scholarly journals The effect of leptin replacement on sleep-disordered breathing in the leptin-deficient ob/ob mouse

2016 ◽  
Vol 120 (1) ◽  
pp. 78-86 ◽  
Author(s):  
H. Pho ◽  
A. B. Hernandez ◽  
R. S. Arias ◽  
E. B. Leitner ◽  
S. Van Kooten ◽  
...  
Keyword(s):  
Airway Obstruction ◽  
Duty Cycle ◽  
Rem Sleep ◽  
Minute Ventilation ◽  
Upper Airway ◽  
Neuromuscular Control ◽  
Inspiratory Flow ◽  
Upper Airway Obstruction ◽  
Airflow Limitation ◽  
Breathing Patterns

Obese leptin-deficient ( ob/ob) mice demonstrate defects in upper airway structural and neuromuscular control. We hypothesized that these defects predispose to upper airway obstruction during sleep, and improve with leptin administration. High-fidelity polysomnographic recordings were conducted to characterize sleep and breathing patterns in conscious, unrestrained ob/ob mice (23 wk, 67.2 ± 4.1 g, n = 13). In a parallel-arm crossover study, we compared responses to subcutaneous leptin (1 μg/h) vs. vehicle on respiratory parameters during NREM and REM sleep. Upper airway obstruction was defined by the presence of inspiratory airflow limitation (IFL), as characterized by an early inspiratory plateau in airflow at a maximum level (V̇imax) with increasing effort. The severity of upper airway obstruction (V̇imax) was assessed along with minute ventilation (V̇e), tidal volume (VT), respiratory rate (RR), inspiratory duty cycle, and mean inspiratory flow at each time point. IFL occurred more frequently in REM sleep (37.6 ± 0.2% vs. 1.1 ± 0.0% in NREM sleep, P < 0.001), and leptin did not alter its frequency. V̇imax (3.7 ± 1.1 vs. 2.7 ± 0.8 ml/s, P < 0.001) and V̇e increased (55.4 ± 22.0 vs. 39.8 ± 16.4 ml/min, P < 0.001) with leptin vs. vehicle administration. The increase in V̇e was due to a significant increase in VT (0.20 ± 0.06 vs. 0.16 ± 0.05 ml, P < 0.01) rather than RR. Increases in V̇e were attributable to increases in mean inspiratory flow (2.5 ± 0.8 vs. 1.8 ± 0.6 ml/s, P < 0.001) rather than inspiratory duty cycle. Similar increases in V̇e and its components were observed in non-flow-limited breaths during NREM and REM sleep. These responses suggest that leptin stabilized pharyngeal patency and increased drive to both the upper airway and diaphragm during sleep.

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.

Effect of respiratory apparatus on respiration

1984 ◽  
Vol 57 (2) ◽  
pp. 475-480 ◽  
Author(s):  
C. Weissman ◽  
J. Askanazi ◽  
J. Milic-Emili ◽  
J. M. Kinney
Keyword(s):  
Tidal Volume ◽  
Duty Cycle ◽  
Breathing Pattern ◽  
Minute Ventilation ◽  
Inspiratory Flow ◽  
Percentage Increase ◽  
Breathing Patterns ◽  
Normal Volunteers ◽  
Abdominal Operation ◽  
Respiratory Apparatus

A mouthpiece plus noseclip (MP & NC) is frequently used in performing measurements of breathing patterns. Although the effects the apparatus exerts on breathing patterns have been studied, the mechanism of the changes it causes remains unclear. The current study examines the effects on respiratory patterns of a standard (17-mm-diam) MP & NC during room air (RA) breathing and the administration of 2 and 4% CO2 in normal volunteers and in patients 2–4 days after abdominal operation. When compared with values obtained with a noninvasive canopy system, the MP & NC induced increases in minute ventilation (VE), tidal volume (VT), and mean inspiratory flow (VT/TI), but not frequency (f) or inspiratory duty cycle, during both RA and CO2 administration. The percentage increase in VE, VT, and VT/TI caused by the MP & NC decreased as the concentration of CO2 increased. During RA breathing, the application of noseclip alone resulted in a decrease in f and an increase in VT, but VE and VT/TI were unchanged. The changes were attenuated during the administration of 2 and 4% CO2. Reducing the diameter of the mouthpiece to 9 mm abolished the alterations in breathing pattern observed with the larger (17-mm) diameter MP.

