Upper Airway Dilator Muscles Research Articles

Motor control of the palatoglossus and genioglossus during changes in breathing route.

High activity of upper airway dilator muscles is thought to be critical in preventing sleep-related upper airway collapse. To date, most of the research regarding upper airway dilator muscles has focused on the genioglossus muscle, which protrudes the tongue and opens the retroglossal airway. However, collapse commonly occurs in the retropalatal region. We therefore aimed to examine the motor control of the palatoglossus muscle as well as investigate breathing route-related changes in genioglossus and palatoglossus motor units. Single motor unit recordings of the genioglossus and palatoglossus were made simultaneously in healthy individuals during wakefulness while breathing through the nose with the mouth closed (NMC), nose with mouth open (NMO) or orally (OMO). The palatoglossus was found to have all 5 motor unit firing patterns that have been observed in other upper airway dilator muscles, but during nasal breathing had a higher proportion of tonically active but inspiratory modulated motor units as compared to the genioglossus (67% vs 30%). When still breathing nasally but with the mouth open, the units with an expiratory firing pattern in genioglossus, and all firing patterns in palatoglossal, increased their firing rates compared to nasal breathing with the mouth closed (GG: 17.8±4.9 vs 23.1±4.8 Hz, PG: 17.0±4.0 vs 19.3±4.0 Hz). Finally, oral breathing resulted in dramatic reductions in the number of palatoglossal motor units that were firing (35 units vs 92 during nasal breathing). Palatoglossus activity may contribute importantly to airway collapsibility and may provide an alternate pathway for preventing sleep-related airway collapse.

Stimulation of the internal superior laryngeal nerve as a potential therapy for obstructive sleep apnea in a porcine model.

Impaired pharyngeal sensing of negative pressure (NP) can lead to a blunted response of the upper airway dilator muscles and contribute to the development of obstructive sleep apnea (OSA). This response is modulated by the nerve fibers in the internal branch of the superior laryngeal nerve (iSLN), mediating negative pressure sensation. Artificial excitation of these fibers could be a potential treatment target for OSA. To evaluate this, electrostimulation of the iSLN was performed in a porcine-isolated upper airway model. Artificial obstructions were induced by varying the levels of negative pressure, and the ability of the animal to resolve these obstructions was evaluated. The pressure at which the animal was still able to resolve the obstruction was quantified as "Resolvable Pressure." Thereby, the effects on pharyngeal patency (n = 35) and the duration of the therapeutic effect outlasting the stimulation (n = 6) were quantified. Electrostimulation before the introduction of an artificial obstruction improved the median resolvable pressure from -28.3 cmH2O [IQR: -45.9; -26.1] to -92.6 cmH2O [IQR: -105.1; -78.6]. The median therapeutic effect was found to outlast the last stimulation burst applied by 163 s when five stimulation bursts were applied in short succession [IQR: 58; 231], 58 s when two were applied [IQR: 7; 65], and 6 s when one was applied [IQR: 0; 51]. Stimulation of the iSLN increased electromyography (EMG) in the genioglossus (GG). The proposed treatment concept can improve pharyngeal patency in the model. Transfer of the results to clinical application could enable the development of a new neuromodulation therapy for OSA.NEW & NOTEWORTHY Electrostimulation before the introduction of an artificial obstruction to induce artificial sleep apnea in the pig model improves the response of the upper airway to negative pressure (NP). The electrostimulation creates a sustained therapeutic effect that outlasts the initial electrostimulation. The use of this therapy in clinical practice has the potential to treat obstructive sleep apnea (OSA).

A novel TASK channel antagonist nasal spray reduces sleep apnea severity in physiological responders: a randomized, blinded, trial.

