Atrial Fibrillation Promotion by Intermittent Hypoxia in the Rat

Obstructive sleep apnea (OSA) is a significant risk factor for developing atrial fibrillation (AF) in clinical populations, but the underlying mechanisms are unknown. Intermittent hypoxia (IH), as elicited by nocturnal airway obstructive events in OSA patients, has been implicated as the mediator of OSA-related cardiovascular outcomes. However, the role of IH in OSA-related atrial arrhythmogenesis has not been reported. For the first time, this thesis demonstrates AF promotion in a rodent model of OSA using IH to mimic hypoxic events, and investigates the underlying vulnerable substrates of induced AF. Rats exposed to IH for 7 days had significantly enhanced AF vulnerability compared to control animals exposed to normoxic conditions using both programmed electrical stimulation and atrial burst pacing to evaluate AF susceptibility. Enhanced AF vulnerability was accompanied by a number of atrial substrate changes that have not been reported previously in an IH model of OSA, including (1) lowered atrial Cx 43 content, (2) heightened cholinergic sensitivity with increased muscarinic receptor protein expression, and (3) alterations in adrenergic function characterized by enhanced responses to propranolol and blunted responses to isoproterenol. These findings highlight a potential causal role for chronic IH in OSA-related AF susceptibility and in the formation of AF-promoting vulnerable substrates