scholarly journals Leptin receptor expression in the dorsomedial hypothalamus stimulates breathing during NREM sleep in db/db mice

2020 ◽  
Author(s):  
Huy Pho ◽  
Slava Berger ◽  
Carla Freire ◽  
Lenise J Kim ◽  
Mi-Kyung Shin ◽  
...  
Keyword(s):  
Airway Obstruction ◽  
Leptin Receptor ◽  
Minute Ventilation ◽  
Upper Airway ◽  
Nrem Sleep ◽  
Receptor Expression ◽  
Upper Airway Obstruction ◽  
Dorsomedial Hypothalamus ◽  
Obstructive Sleep ◽  
Alveolar Hypoventilation

ABSTRACTObesity can lead to recurrent upper airway obstruction (obstructive sleep apnea, OSA) during sleep as well as alveolar hypoventilation. We have previously shown that leptin stimulates breathing and treats OSA in leptin-deficient ob/ob mice and leptin-resistant diet-induced obese mice. Our previous data also suggest that leptin’s respiratory effects may occur in the dorsomedial hypothalamus (DMH). We selectively expressed leptin receptor LepRb in the DMH neurons of obese LepRb-deficient db/db mice (LepRb-DMH mice), which hypoventilate at baseline, and showed that intracerebroventricular injection of leptin in these animals increased inspiratory flow, tidal volume and minute ventilation during NREM sleep without any effect on the quality of NREM sleep or CO2 production. Leptin had no effect on upper airway obstruction in LepRb-DMH animals. We conclude that leptin stimulates breathing and treats obesity related hypoventilation acting on LepRb-positive neurons in the DMH.

scholarly journals Compensatory responses to upper airway obstruction in obese apneic men and women

2012 ◽  
Vol 112 (3) ◽  
pp. 403-410 ◽  
Author(s):  
Chien-Hung Chin ◽  
Jason P. Kirkness ◽  
Susheel P. Patil ◽  
Brian M. McGinley ◽  
Philip L. Smith ◽  
...  
Keyword(s):  
Sleep Apnea ◽  
Airway Obstruction ◽  
Rem Sleep ◽  
Minute Ventilation ◽  
Upper Airway ◽  
Nrem Sleep ◽  
Upper Airway Obstruction ◽  
Men And Women ◽  
Compensatory Responses ◽  
Obstructive Sleep

Defective structural and neural upper airway properties both play a pivotal role in the pathogenesis of obstructive sleep apnea. A more favorable structural upper airway property [pharyngeal critical pressure under hypotonic conditions (passive Pcrit)] has been documented for women. However, the role of sex-related modulation in compensatory responses to upper airway obstruction (UAO), independent of the passive Pcrit, remains unclear. Obese apneic men and women underwent a standard polysomnography and physiological sleep studies to determine sleep apnea severity, passive Pcrit, and compensatory airflow and respiratory timing responses to prolonged periods of UAO. Sixty-two apneic men and women, pairwise matched by passive Pcrit, exhibited similar sleep apnea disease severity during rapid eye movement (REM) sleep, but women had markedly less severe disease during non-REM (NREM) sleep. By further matching men and women by body mass index and age ( n = 24), we found that the lower NREM disease susceptibility in women was associated with an approximately twofold increase in peak inspiratory airflow ( P = 0.003) and inspiratory duty cycle ( P = 0.017) in response to prolonged periods of UAO and an ∼20% lower minute ventilation during baseline unobstructed breathing (ventilatory demand) ( P = 0.027). Thus, during UAO, women compared with men had greater upper airway and respiratory timing responses and a lower ventilatory demand that may account for sex differences in sleep-disordered breathing severity during NREM sleep, independent of upper airway structural properties and sleep apnea severity during REM sleep.

scholarly journals Leptin receptor expression in the dorsomedial hypothalamus stimulates breathing during NREM sleep in db/db mice

SLEEP ◽  
2021 ◽  
Author(s):  
Huy Pho ◽  
Slava Berger ◽  
Carla Freire ◽  
Lenise J Kim ◽  
Mi-Kyung Shin ◽  
...  
Keyword(s):  
Airway Obstruction ◽  
Leptin Receptor ◽  
Upper Airway ◽  
Nrem Sleep ◽  
Upper Airway Obstruction ◽  
Co2 Production ◽  
Dorsomedial Hypothalamus ◽  
Leptin Signaling ◽  
Arterial Blood ◽  
Obesity Hypoventilation

