scholarly journals Intermittent hypercapnic hypoxia during sleep does not induce ventilatory long-term facilitation in healthy males

2017 ◽  
Vol 123 (3) ◽  
pp. 534-543 ◽  
Author(s):  
Naomi L. Deacon ◽  
R. Doug McEvoy ◽  
Daniel L. Stadler ◽  
Peter G. Catcheside
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Arousal State ◽  
Obstructive Sleep ◽  
Hypercapnic Hypoxia ◽  
Long Term Facilitation ◽  
Healthy Males ◽  
Gas Exposure

Intermittent hypoxia-induced ventilatory neuroplasticity is likely important in obstructive sleep apnea pathophysiology. Although concomitant CO2levels and arousal state critically influence neuroplastic effects of intermittent hypoxia, no studies have investigated intermittent hypercapnic hypoxia effects during sleep in humans. Thus the purpose of this study was to investigate if intermittent hypercapnic hypoxia during sleep induces neuroplasticity (ventilatory long-term facilitation and increased chemoreflex responsiveness) in humans. Twelve healthy males were exposed to intermittent hypercapnic hypoxia (24 × 30 s episodes of 3% CO2and 3.0 ± 0.2% O2) and intermittent medical air during sleep after 2 wk washout period in a randomized crossover study design. Minute ventilation, end-tidal CO2, O2saturation, breath timing, upper airway resistance, and genioglossal and diaphragm electromyograms were examined during 10 min of stable stage 2 sleep preceding gas exposure, during gas and intervening room air periods, and throughout 1 h of room air recovery. There were no significant differences between conditions across time to indicate long-term facilitation of ventilation, genioglossal or diaphragm electromyogram activity, and no change in ventilatory response from the first to last gas exposure to suggest any change in chemoreflex responsiveness. These findings contrast with previous intermittent hypoxia studies without intermittent hypercapnia and suggest that the more relevant gas disturbance stimulus of concomitant intermittent hypercapnia frequently occurring in sleep apnea influences acute neuroplastic effects of intermittent hypoxia. These findings highlight the need for further studies of intermittent hypercapnic hypoxia during sleep to clarify the role of ventilatory neuroplasticity in the pathophysiology of sleep apnea.NEW & NOTEWORTHY Both arousal state and concomitant CO2levels are known modulators of the effects of intermittent hypoxia on ventilatory neuroplasticity. This is the first study to investigate the effects of combined intermittent hypercapnic hypoxia during sleep in humans. The lack of neuroplastic effects suggests a need for further studies more closely replicating obstructive sleep apnea to determine the pathophysiological relevance of intermittent hypoxia-induced ventilatory neuroplasticity.

scholarly journals The impact of arousal state, sex, and sleep apnea on the magnitude of progressive augmentation and ventilatory long-term facilitation

2013 ◽  
Vol 114 (1) ◽  
pp. 52-65 ◽  
Author(s):  
Ziauddin Syed ◽  
Ho-Sheng Lin ◽  
Jason H. Mateika
Keyword(s):  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Recovery Period ◽  
Apnea Hypopnea Index ◽  
Arousal State ◽  
Obstructive Sleep ◽  
End Tidal ◽  
Long Term Facilitation ◽  
The Impact

We examined the impact of arousal state, sex, and obstructive sleep apnea (OSA) on the magnitude of progressive augmentation of the hypoxic ventilatory response and ventilatory long-term facilitation (vLTF). We also examined whether exposure to intermittent hypoxia during sleep has an impact on the apnea-hypopnea index (AHI) in individuals with OSA. Ten men and seven women with OSA, along with ten healthy men and ten healthy women, were exposed to twelve 2-min episodes of hypoxia (end-tidal Po2: 50 Torr) in the presence of sustained hypercapnia (end-tidal Pco2: 3 Torr above baseline), followed by a 30-min recovery period during wakefulness and sleep. The OSA participants completed an additional sham study during sleep. The AHI during the first hour of sleep following the intermittent hypoxia and sham protocols were compared. Progressive augmentation was only evident during wakefulness and was enhanced in the OSA participants. vLTF was evident during wakefulness and sleep. When standardized to baseline, vLTF was greater during wakefulness and was enhanced in the OSA group (men: wakefulness 1.39 ± 0.08 vs. sleep 1.14 ± 0.03; women: wakefulness 1.35 ± 0.03 vs. sleep 1.16 ± 0.05 fraction of baseline; P ≤ 0.001) compared with control (men: wakefulness 1.19 ± 0.03 vs. sleep 1.09 ± 0.03; women: wakefulness 1.26 ± 0.05 vs. sleep 1.08 ± 0.04 fraction of baseline; P ≤ 0.001). The AHI following exposure to intermittent hypoxia was increased (intermittent hypoxia 72.8 ± 7.3 vs. sham 56.5 ± 7.0 events/h; P ≤ 0.01). Sex-related differences were not observed for the primary measures. We conclude that progressive augmentation is not evident, and the magnitude of vLTF is diminished during sleep compared with wakefulness in men and women. However, when present, the phenomena are enhanced in individuals with OSA. The AHI data indicate that, under the prevailing experimental conditions, vLTF did not serve to mitigate apnea severity.

