Abstract P1105: Inflammatory Bowel Disease Induced Autonomic Dysregulation Increases The Risk For Atrial Fibrillation

Abstract

Introduction: Ulcerative colitis causes inflammation of the innermost lining of the colon and rectum. The disease has a relapsing and remitting course and is accompanied by extraintestinal manifestations such as an increased risk for atrial fibrillation (AF). Here we will test the hypothesis that during active colitis, dysregulation of parasympathetic signaling increases the propensity for atrial arrhythmic events. Methods: Dextran Sulfate Sodium (DSS: 3%, 7days) treated mice (C57BL/6) exhibit disrupted intestinal barrier function that mimics the disease phenotype of active colitis. Changes in atrial electrophysiology was quantified in-vivo (EKG) and in the Langendorff (LD)-perfused heart (atrial electrograms) during peak inflammation (DSS A ) and remission (DSS R ). Results: During peak inflammation, structural remodeling was reflected in a decreased heart weight to tibia length ratio (Control (CTL A ): 9.9±0.4 mg/mm, n=10; DSS A : 8.8±0.3 mg/mm, n=12; p<0.05) whereas electrophysiological atrial remodeling was supported by a prolonged P-wave duration (CTL A : 25.5±0.6 ms, n=10; DSS A : 31.2±0.6 ms, n=24; p<0.0001) and shortened atrial effective refractory period (CTL A : 27.3±1.7 ms, n=4; DSS A : 19.3±0.6 ms, n=4; p<0.01). In comparison to CTL A , DSS A mice exhibited autonomic dysregulation reflected in an attenuated heart rate (HR) variability and a decreased change in HR in response to the muscarinic receptor blocker atropine (CTL A : 7.6±1.8 %, n=5; DSS A : 2.2±0.7 %, n=7; p<0.01). The decreased vagal tone in DSS A coincided with an exaggerated response to the parasympathomimetic carbachol (CCh, 150ng/g) that resulted in a larger decrease in HR (in vivo: CTL A : -12.3±3.1 %, n=10; DSS A : -46.0±5.6 %, n=10; p<0.0001) and increased number of spontaneous arrhythmic events (CTL A : 1.7±0.6 events/min, n=10; DSS A : 9.8±3.8 events/min, n=10; p<0.05) in vivo and in the LD-configuration. The susceptibility for pacing induced AF trended to be increased in DSS A animals. Structural and electrophysiological changes were reversible upon remission. Conclusion: Active colitis induces transient structural and electrophysiological remodeling. We propose that dysregulation of cholinergic signaling drives the increased propensity for atrial arrhythmia.