Abstract Study Objectives Obesity leads to obstructive sleep apnea (OSA), which is recurrent upper airway obstruction during sleep, and obesity hypoventilation syndrome (OHS), hypoventilation during sleep resulting in daytime hypercapnia. Impaired leptin signaling in the brain was implicated in both conditions, but mechanisms are unknown. We have previously shown that leptin stimulates breathing and treats OSA and OHS in leptin- deficient ob/ob mice and leptin-resistant diet-induced obese mice and that leptin’s respiratory effects may occur in the dorsomedial hypothalamus (DMH). We hypothesized that leptin receptor LepR b–deficient db/db mice have obesity hypoventilation and that restoration of leptin signaling in the DMH will increase ventilation during sleep in these animals. Methods We measured arterial blood gas in unanesthetized awake db/db mice. We subsequently infected these animals with Ad-LepR  b or control Ad-mCherry virus into the DMH and measured ventilation during sleep as well as CO2 production after intracerebroventricular (ICV) infusions of phosphate-buffered saline or leptin. Results Awake db/db mice had elevated CO2 levels in the arterial blood. Ad-LepR  b infection resulted in LepR  b expression in the DMH neurons in a similar fashion to wildtype mice. In LepR  b-DMH db/db mice, ICV leptin shortened REM sleep and increased inspiratory flow, tidal volume and minute ventilation during NREM sleep without any effect on the quality of NREM sleep or CO2 production. Leptin had no effect on upper airway obstruction in these animals. Conclusion Leptin stimulates breathing and treats obesity hypoventilation acting on LepR b-positive neurons in the DMH.

Central sleep apnea and hypoventilation syndromes

2017 ◽  
Author(s):  
Mithri R. Junna ◽  
Bernardo J. Selim ◽  
Timothy I. Morgenthaler
Keyword(s):  
Sleep Apnea ◽  
Airway Obstruction ◽  
Noninvasive Positive Pressure Ventilation ◽  
Central Sleep Apnea ◽  
Upper Airway ◽  
Upper Airway Obstruction ◽  
Positive Pressure ◽  
Adaptive Servo Ventilation ◽  
Obstructive Sleep ◽  
Alveolar Hypoventilation

Sleep disordered breathing (SDB) may occur in a variety of ways. While obstructive sleep apnea is the most common of these, this chapter reviews the most common types of SDB that occur independently of upper airway obstruction. In many cases, there is concurrent upper airway obstruction and neurological respiratory dysregulation. Thus, along with attempts to correct the underlying etiologies (when present), stabilization of the upper airway is most often combined with flow generators (noninvasive positive pressure ventilation devices) that modulate the inadequate ventilatory pattern. Among these devices, when continuous positive airway pressure (CPAP) alone does not allow correction of SDB, adaptive servo-ventilation (ASV) is increasingly used for non-hypercapnic types of central sleep apnea (CSA), while bilevel PAP in spontaneous-timed mode (BPAP-ST) is more often reserved for hypercapnic CSA/alveolar hypoventilation syndromes. Coordination of care among neurologists, cardiologists, and sleep specialists will often benefit such patients.

scholarly journals Leptin and the control of pharyngeal patency during sleep in severe obesity

2014 ◽  
Vol 116 (10) ◽  
pp. 1334-1341 ◽  
Author(s):  
Steven D. Shapiro ◽  
Chien-Hung Chin ◽  
Jason P. Kirkness ◽  
Brian M. McGinley ◽  
Susheel P. Patil ◽  
...  
Keyword(s):  
Airway Obstruction ◽  
Critical Pressure ◽  
Minute Ventilation ◽  
Upper Airway ◽  
Upper Airway Obstruction ◽  
Obese Women ◽  
Compensatory Mechanisms ◽  
Serum Leptin ◽  
Compensatory Responses ◽  
Obstructive Sleep

Rationale: Obesity imposes mechanical loads on the upper airway, resulting in flow limitation and obstructive sleep apnea (OSA). In previous animal models, leptin has been considered to serve as a stimulant of ventilation and may prevent respiratory depression during sleep. We hypothesized that variations in leptin concentration among similarly obese individuals will predict differences in compensatory responses to upper airway obstruction during sleep. Methods: An observational study was conducted in 23 obese women [body mass index (BMI): 46 ± 3 kg/m2, age: 41 ± 12 yr] and 3 obese men (BMI: 46 ± 3 kg/m2, age: 43 ± 4 yr). Subjects who were candidates for bariatric surgery were recruited to determine upper airway collapsibility under hypotonic conditions [pharyngeal critical pressure (passive PCRIT)], active neuromuscular responses to upper airway obstruction during sleep, and overnight fasting serum leptin levels. Compensatory responses were defined as the differences in peak inspiratory airflow (ΔVImax), inspired minute ventilation (ΔVI), and pharyngeal critical pressure (ΔPCRIT) between the active and passive conditions. Results: Leptin concentration was not associated with sleep disordered breathing severity, passive PCRIT, or baseline ventilation. In the women, increases in serum leptin concentrations were significantly associated with increases in ΔVImax ( r2 = 0.44, P < 0.001), ΔVI ( r2 = 0.40, P < 0.001), and ΔPCRIT ( r2 = 0.19, P < 0.04). These responses were independent of BMI, waist-to-hip ratio, neck circumference, or sagittal girth. Conclusion: Leptin may augment neural compensatory mechanisms in response to upper airway obstruction, minimizing upper airway collapse, and/or mitigating potential OSA severity. Variability in leptin concentration among similarly obese individuals may contribute to differences in OSA susceptibility.

