The effect of sleep on reflex genioglossus muscle activation by stimuli of negative airway pressure in humans.

The present study was designed to determine the effect of sleep on reflex pharyngeal dilator muscle activation by stimuli of negative airway pressure in human subjects. Intra-oral bipolar surface electrodes were used to record genioglossus electromyogram (EMG) responses to 500 ms duration pressure stimuli of 0 and -25 cmH2O applied, via a face-mask, in four normal subjects. Stimuli were applied during early inspiration in wakefulness and in periods of non-rapid-eye-movement (non-REM) sleep, defined by electroencephalographic (EEG) criteria. The rectified and integrated EMG responses to repeated interventions were bin averaged for the 0 and -25 cmH2O stimuli applied in wakefulness and sleep. Response latency was defined as the time when the EMG activity significantly increased above prestimulus levels. Response magnitude was quantified as the in ratio of the EMG activity for an 80 ms post-stimulus period to an 80 ms prestimulus period; data from after the subject's voluntary reaction time for tongue protrusion (range, 150-230 ms) were not analysed. Application of the -25 cmH2O stimuli caused genioglossus muscle activation in wakefulness and sleep, but in all subjects response magnitude was reduced in sleep (mean decrease, 61%; range, 52-82%; P = 0.011, Student's paired t test). In addition, response latency was increased in sleep in each subject (mean latency awake, 38 ms; range, 30-50 ms; mean latency asleep, 75 ms; range, 40-110 ms; P = 0.072, Student's paired t test). Application of the -25 cmH2O stimuli caused arousal from sleep on 90% occasions, but in all cases the reflex genioglossus muscle responses (maximum latency, 110 ms) always proceeded any sign of EEG arousal (mean time to arousal, 643 ms; range, 424-760 ms). These results show that non-REM sleep attenuates reflex genioglossus muscle activation by stimuli of negative airway pressure. Attenuation of this reflex by sleep may impair the ability of the upper airway to defend itself from suction collapse by negative pressures generated during inspiration; this may have implications for the pathogenesis of obstructive sleep apnoea.     

Variability of human upper airway collapsibility during sleep and the influence of body posture and sleep stage

The critical pressure at which the pharynx collapses (Pcrit) is an objective measurement of upper airway collapsibility, an important pathogenetic factor in obstructive sleep apnoea. This study examined the inherent variability of passive Pcrit measurement during sleep and evaluated the effects of sleep stage and body posture on Pcrit. Repeated measurements of Pcrit were assessed in 23 individuals (15 male) with diagnosed obstructive sleep apnoea throughout a single overnight sleep study. Body posture and sleep stage were unrestricted. Applied upper airway pressure was repetitively reduced to obtain multiple measurements of Pcrit. In 20 subjects multiple measurements of Pcrit were obtained. The overall coefficient of repeatability for Pcrit measurement was 4.1 cm H₂O. Considering only the lateral posture, the coefficient was 4.8 cm H₂O. It was 3.3 cm H₂O in the supine posture. Pcrit decreased from the supine to lateral posture [supine mean 2.5 cm H₂O, 95% confidence interval (CI) 1.4–3.6; lateral mean 0.3 cm H₂O, 95% CI ?0.8–1.4, P = 0.007] but did not vary with sleep stage (P = 0.91). This study has shown that the overall coefficient of repeatability was 4.1 cm H₂O, implying that the minimum detectable difference, with 95% probability, between two repeated Pcrit measurements in an individual is 4.1 cm H₂O. Such variability in overnight measures of Pcrit indicates that a single unqualified value of Pcrit cannot be used to characterize an individual’s overall collapsibility during sleep. When within‐subject variability is accounted for, change in body posture from supine to lateral significantly decreases passive pharyngeal collapsibility.     

