9 cmH2O) between the men and women. A multiple linear regression to correct for the effects of age and body mass index confirmed that gender had no effect on resistance. In protocol 2, Pcrit was measured in eight men and eight women without sleep-disordered breathing. We found no difference in Pcrit (-10.4 +/- 3.1 vs. -8.8 +/- 2.7 cmH2O) between men and women. We conclude that there are no significant differences in collapsibility between men and women. We present an unifying hypothesis to explain the divergent findings of gender differences in upper airway physiology.     

Influence of tongue muscle contraction and transmural pressure on nasopharyngeal geometry in the rat

The mammalian pharynx is a hollow muscular tube that participates in ingestion and respiration, and its size, shape, and stiffness can be altered by contraction of skeletal muscles that lie inside or outside of its walls. MRI was used to determine the interaction between pharyngeal pressure and selective stimulation of extrinsic tongue muscles on the shape of the rat nasopharynx. Pressure (-9, -6, -3, 3, 6, and 9 cmH?O) was applied randomly to the isolated pharyngeal airway of anesthetized rats that were positioned in a 4.7-T MRI scanner. The anterior-posterior (AP) and lateral diameters of the nasopharynx were measured in eight axial slices at each level of pressure, with and without bilateral hypoglossal nerve stimulation (0.1-ms pulse, 1/3 maximal force, 80 Hz). The rat nasopharynx is nearly circular, and positive pharyngeal pressure caused similar expansion of AP and lateral diameters; as a result, airway shape (ratio of lateral to AP diameter) remained constant. Negative pressure did not change AP or lateral diameter significantly, suggesting that a negative pressure reflex activated the tongue or other pharyngeal muscles. Stimulation of tongue protrudor muscles alone or coactivation of protrudor and retractor muscles caused greater AP than lateral expansion, making the nasopharynx slightly more elliptical, with the long axis in the AP direction. These effects tended to be more pronounced at negative pharyngeal pressures and greater in the caudal than rostral nasopharynx. These data show that stimulation of rodent tongue muscles can adjust pharyngeal shape, extending previous work showing that tongue muscle contraction alters pharyngeal compliance and volume, and provide physiological insight that can be applied to the treatment of obstructive sleep apnea.     

Pharyngeal critical pressure in children with mild sleep-disordered breathing.

There is evidence that narrowing or collapse of the pharynx can contribute to obstructive sleep-disordered breathing (SDB) in adults and children. However, studies in children have focused on those with relatively severe SDB who generally were recruited from sleep clinics. It is unclear whether children with mild SDB who primarily have hypopneas, and not frank apnea, also have more collapsible airways. We estimated airway collapsibility in 10 control subjects (9.4 +/- 0.5 yr old; 1.9 +/- 0.2 hypopneas/h) and 7 children with mild SDB (10.6 +/- 0.5 yr old; 11.5 +/- 0.1 hypopneas/h) during stable, non-rapid eye movement sleep. None of the subjects had clinically significant enlargement of the tonsils or adenoids, nor had any undergone previous tonsillectomy or adenoidectomy. Airway collapsibility was measured by brief (2-breath duration) and sudden reductions in pharyngeal pressure by connecting the breathing mask to a negative pressure source. Negative pressure applications ranging from -1 to -20 cmH(2)O were randomly applied in each subject while respiratory airflow and mask pressure were measured. Flow-pressure curves were constructed for each subject, and the x-intercept gave the pressure at zero flow, the so-called critical pressure of the upper airway (Pcrit). Pcrit was significantly higher in children with SDB than in controls (-10.8 +/- 2.8 vs. -15.7 +/- 1.2 cmH(2)O; P < 0.05). There were no significant differences in the slopes of the pressure-flow relations or in baseline airflow resistance. These data support the concept that intrinsic pharyngeal collapsibility contributes to mild SDB in children.     

Respiratory control stability and upper airway collapsibility in men and women with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is two to three times more common in men as in women. The mechanisms leading to this difference are currently unclear but could include gender differences in respiratory stability [loop gain (LG)] or upper airway collapsibility [pharyngeal critical closing pressure (Pcrit)]. The aim of this study was to compare LG and Pcrit between men and women with OSA to determine whether the factors contributing to apnea are similar between genders. The first group of 11 men and 11 women were matched for OSA severity (mean +/- SE apnea-hypopnea index = 43.8 +/- 6.1 and 44.1 +/- 6.6 events/h). The second group of 12 men and 12 women were matched for body mass index (BMI; 31.6 +/- 1.9 and 31.3 +/- 1.8 kg/m2, respectively). All measurements were made during stable supine non-rapid eye movement sleep. LG was determined using a proportional assist ventilator. Pcrit was measured by progressively dropping the continuous positive airway pressure level for three to five breaths until airway collapse. Apnea-hypopnea index-matched women had a higher BMI than men (38.0 +/- 2.4 vs. 30.0 +/- 1.9 kg/m2; P = 0.03), but LG and Pcrit were similar between men and women (LG: 0.37 +/- 0.02 and 0.37 +/- 0.02, respectively, P = 0.92; Pcrit: 0.35 +/- 0.62 and -0.18 +/- 0.87, respectively, P = 0.63). In the BMI-matched subgroup, women had less severe OSA during non-rapid eye movement sleep (30.9 +/- 7.4 vs. 52.5 +/- 8.1 events/h; P = 0.04) and lower Pcrit (-2.01 +/- 0.62 vs. 1.16 +/- 0.83 cmH2O; P = 0.005). However, LG was not significantly different between genders (0.38 +/- 0.02 vs. 0.33 +/- 0.03; P = 0.14). These results suggest that women may be protected from developing OSA by having a less collapsible upper airway for any given degree of obesity.     

