Instability of Ventilatory Control in Patients with Obstructive Sleep Apnea

Hudgel, David W.; Gordon, Elizabeth A.; Thanakitcharu, Sitthep; Bruce, Eugene N.

doi:10.1164/ajrccm.158.4.9712105

Cited by 107 publications

(103 citation statements)

References 25 publications

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“…Moreover, these results indicate that ovarian hormones do not necessarily protect against the effects of early life stress on respiratory control development. In light of the present data, we propose that, with such enhancement of the CO 2 chemoreflex, NMS rats may be more susceptible to develop respiratory disorders associated with neural control dysfunction such as respiratory instability during sleep or panic attacks (10,13,19,28,32). Should data support this hypothesis, NMS may be a valuable model to understand these pathologies.…”

Section: Nms and Sex-specific Plasticity Of The Hypercapnic Ventilatomentioning

confidence: 58%

Neonatal maternal separation induces sex-specific augmentation of the hypercapnic ventilatory response in awake rat

Genest

Gulemetova²,

Laforest³

et al. 2007

Journal of Applied Physiology

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Genest S-E, Gulemetova R, Laforest S, Drolet G, Kinkead R. Neonatal maternal separation induces sex-specific augmentation of the hypercapnic ventilatory response in awake rat. J Appl Physiol 102: 1416 -1421, 2007. First published December 21, 2006; doi:10.1152/japplphysiol.00454.2006.-Neonatal maternal separation (NMS) is a form of stress that exerts persistent, sex-specific effects on the hypoxic ventilatory response. Adult male rats previously subjected to NMS show a 25% increase in the response, whereas NMS females show a response 30% lower than controls (8). To assess the extent to which NMS affects ventilatory control development, we tested the hypothesis that NMS alters the ventilatory response to hypercapnia in awake, unrestrained rats. Pups subjected to NMS were placed in a temperature-and humidity-controlled incubator 3 h/day for 10 consecutive days (P3 to P12). Control pups were undisturbed. At adulthood (8 to 10 wk old), rats were placed in a plethysmography chamber for measurement of ventilatory parameters under baseline and hypercapnic conditions (inspired CO2 fraction ϭ 0.05). After 20 min of hypercapnia, the minute ventilation response measured in NMS males was 47% less than controls, owing to a lower tidal volume response (22%). Conversely, females previously subjected to NMS showed minute ventilation and tidal volume responses 63 and 18% larger than controls respectively. Although a lower baseline minute ventilation contributes to this effect, the higher minute ventilation/ CO2 production response observed in NMS females suggests a greater responsiveness to CO2/H ϩ in this group. We conclude that NMS exerts sex-specific effects on the hypercapnic ventilatory response and that the neural mechanisms affected by NMS likely differ from those involved in the hypoxic chemoreflex.control of breathing; plasticity; hypercapnia; sexual dimorphism THE NEONATAL ENVIRONMENT is critical to proper development of neurophysiological function. The formation and fine tuning of neural circuits during early life require adequate sensory guidance, and conditions providing excessive or insufficient levels of stimulation can disrupt system development and compromise their subsequent performance throughout life. The olfactory, tactile, and auditory stimuli that the mother provides her offspring following birth are among the most potent environmental factors contributing to the "neonatal programming" of neural circuits (12,22). Although the life-long consequences of disrupting motherpup interactions have been mainly associated with behavioral and neuroendocrine dysfunction (1, 2, 20), less is known about the impact of mother-pup interaction on other homeostatic functions such as cardiorespiratory regulation. Accordingly, we showed that neonatal maternal separation (NMS) disrupts cardiorespiratory responses to moderate hypoxia in a persistent and sex-specific fashion (8,16). In addition to eliciting the well described enhancement of basal hypothalamo-pituitary-adrenal axis function in rats (34; for review see Ref. 5), we...

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Section: Nms and Sex-specific Plasticity Of The Hypercapnic Ventilatomentioning

confidence: 58%

Neonatal maternal separation induces sex-specific augmentation of the hypercapnic ventilatory response in awake rat

Genest

Gulemetova²,

Laforest³

et al. 2007

Journal of Applied Physiology

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“…In fact, irregular breathing has been shown to lead to obstructive apnea-hypopnea. [3][4][5][6][7] In this regard, especially in NREM sleep which is the phase that breathing behavior is controlled mainly by chemical control, when arousal occurs, breathing becomes irregular. Invoking the engineering term "loop gain", this phenomenon might occur if the respiratory system responded dynamically more to the disturbance, which in this case are the changes in ventilation with sleep onset and arousals.…”

Section: Discussionmentioning

confidence: 99%

“…In NREM sleep, detailed physiologic studies detect dynamic changes in ventilatory control during state transitions, which are considered to induce irregular breathing, and lead to obstructive apnea and/or hypopnea. [3][4][5][6][7] Detailed studies in REM sleep are absent, leaving an opportunity for the clinical polysomnogram to inform not only REM-predominant OSA but the possibility of NREM predominant OSA as well. …”

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confidence: 99%

Nonrapid Eye Movement-Predominant Obstructive Sleep Apnea: Detection and Mechanism

