Activity Of Upper Airway Muscles Research Articles

Direct optogenetic activation of upper airway muscles in an acute model of upper airway hypotonia mimicking sleep onset.

Obstructive sleep apnea (OSA), where the upper airway collapses repeatedly during sleep due to inadequate dilator muscle tone, is challenging to treat as current therapies are poorly tolerated or have variable and unpredictable efficacy. We propose a novel, optogenetics-based therapy, that stimulates upper airway dilator muscle contractions in response to light. To determine the feasibility of a novel optogenetics-based OSA therapy, we developed a rodent model of human sleep-related upper airway muscle atonia. Using this model, we evaluated intralingual delivery of candidate optogenetic constructs, notably a muscle-targeted approach that will likely have a favorable safety profile. rAAV serotype 9 viral vectors expressing a channelrhodopsin-2 variant, driven by a muscle-specific or nonspecific promoter were injected into rat tongues to compare strength and specificity of opsin expression. Light-evoked electromyographic responses were recorded in an acute, rodent model of OSA. Airway dilation was captured with ultrasound. The muscle-specific promoter produced sufficient opsin expression for light stimulation to restore and/or enhance electromyographic signals (linear mixed model, F = 140.0, p < 0.001) and induce visible tongue contraction and airway dilation. The muscle-specific promoter induced stronger (RM-ANOVA, F(1,8) = 10.0, p = 0.013) and more specific opsin expression than the nonspecific promoter in an otherwise equivalent construct. Viral DNA and RNA were robust in the tongue, but low or absent in all other tissues. Significant functional responses to direct optogenetic muscle activation were achieved following muscle-specific promoter-driven rAAV-mediated transduction, providing proof-of-concept for an optogenetic therapy for patients with inadequate dilator muscle activity during sleep.

Adaptive responses to chronic intermittent hypoxia: contributions from the European Sleep Apnoea Database (ESADA) Cohort.

Obstructive sleep apnoea (OSA) is a common disease in the general population, and is associated with increased cardiovascular risk and several comorbidities. Obesity favours upper airway collapsibility, but other pathophysiological traits have been identified, i.e. upper airway muscle activity, modulation of the respiratory drive, and the arousal threshold. OSA causes chronic intermittent hypoxia, inflammatory activation and autonomic imbalance with diurnal and nocturnal sympathetic hyperactivity. Disentangling so many components to investigate the pathogenesis of OSA's consequences is very hard clinically. However, albeit imperfect, clinical medicine constitutes a major source of inspiration for basic research, and a mutual exchange of information is essential between clinicians and physiologists to improve our understanding of disease states. OSA is no exception, and this narrative review will summarize the results of clinical studies performed over the years by the European Sleep Apnoea Database (ESADA) Study Group, to explore the variables linked to markers of intermittent hypoxia as opposed to the traditional assessment of OSA severity based on the frequency of respiratory events during sleep (the Apnoea Hypopnoea Index). The results of the clinical studies indicate that intermittent hypoxia variables are associated with several comorbidities, although evidence of a cause-effect relationship is still missing in many cases. It is also possible that adaptive rather than maladaptive responses could be evoked by intermittent hypoxia. The intensity, duration and frequency of intermittent hypoxia episodes causing adaptive rather than maladaptive responses, and their clinical implications, deserve further investigation.

Physiological responses and perceived comfort to high-flow nasal cannula therapy in awake adults: effects of flow magnitude and temperature.