Mechanical effects of genioglossus muscle stimulation on the pharyngeal airway by MRI in cats

To examine the regional mechanical effects of selective genioglossus muscle activation on pharyngeal airway size and function, magnetic resonance images of the pharyngeal airway were obtained in five paralyzed, anesthetized cats over a range of positive and negative pressures in an isolated, sealed upper airway. When all results across pressure levels and pharyngeal regions were analyzed, genioglossus stimulation significantly increased the cross-sectional area (CSA) of the nasopharyngeal airway. Within specific regions, stimulation tended toward significantly increasing cross-sectional airway area in the mid-nasopharynx. Despite its dilating effect, genioglossus muscle stimulation did not alter compliance in the nasopharyngeal airway, as evidenced by the similar slopes of the pressure versus cross-sectional area relationships with and without stimulation. Finally, airway shape in the mid pharynx became more circular with either increased airway pressure or genioglossus stimulation. The results indicate that selective stimulation of the genioglossus muscle dilates the nasopharynx and provide evidence that stimulation of the genioglossus alone does not alter airway compliance.     

The effect of lung stretch during sleep on airway mechanics in overweight and obese asthma

Both obesity and sleep reduce lung volume and limit deep breaths, possibly contributing to asthma. We hypothesize that increasing lung volume dynamically during sleep would reduce airway resistance in asthma. Asthma (n = 10) and control (n = 10) subjects were studied during sleep at baseline and with increased lung volume via bi-level positive airway pressure (BPAP). Using forced oscillations, respiratory system resistance (R_rs) and reactance (X_rs) were measured during sleep and R_rs was partitioned to upper and lower airway resistance (R_up, R_low) using an epiglottic pressure catheter. R_rs and R_up increased with sleep (p < 0.01) and X_rs was decreased in REM (p = 0.02) as compared to wake. R_rs, R_up, and R_low, were larger (p < 0.01) and X_rs was decreased (p < 0.02) in asthma. On BPAP, R_rs and R_up were decreased (p < 0.001) and X_rs increased (p < 0.01), but R_low was unchanged. High R_up was observed in asthma, which reduced with BPAP. We conclude that the upper airway is a major component of R_rs and larger lung volume changes may be required to alter R_low.     

The influence of a transmucosal cholinergic agonist on pharyngeal muscle activity

STUDY OBJECTIVE: To assess the effect of high local oral nicotine administration on the upper airway (UA) of normal males during wakefulness. DESIGN: Nonrandomized study. SETTING: Brigham & Women's Hospital General Clinical Research Center. PARTICIPANTS: Two groups of 13 and 12 normal male subjects were evaluated. INTERVENTIONS: A "Fast acting" or "Intermediate acting" 2 mg transmucosal nicotine patch was attached to an upper molar tooth of study participants during wakefulness. MEASUREMENTS: All data were collected prior to, and at several time points after, patch placement. Data measured included serum nicotine levels, genioglossal EMG, and pharyngeal resistance during basal breathing as well as the UA muscle response and UA collapsibility during negative UA pressure pulses. RESULTS: None of the variables measured showed a statistically significant change with either nicotine patch despite a significant rise (p<0.05) in nicotine serum levels post patch placement in both groups. In several subjects, muscle activity and responsiveness to negative pressure increased after application of both patches and returned to near baseline levels at the last time point measured, a response consistent with the time course of nicotine release in both patches. CONCLUSIONS: Oral nicotine administration failed to consistently increase GG muscle activation which may be a problem of local bioavailability of nicotine in the muscle.     

Tongue mechanical characteristics and genioglossus muscle EMG in obstructive sleep apnoea patients

The increased genioglossus muscle (GGm) activity seen in obstructive sleep apnoea syndrome (OSAS) may lead to increased fatigability or longer recovery time of the tongue. Maximal force, endurance, and recovery times of the tongue, electromyogram (EMG) absolute value, and EMG spectral analysis of the GGm obtained during submaximal contractions were compared in eight individuals without chronic snoring and eight OSAS patients. Endurance time values were not significantly different between the two groups (P = 0.40). Time to recovery of initial maximal force was significantly greater in the OSAS group (P = 0.01). Final EMG median frequency was significantly higher (P = 0.01) and the final low-frequency EMG component smaller in the OSAS patients (P = 0.02). Patients did not have changes in endurance time or fatigability but had longer recovery times and changes in spectral analysis variations. This functional investigation may be helpful in determining the presence of OSAS and the potential contribution of the tongue to pharyngeal obstruction.     

