Dataset Information

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

ABSTRACT: 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 ?V 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).

SUBMITTER: Taranto-Montemurro L

PROVIDER: S-EPMC5566293 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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

Taranto-Montemurro Luigi L Sands Scott A SA Azarbarzin Ali A Marques Melania M de Melo Camila M CM Edwards Bradley A BA Eckert Danny J DJ Messineo Ludovico L White David P DP Wellman Andrew A

Annals of the American Thoracic Society 20170701 7

<h4>Rationale</h4>The reduction in upper airway muscle activity from wakefulness to sleep plays a key role in the development of obstructive sleep apnea. Potassium (K<sup>+</sup>) 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<sup>+</sup> channel blocker, increased ge ...[more]

PMID: 28387543

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Project description:Inspiratory tongue dilatory movement is believed to be mediated via changes in neural drive to genioglossus. However, this has not been studied during quiet breathing in humans. Therefore, this study investigated this relationship and its potential role in obstructive sleep apnoea (OSA). During awake supine quiet nasal breathing, inspiratory tongue dilatory movement, quantified with tagged magnetic resonance imaging, and inspiratory phasic genioglossus EMG normalised to maximum EMG were measured in nine controls [apnoea-hypopnea index (AHI) ≤5 events/h] and 37 people with untreated OSA (AHI >5 events/h). Measurements were obtained for 156 neuromuscular compartments (85%). Analysis was adjusted for nadir epiglottic pressure during inspiration. Only for 106 compartments (68%) was a larger anterior (dilatory) movement associated with a higher phasic EMG [mixed linear regression, beta = 0.089, 95% CI [0.000, 0.178], t(99) = 1.995, P = 0.049, hereafter EMG↗/mvt↗]. For the remaining 50 (32%) compartments, a larger dilatory movement was associated with a lower phasic EMG [mixed linear regression, beta = -0.123, 95% CI [-0.224, -0.022], t(43) = -2.458, P = 0.018, hereafter EMG↘/mvt↗]. OSA participants had a higher odds of having at least one decoupled EMG↘/mvt↗ compartment (binary logistic regression, odds ratio [95% CI]: 7.53 [1.19, 47.47] (P = 0.032). Dilatory tongue movement was minimal (>1 mm) in nearly all participants with only EMG↗/mvt↗ compartments (86%, 18/21). These results demonstrate that upper airway dilatory mechanics cannot be predicted from genioglossus EMG, particularly in people with OSA. Tongue movement associated with minimal genioglossus activity suggests co-activation of other airway dilator muscles. KEY POINTS: Inspiratory tongue movement is thought to be mediated through changes in genioglossus activity. However, it is unknown if this relationship is altered by obstructive sleep apnoea (OSA). During awake supine quiet nasal breathing, inspiratory tongue movement, quantified with tagged magnetic resonance imaging (MRI), and inspiratory phasic genioglossus EMG normalised to maximum EMG were measured in four tongue compartments of people with and without OSA. Larger tongue anterior (dilatory) movement was associated with higher phasic genioglossus EMG for 68% of compartments. OSA participants had an ∼7-times higher odds of having at least one compartment for which a larger anterior tongue movement was not associated with a higher phasic EMG than controls. Therefore, higher genioglossus phasic EMG does not consistently translate into tongue dilatory movement, particularly in people with OSA. Large dilatory tongue movements can occur despite minimal genioglossus inspiratory activity, suggesting co-activation of other pharyngeal muscles.

Project description:Evidence indicates that men and African Americans may be more susceptible to weight gain resulting from sleep loss than women and whites, respectively. Increased daily caloric intake is a major behavioral mechanism that underlies the relation between sleep loss and weight gain.We sought to assess sex and race differences in caloric intake, macronutrient intake, and meal timing during sleep restriction.Forty-four healthy adults aged 21-50 y (mean ± SD: 32.7 ± 8.7 y; n = 21 women, n = 16 whites) completed an in-laboratory protocol that included 2 consecutive baseline nights [10 or 12 h time in bed (TIB)/night; 2200-0800 or 2200-1000] followed by 5 consecutive sleep-restriction nights (4 h TIB/night; 0400-0800). Caloric intake and meal-timing data were collected during the 2 d after baseline sleep and the first 3 d after sleep restriction.During sleep restriction, subjects increased daily caloric intake (P < 0.001) and fat intake (P = 0.024), including obtaining more calories from condiments, desserts, and salty snacks (Ps < 0.05) and consumed 532.6 ± 295.6 cal during late-night hours (2200-0359). Relative to women, men consumed more daily calories during baseline and sleep restriction, exhibited a greater increase in caloric intake during sleep restriction (d = 0.62), and consumed a higher percentage of daily calories during late-night hours (d = 0.78, Ps < 0.05). African Americans and whites did not significantly differ in daily caloric intake, increased caloric intake during sleep restriction, or meal timing. However, African Americans consumed more carbohydrates, less protein, and more caffeine-free soda and juice than whites did during the study (Ps < 0.05).Men may be more susceptible to weight gain during sleep loss than women due to a larger increase in daily caloric intake, particularly during late-night hours. These findings are relevant to the promotion of public health awareness by highlighting nutritional risk factors and modifiable behaviors for weight gain related to sleep-wake timing.

Dataset Information

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

Publications

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

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