Clinical use of heated, high-flow nasal cannula (HFNC) for noninvasive respiratory support is increasing and may have a therapeutic role in stabilizing the upper airway in obstructive sleep apnea (OSA). However, physiological mechanisms by which HFNC therapy may improve upper airway function and effects of different temperature modes are unclear. Accordingly, this study aimed to determine effects of incremental flows and temperature modes (heated and nonheated) of HFNC on upper airway muscle activity (genioglossus), pharyngeal airway pressure, breathing parameters, and perceived comfort. Six participants (2 females, aged 35 ± 14 yr) were studied during wakefulness in the supine position and received HFNC at variable flows (0-60 L/min) during heated (37°C) and nonheated (21°C) modes. Breathing parameters via calibrated Respitrace inductance bands (chest and abdomen), upper airway pressures via airway transducers, and genioglossus muscle activity via intramuscular bipolar fine wire electrodes were measured. Comfort levels during HFNC were quantified using a visual analog scale. Increasing HFNC flows did not increase genioglossus muscle activation despite increased negative epiglottic pressure swings (P = 0.009). HFNC provided ∼7 cmH2O positive airway pressure at 60 L/min in nonheated and heated modes. In addition, increasing the magnitude of HFNC flow reduced breathing frequency (P = 0.045), increased expiratory time (P = 0.040), increased peak inspiratory flow (P = 0.002), and increased discomfort (P = 0.004). Greater discomfort occurred at higher flows in the nonheated versus the heated mode (P = 0.034). These findings provide novel insight into key physiological changes that occur with HFNC for respiratory support and indicate that the primary mechanism for improved upper airway stability is positive airway pressure, not increased pharyngeal muscle activity.NEW & NOTEWORTHY This study evaluated upper airway muscle function, breathing, and comfort across different HFNC flows and temperatures. There were no increases in genioglossus muscle activity at higher flows despite greater negative epiglottic pressure swings. Increasing negative pressure swings was associated with increasing discomfort in the nonheated mode. HFNC was associated with ∼7 cmH2O increase in positive airway pressure, which may be the primary mechanism for upper airway stability with HFNC rather than increases in pharyngeal muscle activity.

Corticomotor control of airway calibre in obstructive sleep apnoea syndrome.

Corticomotor control of airway calibre in obstructive sleep apnoea syndrome.

Upper Airway Collapsibility during Dexmedetomidine and Propofol Sedation in Healthy Volunteers: A Nonblinded Randomized Crossover Study.

Dexmedetomidine is a sedative promoted as having minimal impact on ventilatory drive or upper airway muscle activity. However, a trial recently demonstrated impaired ventilatory drive and induction of apneas in sedated volunteers. The present study measured upper airway collapsibility during dexmedetomidine sedation and related it to propofol. Twelve volunteers (seven female) entered this nonblinded, randomized crossover study. Upper airway collapsibility (pharyngeal critical pressure) was measured during low and moderate infusion rates of propofol or dexmedetomidine. A bolus dose was followed by low (0.5 μg · kg · h or 42 μg · kg · min) and moderate (1.5 μg · kg · h or 83 μg · kg · min) rates of infusion of dexmedetomidine and propofol, respectively. Complete data sets were obtained from nine volunteers (median age [range], 46 [23 to 66] yr; body mass index, 25.4 [20.3 to 32.4] kg/m). The Bispectral Index score at time of pharyngeal critical pressure measurements was 74 ± 10 and 65 ± 13 (mean difference, 9; 95% CI, 3 to 16; P = 0.011) during low infusion rates versus 57 ± 16 and 39 ± 12 (mean difference, 18; 95% CI, 8 to 28; P = 0.003) during moderate infusion rates of dexmedetomidine and propofol, respectively. A difference in pharyngeal critical pressure during sedation with dexmedetomidine or propofol could not be shown at either the low or moderate infusion rate. Median (interquartile range) pharyngeal critical pressure was -2.0 (less than -15 to 2.3) and 0.9 (less than -15 to 1.5) cm H2O (mean difference, 0.9; 95% CI, -4.7 to 3.1) during low infusion rates (P = 0. 595) versus 0.3 (-9.2 to 1.4) and -0.6 (-7.7 to 1.3) cm H2O (mean difference, 0.0; 95% CI, -2.1 to 2.1; P = 0.980) during moderate infusion of dexmedetomidine and propofol, respectively. A strong linear relationship between pharyngeal critical pressure during dexmedetomidine and propofol sedation was evident at low (r = 0.82; P = 0.007) and moderate (r = 0.90; P < 0.001) infusion rates. These observations suggest that dexmedetomidine sedation does not inherently protect against upper airway obstruction.

Sciatic nerve stimulation and its effects on upper airway resistance in the anesthetized rabbit model relevant to sleep apnea.