Discharge patterns of human genioglossus motor units during sleep onset

STUDY OBJECTIVES: Multiunit electromyogram recordings of genioglossus have demonstrated an abrupt reduction in the muscle's activity at sleep onset. Recent evidence from single motor unit recordings indicates that the human genioglossus muscle consists of motor units with a variety of discharge patterns. The aim of the present study was to determine the effect of sleep onset on the activity of individual motor units as a function of their particular discharge pattern. DESIGN: Genioglossus activity was assessed using intramuscular fine-wire electrodes via a percutaneous approach. Sleep onsets (alpha-to-theta transitions) were identified and the genioglossus electromyogram recordings analyzed for single motor unit activity. SETTING: Sleep research laboratory. PARTICIPANTS: Sleep and respiratory data were collected in 8 healthy subjects (6 men). MEASUREMENTS AND RESULTS: One hundred twenty-seven motor units were identified: 23% inspiratory phasic, 45% inspiratory tonic, 4% expiratory phasic, 9% expiratory tonic, 16% tonic, and 3% other. Approximately 50% of inspiratory units (phasic and tonic) ceased activity entirely at sleep onset, whereas those inspiratory units that continued to be active showed a reduction in the proportion of each breath over which they were active. However, the rate of discharge of inspiratory units during the period they did fire was not altered. In contrast, tonic and expiratory units were unaffected by sleep onset, maintaining their discharge pattern over the alpha-to-theta transition. CONCLUSIONS: Central control of inspiratory motoneuron output differs from that of tonic and expiratory units during sleep onset, suggesting that the maintenance of airway patency during sleep may become more reliant on the stiffening properties of tonic and expiratory modulated motor units.     

Neuromuscular specializations of the pharyngeal dilator muscles: II. Compartmentalization of the canine genioglossus muscle

The genioglossus (GG) muscle is divided into horizontal and oblique compartments that are the main protrusor and depressor muscles of the tongue, respectively. In humans the GG plays an important role in speech articulation, swallowing, and inspiratory dilation of the pharynx. At present, little is known about the neuromuscular specializations of the GG in any mammal. This study examined the specializations of these compartments in the canine tongue using a variety of anatomical and histochemical techniques. Six canine GG muscles were sectioned and stained for myofibrillar ATPase to study muscle fiber types; five whole-mount GG muscles were stained for acetylcholinesterase (AChE) to study the distribution of motor endplates; and eight whole mount GG muscles were processed with Sihler's stain to study the entire nerve supply pattern. In addition, the arrangement of muscle fibers of the GG within the tongue was also determined (N = 3). The most notable difference between the compartments of the GG was their proportions of fast and slow twitch muscle fibers: the horizontal compartment contained 64% slow twitch muscle fibers compared to 41% in the oblique compartment. In addition, although the oblique compartment appeared to be grossly homogeneous, it could be divided into thirds by significant differences in the percentages of slow twitch fibers: posterior (23%), middle (15%), and anterior (56%; P < 0.05). The muscle fibers of the oblique GG within the tongue were found to be divided into medial and lateral layers that run vertically and transversely, respectively. The nerve supply to each third of the oblique GG formed a plexus with the anterior third being the densest. The innervation pattern of the oblique GG was also notable as terminal nerve branches coursing parallel to the muscle fascicles gave off perpendicular secondary branches along each motor endplate band. These secondary nerve branches connected the primary nerves and formed a regularly spaced grid throughout the compartment. Evidently, the two compartments of the GG exhibited different anatomical specializations. The horizontal had a slow muscle fiber profile and simple innervation pattern; these qualities are possibly related to its single force vector and respiratory related activity. The oblique compartment had a relatively fast muscle fiber profile with evidence for three separate functional subdivisions. The most anterior part was noticeably different, and was presumably specialized for fine motor control of the tip of the tongue. The vertically oriented fibers of the oblique GG within the tongue body may function as a midline depressor of the tongue, whereas its transversely oriented fibers could play a role in narrowing the tongue during other motor tasks.     