Preclinical and human physiological studies indicate that topical, selective TASK 1/3 K+ channel antagonism increases upper airway dilator muscle activity and reduces pharyngeal collapsibility during anesthesia and nasal breathing during sleep. The primary aim of this study was to determine the effects of BAY2586116 nasal spray on obstructive sleep apnea (OSA) severity and whether individual responses vary according to differences in physiological responses and route of breathing. Ten people (5 females) with OSA [apnea-hypopnea index (AHI) = 47 ± 26 events/h (means ± SD)] who completed previous sleep physiology studies with BAY2586116 were invited to return for three polysomnography studies to quantify OSA severity. In random order, participants received either placebo nasal spray (saline), BAY2586116 nasal spray (160 µg), or BAY2586116 nasal spray (160 µg) restricted to nasal breathing (chinstrap or mouth tape). Physiological responders were defined a priori as those who had improved upper airway collapsibility (critical closing pressure ≥2 cmH2O) with BAY2586116 nasal spray (NCT04236440). There was no systematic change in apnea-hypopnea index (AHI3) from placebo versus BAY2586116 with either unrestricted or nasal-only breathing versus placebo (47 ± 26 vs. 43 ± 27 vs. 53 ± 33 events/h, P = 0.15). However, BAY2586116 (unrestricted breathing) reduced OSA severity in physiological responders compared with placebo (e.g., AHI3 = 28 ± 11 vs. 36 ± 12 events/h, P = 0.03 and ODI3 = 18 ± 10 vs. 28 ± 12 events/h, P = 0.02). Morning blood pressure was also lower in physiological responders after BAY2586116 versus placebo (e.g., systolic blood pressure = 137 ± 24 vs. 147 ± 21 mmHg, P < 0.01). In conclusion, BAY2586116 reduces OSA severity during sleep in people who demonstrate physiological improvement in upper airway collapsibility. These findings highlight the therapeutic potential of this novel pharmacotherapy target in selected individuals.NEW & NOTEWORTHY Preclinical findings in pigs and humans indicate that blocking potassium channels in the upper airway with topical nasal application increases pharyngeal dilator muscle activity and reduces upper airway collapsibility. In this study, BAY2586116 nasal spray (potassium channel blocker) reduced sleep apnea severity in those who had physiological improvement in upper airway collapsibility. BAY2586116 lowered the next morning's blood pressure. These findings highlight the potential for this novel therapeutic approach to improve sleep apnea in certain people.

P033 Assessment of Upper Airway Dilator Muscle Function and Collapsibility in People with Multiple Sclerosis with Versus without Sleep Apnea

Abstract Introduction Upper airway reflex responses to negative pressure are important to prevent upper airway narrowing and closure. Recent evidence indicates ~30% of people with multiple sclerosis (MS) have an impaired upper airway dilator reflex response. Thus, the aims of this study were to compare genioglossus muscle reflex responses and upper airway collapsibility in non-obese people with MS, with and without OSA. Methods Non-obese adults with MS and OSA vs MS without OSA were instrumented with pressure sensors at the choanae and epiglottis. Bipolar fine wires were inserted into the genioglossus. A nasal mask and pneumotachograph were attached to a breathing circuit to deliver brief (~250ms) suction pressure (~-12cmH2O) during early inspiration every 2-10 breaths while awake. Genioglossus reflex onset latency, peak latency and peak amplitude were quantified. The upper airway collapsibility index was the percent difference between choanal and epiglottic airway pressures during negative pressure. Results 15 people with MS (6 males), aged 48±13years, BMI=25±3kg/m-2 and AHI=13±17events/h (mean±SD) were studied. 47% had OSA (AHI&amp;gt;10events/h). Genioglossus reflex excitation onset latency (22±2 vs. 24±19ms), peak excitation latency (37±11 vs. 38±23ms) and peak amplitude (258±125 vs. 205±95%) were not different between OSA vs. non-OSA. The upper airway was more collapsible in people with OSA (49±32 vs. 17±16%, p=0.04). Conclusions There is a high prevalence of OSA among non-obese people with MS. There was no systematic difference in upper airway dilator muscle function. However, the upper airway is ~65% more collapsible in people with MS and OSA despite absence of obesity.

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.

Translation of obstructive sleep apnea pathophysiology and phenotypes to personalized treatment: a narrative review.