Obstructive sleep apnea (OSA) is a disorder characterized by collapse of the velopharynx and/or oropharynx during sleep when drive to the upper airway is reduced. Here, we explore an indirect approach for activation of upper airway muscles that might affect airway dynamics, namely, unilateral electrical stimulation of the afferent fibers of the sciatic nerve, in an anesthetized rabbit model. A nerve cuff electrode was placed around the sciatic and hypoglossal nerves to deliver stimulus while airflow, air pressure, and alae nasi electromyogram (EMG) were monitored both before and after sciatic transection. Sciatic nerve stimulation increased respiratory effort, rate, and alae nasi EMG, which persisted for seconds after stimulation; however, upper airway resistance was unchanged. Hypoglossal stimulation reduced resistance without altering drive. Although sciatic nerve stimulation is not ideal for treating OSA, it remains a target for altering respiratory drive. NEW & NOTEWORTHY Previously, sciatic nerve stimulation has been shown to activate upper airway and chest wall muscles. The supposition that resistance through the upper airway would be reduced with this afferent reflex was disproven. Findings were in contrast with the effect of hypoglossal nerve stimulation, which was shown to decrease resistance without changing muscle activation or ventilatory drive.

Effect of 4-Aminopyridine on Genioglossus Muscle Activity during Sleep in Healthy Adults.

The reduction in upper airway muscle activity from wakefulness to sleep plays a key role in the development of obstructive sleep apnea. Potassium (K+) channels have been recently identified as the downstream mechanisms through which hypoglossal motoneuron membrane excitability is reduced both in non-rapid eye movement (NREM) sleep and REM sleep. In animal models, the administration of 4-aminopyridine (4-AP), a voltage-gated K+ channel blocker, increased genioglossus activity during wakefulness and across all sleep stages. We tested the hypothesis that administration of a single dose of 4-AP 10 mg extended release would increase genioglossus activity (electromyography of the genioglossus muscle [EMGGG]) during wakefulness and sleep, and thereby decrease pharyngeal collapsibility. We performed a randomized controlled crossover proof-of-concept trial in 10 healthy participants. Participants received active treatment or placebo in randomized order 3 hours before bedtime in the physiology laboratory. EMGGG during wakefulness and NREM sleep and upper airway collapsibility measured during NREM sleep were unchanged between placebo and 4-AP nights. Tonic but not phasic EMGGG during REM sleep was higher on the 4-AP night when measured as a percentage of maximal voluntary activation (median [interquartile range] 0.3 [0.5] on placebo vs. 0.8 [1.9] %max on 4 AP; P = 0.04), but not when measured in μV or as a percentage of wakefulness value. A single dose of 4-AP 10 mg extended release showed only a small increase in tonic EMGGG during REM sleep in this group of healthy subjects. We speculate that a higher dose of 4-AP may further increase EMGGG. However, given the potentially severe, dose-related adverse effects of this drug, including seizures, the administration of 4-AP does not appear to be an effective strategy to increase genioglossus activity during sleep in humans. Clinical Trial registered with clinicaltrials.gov (NCT02656160).

Mild Intermittent Hypoxia with Sustained Hypercapnia Improves Airflow, Reduces Therapeutic CPAP and Blood Pressure in Participants with Obstructive Sleep Apnea

Intermittent hypoxia (IH) elicits long term facilitation of ventilation and upper airway muscle activity. The latter form of plasticity could contribute to stabilizing the upper airway. Based on this possibility, we examined if administration of mild IH accompanied by sustained hypercapnia reduces the continuous positive airway pressure (CPAP) required to treat obstructive sleep apnea (OSA). In addition, we investigated if daily exposure to mild IH would elicit changes in the autonomic nervous system, leading to a decrease in blood pressure in individuals with OSA.MethodsTen male participants with OSA initially visited the laboratory to confirm the presence of sleep apnea, while a second visit was used to determine the therapeutic CPAP (TP). On a third visit, the participants completed a sham protocol (i.e. normoxic and normocapnic conditions), which mimicked the timeframe of the IH protocol that would be introduced in a subsequent visit, while being treated with TP. During the sham recovery period, the CPAP was reduced in a step‐wise fashion to measure the change in flow and upper airway resistance. On a fourth visit participants were treated with TP. PETCO2 levels were increased and sustained 3 mmHg above baseline. Subsequently, twelve 2‐minute episodes of hypoxia (PETO2 ≈ 50 mmHg) separated by 2‐minute intervals of normoxia were administered. During recovery, the CPAP was reduced in a step‐wise fashion until flow limitation was evident. In a separate set of experiments two subjects with OSA underwent daily exposure to IH on 15 occasions over 3 weeks.ResultsFollowing exposure to intermittent hypoxia minute ventilation (P &lt; 0.001) and tidal volume (P &lt; 0.001) during end‐recovery and the step‐downs in positive pressure were greater compared to B2 (P &lt; 0.001). Inspiratory flow and resistance remained at baseline levels following exposure to intermittent hypoxia after TP was reduced by 5 cmH2O. In contrast, after completion of the sham protocol inspiratory flow was reduced (P &lt; 0.001) and resistance was increased (P &lt; 0.01) in response to the 5 cmH2O reduction in positive airway pressure. Preliminary data in two participants showed that daily exposure to IH over a 3 week period led to a decrease in systolic (144 ± 1 vs. 128 ± 5 mmHg) blood pressure and an increase in baroreceptor sensitivity (6.5 ± 0.06 vs. 17.9 ± 1.7 ms/mmHg). CPAP compliance data was retrieved from one individual. CPAP use increased from 2 h 52 minutes in the 1st week to 5 h 52 minutes in the 3rd week.ConclusionThe administration of mild IH and sustained hypercapnia decreases the CPAP required to eliminate apneic events. Additionally, increases in resistance and decreases in flow following CPAP step‐downs were significantly mitigated following IH with sustained hypercapnia. Preliminary data from 2 individuals showed that mild IH could effectively treat cardiovascular co‐morbidities directly and indirectly by increasing CPAP compliance via reductions in TP.Support or Funding InformationVA Merit Award ‐ Department of Veterans Affairs

