Neuromechanical control of the isolated upper airway of mice

Liu, Audrey; Pichard, Luis E.; Schneider, Hartmut; Patil, Susheel P.; Smith, Philip L.; Polotsky, Vsevolod Y.; Schwartz, Alan R.

doi:10.1152/japplphysiol.90461.2008

Cited by 14 publications

(16 citation statements)

References 60 publications

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“…These flow-limited breaths were characterized by a decrease in inspiratory flow, an increase in inspiratory time, an increase in respiratory movement, and negative effort dependence, all of which are consistent with the development of dynamic upper airway obstruction (42). Previous studies have suggested that the most likely site of extrathoracic obstruction in the mouse is the pharynx (4,5,21,36). IFL in a sleeping mouse is a novel, potentially intriguing finding and suggests that this strain might serve as mouse model of OSA.…”

Section: Mouse Polysomnography and Iflsupporting

confidence: 64%

Novel whole body plethysmography system for the continuous characterization of sleep and breathing in a mouse

Hernandez

Kirkness

Smith

et al. 2012

Journal of Applied Physiology

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Sleep is associated with marked alterations in ventilatory control that lead to perturbations in respiratory timing, breathing pattern, ventilation, pharyngeal collapsibility, and sleep-related breathing disorders (SRBD). Mouse models offer powerful insight into the pathogenesis of SRBD; however, methods for obtaining the full complement of continuous, high-fidelity respiratory, electroencephalographic (EEG), and electromyographic (EMG) signals in unrestrained mice during sleep and wake have not been developed. We adapted whole body plethysmography to record EEG, EMG, and respiratory signals continuously in unrestrained, unanesthetized mice. Whole body plethysmography tidal volume and airflow signals and a novel noninvasive surrogate for respiratory effort (respiratory movement signal) were validated against simultaneously measured gold standard signals. Compared with the gold standard, we validated 1) tidal volume (correlation, R(2) = 0.87, P < 0.001; and agreement within 1%, P < 0.001); 2) inspiratory airflow (correlation, R(2) = 0.92, P < 0.001; agreement within 4%, P < 0.001); 3) expiratory airflow (correlation, R(2) = 0.83, P < 0.001); and 4) respiratory movement signal (correlation, R(2) = 0.79-0.84, P < 0.001). The expiratory airflow signal, however, demonstrated a decrease in amplitude compared with the gold standard. Integrating respiratory and EEG/EMG signals, we fully characterized sleep and breathing patterns in conscious, unrestrained mice and demonstrated inspiratory flow limitation in a New Zealand Obese mouse. Our approach will facilitate studies of SRBD mechanisms in inbred mouse strains and offer a powerful platform to investigate the effects of environmental and pharmacological exposures on breathing disturbances during sleep and wakefulness.

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Section: Mouse Polysomnography and Iflsupporting

confidence: 64%

Novel whole body plethysmography system for the continuous characterization of sleep and breathing in a mouse

Hernandez

Kirkness

Smith

et al. 2012

Journal of Applied Physiology

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“…Obesity also is an important factor affecting upper airway motor tone and airway collapsibility in humans (Schwartz et al, 1991; O'Donnell et al, 2000). Obese rodents, like obese humans, have less negative upper airway critical pressures than their lean controls (Ogasa et al, 2004; O'Donnell et al, 2000) and obese mice exhibit tonic upper airway activation under anesthesia (Liu et al, 2008; Brennick et al, 2009). However, the available evidence suggests that the levels and patterns of lingual EMG across sleep-wake states are similar in obese and lean rats (Sood et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Electromyographic activity at the base and tip of the tongue across sleep–wake states in rats

Kubin

2009

Respiratory Physiology & Neurobiology

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Obstructive sleep apnea (OSA) patients have elevated tonic and phasic inspiratory activity in the genioglossus and other upper airway muscles during wakefulness; this protects their upper airway from collapse. In this group, sleep-related decrements of upper airway motor tone result in sleeprelated upper airway obstructions. We previously reported that in the rat, a species widely used to study the neural mechanisms of both sleep and breathing, lingual electromyographic activity (EMG) is minimal or absent during slow-wave sleep (SWS) and then gradually increases after the onset of rapid eye movement sleep (REMS) due to the appearance of large phasic bursts. Here, we investigated whether sleep-wake patterns and respiratory modulation of lingual EMG depend on the site of EMG recording within the tongue. In nine chronically instrumented rats, we recorded from 17 sites within the tongue and from the diaphragm across sleep-wake states. We quantified lingual EMG in successive 10 s intervals of continuous 2 h recordings (1-3 pm). We found that sleep-wake patterns of lingual EMG did not differ between the base and tip of the tongue, and that respiratory modulation was extremely rare regardless of the recording site. We also determined that the often rhythmic lingual bursts during REMS do not occur with respiratory rhythmicity. This pattern differs from that in OSA subjects who, unlike rats, have collapsible upper airway, exhibit prominent respiratory-modulation of upper airway motor tone during quiet wakefulness, retain considerable tonic and inspiratory phasic activity during SWS, and show nadirs of activity during REMS.