Effect of surface tension of mucosal lining liquid on upper airway mechanics in anesthetized humans.

Upper airway (UA) patency may be influenced by surface tension (gamma) operating within the (UAL). We examined the role of gamma of UAL in the maintenance of UA patency in eight isoflurane-anesthetized supine human subjects breathing via a nasal mask connected to a pneumotachograph attached to a pressure delivery system. We evaluated 1). mask pressure at which the UA closed (Pcrit), 2). UA resistance upstream from the site of UA collapse (RUS), and 3). mask pressure at which the UA reopened (Po). A multiple pressure-transducer catheter was used to identify the site of airway closure (velopharyngeal in all subjects). UAL samples (0.2 microl) were collected, and the gamma of UAL was determined by using the "pull-off force" technique. Studies were performed before and after the intrapharyngeal instillation of 5 ml of exogenous surfactant (Exosurf, Glaxo Smith Kline). The gamma of UAL decreased from 61.9 +/- 4.1 (control) to 50.3 +/- 5.0 mN/m (surfactant; P < 0.02). Changes in Po, RUS, and Po - Pcrit (change = control - surfactant) were positively correlated with changes in gamma (r2 > 0.6; P < 0.02) but not with changes in Pcrit (r2 = 0.4; P > 0.9). In addition, mean peak inspiratory airflow (no flow limitation) significantly increased (P < 0.04) from 0.31 +/- 0.06 (control) to 0.36 +/- 0.06 l/s (surfactant). These findings suggest that gamma of UAL exerts a force on the UA wall that hinders airway opening. Instillation of exogenous surfactant into the UA lowers the gamma of UAL, thus increasing UA patency and augmenting reopening of the collapsed airway.     

Pharyngeal resistance in normal humans: influence of gender, age, and obesity

Investigation into the etiology of obstructive sleep apnea is beginning to focus increasing attention on upper airway anatomy and physiology (patency and resistance). Before conclusions concerning upper airway resistance in these patients can be made, the normal range of supraglottic and, more specifically, pharyngeal resistance needs to be better defined. We measured supraglottic and pharyngeal resistances during nasal breathing in a normal population of 35 men and women. Our technique measured epiglottic pressure with a balloon-tipped catheter, choanal pressure using anterior rhinometry, and flow with a sealed face mask and pneumotachograph. Resistance was measured at a flow rate of 300 ml/s during inspiration. Men had a mean pharyngeal resistance (choanae to epiglottis) of 4.6 +/- 0.8 (SE) cmH2O X l-1 X s, whereas women demonstrated a significantly (P less than 0.01) lower value, 2.3 +/- 0.3 cmH2O X l-1 X s. Supraglottic resistance was also higher in men (P = 0.01). Age (r = 0.73, P less than 0.01) correlated closely with pharyngeal resistance in men, but no such correlations could be found in women. These results may have implications in the epidemiology of obstructive sleep apnea.     

Effect of geniohyoid and sternohyoid muscle contraction on upper airway resistance in the cat.

Previous investigators (van Lunteren et al. J. Appl. Physiol. 62: 582-590, 1987) have suggested that the geniohyoid and sternohyoid muscles may act as upper airway dilators in the cat. To investigate the effect of geniohyoid and sternohyoid contraction on inspiratory upper airway resistance (UAR), we studied five adult male cats anesthetized with ketamine and xylazine during spontaneous room-air breathing. Inspiratory nasal airflow was measured by sealing the lips and constructing a nose mask. Supraglottic pressure was measured using a transpharyngeal catheter placed above the larynx. Mask pressure was measured using a separate catheter. Geniohyoid and sternohyoid lengths were determined by sonomicrometry. Geniohyoid and sternohyoid contraction was stimulated by direct muscle electrical stimulation with implanted wire electrodes. Mean inspiratory UAR was determined for spontaneous breaths under three conditions: 1) baseline (no muscle stimulation), 2) geniohyoid contraction alone, and 3) sternohyoid contraction alone. Geniohyoid contraction alone produced no significant reduction in inspiratory UAR [unstimulated, 17.75 +/- 0.86 (SE) cmH2O.l-1.s; geniohyoid contraction, 19.24 +/- 1.10]. Sternohyoid contraction alone also produced no significant reduction in inspiratory UAR (unstimulated, 15.74 +/- 0.92 cmH2O.l-1.s; sternohyoid contraction, 14.78 +/- 0.78). Simultaneous contraction of the geniohyoid and sternohyoid muscles over a wide range of muscle lengths produced no consistent change in inspiratory UAR. The geniohyoid and sternohyoid muscles do not appear to function consistently as upper airway dilator muscles when UAR is used as an index of upper airway patency in the cat.     

