Determinants of atrial fibrillation in an animal model of obesity and acute obstructive sleep apnea

BACKGROUND Obesity and obstructive sleep apnea (OSA) are risk factors for atrial fibrillation (AF), but the underlying mechanisms are poorly understood. OBJECTIVE The purpose of this study was to assess the mechanisms underlying AF promotion by obesity and OSA in rat models. METHODS Zucker obese rats (ORs) and lean rats (LRs) were intubated and ventilated with air and 2% isoflurane. OSA was mimicked by stopping the ventilator and closing the airway for 40 seconds. For nonobstructive control periods, the protocol was repeated with an open airway. Fifteen seconds after apnea onset, AF susceptibility was tested with 6 atrial burst pacing cycles (25 Hz, 3 seconds, 1-second intercycle pauses). RESULTS AF was not inducible in ORs or LRs at baseline or in nonobstructive control periods. AF was induced in 24 of 28 ORs (85.7%) vs 5 of 18 LRs (27.8%) during obstructive apnea (P <.001). Negative intrathoracic pressure generation (esophageal pressure monitoring) was substantial during obstructive apnea. Echocardiography showed left ventricular hypertrophy with diastolic dysfunction in ORs. Obstructive apnea caused acute left atrial (LA) dilation, increasing LA diameter significantly more in ORs than in LRs. To clarify AF mechanisms, 24 AF-inducible ORs were divided into 4 groups: saline (n = 5), pharmacologic autonomic blockade (n = 7), respiratory muscle paralysis with rocuronium (n = 6), and inferior vena cava (IVC) balloon occlusion to unload the LA (n = 6). Balloon catheter-induced IVC occlusion prevented LA distension during obstructive apnea, leading to 83.3% AF prevention (P <.05). Rocuronium also was protective (66.7%), but autonomic blockade had smaller effects (42.9% prevention). CONCLUSION Obesity and acute obstructive apnea interacted to promote AF in this model. Forced inspiration-induced acute LA distension related to diastolic dysfunction may be an important component of the arrhythmogenic substrate for AF during OSA episodes in obese patients.