Obstructive Sleep Apnea (OSA) arises due to periodic blockage of the upper airway (UA) during sleep, as negative pressure generated during inspiration overcomes the force exerted by the UA dilator muscles to maintain patency. This imbalance is primarily seen in individuals with a narrowed UA, attributable to factors such as inherent craniofacial anatomy, neck fat accumulation, and rostral fluid shifts in the supine posture. Sleep-induced attenuation of UA dilating muscle responsiveness, respiratory instability, and high loop gain further exacerbate UA obstruction. The widespread comorbidity profile of OSA, encompassing cardiovascular, metabolic, and neuropsychiatric domains, suggests complex bidirectional relationships with conditions like heart failure, stroke, and metabolic syndrome. Recent advances have delineated distinct OSA phenotypes beyond mere obstruction frequency, showing links with specific symptomatic manifestations. It is vital to bridge the gap between measurable patient characteristics, phenotypes, and underlying pathophysiological traits to enhance our understanding of OSA and its interplay with related outcomes. This knowledge could stimulate the development of tailored therapies targeting specific phenotypic and pathophysiological endotypes. This review aims to elucidate the multifaceted pathophysiology of OSA, focusing on the relationships between UA anatomy, functional traits, clinical manifestations, and comorbidities. The ultimate objective is to pave the way for a more personalized treatment paradigm in OSA, offering alternatives to continuous positive airway pressure therapy for selected patients and thereby optimizing treatment efficacy and adherence. There is an urgent need for personalized treatment strategies in the ever-evolving field of sleep medicine, as we progress from a 'one-size-fits-all' to a 'tailored-therapy' approach.

Night-to-Night Variability of Polysomnography-Derived Physiologic Endotypic Traits in Patients With Moderate to Severe OSA

Emerging data suggest that determination of physiologic endotypic traits (eg, loop gain) may enable precision medicine in OSA. Does a single-night assessment of polysomnography-derived endotypic traits provide reliable estimates in moderate to severe OSA? Two consecutive in-lab polysomnography tests from a clinical trial (n= 67; male, 69%; mean ± SD age, 61 ± 10 years; apnea-hypopnea index [AHI] 53 ± 22 events/h) were used for the reliability analysis. Endotypic traits, reflecting upper airway collapsibility (ventilation at eupneic drive [Vpassive]), upper airway dilator muscle tone (ventilation at the arousal threshold [Vactive]),loop gain (stability of ventilatory control, LG1), and arousal threshold (ArTh) were determined. Reliability was expressed as an intraclass correlation coefficient (ICC). Minimal detectable differences (MDDs) were computed to provide an estimate of maximum spontaneous variability. Further assessment across four repeated polysomnography tests was performed in a subcohort (n= 22). Reliability of endotypic traits between the two consecutive nights was moderate to good (ICC: Vpassive= 0.82, Vactive= 0.76, LG1= 0.72, ArTh= 0.83). Variability in AHI, but not in body position or in sleep stages, was associated with fluctuations in Vpassive and Vactive (r= -0.49 and r= -0.41, respectively; P< .001 for both). MDDs for single-night assessments were: Vpassive= 22, Vactive= 34, LG1= 0.17, and ArTh= 21. Multiple assessments (mean of two nights, n= 22) further reduced MDDs by approximately 20%to 30%. Endotypic trait analysis using a single standard polysomnography shows acceptable reliability and reproducibility in patients with moderate to severe OSA. The reported MDDs of endotypic traits may facilitate the quantification of relevant changes and may guide future evaluation of interventions in OSA.

Med Check: Psilocybin for OCD, Nuplazid Vote, and More

Med Check: Psilocybin for OCD, Nuplazid Vote, and More

Severity of nasopharyngeal collapse before and after corrective upper airway surgery in brachycephalic dogs.

To determine the severity of nasopharyngeal collapse in brachycephalic dogs before and after corrective airway surgery. Twenty-three brachycephalic dogs (21 with clinical signs referrable to the upper airway) and nine clinically normal nonbrachycephalic dogs (controls). Dogs were evaluated with fluoroscopy awake and standing with the head in a neutral position. The magnitude of nasopharyngeal collapse was measured as the maximum reduction in the dorsoventral dimension of the nasopharynx during respiration and expressed as a percentage. Brachycephalic dogs were anesthetized, the airway evaluated, and corrective upper airway surgery (alaplasty, staphylectomy, sacculectomy, tonsillectomy) was performed. A cohort (n=11) of the surgically treated brachycephalic dogs had fluoroscopy repeated a minimum of 6 weeks after surgery. Median preoperative reduction in the dorsoventral dimensions of the nasopharynx was greater in brachycephalic dogs (65%; range: 8-100%) than in controls (10%; range: 1-24%, p=.0001). Surgery did not improve the reduction in dorsoventral diameter of the nasopharynx during respiration in brachycephalic dogs (n=11) postoperatively (p=.0505). Nasopharyngeal collapse was a common and sometimes severe component of brachycephalic airway obstruction syndrome in the cohort of dogs evaluated. The lack of significant postoperative improvement may represent a type II error, a failure to adequately address anatomical abnormalities that increase resistance to airflow, or inadequate upper airway dilator muscle function in some brachycephalic dogs.

