Impact of intermittent hypoxia on long-term facilitation of minute ventilation and heart rate variability in men and women: do sex differences exist?

Wadhwa, Harpreet; Gradinaru, Ciprian; Gates, Gregory J.; Badr, M. Safwan; Mateika, Jason H.

doi:10.1152/japplphysiol.01273.2007

Cited by 86 publications

(95 citation statements)

References 52 publications

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“…Thus, it is plausible that vascular and other cardiac responses to OSA-related stressors may differ in men and women and explain differences in stroke predilection. For example, autonomic nervous system responses to intermittent hypoxia are greater in men than women (33).…”

Section: Discussionmentioning

confidence: 99%

Obstructive Sleep Apnea–Hypopnea and Incident Stroke

Redline¹,

Yenokyan

Gottlieb³

et al. 2010

Am J Respir Crit Care Med

1,117

494

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Rationale: Although obstructive sleep apnea is associated with physiological perturbations that increase risk of hypertension and are proatherogenic, it is uncertain whether sleep apnea is associated with increased stroke risk in the general population. Objectives: To quantify the incidence of ischemic stroke with sleep apnea in a community-based sample of men and women across a wide range of sleep apnea. Methods: Baseline polysomnography was performed between 1995 and 1998 in a longitudinal cohort study. The primary exposure was the obstructive apnea-hypopnea index (OAHI) and outcome was incident ischemic stroke. Measurements and Main Results: A total of 5,422 participants without a history of stroke at the baseline examination and untreated for sleep apnea were followed for a median of 8.7 years. One hundred ninety-three ischemic strokes were observed. In covariate-adjusted Cox proportional hazard models, a significant positive association between ischemic stroke and OAHI was observed in men (P value for linear trend: P 5 0.016). Men in the highest OAHI quartile (.19) had an adjusted hazard ratio of 2.86 (95% confidence interval, 1.1-7.4). In the mild to moderate range (OAHI, 5-25), each one-unit increase in OAHI in men was estimated to increase stroke risk by 6% (95% confidence interval, 2-10%). In women, stroke was not significantly associated with OAHI quartiles, but increased risk was observed at an OAHI greater than 25. Conclusions: The strong adjusted association between ischemic stroke and OAHI in community-dwelling men with mild to moderate sleep apnea suggests that this is an appropriate target for future stroke prevention trials.Keywords: sleep apnea; stroke; epidemiology Approximately 15.3 million strokes occur annually worldwide, and about one-third of these are fatal (1). Stroke is not only the second leading cause of death globally, but it also accounts for significant disability, institutionalization, and health care costs (2). Because stroke rates increase exponentially with advancing age, the public health importance of strokes is likely to increase as the population ages. The risk of stroke is particularly high in African Americans, American Indians, and elderly women (2). Numerous studies have identified risk factors for stroke, including hypertension, atrial fibrillation, diabetes, and smoking (2-5). Even after considering these well-recognized risk factors, there is substantial variation in stroke rates and stroke-related outcomes.Emerging data implicate obstructive sleep apnea (OSA) in the pathogenesis of risk factors associated with ischemic stroke (i.e., hypertension, coronary heart disease, diabetes, and atrial fibrillation) (6). These associations are believed to be mediated by adverse physiological responses to recurrent periods of pharyngeal occlusion and consequent oxyhemoglobin desaturation-resaturation. These responses result in free radical generation, release of proinflammatory and prothrombotic mediators, and surges in sympathetic nervous system activity and blood pressure. Th...

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Section: Discussionmentioning

confidence: 99%

Obstructive Sleep Apnea–Hypopnea and Incident Stroke

Redline¹,

Yenokyan

Gottlieb³

et al. 2010

Am J Respir Crit Care Med

1,117

494

View full text Add to dashboard Cite

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“…PA has been described in the carotid sinus, hypoglossal, and phrenic nerves of anesthetized rats (59, 104), and the genioglossus muscle of humans (141). Furthermore, ventilatory PA has been described in awake ducks (256), goats (399), rabbits (370), and awake and sleeping humans (141,207,407). In contrast, several studies reported an absence of PA in response to intermittent hypoxic protocols in rats (240, 292) and humans (185,232,237).…”

