title: Arousal From Sleep and Sympathetic Excitation During Wakefulness.
abstract: Obstructive apnea during sleep elevates the set point for efferent sympathetic outflow during wakefulness. Such resetting is attributed to hypoxia-induced upregulation of peripheral chemoreceptor and brain stem sympathetic function. Whether recurrent arousal from sleep also influences daytime muscle sympathetic nerve activity is unknown. We therefore tested, in a cohort of 48 primarily nonsleepy, middle-aged, male (30) and female (18) volunteers (age: 59±1 years, mean±SE), the hypothesis that the frequency of arousals from sleep (arousal index) would relate to daytime muscle sympathetic burst incidence, independently of the frequency of apnea or its severity. Polysomnography identified 24 as having either no or mild obstructive sleep apnea (apnea-hypopnea index <15 events/h) and 24 with moderate-to-severe obstructive sleep apnea (apnea-hypopnea index >15 events/h). Burst incidence correlated significantly with arousal index (r=0.53; P<0.001), minimum oxygen saturation (r=-0.43; P=0.002), apnea-hypopnea index (r=0.41; P=0.004), age (r=0.36; P=0.013), and body mass index (r=0.33; P=0.022) but not with oxygen desaturation index (r=0.28; P=0.056). Arousal index was the single strongest predictor of muscle sympathetic nerve activity burst incidence, present in all best subsets regression models. The model with the highest adjusted R2(0.456) incorporated arousal index, minimum oxygen saturation, age, body mass index, and oxygen desaturation index but not apnea-hypopnea index. An apnea- and hypoxia-independent effect of sleep fragmentation on sympathetic discharge during wakefulness could contribute to intersubject variability, age-related increases in muscle sympathetic nerve activity, associations between sleep deprivation and insulin resistance or insomnia and future cardiovascular events, and residual adrenergic risk with persistence of hypertension should therapy eliminate obstructive apneas but not arousals.
authors.affiliation: From the University Health Network and Mount Sinai Hospital Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: Keri S
authors.initials: KS
authors.lastname: Taylor
authors.affiliation: From the University Health Network and Mount Sinai Hospital Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Murai
authors.affiliation: From the University Health Network and Mount Sinai Hospital Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Millar
authors.affiliation: From the University Health Network and Mount Sinai Hospital Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Haruki
authors.affiliation: From the University Health Network and Mount Sinai Hospital Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: Derek S
authors.initials: DS
authors.lastname: Kimmerly
authors.affiliation: From the University Health Network and Mount Sinai Hospital Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: Beverley L
authors.initials: BL
authors.lastname: Morris
authors.affiliation: From the University Health Network and Mount Sinai Hospital Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Tomlinson
authors.affiliation: From the University Health Network and Mount Sinai Hospital Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: T Douglas
authors.initials: TD
authors.lastname: Bradley
authors.affiliation: From the University Health Network and Mount Sinai Hospital Department of Medicine, University of Toronto, Ontario, Canada. john.floras@utoronto.ca.
authors.forename: John S
authors.initials: JS
authors.lastname: Floras
mesh_terms: D000367:Age Factors; D001143:Arousal / Q000502:physiology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000502:physiology; D017286:Polysomnography / Q000379:methods; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014851:Wakefulness / Q000502:physiology*
keywords: apnea; arousal; obstructive sleep apnea; sleep; sympathetic nervous system