Is Continuous Positive Airway Pressure All There Is? Alternative Perioperative Treatments for Obstructive Sleep Apnea

Is Continuous Positive Airway Pressure All There Is? Alternative Perioperative Treatments for Obstructive Sleep Apnea

0754 Effects of Atomoxetine plus a Hypnotic on Obstructive Sleep Apnea (OSA) Severity in Patients with a Moderately Collapsible Pharyngeal Airway

Abstract Introduction The combination of atomoxetine and oxybutynin has demonstrated efficacy in the treatment of OSA. Oxybutynin may play a role as an upper airway dilator muscle activator and/or a hypnotic to improve sleep quality. We assessed the effectiveness of atomoxetine when combined with one of two hypnotics. Trazodone is a known hypnotic with possible effects on pharyngeal muscle activity. The other is lemborexant, an orexin antagonist. The effects of both combinations were assessed in patients with OSA and a moderately collapsible pharyngeal airway. Methods Recruited patients were 18 – 65 years of age, with an AHI 4 (4% desaturation criteria) of 10 – 55 and a BMI &amp;lt; 40 kg/m2. Each had to have a moderately collapsible pharyngeal airway using previously defined criteria based on the average percent desaturation during obstructive events (&amp;lt; 8%) and the ratio of hypopneas to total events (&amp;gt; 50%). After a qualifying PSG, each patient spent three nights in the sleep laboratory with approximately one week between studies. Nights were randomized to placebo, atomoxetine 80 mg plus trazodone 100 mg, and atomoxetine 80 mg plus lemborexant 10 mg. Primary outcomes were AHI 4 and the sleep apnea specific hypoxic burden (HB), the area under the SpO2 curve associated with disordered breathing events. Results Fifteen patients completed the trial (median [interquartile range] age was 52 [48-55] and BMI was 33.6 [30 – 35.1] kg/m2. Atomoxetine plus trazodone showed a strong trend for AHI 4 reduction from placebo (from 18.2 [11.8 – 31.3] to 7.4 [5.4 – 16.1] events/h, p=0.064), a significant reduction in HB from placebo (from 48.2 [31.2 – 79.6] to 18.7 [14.9 – 43.5] % min/h) and a trend for a reduction in HB with atomoxetine plus lemborexant (from 34.1 [12.1 – 128.8] to 18.7 [14.9 – 43.5] % min/h, p=0.055). There was no change in total sleep time or arousal index between treatment arms. Mild adverse events were reported on atomoxetine plus trazodone (2/15 sinusitis, 1/15 heartburn). Conclusion In OSA patients with a moderately collapsible upper airway, the combination of atomoxetine plus trazodone yielded clinically meaningful improvements in measures of sleep disordered breathing and oxygenation while atomoxetine plus lemborexant produced smaller effects. Support (If Any) This study was supported by Apnimed.

Beyond Usual Care: A Multidisciplinary Approach Towards the Treatment of Obstructive Sleep Apnoea.

