Serotonergic Stimulation of the Genioglossus and the  Response to Nasal Continuous Positive Airway Pressure

Sunderram, Jagadeeshan; Parisi, Richard A.; Strobel, Richard

doi:10.1164/ajrccm.162.3.9907077

Cited by 48 publications

(20 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may therefore indicate the need of different therapeutic strategies for these "different" pathogenic forms of OSAS (obese versus nonobese). For instance, serotoninergic drugs enhance upper airway electromyogram (EMG) activity in nonobese healthy volunteers [36] and seem to reduce the apnoea/hypopnoea index in nonobese patients with OSAS [37]. The eventual uncovering of the cellular mechanisms underlying the abnormal endurance capacity observed in the study in nonobese patients with OSAS may lead to more target-oriented pharmacological therapies.…”

Section: Discussionmentioning

confidence: 99%

Effects of obesity upon genioglossus structure and function in obstructive sleep apnoea

Carrera¹,

Barbé²,

Sauleda³

et al. 2004

Eur Respir J

View full text Add to dashboard Cite

Obesity is a common feature of the obstructive sleep apnoea syndrome. It can influence the structure and function of skeletal muscles. However, its effects upon the upper airway muscles have not been explored directly.This study assessed the structure and function of the genioglossus in patients with obstructive sleep apnoea syndrome and in healthy subjects (with and without obesity, defined by a body mass index >30 kg·m−2). Further, to investigate the effects of continuous positive airway pressure (CPAP) treatment, patients with obstructive sleep apnoea syndrome after at least 1 yr under CPAP were also studied.The study found that obese and nonobese patients showed differentin vitrogeniglossus endurance properties. In obese patients, geniglossus endurance was indistinguishable from normal while, nonobese patients, at diagnosis, showed increased genioglossus fatigability; this was not observed in patients treated with CPAP. By contrast, patients with obstructive sleep apnoea syndrome showed at diagnosis a higher percentage of type II fibres than controls and patients under CPAP treatment independently of obesity. This difference is mainly due to a predominance of subtype IIb fibre. This difference was not observed in the group of patients treated with CPAP. Genioglossus twitch force was normal in all patients.These results suggest that different pathogenic mechanisms may underlie the development of obstructive sleep apnoea syndrome in obese and nonobese patients. This observation may have potential clinical implications.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of obesity upon genioglossus structure and function in obstructive sleep apnoea

Carrera¹,

Barbé²,

Sauleda³

et al. 2004

Eur Respir J

View full text Add to dashboard Cite

show abstract

“…Orexin seems to stabilize wakefulness and promote arousal (24). The activity of orexin neurons does vary with sleep-wake state (249) and orexin neurons provide excitatory inputs to nuclei that regulate arousal (203, 221). But the degree of circadian variation in orexin levels in cerebrospinal fluid of rats is quite large; it is two-fold, being highest during the active period of the cycle, suggesting an important circadian role that acts above and beyond the wake-sleep state cycle (44, 271).…”

Section: The Location Of Central Chemoreceptorsmentioning

confidence: 99%

Central Chemoreceptors: Locations and Functions

Nattie¹,

Li²

2012

Comprehensive Physiology

204

139

View full text Add to dashboard Cite

Central chemoreception traditionally refers to a change in ventilation attributable to changes in CO2/H+ detected within the brain. Interest in central chemoreception has grown substantially since the previous Handbook of Physiology published in 1986. Initially, central chemoreception was localized to areas on the ventral medullary surface, a hypothesis complemented by the recent identification of neurons with specific phenotypes near one of these areas as putative chemoreceptor cells. However, there is substantial evidence that many sites participate in central chemoreception some located at a distance from the ventral medulla. Functionally, central chemoreception, via the sensing of brain interstitial fluid H+, serves to detect and integrate information on 1) alveolar ventilation (arterial PCO2), 2) brain blood flow and metabolism and 3) acid-base balance, and, in response, can affect breathing, airway resistance, blood pressure (sympathetic tone) and arousal. In addition, central chemoreception provides a tonic ‘drive’ (source of excitation) at the normal, baseline PCO2 level that maintains a degree of functional connectivity among brainstem respiratory neurons necessary to produce eupneic breathing. Central chemoreception responds to small variations in PCO2 to regulate normal gas exchange and to large changes in PCO2 to minimize acid-base changes. Central chemoreceptor sites vary in function with sex and with development. From an evolutionary perspective, central chemoreception grew out of the demands posed by air vs. water breathing, homeothermy, sleep, optimization of the work of breathing with the ‘ideal’ arterial PCO2, and the maintenance of the appropriate pH at 37°C for optimal protein structure and function.

show abstract

“…Hypoglossal motoneurons in cats and hypoglossal nerve activity in rats are stimulated via 5-HT2 receptor activation (7,23). A selective serotonin reuptake inhibitor (SSRI), paroxetine, increases genioglossal electromyographic activity in normal subjects (41). Some SSRIs decrease the apnea index during non-rapid eye movement sleep in patients with obstructive sleep apnea (OSA) (12,21).…”

mentioning

confidence: 99%

Compensatory airway dilation and additive ventilatory augmentation mediated by dorsomedial medullary 5-hydroxytryptamine 2 receptor activity and hypercapnia

Kanamaru¹,

Homma²

2007

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

5-HT2 receptor activity in the hypoglossal nucleus and hypercapnia is associated with airway dilation. 5-HT neurons in the medullary raphe and hypercapnia are responsible for tidal volume change. In this study, the effects of 5-HT2 receptors in the dorsomedial medulla oblongata (DMM), which receives projections from the medullary raphe, and hypercapnia on airway resistance and respiratory variables were studied in mice while monitoring 5-HT release in the DMM. A microdialysis probe was inserted into the DMM of anesthetized adult mice. Each mouse was placed in a double-chamber plethysmograph. After recovery from anesthesia, the mice were exposed to stepwise increases in CO(2) inhalation (5%, 7%, and 9% CO(2) in O(2)) at 8-min intervals with a selective serotonin reuptake inhibitor, fluoxetine, or fluoxetine plus a 5-HT2 receptor antagonist, LY-53857 in the DMM. In response to fluoxetine plus LY-53857 coperfusion, specific airway resistance was increased, and tidal volume and minute ventilation were decreased. CO(2) inhalation with fluoxetine plus LY-53857 coperfusion in the DMM largely decreased airway resistance and additively increased minute ventilation. Thus, 5-HT2 receptor activity in the DMM increases basal levels of airway dilation and ventilatory volume, dependent on central inspiratory activity and the volume threshold of the inspiratory off-switch mechanism. Hypercapnia with low 5-HT2 receptor activity in the DMM largely recovers airway dilation and additively increases ventilatory volume. Interaction between 5-HT2 receptor activity in the DMM and CO(2) drive may elicit a cycle of hyperventilation with airway dilation and hypoventilation with airway narrowing.

show abstract

Serotonergic Stimulation of the Genioglossus and the Response to Nasal Continuous Positive Airway Pressure

Cited by 48 publications

References 25 publications

Effects of obesity upon genioglossus structure and function in obstructive sleep apnoea

Effects of obesity upon genioglossus structure and function in obstructive sleep apnoea

Central Chemoreceptors: Locations and Functions

Compensatory airway dilation and additive ventilatory augmentation mediated by dorsomedial medullary 5-hydroxytryptamine 2 receptor activity and hypercapnia

Contact Info

Product

Resources

About