Effects on upper airway collapsibility of presence of a pharyngeal catheter

Catheters that traverse the pharynx are often in place during clinical or research evaluations of upper airway function. The purpose of this study was to determine whether the presence of such catheters affects measures of upper airway collapsibility itself. To do so, pharyngeal critical closing pressure (Pcrit) and resistance upstream of the site of collapse Rus) were assessed in 24 propofol‐anaesthetized subjects (14 men) with and without a multi‐sensor oesophageal catheter (external diameter 2.7 mm) in place. Anaesthetic depth and posture were maintained constant throughout each study. Six subjects had polysomnography(PSG)‐defined obstructive sleep apnea (OSA) and 18 either did not have or were at low risk of OSA. Airway patency was maintained with positive airway pressure. At intervals, pressure was reduced by varying amounts to induce varying degrees of inspiratory flow limitation. The slope of the pressure flow relationship for flow‐limited breaths defined Rus. Pcrit was similar with the catheter in and out (?1.5 ± 5.4 cmH₂O and ?2.1 ± 5.6 cmH₂O, respectively, P = 0.14, n = 24). This remained the case both for those with PSG‐defined OSA (3.9 ± 2.2 cmH₂O and 2.6 ± 1.4 cmH₂O, n = 6) and those at low risk/without OSA (?3.3 ± 4.9 cmH₂O and ‐3.7 ± 5.6 cmH₂O, respectively, n = 18). Rus was similar with the catheter in and out (20.0 ± 12.3 cmH₂O mL^?1 s^?1 and 16.8 ± 10.1 cmH₂O mL^?1 s^?1, P = 0.22, n = 24). In conclusion, the presence of a small catheter traversing the pharynx had no significant effect on upper airway collapsibility in these anaesthestized subjects, providing reassurance that such measures can be made reliably in their presence.     

Assessment of upper airway mechanics during sleep

Obstructive sleep apnea, which is the most prevalent sleep breathing disorder, is characterized by recurrent episodes of upper airway collapse and reopening. However, the mechanical properties of the upper airway are not directly measured in routine polysomnography because only qualitative sensors (thermistors for flow and thoraco-abdominal bands for pressure) are used. This review focuses on two techniques that quantify upper airway obstruction during sleep. A Starling model of collapsible conduit allows us to interpret the mechanics of the upper airway by means of two parameters: the critical pressure (P_crit) and the upstream resistance (R_up). A simple technique to measure P_crit and R_up involves the application of different levels of continuous positive airway pressure (CPAP) during sleep. The forced oscillation technique is another non-invasive procedure for quantifying upper airway impedance during the breathing cycle in sleep studies. The latest developments in these two methods allow them to be easily applied on a routine basis in order to more fully characterize upper airway mechanics in patients with sleep breathing disorders.     

Long-term facilitation of genioglossus activity is present in normal humans during NREM sleep

Episodic hypoxia (EH) is followed by increased ventilatory motor output in the recovery period indicative of long-term facilitation (LTF). We hypothesized that episodic hypoxia evokes LTF of genioglossus (GG) muscle activity in humans during non-rapid eye movement sleep (NREM) sleep. We studied 12 normal non-flow limited humans during stable NREM sleep. We induced 10 brief (3 min) episodes of isocapnic hypoxia followed by 5 min of room air. Measurements were obtained during control, hypoxia, and at 5, 10, 20, 30 and 40 min of recovery, respectively, for minute ventilation (V(I)), supraglottic pressure (P(SG)), upper airway resistance (R(UA)) and phasic GG electromyogram (EMG(GG)). In addition, sham studies were conducted on room air. During hypoxia there was a significant increase in phasic EMG(GG) (202.7+/-24.1% of control, p<0.01) and in V (I) (123.0+/-3.3% of control, p<0.05); however, only phasic EMG(GG) demonstrated a significant persistent increase throughout the recovery. (198.9+/-30.9%, 203.6+/-29.9% and 205.4+/-26.4% of control, at 5, 10, and 20 min of recovery, respectively, p<0.01). In multivariate regression analysis, age and phasic EMG(GG) activity during hypoxia were significant predictors of EMG(GG) at recovery 20 min. No significant changes in any of the measured parameters were noted during sham studies. CONCLUSION: (1) EH elicits LTF of GG in normal non-flow limited humans during NREM sleep, without concomitant ventilatory or mechanical LTF. (2) GG activity during the recovery period correlates with the magnitude of GG activation during hypoxia, and inversely with age.     