Obstructive Sleep Apnoea (OSA) is common and characterised by repeated apnoeas and hypopnoeas while asleep due to collapse of the upper airway. OSA can have a significant impact on physical and mental health and, when left untreated, is associated with increased risk of developing cardiovascular ill health. Besides cardiorespiratory implications excessive daytime sleepiness, morning headaches, limited memory function and lack of concentration are some further symptoms caused by OSA. Continuous Positive Airway Pressure (CPAP) therapy is the evidence-based treatment to maintain upper airway patency in patients with moderate to severe OSA. Proper adherence to CPAP therapy successfully abolishes nocturnal apnoeas and hypopnoeas, and diminishes consequences of uncontrolled OSA, such as treatment resistant hypertension. However, long term adherence to CPAP remains an unresolved limitation of this method. Although alternatives to CPAP therapy may be less efficacious, there is a variety of non-CPAP treatments that includes conventional lifestyle advice, postural advice, the use of mandibular advancement devices (MADs), surgical treatment options, such as uvulopalatopharyngoplasty, tonsillectomy, or maxillomandibular advancement, and the use of electrical stimulation of the upper airway dilator muscles. Hypoglossal Nerve Stimulation is available as an invasive (HNS) and a transcutaneous (TESLA) approach. For the management of “difficult-to-treat” patients with OSA, particularly in those in whom first line therapy proved to be unsuccessful, a multidisciplinary team approach may be helpful to incorporate the available options of non-CPAP therapy and provide appropriate choices. Symptom control, patient-related outcome measures and long-term cardiovascular health should be prioritised when choosing long-term therapies to treat OSA. The inclusion of patients in the choice of successful management options of their condition will facilitate better long-term adherence. Advancing clinical trials in the field will further help to resolve the relative lack of evidence for effective non-CPAP methods.

P005 The effect of alcohol on the motor control of the genioglossus muscle

Abstract Rationale Alcohol is recognised to worsen snoring and obstructive sleep apnea (OSA). This effect is thought to be due to alcohol’s depressant effect on upper airway dilator muscles such as the genioglossus, but how alcohol reduces genioglossus activity is unknown. The aim of this study was to investigate alcohol’s effect on genioglossus single motor units (SMUs). Methods Healthy individuals visited the lab on two days (Alcohol: breath alcohol concentration ~0.08% or Placebo). They were instrumented with a nasal mask, 4 intramuscular genioglossus SMU EMG wires and an ear oximeter. They were exposed to 8–12 hypoxia trials (45-60s of 10%O2 followed by one breath of 100%O2) while awake. The SMUs were sorted according to their firing patterns with respect to respiration and were quantified during baseline, hypoxia, hyperoxia and recovery. Results The total number of SMUs recorded at baseline (68 and 67 respectively) and their distribution (ET: 29 vs 22, IP: 5 vs 10, IT: 8 vs 20 and TT: 26 vs 15 respectively) was similar between conditions. The discharge frequency did not differ between conditions (21Hz vs 22.4Hz, p&amp;gt;0.08). There was no difference between placebo and alcohol in the number (101 vs 88 respectively) and distribution (ET: 35 vs 32, IP: 22 vs 16, IT: 14 vs 22 and TT: 30 vs 17 respectively, p&amp;lt;0.05) of SMUs during hypoxia. Afterdischarge following hypoxia was also not different between conditions. Conclusion Alcohol has little effect on genioglossus SMUs and afterdischarge. OSA following alcohol may be related to increased upper airway resistance/nasal congestion.

A Pilot Randomized Controlled Trial of Effect of Genioglossus Muscle Strengthening on Obstructive Sleep Apnea Outcomes.

The genioglossus is a major upper airway dilator muscle. Our goal was to assess the efficacy of upper airway muscle training on Obstructive Sleep Apnea (OSA) as an adjunct treatment. Sixty-eight participants with OSA (AHI > 10/h) were recruited from our clinic. They fall into the following categories: (a) Treated with Automatic Positive Airway Pressure (APAP), (n = 21), (b) Previously failed APAP therapy (Untreated), (n = 25), (c) Treated with Mandibular Advancement Splint (MAS), (n = 22). All subjects were given a custom-made tongue strengthening device. We conducted a prospective, randomized, controlled study examining the effect of upper airway muscle training. In each subgroup, subjects were randomized to muscle training (volitional protrusion against resistance) or sham group (negligible resistance), with a 1:1 ratio over 3 months of treatment. In the baseline and the final visit, subjects completed home sleep apnea testing, Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), SF-36 (36-Item Short Form Survey), and Psychomotor Vigilance Test (PVT). Intervention (muscle training) did not affect the AHI (Apnea-Hypopnea Index), (p-values > 0.05). Based on PSQI, ESS, SF-36 scores, and PVT parameters, the changes between the intervention and sham groups were not significant, and the changes were not associated with the type of treatment (p-value > 0.05). The effectiveness of upper airway muscle training exercise as an adjunct treatment requires further study.