Accelerometry of Adductor Pollicis Muscle Predicts Recovery of Respiratory Function from Meeting Abstracts

2003 ◽  
Vol 98 (6) ◽  
pp. 1333-1337 ◽  
Author(s):  
Matthias Eikermann ◽  
Harald Groeben ◽  
Johannes Hüsing ◽  
Jürgen Peters
Keyword(s):  
Airway Obstruction ◽  
Neuromuscular Blockade ◽  
Forced Vital Capacity ◽  
Respiratory Function ◽  
Vital Capacity ◽  
Upper Airway ◽  
Inspiratory Flow ◽  
Upper Airway Obstruction ◽  
Residual Paralysis ◽  
Adductor Pollicis Muscle

Background Residual paralysis increases the risk of pulmonary complications but is difficult to detect. To test the hypothesis that accelerometry predicts effects of residual paralysis on pulmonary and upper airway function, the authors related tests of pulmonary and pharyngeal function to accelerometry of adductor pollicis muscle in 12 partially paralyzed volunteers. Methods Rocuronium (0.01 mg/kg + 2-10 microg x kg-1 x min-1) was administered to maintain train-of-four (TOF) ratios (assessed every 15 s) of approximately 0.5 and 0.8 over a period of more than 5 min. The authors evaluated pharyngeal and facial muscle functions during steady state relaxation and performed spirometric measurements every 5 min until recovery. Upper airway obstruction was defined as a mean ratio of expiratory and inspiratory flow at 50% of vital capacity of greater than 1. The TOF ratio associated with "acceptable" pulmonary recovery (forced vital capacity and forced inspiratory volume in 1 s of &gt; or =90% of baseline) was calculated using a linear regression model. Results At peak blockade (TOF ratio 0.5 +/- 0.16), forced inspiratory flow was impaired (53 +/- 19%) to a greater degree than forced expiratory flow (75 +/- 20%) with a mean ratio of expiratory and inspiratory flow at 50% of vital capacity of 1.18 +/- 0.6. Upper airway obstruction, observed in 8 of 12 volunteers, paralleled an impaired ability to swallow reported by 10 of 12 volunteers. In contrast, all volunteers except one could sustain a head lift for more than 5 s. The authors calculated that a mean TOF ratio of 0.56 (95% confidence interval, 0.22-0.71) predicts "acceptable" recovery of forced vital capacity, whereas forced inspiratory volume in 1 s was impaired until a TOF ratio of 0.95 (0.82-1.18) was reached. A 100% recovery of TOF ratio predicts an acceptable recovery of forced vital capacity, forced inspiratory volume in 1 s, and mean ratio of expiratory and inspiratory flow at 50% of vital capacity in 93%, 73%, and 88% of measurements (calculated negative predictive values), respectively. Conclusion Impaired inspiratory flow and upper airway obstruction frequently occur during minimal neuromuscular blockade (TOF ratio 0.8), and extubation may put the patient at risk. Although a TOF ratio of unity predicts a high probability of adequate recovery from neuromuscular blockade, respiratory function can still be impaired.

Analysis of Inspiratory Flow Shapes in Patients With Partial Upper-Airway Obstruction During Sleep

CHEST Journal ◽  
2001 ◽  
Vol 119 (1) ◽  
pp. 37-44 ◽  
Author(s):  
Tero Aittokallio ◽  
Tarja Saaresranta ◽  
Päivi Polo-Kantola ◽  
Olli Nevalainen ◽  
Olli Polo
Keyword(s):  
Airway Obstruction ◽  
Upper Airway ◽  
Inspiratory Flow ◽  
Upper Airway Obstruction ◽  
Partial Upper Airway Obstruction

Indices of Upper Airway Obstruction in Patients with Simultaneous Chronic Airflow Limitation

Respiration ◽  
1994 ◽  
Vol 61 (3) ◽  
pp. 121-125 ◽  
Author(s):  
Eduardo García-Pachón ◽  
Pere Casan ◽  
Joaquín Sanchis
Keyword(s):  
Airway Obstruction ◽  
Upper Airway ◽  
Upper Airway Obstruction ◽  
Airflow Limitation

Assessment of Changes in Upper Airway Obstruction by Automatic Identification of Inspiratory Flow Limitation During Sleep

2009 ◽  
Vol 56 (8) ◽  
pp. 2006-2015 ◽  
Author(s):  
Christian Morgenstern ◽  
Matthias Schwaibold ◽  
Winfried J. Randerath ◽  
Armin Bolz ◽  
Raimon Jane
Keyword(s):  
Airway Obstruction ◽  
Upper Airway ◽  
Inspiratory Flow ◽  
Upper Airway Obstruction ◽  
Automatic Identification ◽  
Flow Limitation

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.

Upper airway obstruction assessment: Peak inspiratory flow and clinical COPD Questionnaire

2018 ◽  
Vol 43 (5) ◽  
pp. 1303-1311
Author(s):  
J. Sanchez-Guerrero ◽  
J. Guerlain ◽  
S. Samaha ◽  
A. Burgess ◽  
J. Lacau St Guily ◽  
...  
Keyword(s):  
Airway Obstruction ◽  
Upper Airway ◽  
Inspiratory Flow ◽  
Upper Airway Obstruction ◽  
Peak Inspiratory Flow

Inspiratory Flow Volume Loops and the Diagnosis of Upper Airway Obstruction

2008 ◽  
Vol 15 (5) ◽  
pp. 274-282 ◽  
Author(s):  
Carl R. Pavel ◽  
Michael J. Morris ◽  
Karin L. Nicholson ◽  
Jackie A. Hayes
Keyword(s):  
Airway Obstruction ◽  
Upper Airway ◽  
Inspiratory Flow ◽  
Upper Airway Obstruction ◽  
Flow Volume

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.

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