OSAHS鼻咽联合手术围手术期咽腔间距解剖变化及临床意义

目的　观察并分析阻塞性睡眠呼吸暂停低通气综合征（OSAHS）鼻、咽联合手术围手术期咽腔间距解剖变化的规律,及其对术后治疗、气管切开术选择的临床指导意义。 方法　选择确诊为鼻、咽多平面狭窄的OSAHS患者50例,全麻下行改良悬雍垂腭咽成形术、鼻腔扩容术和/或鼻咽部腺样体切除术。测量术前清醒坐位,术前全麻卧位,术后全麻卧位,术后第1、2、3 d清醒坐位的咽腔间距,并记录术后当晚最低血氧饱和度和平均血氧饱和度,观察有无并发症。 结果　术后第1、2、3 d坐位时咽腔各间距测量值均大于术前坐位值,软腭长度小于术前。全麻术前卧位咽腔间距小于清醒坐位。全麻术后卧位咽腔间距大于全麻术前卧位。术后当晚平均血氧和最低血氧饱和度均高于术前。术后无呼吸困难、无术区出血,未行气管切开术。 结论　OSAHS鼻、咽部多平面联合手术术后气道得到明显扩张,未出现急性梗阻及渐进性狭窄所致呼吸困难。在严格把握适应症及密切监护的前提下可不行气管切开术。     

Dynamic lung mechanics in late-stage emphysema before and after lung volume reduction surgery

This study evaluated the effects of lung volume reduction surgery (LVRS) on the heterogeneity of lung function in awake, late-stage emphysema patients with measurements taken before and after full recovery from LVRS. We assessed standard clinical measures of lung function and functional heterogeneity in six awake, late-stage emphysema patients before and 6 months after LVRS. Functional heterogeneity was quantified by measuring dynamic inspiratory resistance (R(L)(insp)) and elastance (E(L)(insp)) over a frequency range that included normal breathing ( approximately 0.33-8 Hz). Since LVRS involves targeted resection of emphysematous regions of the lung, we hypothesized that emphysema patients would be functionally more homogeneous post-LVRS. We also compared our measures of functional heterogeneity with indices of anatomic heterogeneity and severity using high-resolution computed tomography (HRCT). After LVRS, 6 min walk distance increased by 22% (940+/-91 versus 1158+/-299, p=0.031) and recoil pressure at TLC increased (9.0+/-2.0 versus 14+/-5, p=0.031), but changes in R(L)(insp) and E(L)(insp) varied greatly between subjects. A measure of anatomic severity quantified using HRCT positively correlated with airway resistance (r(s)=0.89, p=0.048). These results suggest that subjects with more severe disease as assessed by HRCT criteria had reduced overall effective airway caliber consequent to active airway constriction, reduced parenchymal tethering, and/or loss of parallel lung units. Furthermore, LVRS may not necessarily improve lung function via a substantial reduction in mechanical heterogeneity.     

Acute effects of paroxetine on genioglossus activity in obstructive sleep apnea

STUDY OBJECTIVE: To determine the acute effects of paroxetine on genioglossus activity during NREM sleep. DESIGN: A single dose of Paroxetine (40 mg) or placebo was administered four hours before bedtime on nights separated by one week in a double blind randomized crossover manner. The moving time average of genioglossus muscle activity (EMGgg) expressed as a percentage of maximum was measured using a mouthpiece electrode customized for each subject. The peak inspiratory and tonic values of EMGgg and the corresponding esophageal pressure deflections (DP) during the last three occluded breaths of obstructive apneas during NREM sleep were analyzed. SETTING: NA. PARTICIPANTS: 8 adult men with severe obstructive sleep apnea (OSA). INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Paroxetine increased the peak inspiratory EMGgg (29.8+/-2.4 (SE) versus 24.4+/-2.7 % max, p<0.05) and peak EMGgg/DP ratio (0.78+/-0.12 versus 0.65+/-0.11 % max/cm H2O, p<0.01) but not the tonic EMGgg (11.6+/-0.9 versus 9.8+/-0.7 % max) nor the DP (39.4+/-2.2 versus 38.2+/-2.8 cm H2O). Linear regression analysis of the peak inspiratory EMGgg versus DP relationship showed that paroxetine increased the slope (0.62+/-0.11 versus 0.49+/-0.09 % max/cm H2O, p<0.01). However, the apnea + hypopnea index (paroxetine: 75.2+/-5.5 versus placebo: 73.7+/-6.9 events/hour) did not differ. CONCLUSIONS: Paroxetine augmented peak inspiratory genioglossus activity during NREM sleep but this effect was not sufficient to decrease the frequency of obstructive apnea in this group with severe OSA.     