Research progress of obstructive sleep apnea hypopnea syndrome and upper airway dilator muscles

阻塞性睡眠呼吸暂停低通气综合征（OSAHS）是一种临床常见的睡眠呼吸障碍性疾病，发病率正在逐年上升。上气道扩张肌结构和功能异常是OSAHS的重要致病机制之一。大量研究发现，OSAHS引起的慢性间歇性缺氧（CIH）、高碳酸血症、睡眠片段化可通过各种机制影响上气道扩张肌的结构和功能，形成恶性循环加重病情。因此，本文现就OSAHS与上气道扩张肌的相互关系及可能的机制综述如下。.

Vulnerability to Postoperative Complications in Obstructive Sleep Apnea: Importance of Phenotypes.

Obstructive sleep apnea (OSA) is a common comorbidity in patients undergoing surgical procedures. Patients with OSA are at heightened risk of postoperative complications. Current treatments for OSA focus on alleviating upper airway collapse due to impaired upper airway anatomy. Although impaired upper airway anatomy is the primary cause of OSA, the pathogenesis of OSA is highly variable from person to person. In many patients, nonanatomical traits play a critical role in the development of OSA. There are 4 key traits or "phenotypes" that contribute to OSA pathogenesis. In addition to (1) impaired upper airway anatomy, nonanatomical contributors include: (2) impaired upper airway dilator muscle responsiveness; (3) low respiratory arousal threshold (waking up too easily to minor airway narrowing); and (4) unstable control of breathing (high loop gain). Each of these phenotypes respond differently to postoperative factors, such as opioid medications. An understanding of these phenotypes and their highly varied interactions with postoperative risk factors is key to providing safer personalized care for postoperative patients with OSA. Accordingly, this review describes the 4 OSA phenotypes, highlights how the impact on OSA severity from postoperative risk factors, such as opioids and other sedatives, is influenced by OSA phenotypes, and outlines how this knowledge can be applied to provide individualized care to minimize postoperative risk in surgical patients with OSA.

Perioperative Management of the Patient With Obstructive Sleep Apnea: A Narrative Review.

The prevalence of obstructive sleep apnea (OSA) has reached 1 billion people worldwide, implying significant risk for the perioperative setting as patients are vulnerable to cardiopulmonary complications, critical care requirement, and unexpected death. This review summarizes main aspects and considerations for the perioperative management of OSA, a condition of public health concern. Critical determinants of perioperative risk include OSA-related changes in upper airway anatomy with augmented collapsibility, diminished capability of upper airway dilator muscles to respond to airway obstruction, disparities in hypoxemia and hypercarbia arousal thresholds, and instability of ventilatory control. Preoperative OSA screening to identify patients at increased risk has therefore been implemented in many institutions. Experts recommend that in the absence of severe symptoms or additional compounding health risks, patients may nevertheless proceed to surgery, while heightened awareness and the adjustment of postoperative care is required. Perioperative caregivers should anticipate difficult airway management in OSA and be prepared for airway complications. Anesthetic and sedative drug agents worsen upper airway collapsibility and depress central respiratory activity, while the risk for postoperative respiratory compromise is further increased with the utilization of neuromuscular blockade. Consistently, opioid analgesia has proven to be complex in OSA, as patients are particularly prone to opioid-induced respiratory depression. Moreover, basic features of OSA, including intermittent hypoxemia and repetitive sleep fragmentation, gradually precipitate a higher sensitivity to opioid analgesic potency along with an increased perception of pain. Hence, regional anesthesia by blockade of neural pathways directly at the site of surgical trauma as well as multimodal analgesia by facilitating additive and synergistic analgesic effects are both strongly supported in the literature as interventions that may reduce perioperative complication risk. Health care institutions are increasingly allocating resources, including those of postoperative enhanced monitoring, in an effort to increase patient safety. The implementation of evidence-based perioperative management strategies is however burdened by the rising prevalence of OSA, the large heterogeneity in disease severity, and the lack of evidence on the efficacy of costly perioperative measures. Screening and monitoring algorithms, as well as reliable risk predictors, are urgently needed to identify OSA patients that are truly in need of extended postoperative surveillance and care. The perioperative community is therefore challenged to develop feasible pathways and measures that can confer increased patient safety and prevent complications in patients with OSA.