Yamauchi

Fujita

Kumamoto

et al. 2015

Journal of Clinical Sleep Medicine

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Study Objectives: Obstructive sleep apnea (OSA) can be severe and present in higher numbers during rapid eye movement (REM) than nonrapid eye movement (NREM) sleep; however, OSA occurs in NREM sleep and can be predominant. In general, ventilation decreases an average 10% to 15% during transition from wakefulness to sleep, and there is variability in just how much ventilation decreases. As dynamic changes in ventilation contribute to irregular breathing and breathing during NREM sleep is mainly under chemical control, our hypothesis is that patients with a more pronounced reduction in ventilation during the transition from wakefulness to NREM sleep will have NREM-predominant rather than REM-predominant OSA. Methods: A retrospective analysis of 451 consecutive patients (apnea-hypopnea index [AHI] > 5) undergoing diagnostic polysomnography was performed, and breath-tobreath analysis of the respiratory cycle duration, tidal volume, and estimated minute ventilation before and after sleep onset were examined. Values were calculated using respiratory inductance plethysmography. The correlation between the percent change in estimated minute ventilation during wakesleep transitions and the percentage of apnea-hypopneas in NREM sleep (%AHI in NREM; defi ned as (AHI-NREM) / [(AHI-NREM) + (AHI-REM)] × 100) was the primary outcome. Results: The decrease in estimated minute ventilation during wake-sleep transitions was 15.0 ± 16.6% (mean ± standard deviation), due to a decrease in relative tidal volume. This decrease in estimated minute ventilation was signifi cantly correlated with %AHI in NREM (r = −0.222, p < 0.01). 1,2 In general, upper airway obstruction and hypopnea is in REM sleep when upper airway muscle tonus is decreased as compared to nonrapid eye movement (NREM) sleep. However, OSA occurring predominantly in NREM sleep or equally in a numeric manner in both REM and NREM sleep is also encountered in clinical practice; neither prevalence nor mechanisms driving the relative distribution of REM and NREM events have been considered in any detail. In NREM sleep, detailed physiologic studies detect dynamic changes in ventilatory control during state transitions, which are considered to induce irregular breathing, and lead to obstructive apnea and/or hypopnea. [3][4][5][6][7] Detailed studies in REM sleep are absent, leaving an opportunity for the clinical polysomnogram to inform not only REM-predominant OSA but the possibility of NREM predominant OSA as well. ConclusionsVentilation decreases an average of 10% to 15% during the transition from wakefulness to sleep due mainly to a decrease in tidal volume; however, the literature reports substantial

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“…32 The pathophysiology is unclear but may relate to effects of atrial arrhythmias on cardiac afferent autonomic activity and central nervous system mechanisms that direct ventilatory control and airway muscle activity. 33,34 The use of the Berlin questionnaire to identify patients with OSA may be seen as a limitation of the study, because overnight sleep studies are the gold standard for the diagnosis of OSA. However, in addition to the questionnaire's established validity in a primary care setting, 17 we confirmed that it was extremely accurate in the present study population.…”

Section: Discussionmentioning

confidence: 99%

Association of atrial fibrillation and obstructive sleep apnea

Gami¹,

Pressman²,

Caples³

2004

ACC Current Journal Review

178

213

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Background-Obstructive sleep apnea (OSA) is associated with recurrent atrial fibrillation (AF) after electrocardioversion.OSA is highly prevalent in patients who are male, obese, and/or hypertensive, but its prevalence in patients with AF is unknown. Methods and Results-We prospectively studied consecutive patients undergoing electrocardioversion for AF (nϭ151) and consecutive patients without past or current AF referred to a general cardiology practice (nϭ312). OSA was diagnosed with the Berlin questionnaire, which is validated to identify patients with OSA. We also assessed its accuracy compared with polysomnography in a sample of the study population. Groups were compared with the 2-tailed t, Wilcoxon, and 2 tests. Logistic regression modeled the association of AF and OSA after adjustment for relevant covariates. Patients in each group had similar age, gender, body mass index, and rates of diabetes, hypertension, and congestive heart failure. The questionnaire performed with 0.86 sensitivity, 0.89 specificity, and 0.97 positive predictive value in our sample. The proportion of patients with OSA was significantly higher in the AF group than in the general cardiology group (49% versus 32%, Pϭ0.0004). The adjusted odds ratio for the association between AF and OSA was 2.19 (95% CI 1.40 to 3.42, Pϭ0.0006). Conclusions-The novel finding of this study is that a strong association exists between OSA and AF, such that OSA is strikingly more prevalent in patients with AF than in high-risk patients with multiple other cardiovascular diseases. The coinciding epidemics of obesity and AF underscore the clinical importance of these results.

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Instability of Ventilatory Control in Patients with Obstructive Sleep Apnea

Cited by 107 publications

References 25 publications

Neonatal maternal separation induces sex-specific augmentation of the hypercapnic ventilatory response in awake rat

Neonatal maternal separation induces sex-specific augmentation of the hypercapnic ventilatory response in awake rat

Nonrapid Eye Movement-Predominant Obstructive Sleep Apnea: Detection and Mechanism

Association of atrial fibrillation and obstructive sleep apnea

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