scholarly journals 1244 A Curious Case of ASV Failure

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A474-A474
Author(s):  
Nishant Chaudhary ◽  
Mirna Ayache ◽  
John Carter
Keyword(s):  
Sleep Apnea ◽  
Airway Obstruction ◽  
Airway Pressure ◽  
Positive Airway Pressure ◽  
Central Sleep Apnea ◽  
Upper Airway ◽  
Upper Airway Obstruction ◽  
Neck Extension ◽  
Sleep Study ◽  
Obstructive Sleep

Abstract Introduction Positive airway pressure-induced upper airway obstruction has been reported with the treatment of obstructive sleep apnea (OSA) using continuous positive airway pressure (CPAP) along with an oronasal interface. Here we describe a case of persistent treatment emergent central sleep apnea (TECSA) inadequately treated with adaptive servo ventilation (ASV), with an airflow pattern suggestive of ASV-induced upper airway obstruction. Report of Case A 32-year-old male, with severe OSA (apnea hypopnea index: 52.4) and no other significant past medical history, was treated with CPAP and required higher pressures during titration sleep studies to alleviate obstructive events, despite a Mallampati Class II airway and a normal body mass index. Drug-Induced Sleep Endoscopy (DISE) showed a complete velopharynx and oropharynx anterior posterior (AP) collapse, long soft palate, which improved with neck extension. CPAP therapy, however, did not result in any symptomatic benefit and compliance reports revealed high residual AHI and persistent TECSA. He underwent an ASV titration sleep study up to a final setting of expiratory positive airway pressure 9 cm H2O, pressure support 6-15 cm H2O (auto-rate), with a full-face mask due to high oral leak associated with the nasal interface. The ASV device detected central apneas and provided mandatory breaths, but did not capture the thorax or abdomen, despite normal mask pressure tracings. Several such apneas occurred, with significant oxyhemoglobin desaturation. Conclusion We postulate that the ASV failure to correct central sleep apnea as evidenced by the absence of thoracoabdominal inspiratory effort, occurred due to ASV-induced upper airway obstruction. Further treatment options for this ASV phenomenon are to pursue an ASV-assisted DISE and determine the effectiveness of adjunctive therapy including neck extension, nasal mask with a mouth closing device and a mandibular assist device.

Upper airway obstruction in the critically ill

2016 ◽  
Author(s):  
Edmond Cohen
Keyword(s):  
Airway Obstruction ◽  
Pulmonary Function Tests ◽  
Upper Airway ◽  
Sleep Apnoea ◽  
Upper Airway Obstruction ◽  
Breath Sounds ◽  
Obstructive Sleep ◽  
Increased Risk ◽  
Facial Swelling ◽  
Conscious Patient

Upper airway obstruction (UAO) from any cause should be considered a life-threatening emergency. In a conscious patient, UAO may present as respiratory distress, stridor, dyspnoea, altered voice, cyanosis, cough, decreased or absent breath sounds, wheezing, the hand-to-the-throat choking sign in the case of a foreign body, facial swelling, and distended neck veins. The cause of UAO should be identified and airway management devices must be immediately available prior to any airway manipulation CT scan, flexible bronchoscopy, and pulmonary function tests should be performed to evaluate the cause and the extent of the obstruction. Obstructive sleep apnoea (OSA) patients are at increased risk of developing UAO. Endotracheal intubation, insertion of a supraglottic device, laser therapy, and endotracheal stents maybe life-saving

Relief of Upper Airway Obstruction by Adenotonsillectomy

1986 ◽  
Vol 94 (4) ◽  
pp. 476-480 ◽  
Author(s):  
William P. Potsic ◽  
Patrick S. Pasquariello ◽  
Christine Corso Baranak ◽  
Roger R. Marsh ◽  
Linda M. Miller
Keyword(s):  
Airway Obstruction ◽  
Sleep Disturbances ◽  
Upper Airway ◽  
Upper Airway Obstruction ◽  
Respiratory Sounds ◽  
Obstructive Sleep ◽  
Computer Aided Analysis ◽  
A Prospective Study ◽  
And Behavior ◽  
Postoperative Improvement

Adenotonsillectomy is often performed to relieve upper airway obstruction, even in children who do not present with severe apnea. Although adenotonsillectomy provides dramatic relief from obstructive sleep apnea, little evidence is available as to the efficacy of surgery in the far more prevalent cases of partial airway obstruction. We report the results of a prospective study of 100 children with adenotonsillar obstruction (without severe apnea) and 50 age-matched control children. The majority of patients exhibited appreciable sleep disturbances preoperatively, as compared to controls, and had substantial postoperative improvement, as demonstrated by parental questionnaire and sleep sonography—the computer-aided analysis of respiratory sounds. Mouth breathing and behavior problems were also prevalent preoperatively and were affected positively by adenotonsillectomy. It appears that surgery in such cases can have far-ranging benefits, even for the child whose obstruction does not demonstrate severe apnea.

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