Mechanisms of the deep, slow-wave, sleep-related increase of upper airway muscle tone in healthy humans

Upper airway muscle activity is reportedly elevated during slow-wave sleep (SWS) when compared with lighter sleep stages. To uncover the possible mechanisms underlying this elevation, we explored the correlation between different indices of central and reflex inspiratory drive, such as the changes in airway pressure and end-expiratory CO2 and the changes in the genioglossus (GG) and tensor palatini (TP) muscle activity accompanying transitions from the lighter N2 to the deeper N3 stage of non-rapid eye movement (NREM) sleep in healthy young adult men. Forty-six GG and 38 TP continuous electromyographic recordings were obtained from 16 men [age: 20 ± 2.5 (SD) yr; body mass index: 22.5 ± 1.8 kg/m2] during 32 transitions from NREM stages N2 to N3. GG but not TP activity increased following transition into N3 sleep, and the increase was positively correlated with more negative airway pressure, increased end-tidal CO2, increased peak inspiratory flow, and increased minute ventilation. None of these correlations was statistically significant for TP. Complementary GG and TP single motor unit analysis revealed a mild recruitment of GG units and derecruitment of TP units during the N2 to N3 transitions. These findings suggest that, in healthy individuals, the increased GG activity during SWS is driven primarily by reflex stimulation of airway mechanoreceptors and central chemoreceptors.NEW & NOTEWORTHY The characteristic increase in the activity of the upper airway dilator muscle genioglossus during slow-wave sleep (SWS) in young healthy individuals was found to be related to increased stimulation of airway mechanoreceptors and central chemoreceptors. No evidence was found for the presence of a central SWS-specific drive stimulating genioglossus activity in young healthy individuals. However, it remains to be determined whether a central drive exists in obstructive sleep apnea patients.

Neural Control of the Upper Airway: Respiratory and State-Dependent Mechanisms.

Upper airway muscles subserve many essential for survival orofacial behaviors, including their important role as accessory respiratory muscles. In the face of certain predisposition of craniofacial anatomy, both tonic and phasic inspiratory activation of upper airway muscles is necessary to protect the upper airway against collapse. This protective action is adequate during wakefulness, but fails during sleep which results in recurrent episodes of hypopneas and apneas, a condition known as the obstructive sleep apnea syndrome (OSA). Although OSA is almost exclusively a human disorder, animal models help unveil the basic principles governing the impact of sleep on breathing and upper airway muscle activity. This article discusses the neuroanatomy, neurochemistry, and neurophysiology of the different neuronal systems whose activity changes with sleep-wake states, such as the noradrenergic, serotonergic, cholinergic, orexinergic, histaminergic, GABAergic and glycinergic, and their impact on central respiratory neurons and upper airway motoneurons. Observations of the interactions between sleep-wake states and upper airway muscles in healthy humans and OSA patients are related to findings from animal models with normal upper airway, and various animal models of OSA, including the chronic-intermittent hypoxia model. Using a framework of upper airway motoneurons being under concurrent influence of central respiratory, reflex and state-dependent inputs, different neurotransmitters, and neuropeptides are considered as either causing a sleep-dependent withdrawal of excitation from motoneurons or mediating an active, sleep-related inhibition of motoneurons. Information about the neurochemistry of state-dependent control of upper airway muscles accumulated to date reveals fundamental principles and may help understand and treat OSA. © 2016 American Physiological Society. Compr Physiol 6:1801-1850, 2016.