Section: Physiological and Molecular Responses To Episodic Hypoxic Exmentioning

confidence: 99%

“…LTF has been observed in a wide variety of animals, both as increased ventilation or enhanced phrenic nerve activity in awake or anesthetized animals, respectively (105, 256, 269, 321, 395). Ventilatory LTF (mediated by LTF of the phrenic nerve) has been observed in anesthetized cats (103,251) and rabbits (370), conscious dogs (44), ducks (256), and goats (399), in awake or in anesthetized mice and rats (14, 144, 292, 312, 395), and in awake or sleeping humans (12, 269, 407). In addition to LTF of the phrenic nerve, LTF has been reported in the vagal nerve in rats (383), in the hypoglossal nerve in cats (231), rats (104, 106, 243), and humans (48,141), and in the upper airway muscles in rats (289).…”

Section: Physiological and Molecular Responses To Episodic Hypoxic Exmentioning

confidence: 99%

Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

Pamenter

Powell

2016

Comprehensive Physiology

108

101

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Ventilatory responses to hypoxia vary widely depending on the pattern and length of hypoxic exposure. Acute, prolonged, or intermittent hypoxic episodes can increase or decrease breathing for seconds to years, both during the hypoxic stimulus, and also after its removal. These myriad effects are the result of a complicated web of molecular interactions that underlie plasticity in the respiratory control reflex circuits and ultimately control the physiology of breathing in hypoxia. Since the time domains of the physiological hypoxic ventilatory response (HVR) were identified, considerable research effort has gone toward elucidating the underlying molecular mechanisms that mediate these varied responses. This research has begun to describe complicated and plastic interactions in the relay circuits between the peripheral chemoreceptors and the ventilatory control circuits within the central nervous system. Intriguingly, many of these molecular pathways seem to share key components between the different time domains, suggesting that varied physiological HVRs are the result of specific modifications to overlapping pathways. This review highlights what has been discovered regarding the cell and molecular level control of the time domains of the HVR, and highlights key areas where further research is required. Understanding the molecular control of ventilation in hypoxia has important implications for basic physiology and is emerging as an important component of several clinical fields.

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“…IH protocol (eight 4-min periods of hypoxia (inspiratory oxygen fraction (FIO 2 ) 8%), separated by 5 min of normoxia (FIO 2 21%)) describe an increase in both tidal volume and breathing frequency [37,38]. Thus, findings regarding the ventilatory pattern of IH-induced LTF is equivocal, and probably the result of varying IH protocols.…”

Section: Resting Ventilationmentioning

confidence: 99%

Human intermittent hypoxia-induced respiratory plasticity is not caused by inflammation

et al. 2015

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Ventilatory instability, reflected by enhanced acute hypoxic (AHVR) and hypercapnic (AHCVR) ventilatory responses is a fundamental component of obstructive sleep apnoea (OSA) pathogenesis. Intermittent hypoxia-induced inflammation is postulated to promote AHVR enhancement in OSA, although the role of inflammation in intermittent hypoxia-induced respiratory changes in humans has not been examined. Thus, this study assessed the role of inflammation in intermittent hypoxiainduced respiratory plasticity in healthy humans.In a double-blind, placebo-controlled, randomised crossover study design, 12 males were exposed to 6 h of intermittent hypoxia on three occasions. Prior to intermittent hypoxia exposures, participants ingested (for 4 days) either placebo or the nonsteroidal anti-inflammatory drugs indomethacin (nonselective cyclooxygenase (COX) inhibitor) and celecoxib (selective COX-2 inhibitor). Pre-and post-intermittent hypoxia resting ventilation, AHVR, AHCVR and serum concentration of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α were assessed.Pre-intermittent hypoxia resting ventilation, AHVR, AHCVR and TNF-α concentrations were similar across all three conditions ( p⩾0.093). Intermittent hypoxia increased resting ventilation and the AHVR similarly across all conditions ( p=0.827), while the AHCVR was increased ( p=0.003) and TNF-α was decreased ( p=0.006) with only selective COX-2 inhibition.These findings indicate that inflammation does not contribute to human intermittent hypoxia-induced respiratory plasticity. Moreover, selective COX-2 inhibition augmented the AHCVR following intermittent hypoxia exposure, suggesting that selective COX-2 inhibition could exacerbate OSA severity by increasing ventilatory instability. @ERSpublications Nonsteroidal anti-inflammatory drugs do not prevent intermittent hypoxia-induced respiratory plasticity in humans http://ow.ly/MDiCk

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Impact of intermittent hypoxia on long-term facilitation of minute ventilation and heart rate variability in men and women: do sex differences exist?

Cited by 86 publications

References 52 publications

Obstructive Sleep Apnea–Hypopnea and Incident Stroke

Obstructive Sleep Apnea–Hypopnea and Incident Stroke

Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

Human intermittent hypoxia-induced respiratory plasticity is not caused by inflammation

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