Atrial Arrhythmia and Autonomics in an Intermittent Hypoxia Rat Model of Obstructive Sleep Apnea

Abstract

IntroductionObstructive sleep apnea (OSA) is a risk factor for developing atrial fibrillation (AF), but the mechanisms underlying AF are unknown. OSA is characterized by airway obstruction and intermittent hypoxia (IH), which has been implicated in the induction of cardiovascular dysfunction. However, the role of IH in predisposing the atria to AF is not understood.HypothesisThis study tested the hypothesis that chronic repetitive IH enhances autonomic responses, and predisposes the atria to AF.Materials and MethodsAdult, male Sprague‐Dawley rats were exposed to normoxia or repeated cycles of 120 s 21% O2 alternated with 80 s 6.5–8% O2 for 8h/day for 7 days. Rats exposed to 7 days of IH or normoxia had in vivo intracardiac electrophysiology studies to evaluate electrophysiological characteristics and susceptibility to electrical inducibility of AF. Atrial effective refractory periods were determined using programmed electrical stimulation (PES) at two atrial locations. Susceptibility to electrically induced AF was determined using PES with 8 stimuli at basic drive cycle lengths of 150 or 100 ms followed by a sequentially premature single extrastimumus and burst pacing using up to 30, 1 sec burst at 50 Hz.ResultsRats following 7‐days of IH exposure were more susceptible to electrical induction of atrial arrhythmia than normoxic controls (50% vs 0%, respectively, P < 0.05). This was accompanied by an increase in inducibility in the presence of carbachol which was blocked by atropine and darifenacin. The response to isoproterenol were enhanced in the normoxic but not in the IH rats, and the effects of propranolol were less pronounced in the IH rats.ConclusionsWe have demonstrated for the first time that repeated exposure to IH in rats produced enhanced sensitivity to atrial arrhythmias. These novel findings implicating IH as a critical promoter of AF in an OSA model. Accentuation with cholinergic agonists and blockade with nonspecific and M3 specific antagonists is consistent with sensitivity to parasympathetic activation which is known to predispose the atria to AF. The diminished response to sympathetic agents suggests a potential desensitization to adrenergic activation in the IH rats. These novel findings provide an indication of the importance of IH in OSA and susceptibility to atrial arrhythmia and potential for novel therapies in OSA.Support or Funding InformationSupported in part by the Heart and Stroke Foundation of Ontario