Chapter 13 - Sleep–Wake Control of the Upper Airway by Noradrenergic Neurons, with and without Intermittent Hypoxia

Hypoglossal (XII) motoneurons innervate muscles of the tongue whose tonic and inspiratory modulated activity protects the upper airway from collapse in patients affected by the obstructive sleep apnea (OSA) syndrome. Both norepinephrine and serotonin provide wakefulness-related excitatory drives that maintain activity in XII motoneurons, with the noradrenergic system playing a particularly prominent role in rats. When noradrenergic and serotonergic drives are antagonized, no further decline of XII nerve activity occurs during pharmacologically induced rapid eye movement (REM) sleep-like state. This is the best evidence to date that, at least in this model, the entire REM sleep-related decline of upper airway muscle tone results from withdrawal of these two excitatory inputs. A major component of noradrenergic input to XII motoneurons originates from pontine noradrenergic neurons that have state-dependent patterns of activity, maximal during wakefulness, and minimal, or absent during REM sleep. Our data suggest that not all ventrolateral medullary catecholaminergic neurons follow this pattern, with adrenergic C1 neurons probably increasing their activity during REM sleep. When rats are subjected to chronic-intermittent hypoxia, noradrenergic drive to XII motoneurons is increased by mechanisms that include sprouting of noradrenergic terminals in the XII nucleus, and increased expression of α1-adrenoceptors; an outcome that may underlie the elevated baseline activity of upper airway muscles during wakefulness in OSA patients.

The human upper airway: more than a floppy tube

the multifunctional upper airway, its mechanical properties, and the muscles that control its shape and size are complex ([Fig. 1][1]). As highlighted by Fregosi and Ludlow ([7][2]) in their mini-review on activation of upper airway muscles during breathing and swallowing, precise coordination of

Activation of upper airway muscles during breathing and swallowing

The upper airway is a complex muscular tube that is used by the respiratory and digestive systems. The upper airway is invested with several small and anatomically peculiar muscles. The muscle fiber orientations and their nervous innervation are both extremely complex, and how the activity of the muscles is initiated and adjusted during complex behaviors is poorly understood. The bulk of the evidence suggests that the entire assembly of tongue and laryngeal muscles operate together but differently during breathing and swallowing, like a ballet rather than a solo performance. Here we review the functional anatomy of the tongue and laryngeal muscles, and their neural innervation. We also consider how muscular activity is altered as respiratory drive changes, and briefly address upper airway muscle control during swallowing.

Phasic Genioglossus and Palatoglossus Muscle Activity during Recovery from Sevoflurane Anesthesia

Inhalational anesthetic effects on upper airway muscle activity in children are largely unknown. The authors tested the hypothesis that phasic inspiratory genioglossus and palatoglossus activity increases during recovery from sevoflurane anesthesia in a dose-dependent manner in children. Sixteen children, aged 2.0 to 6.9 yr, scheduled for elective urological surgery were studied. Electromyogram recordings were acquired using intramuscular needle electrodes during spontaneous ventilation. After a 15-min period of equilibration, electromyogram activity was recorded over 30 s at each of three end-tidal concentrations, 1.5, 1.0, and 0.5 minimum alveolar concentration (MAC), administered in sequence. Phasic genioglossus activity was noted in four children at 1.5 MAC, five at 1.0 MAC, and six children at 0.5 MAC sevoflurane. Phasic palatoglossus activity was noted in 4 children at 1.5 MAC, 6 at 1.0 MAC, and 10 children at 0.5 MAC sevoflurane. Both the proportion of children exhibiting phasic activity, and the magnitude of phasic activity increased during recovery from anesthesia. For the genioglossus, decreasing the depth of sevoflurane anesthesia from 1.5 to 1.0 MAC increased phasic activity by approximately 35% and a further decrease to 0.5 MAC more than doubled activity (median [range] at 1.5 and 0.5 MAC: 2.7 μV [0 to 4.0 μV] and 8.6 μV [3.2 to 17.6], respectively; P = 0.029). A similar dose-related increase was recorded at the palatoglossus (P = 0.0002). Genioglossus and palatoglossus activity increases during recovery from sevoflurane anesthesia in a dose-dependent manner over the clinical range of sevoflurane concentrations in children.