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“…A major criticism of using MRI and CT in studies is that they are performed during wakefulness, a period during which upper airway muscles are active, and therefore they do not represent the actual behaviour of the upper airway during sleep . To minimize the confounding effect of neuromuscular activation during wakefulness, we explored airway distensibility/collapsibility during the expiratory phase. The size of the upper airway is determined by the balance between airway flow (luminal pressure) and the inward tissue pressure of upper airway tissue (tissue pressure).…”

Section: Discussionmentioning

confidence: 99%

“…Pharyngeal tissue distensibility is an indicator of the ease with which the airway can be deformed (and therefore also an indicator of the ease with which the airway can collapse) and is a measure of a passive property of the tissues. Innate distensibility and collapsibility are difficult to quantify during wakefulness because of confounding input from neuromuscular activation . During the respiratory cycle in the awake state, the upper airway cross section increases maximally in early expiration, decreases to a minimum at end expiration and remains relatively constant during the inspiratory phase (presumably due to the activation of upper airway dilator muscles) .…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have assessed distensibility by measuring airway pressure during upper airway imaging of airway volume changes (e.g. endoscopy, computed tomography (CT) and MRI) and calculating change in volume per change in pressure (Δpressure/Δvolume) . We have previously studied dynamic changes in the upper airway in patients with OSA while awake and during sleep .…”

Section: Introductionmentioning

confidence: 99%

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Pharyngeal distensibility during expiration is an independent predictor of the severity of obstructive sleep apnoea

et al. 2019

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Background and objective: Pharyngeal distensibility and collapsibility reflect the passive properties of tissue in the airway, are an indicator of the ease with which an airway can be deformed and are related to the severity of obstructive sleep apnoea (OSA). During normal tidal respiration, the collapsibility of the pharynx during expiration is passive without confounding by neuromuscular activation that occurs during inspiration. We evaluated the distensibility and collapsibility of the upper airway in subjects with OSA during wakefulness using sophisticated dynamic computed tomography (CT) imaging. We hypothesized that the dynamic changes of the upper airway during expiration would be related to the severity of OSA. Methods: Twenty-three patients with OSA and eight normal subjects underwent simultaneous measurement of respiratory flow and airway calibre using ultrafast CT. The change in pharyngeal cross-sectional area divided by the change in concomitant flow (as distensibility or collapsibility) was measured and compared across different severities of OSA. Results: The slope of this relationship between delta area and delta flow during expiration was significantly higher in severe OSA when compared with normal controls and mild-moderate OSA. Differences in airway distensibility or collapsibility between severity groups were significant in expiration but not in inspiration. Distensibility or collapsibility contributed most to the apnoeahypopnoea index in regression modelling. Age, gender, and body mass index (BMI) were not significant independent predictors. Conclusion: Our study demonstrates that airway distensibility during the expiratory phase of awake respiration is correlated with the severity of OSA.We have devised an image-based method that can rapidly assess obstructive sleep apnoea (OSA) severity in awake patients. We have shown that, in awake patients, airway distensibility/collapsibility during expiration, but not inspiration, is related to the severity of OSA. Airway distensibility is an independent risk factor for OSA, but not related to anatomical changes in the tongue and soft palate. 584 N-H Chen et al. Bold values indicate statistical significance, P < 0.05. † Higher collinear relationship with AHI, it was excluded in the final regression model. AHI, apnoea-hypopnoea index; BMI, body mass index; LSAT, lowest oxygen saturation; ODI, oxygen desaturation index; OSA, obstructive sleep apnoea; r s , coefficient of Spearman.

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Neuromechanical control of the isolated upper airway of mice

Cited by 14 publications

References 60 publications

Novel whole body plethysmography system for the continuous characterization of sleep and breathing in a mouse

Novel whole body plethysmography system for the continuous characterization of sleep and breathing in a mouse

Electromyographic activity at the base and tip of the tongue across sleep–wake states in rats

Pharyngeal distensibility during expiration is an independent predictor of the severity of obstructive sleep apnoea

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