scholarly journals Chronic Intermittent Hypoxia Induces the Long-Term Facilitation of Genioglossus Corticomotor Activity

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ying Zou ◽  
Wei Wang ◽  
Xinshi Nie ◽  
Jian Kang
Keyword(s):  
Obstructive Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Magnetic Stimulation ◽  
Upper Airway ◽  
Emg Activity ◽  
Chronic Intermittent Hypoxia ◽  
Experimental Conditions ◽  
Obstructive Sleep ◽  
Long Term Facilitation

Obstructive sleep apnea (OSA) is characterized by the repetitive collapse of the upper airway and chronic intermittent hypoxia (CIH) during sleep. It has been reported that CIH can increase the EMG activity of genioglossus in rats, which may be related to the neuromuscular compensation of OSA patients. This study aimed to explore whether CIH could induce the long-term facilitation (LTF) of genioglossus corticomotor activity. 16 rats were divided into the air group (n=8) and the CIH group (n=8). The CIH group was exposed to hypoxia for 4 weeks; the air group was subjected to air under identical experimental conditions in parallel. Transcranial magnetic stimulation (TMS) was applied every ten minutes and lasted for 1 h/day on the 1st, 3rd, 7th, 14th, 21st, and 28th days of air/CIH exposure. Genioglossus EMG was also recorded at the same time. Compared with the air group, the CIH group showed decreased TMS latency from 10 to 60 minutes on the 7th, 14th, 21st, and 28th days. The increased TMS amplitude lasting for 60 minutes was only observed on the 21st day. Genioglossus EMG activity increased only on the 28th day of CIH. We concluded that CIH could induce LTF of genioglossus corticomotor activity in rats.

The influence of episodic hypoxia on upper airway collapsibility in subjects with obstructive sleep apnea

2007 ◽  
Vol 103 (3) ◽  
pp. 911-916 ◽  
Author(s):  
James A. Rowley ◽  
Ihab Deebajah ◽  
Swapna Parikh ◽  
Ali Najar ◽  
Rajib Saha ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Upper Airway ◽  
Obstructive Sleep ◽  
Airway Collapsibility ◽  
Episodic Hypoxia ◽  
Before And After ◽  
Upper Airway Collapsibility ◽  
Long Term Facilitation

We have previously shown that in subjects with obstructive sleep apnea, repetitive hypoxia is associated with long-term facilitation as manifested by decreased upper airway resistance (Rua). Our objective was to study the influence of long-term facilitation on upper airway collapsibility as measured by the critical closing pressure (Pcrit) model and to determine whether changes in Rua correlated with changes in collapsibility. We studied 13 subjects (10 men, 3 women) with a mean apnea-hypopnea index of 43.9 ± 24.0 events/h. In the first protocol with 11 subjects, we measured collapsibility using a Pcrit protocol before and after episodic hypoxia. Brief (3 min) isocapnic hypoxia (inspired O2 fraction = 8%) followed by 5 min of room air was induced 10 times. A sham study without hypoxia was performed on eight subjects. Ventilatory parameters, Rua, and Pcrit before and after episodic hypoxia were measured. At 20 min of recovery, there was no change in minute ventilation but there was a significant decrease in Rua compared with the control period (control, 8.6 ± 4.8 cmH2O·l−1·s vs. recovery, 5.9 ± 3.8 cmH2O·l−1·s; P < 0.05). However, there was no change in Pcrit between the control (2.3 ± 1.9 cmH2O) and recovery (2.7 ± 3.2 cmH2O) periods. No changes in Rua or Pcrit were observed in the sham protocol. We conclude that long-term facilitation of upper airway dilators is not associated with changes in upper airway collapsibility in subjects with obstructive sleep apnea. These results corroborate previous evidence that changes in upper airway resistance and caliber can be dissociated from changes in upper airway collapsibility.