Respiratory modulation of lingual muscle activity across sleep–wake states in rats

In obstructive sleep apnea (OSA) patients, inspiratory activation (IA) of lingual muscles protects the upper airway from collapse. We aimed to determine when rats’ lingual muscles exhibit IA. In 5 Sprague-Dawley and 3 Wistar rats, we monitored cortical EEG and lingual, diaphragmatic and nuchal electromyograms (EMGs), and identified segments of records when lingual EMG exhibited IA. Individual segments lasted 2.4–269s (median: 14.5s), most (89%) occurred during slow-wave sleep (SWS), and they collectively occupied 0.3–6.1% of the total recording time. IA usually started to increase with a delay after SWS onset and ended with an arousal, or declined prior to rapid eye movement sleep. IA of lingual EMG was not accompanied by increased diaphragmatic activity or respiratory rate changes, but occurred when cortical EEG power was particularly low in a low beta-1 frequency range (12.5–16.4Hz). A deep SWS-related activation of upper airway muscles may be an endogenous phenomenon designed to protect the upper airway against collapse.

Reduced c-Fos expression in medullary catecholaminergic neurons in rats 20 h after exposure to chronic intermittent hypoxia.

Persons affected by obstructive sleep apnea (OSA) have increased arterial blood pressure and elevated activity in upper airway muscles. Many cardiorespiratory features of OSA have been reproduced in rodents subjected to chronic-intermittent hypoxia (CIH). We previously reported that, following exposure to CIH, rats have increased noradrenergic terminal density in brain stem sensory and motor nuclei and upregulated expression of the excitatory α(1)-adrenergic receptors in the hypoglossal motor nucleus. This suggested that CIH may enhance central catecholaminergic transmission. We now quantified c-Fos expression in different groups of pontomedullary catecholaminergic neurons as an indirect way of assessing their baseline activity in rats subjected to CIH or sham treatment (7 AM-5 PM daily for 35 days). One day after the last CIH exposure, the rats were gently kept awake for 2.5 h and then were anesthetized and perfused, and their pontomedullary brain sections were subjected to dopamine β-hydroxylase (DBH) and c-Fos immunohistochemistry. DBH-positive cells were counted in the A1/C1, A2/C2, A5, subcoeruleus (sub-C) and A7 groups of catecholaminergic neurons, and the percentages of those expressing c-Fos were determined. We found that fewer DBH cells expressed c-Fos in CIH- than in sham-treated rats in the medulla (significant in the A1 group). In the pons (rostral A5, sub-C, and A7), c-Fos expression did not differ between the CIH- and sham-treated animals. We suggest that, when measured 20 h after the last CIH exposure, catecholaminergic transmission is enhanced through terminal sprouting and receptor upregulation rather than through increased baseline activity in pontomedullary catecholaminergic neurons.

Upper Airway Collapsibility During Wakefulness in Children with Sleep Disordered Breathing, as Determined by the Negative Expiratory Pressure Technique

Upper airway (UA) collapsibility is a major factor in the pathophysiology of sleep disordered breathing (SDB). We hypothesized that the negative expiratory pressure (NEP) technique could distinguish between normal children and children with SDB even during wakefulness. During wakefulness, NEP of -5 and -10 cm H(2)O was applied during expiration in seated and supine positions. UA muscle activity (EMG) was measured using intra-oral electrodes. Sleep laboratory. Twenty children with snoring, 20 with obstructive sleep apnea syndrome (OSAS), and 20 controls. The ratio of the area under the expiratory flow-volume curve during NEP compared to tidal breathing (RatioNEP) was calculated. Similarly, EMG area under the curve during NEP as a ratio of baseline was measured (RatioEMG). There were significant differences in RatioNEP between controls and snorers and controls and OSAS, at both pressures, in both the seated and supine positions; P < 0.0001 for all (e.g., RatioNEP at -5 cm H(2)O, seated: 1.8 ± 0.5, 2.1 ± 0.4, and 3.0 ± 0.6 for OSAS, snorers, and controls, respectively). However, no significant differences were found between snorers and OSAS. For RatioEMG, no significant differences were found between groups. RatioNEP distinguishes between normal children and children with SDB, be it snoring or OSAS, indicating that these children have a more collapsible UA even during wakefulness. However, it does not differentiate between snorers and OSAS, highlighting the important role of UA muscle activity during sleep. NEP technique does not elicit a different UA muscle activity response between controls and children with SDB.

