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Atrial arrhythmias and autonomic dysfunction in rats exposed to chronic intermittent hypoxia.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2018 Jun 01; Vol. 314 (6), pp. H1160-H1168. Date of Electronic Publication: 2018 Feb 09. - Publication Year :
- 2018
-
Abstract
- Obstructive sleep apnea, which involves chronic intermittent hypoxia (CIH), is a major risk factor for developing atrial fibrillation (AF). Whether or not CIH alone alters cardiac mechanisms to support AF is unknown. This study investigated the effects of CIH on atrial electrophysiology and arrhythmia vulnerability and evaluated the role of autonomics in CIH promotion of AF. Adult male Sprague-Dawley rats were exposed to 8 h/day of CIH or normoxia for 7 days. After exposure, rats were anesthetized for intracardiac electrophysiological experiments. Atrial effective refractory periods (AERPs) and AF inducibility were determined using programmed electrical stimulation and burst pacing in the absence and presence of autonomic receptor agonists and antagonists. Western blot analysis measured atrial protein expression of muscarinic M2, M3, and β <subscript>1</subscript> -adrenergic receptors. Compared with normoxia-exposed control rats, CIH-exposed rats had enhanced AF vulnerability using both programmed electrical stimulation and burst pacing, accompanied by greater AERP responses to carbachol and propranolol, lesser responses to isoproterenol, and higher atrial M2 receptor protein levels. Enhanced atrial vulnerability was accentuated by carbachol and abolished by atropine, indicating that the AF-promoting effects of CIH depended principally on parasympathetic activation. Enhancement of atrial vulnerability and AERP shortening with cholinergic agonists in CIH-exposed rats is consistent with sensitivity to parasympathetic activation. Higher responses to adrenergic receptor blockade in CIH-exposed rats is consistent with sympathetic potentiation. These findings implicate CIH as an important mediator of enhanced AF susceptibility in obstructive sleep apnea and provide novel insights into the underlying mechanisms. NEW & NOTEWORTHY Our study demonstrates, for the first time, that chronic intermittent hypoxia alone enhances vulnerability to atrial arrhythmia induction, which depends principally on parasympathetic activation. Enhanced atrial vulnerability was accompanied by heightened electrophysiological responses of the atrial myocardium to carbachol and isoproterenol, dampened responses to propranolol, and increased atrial M2 receptor protein levels.
- Subjects :
- Action Potentials
Animals
Atrial Fibrillation metabolism
Atrial Fibrillation physiopathology
Autonomic Nervous System drug effects
Autonomic Nervous System metabolism
Autonomic Nervous System Diseases metabolism
Autonomic Nervous System Diseases physiopathology
Chronic Disease
Disease Models, Animal
Heart Atria drug effects
Heart Atria metabolism
Hypoxia metabolism
Hypoxia physiopathology
Male
Neurotransmitter Agents pharmacology
Rats, Sprague-Dawley
Receptor, Muscarinic M2 metabolism
Receptor, Muscarinic M3 metabolism
Receptors, Adrenergic, beta-1 metabolism
Refractory Period, Electrophysiological
Sleep Apnea, Obstructive metabolism
Sleep Apnea, Obstructive physiopathology
Atrial Fibrillation etiology
Autonomic Nervous System physiopathology
Autonomic Nervous System Diseases etiology
Heart Atria innervation
Heart Rate drug effects
Hypoxia complications
Sleep Apnea, Obstructive complications
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1539
- Volume :
- 314
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 29424572
- Full Text :
- https://doi.org/10.1152/ajpheart.00173.2017