Clinical trial of a rehabilitation device based on electrical stimulation for patients with obstructive sleep apnoea (OSA): a study protocol

Obstructive sleep apnoea-hypopnoea syndrome (OSA) is a respiratory disorder characterised by repetitive obstruction of the upper airway, leading to several interruptions during sleep. It is currently one of the main public health problems worldwide and one of the main cardiovascular risk factors in developed and intermediate developing countries, whose populations are increasing in rates of obesity and age. One of the common treatments for OSA is a continuous positive airway pressure (CPAP) device, which pumps air through a hose, reaches a mask that the patient has over his or her nose and travels the airway, keeping the upper airway open during sleep and avoiding episodes of airway collapse. The problem is that CPAP is not accepted by some patients due to a lack of adaptation, so alternative treatments may be needed. For some years, there have been explorations of treatments related to electrical stimulation of the muscles of the upper airway as therapy to reduce the number of episodes of apnoea (measured through the apnoea–hypopnoea index) during the night, strengthening these muscles through stimulation. This is the protocol of the first clinical study of a rehabilitation device for home use that not only provides functional stimulation of the upper-airway dilator muscles but also provides sensory stimulation. This device works by strengthening the dilating muscles of the upper respiratory tract and improving the sensory capacity of the laryngo-pharyngeal tract and is based on existing publications on the effectiveness of functional and somatosensory neurostimulation through neuroplasticity in the recovery of neurological deficits. Trial registration: Clinicaltrials.gov NCT04607343 (29/10/2020)

Downregulated hypoxia-inducible factor 1α improves myoblast differentiation under hypoxic condition in mouse genioglossus.

The treatment of obstructive sleep apnea-hypopnea syndrome targets the narrow anatomic structure of the upper airway (UA) and lacks an effective therapy for UA dilator muscle dysfunction. Long-term hypoxia can cause damage to UA dilator muscles and trigger a vicious cycle. We previously confirmed that hypoxia-inducible factor 1α (HIF-1α) upregulation mediates muscle fatigue in hypoxia condition, but the underlying mechanism remains to be determined. The present study investigated the intrinsic mechanisms and related pathways of HIF-1α that affect myoblast differentiation, with an aim to search for compounds that have protective effects in hypoxic condition. Differentiation of myoblasts was induced under hypoxia, and we found that hypoxia significantly inhibits the differentiation of myoblasts, damages the ultrastructure of mitochondria, and reduces the expression of myogenin, PGC-1β and pAMPKα1. HIF-1α has a negative regulation effect on AMPK. Downregulation of HIF-1α increases the expression of the abovementioned proteins, promotes the differentiation of myoblasts, and protects mitochondrial integrity. In addition, mitochondrial biogenesis occurs during myogenic differentiation. Inhibition of the AMPK pathway inhibits mitochondrial biogenesis, decreases the level of PGC-1β, and increases apoptosis. Resveratrol dimer can reverse the mitochondrial damage induced by AMPK pathway inhibition and decrease myoblast apoptosis. Our results provided a regulatory mechanism for hypoxic injury in genioglossus which may contribute to the pathogenesis and treatment of OSAHS.

Pathophysiology of Upper Airway Collapse

Previous pathophysiologic studies have revealed that the upper airway dimension reaches a minimal value at the end of expiration, and pharyngeal negative pressure is not an essential prerequisite for upper airway collapse. Furthermore, pharyngeal collapse occurs in spite of increased activity of upper airway dilator muscles in patients with obstructive sleep apnea (OSA) compared with normal subjects. Pharyngeal sensory threshold is elevated in patients with OSA, which contributes to inadequate activity of upper airway dilator muscles. Pharyngeal narrowing results in several types of airflow limitation, of whom the mechanisms are mainly explained using Starling resistor model and negative effort dependence. Several studies have been conducted over the past years to validate polysomnographic surrogate markers which indicate specific pathophysiologic phenotypes, and such attempts may be able to lead us to personalized treatment for OSA.