Episodic hypoxia induces long-term facilitation of neural drive to tongue protrudor and retractor muscles.

Hypoxic episodes can evoke a prolonged augmentation of inspiratory motor output called long-term facilitation (LTF). Hypoglossal (XII) LTF has been assumed to represent increased tongue protrudor muscle activation and pharyngeal airway dilation. However, recent studies indicate that tongue protrudor and retractor muscles are coactivated during inspiration, a behavior that promotes upper airway patency by reducing airway compliance. These experiments tested the hypothesis that XII LTF is manifest as increased inspiratory drive to both tongue protrudor and retractor muscles. Neurograms were recorded in the medial XII nerve branch (XIIMED; contains tongue protrudor motor axons), the lateral XII nerve branch (XIILAT; contains tongue retractor motor axons), and the phrenic nerve in anesthetized, vagotomized, paralyzed, ventilated male rats. Strict isocapnia was maintained for 60 min after five 3-min hypoxic episodes (arterial Po(2) = 35 +/- 2 Torr) or sham treatment. Peak inspiratory burst amplitude showed a persistent increase in XIIMED, XIILAT, and phrenic nerves during the hour after episodic hypoxia (P < 0.05 vs. sham). This effect was present regardless of the quantification method (e.g., % baseline vs. percent maximum); however, comparisons of the relative magnitude of LTF between neurograms (e.g., XIIMED vs. XIILAT) varied with the normalization procedure. There was no persistent effect of episodic hypoxia on inspiratory burst frequency (P > 0.05 vs. sham). These data demonstrate that episodic hypoxia induces LTF of inspiratory drive to both tongue protrudor and retractor muscles and underscore the potential contribution of tongue muscle coactivation to regulation of upper airway patency.     

弥猴单侧软腭肌肉对针式电极刺激的反应

目的建立针电极口内刺激猴软腭肌肉诱发腭咽闭合运动的模式,取得软腭肌肉运动的有效刺激数值,为软腭肌肉功能重建奠定基础。方法通过解剖成年猕猴软腭的五组肌肉,确定其体表位置;利用实验动物用腭部肌肉电极定位刺激器及针式电极对软腭肌肉进行有效刺激;结合鼻咽纤维镜、头颅侧位X片及软腭造影技术观察、记录肌肉收缩及腭咽闭合动作。结果在猕猴口内定位目标肌肉进行针电极刺激可诱发肌肉收缩。刺激电压为3 V、刺激频率为20 Hz时均能诱发单侧软腭肌肉的有效收缩;单侧腭帆提肌在刺激电压为5 V、20 Hz时可发生腭咽闭合动作。咽腭肌、舌腭肌在刺激电压5 V、刺激频率100 Hz时发生软腭下降动作。腭帆张肌仅发生收缩,而未发生腭咽闭合。应用鼻咽纤维镜和X线成像技术配合能记录腭咽闭合动作。结论弥猴可作为研究软腭肌肉运动模式的实验动物。应用电极刺激软腭肌肉,可初步建立腭咽闭合的动作模式。     

Respiratory changes in diaphragmatic intramuscular pressure

We attempted to measure diaphragmatic tension by measuring changes in diaphragmatic intramuscular pressure (Pim) in the costal and crural parts of the diaphragm in 10 supine anesthetized dogs with Gaeltec 12 CT minitransducers. During phrenic nerve stimulation or direct stimulation of the costal and crural parts of the diaphragm in an animal with the chest and abdomen open, Pim invariably increased and a linear relationship between Pim and the force exerted on the central tendon was found (r greater than or equal to 0.93). During quiet inspiration Pim in general decreased in the costal part (-3.9 +/- 3.3 cmH2O), whereas it either increased or slightly decreased in the crural part (+3.3 +/- 9.4 cmH2O, P less than 0.05). Similar differences were obtained during loaded and occluded inspiration. After bilateral phrenicotomy Pim invariably decreased during inspiration in both parts (costal -4.3 +/- 6.4 cmH2O, crural -3.1 +/- 0.6 cmH2O). Contrary to the expected changes in tension in the muscle, but in conformity with the pressure applied to the muscle, Pim invariably increased during passive inflation from functional residual capacity to total lung capacity (costal +30 +/- 23 cmH2O, crural +18 +/- 18 cmH2O). Similarly, during passive deflation from functional residual capacity to residual volume, Pim invariably decreased (costal -12 +/- 19 cmH2O, crural -12 +/- 14 cmH2O). In two experiments similar observations were made with saline-filled catheters. We conclude that although Pim increases during contraction as in other muscles, Pim during respiratory maneuvers is primarily determined by the pleural and abdominal pressures applied to the muscle rather than by the tension developed by it.