Upper Airway Patency in the Neonate

Extrathoracic portion of the airway can be defined as the upper airway (UAW) which serves both alimentary and respiratory functions. It accounts for a significant portion of the dead space and total airway resistance. Activation of UAW muscles must be precisely coordinated to achieve the desired results in several complex motor acts such as respiration, airway protection, phonation, mastication and swallowing. A patent UAW is vital for survival. This review critically evaluates key factors that influence UAW patency with special emphasis on the neonate. Keywords: Upper airway, neonate, airway patency, genioglossus, airway afferents, arousal, laryngeal pressure, hypercapnia, Extrathoracic portion, posterior cricoarytenoid

Differential respiratory control of the upper airway and diaphragm muscles induced by 5-HT1A receptor ligands

Serotonin (5-HT) has a role in respiratory function and dysfunction. Although 5-HT affects respiratory drive to both phrenic and cranial motoneurons, relatively little is known about the role of 5-HT receptor subtypes in the control of upper airway muscle (UAM) respiratory activity. Here, we performed central injections of 5-HT1A agonist (8-OHDPAT) or antagonist (WAY100635) in anesthetized rats and analyzed changes in the electromyographic activity of several UAM and other cardiorespiratory parameters. We also compared the pattern of Fos expression induced after central injection of a control solution or 8-OHDPAT. Results showed that 8-OHDPAT induced a robust increase in UAM activity, associated with either tachypnea under volatile anesthesia or bradypnea under liquid anesthesia. Injection of WAY100635 switched off UAM respiratory activity and led to bradypnea, suggesting a tonic excitatory role of endogenous 5-HT1A receptor activation. Co-injection of the agonist and the antagonist blocked the effects produced by each drug alone. Besides drug-induced changes in respiratory frequency, only slight increases in surface of diaphragm bursts were observed. Significant increases in Fos expression after 5-HT1A receptor activation were seen in the nucleus tractus solitarius, nucleus raphe pallidus, parapyramidal region, retrotrapezoid nucleus, lateral parabrachial, and Kölliker-Fuse nuclei. This restricted pattern of Fos expression likely identified the neural substrate responsible for the enhancement of UAM respiratory activity observed after 8-OHDPAT injection. These findings suggest an important role for the 5-HT1A receptors in the neural control of upper airway patency and may be relevant to counteract pharyngeal atonia during obstructive sleep apneas.

Evolution of Changes in Upper Airway Collapsibility during Slow Induction of Anesthesia with Propofol

Upper airway collapsibility is known to increase under anesthesia. This study assessed how this increase in collapsibility evolves during slow Propofol induction and how it relates to anesthesia-induced changes in upper airway muscle activity and conscious state. Nine healthy volunteers were studied. Anesthesia was induced with Propofol in a step-wise manner (effect-site concentration steps of 0.5 microg x ml(-1) from 0 to 3 microg x ml(-1) and thereafter to 4 microg x ml(-1) and 6 microg x ml(-1) [target-controlled infusion]). Airway patency was maintained with continuous positive airway pressure. Pharyngeal collapsibility was assessed at each concentration by measuring critical pressure. Intramuscular genioglossus electromyogram and anesthetic depth (bispectral index score) were monitored throughout. Loss of consciousness was defined as failure to respond to loud verbal command. Loss of consciousness occurred at varying Propofol effect-site concentrations between 1.5 and 4.0 microg x ml(-1). Initially genioglossus electromyographic activity was sustained with increases in Propofol concentration, increasing in some individuals. At or approaching loss of consciousness, it decreased, often abruptly, to minimal values with an accompanying increase in critical pressure. In most subjects, bispectral index score decreased alinearly with increasing Propofol concentration with greatest rate of change coinciding with loss of consciousness. Slow stepwise induction of Propofol anesthesia is associated with an alinear increase in upper airway collapsibility. Disproportionate decreases in genioglossus electromyogram activity and increases in pharyngeal critical closing pressure were observed proximate to loss of consciousness, suggesting that particular vulnerability exists after transition from conscious to unconscious sedation. Such changes may have parallels with upper airway behavior at sleep onset.