title: Brain stem activity changes associated with restored sympathetic drive following CPAP treatment in OSA subjects: a longitudinal investigation.
abstract: Obstructive sleep apnea (OSA) is associated with significantly elevated muscle sympathetic nerve activity (MSNA), leading to hypertension and increased cardiovascular morbidity. Although little is known about the mechanisms responsible for the sympathoexcitation, we have recently shown that the elevated MSNA in OSA is associated with altered neural processing in various brain stem sites, including the dorsolateral pons, rostral ventrolateral medulla, medullary raphe, and midbrain. Given the risk associated with elevated MSNA, we aimed to determine if treatment of OSA with continuous positive airway pressure (CPAP) would reduce the elevated MSNA and reverse the brain stem functional changes associated with the elevated MSNA. We performed concurrent recordings of MSNA and blood oxygen level-dependent (BOLD) signal intensity of the brain stem, using high-resolution functional magnetic resonance imaging, in 15 controls and 13 subjects with OSA, before and after 6 mo CPAP treatment. As expected, 6 mo of CPAP treatment significantly reduced MSNA in subjects with OSA, from 54 ± 4 to 23 ± 3 bursts/min and from 77 ± 7 to 36 ± 3 bursts/100 heart beats. Importantly, we found that MSNA-coupled changes in BOLD signal intensity within the dorsolateral pons, medullary raphe, and rostral ventrolateral medulla returned to control levels. That is, CPAP treatment completely reversed brain stem functional changes associated with elevated MSNA in untreated OSA subjects. These data highlight the effectiveness of CPAP treatment in reducing one of the most significant health issues associated with OSA, that is, elevated MSNA and its associated elevated morbidity.
authors.affiliation: School of Medicine, University of Western Sydney, Sydney, Australia;
authors.forename: Linda C
authors.initials: LC
authors.lastname: Lundblad
authors.affiliation: School of Medicine, University of Western Sydney, Sydney, Australia;
authors.forename: Rania H
authors.initials: RH
authors.lastname: Fatouleh
authors.affiliation: Department of Respiratory Medicine, Prince of Wales Hospital, Sydney, Australia;
authors.forename: David K
authors.initials: DK
authors.lastname: McKenzie
authors.affiliation: Department of Respiratory Medicine, Prince of Wales Hospital, Sydney, Australia; Neuroscience Research Australia, Sydney, Australia; and.
authors.forename: Vaughan G
authors.initials: VG
authors.lastname: Macefield
authors.affiliation: Department of Anatomy and Histology, University of Sydney, Sydney, Australia lukeh@anatomy.usyd.edu.au.
authors.forename: Luke A
authors.initials: LA
authors.lastname: Henderson
mesh_terms: D000328:Adult; D000368:Aged; D001933:Brain Stem / Q000473:pathology / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D045422:Continuous Positive Airway Pressure; D005260:Female; D066128:Gray Matter / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000294:innervation / Q000503:physiopathology; D009929:Organ Size; D010100:Oxygen / Q000097:blood; D020181:Sleep Apnea, Obstructive / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D016896:Treatment Outcome
chemical_list: D010100:Oxygen
keywords: continuous positive airway pressure; medullary raphe; muscle sympathetic nerve activity; obstructive sleep apnea; rostral ventrolateral medulla