Long-term facilitation in obstructive sleep apnea patients during NREM sleep

2001 ◽  
Vol 91 (6) ◽  
pp. 2751-2757 ◽  
Author(s):  
Salah E. Aboubakr ◽  
Amy Taylor ◽  
Reason Ford ◽  
Sarosh Siddiqi ◽  
M. Safwan Badr
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Recovery Period ◽  
Upper Airway ◽  
Flow Limitation ◽  
Inspiratory Time ◽  
Nasal Cpap ◽  
Obstructive Sleep ◽  
Long Term Facilitation

Repetitive hypoxia followed by persistently increased ventilatory motor output is referred to as long-term facilitation (LTF). LTF is activated during sleep after repetitive hypoxia in snorers. We hypothesized that LTF is activated in obstructive sleep apnea (OSA) patients. Eleven subjects with OSA (apnea/hypopnea index = 43.6 ± 18.7/h) were included. Every subject had a baseline polysomnographic study on the appropriate continuous positive airway pressure (CPAP). CPAP was retitrated to eliminate apnea/hypopnea but to maintain inspiratory flow limitation (sham night). Each subject was studied on 2 separate nights. These two studies are separated by 1 mo of optimal nasal CPAP treatment for a minimum of 4–6 h/night. The device was capable of covert pressure monitoring. During night 1 (N1), study subjects used nasal CPAP at suboptimal pressure to have significant air flow limitation (>60% breaths) without apneas/hypopneas. After stable sleep was reached, we induced brief isocapnic hypoxia [inspired O2 fraction (Fi O2 ) = 8%] (3 min) followed by 5 min of room air. This sequence was repeated 10 times. Measurements were obtained during control, hypoxia, and at 5, 20, and 40 min of recovery for ventilation, timing ( n = 11), and supraglottic pressure ( n = 6). Upper airway resistance (Rua) was calculated at peak inspiratory flow. During the recovery period, there was no change in minute ventilation (99 ± 8% of control), despite decreased Rua to 58 ± 24% of control ( P < 0.05). There was a reduction in the ratio of inspiratory time to total time for a breath (duty cycle) (0.5 to 0.45, P < 0.05) but no effect on inspiratory time. During night 2 (N2), the protocol of N1 was repeated. N2 revealed no changes compared with N1 during the recovery period. In conclusion, 1) reduced Rua in the recovery period indicates LTF of upper airway dilators; 2) lack of hyperpnea in the recovery period suggests that thoracic pump muscles do not demonstrate LTF; 3) we speculate that LTF may temporarily stabilize respiration in OSA patients after repeated apneas/hypopneas; and 4) nasal CPAP did not alter the ability of OSA patients to elicit LTF at the thoracic pump muscle.

scholarly journals Pathophysiology of Obstructive Sleep Apnea in Aging Women

2021 ◽  
Author(s):  
Qingchao Qiu ◽  
Jason H. Mateika
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Upper Airway ◽  
Loop Gain ◽  
Younger Women ◽  
Arousal Threshold ◽  
Obstructive Sleep ◽  
Aging Women ◽  
Long Term Facilitation

AbstractThe following review is designed to explore the pathophysiology of sleep apnea in aging women. The review initially introduces four endotypes (i.e., a more collapsible airway, upper airway muscle responsiveness, arousal threshold, and loop gain) that may have a role in the initiation of obstructive sleep apnea. Thereafter, sex differences in the prevalence of sleep apnea are considered along with differences in the prevalence that exist between younger and older women. Following this discussion, we consider how each endotype might contribute to the increase in prevalence of sleep apnea in aging women. Lastly, we address how modifications in one form of respiratory plasticity, long-term facilitation, that might serve to mitigate apneic events in younger women may be modified in aging women with obstructive sleep apnea. Overall, the published literature indicates that the prevalence of sleep apnea is increased in aging women. This increase is linked primarily to a more collapsible airway and possibly to reduced responsiveness of upper airway muscle activity. In contrast, modifications in loop gain or the arousal threshold do not appear to have a role in the increased prevalence of sleep apnea in aging women. Moreover, we suggest that mitigation of long-term facilitation could contribute to the increased prevalence of sleep apnea in aging women.

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