Effect of sleep position and sleep stage on the collapsibility of the upper airways in patients with sleep apnea

Collapsibility of the upper airways has been identified as an important pathogenic factor in obstructive sleep apnea (OSA). Objective measures of collapsibility are pharyngeal critical pressure (Pcrit) and resistance of the upstream segment (Rus). To systematically determine the effects of sleep stage and body position we investigated 16 male subjects suffering from OSA. We compared the measures in light sleep, slow-wave sleep, REM sleep and supine vs. lateral positions. The pressure-flow relationship of the upper airways has been evaluated by simultaneous readings of maximal inspiratory airflow (Vimax) and nasal pressure (p-nCPAP). With two-factor repeated measures ANOVA on those 7 patients which had all 6 situations we found a significant influence of body position on Pcrit (p<0.05) whereas there was no significant influence of sleep stage and no significant interaction between body position and sleep stage. When comparing the body positions Pcrit was higher in the supine than in the lateral positions. During light sleep Pcrit decreased from 0.6 +/- 0.8 cm H2O (supine) to -2.2 +/- 3.6 cm H2O (lateral) (p<0.01), during slow-wave sleep Pcrit decreased from 0.3 +/- 1.4 cm H2O (supine) to -1.7 +/- 2.6 (lateral) (p<0.05) and during REM sleep it decreased from 1.2 +/- 1.5 cm H2O to -2.0 +/- 2.2 cm H2O (p<0.05). Changes in Rus revealed no body position nor sleep-stage dependence. Comparing the different body positions Rus was only significantly higher in the lateral position during REM sleep (p<0.05). The results indicate that collapsibility of the upper airways is not mediated by sleep stages but is strongly influenced by body position. As a consequence lower nCPAP pressure is needed during lateral positions compared to supine positions.     

The influence of hospital volume on survival after resection for lung cancer.

BACKGROUND: Among patients who have undergone high-risk operations for cancer, postoperative mortality rates are often lower at hospitals where more of these procedures are performed. We undertook a population-based study to estimate the extent to which the number of procedures performed at a hospital (hospital volume) is associated with survival after resection for lung cancer. METHODS: We studied patients 65 years old or older who received a diagnosis of stage I, II, or IIIA non-small-cell lung cancer between 1985 and 1996, resided in 1 of the 10 study areas covered by the Surveillance, Epidemiology, and End Results Program, and underwent surgery at a hospital that participates in the Nationwide Inpatient Sample (2118 patients and 76 hospitals). RESULTS: The volume of procedures at the hospital was positively associated with the survival of patients (P<0.001). Five years after surgery, 44 percent of patients who underwent operations at the hospitals with the highest volume were alive, as compared with 33 percent of those who underwent operations at the hospitals with the lowest volume. Patients at the highest-volume hospitals also had lower rates of postoperative complications (20 percent vs. 44 percent) and lower 30-day mortality (3 percent vs. 6 percent) than those at the lowest-volume hospitals. CONCLUSIONS: Patients who undergo resection for lung cancer at hospitals that perform large numbers of such procedures are likely to survive longer than patients who have such surgery at hospitals with a low volume of lung-resection procedures.     

The length-force relationship of the human genioglossus in patients with obstructive sleep apnea

During sleep, patients with obstructive sleep apnea (OSA) have repetitive episodes of upper airway collapse, which are terminated by increased activity of upper airway dilator muscles. The repetitive activation of the genioglossus (GG) may result in muscle remodeling. We hypothesized that OSA patients have an altered length-force relationship, increased force generation and/or decreased force maintenance as compared with control subjects. The GG length-force relationship was determined in 12 patients with OSA and 12 normal control subjects. The optimum length of the GG (LO) was at a longer muscle length in OSA patients than in control subjects. At longer muscle lengths, OSA patients produced greater percentages of their maximum protrusion force than control subjects. Force maintenance was not significantly different between the two groups. We conclude that in OSA patients relative to normal controls, the length-force relationship of the GG is altered, specifically at longer muscle lengths. We speculate that the GG is remodeled in OSA patients and that this facilitates airway re-opening to terminate obstructive events.