Abstract 14228: Mechanism of Atrial Fibrillation in an Animal Model of Inflammatory Bowel Disease

Abstract

Introduction: Ulcerative colitis (UC) is an i nflammatory bowel disease with a relapsing and remitting course. UC has extraintestinal manifestations and UC patients exhibit twice the risk for atrial fibrillation (AF) during acute disease activity. The mechanism of AF due to UC remains to be determined. Hypothesis: During acute UC a dysregulation of vagal signaling increases a patients propensity for AF. Methods: Mice (male, C57BL/6) were treated with Dextran Sulfate Sodium (DSS: 3%) supplemented drinking water for 7days that disrupts intestinal barrier function and mimics the disease phenotype of acute UC. Changes in atrial electrophysiology were quantified in vivo (EKG), on the whole heart (Langendorff configuration) and the cellular level (Fluo-4AM) during peak inflammation (DSS A ) and remission (DSS R ). Results: DSS A mice exhibited an attenuated heart rate (HR) in vivo (CTL: 491 ± 11 bpm, n=10; DSS A : 448 ± 11 bpm, n=16; p<0.05) and in excised perfused hearts (Langendorff configuration: CTL: 321 ± 15 bpm, n = 3; DSS A : 256 ± 17 bpm, n = 4; p < 0.05). The P-wave duration was prolonged (in vivo, CTL: 25.5 ± 0.6 ms, n=10; DSS A : 30.2 ± 0.5 ms, n=16; p < 0.0001) and HR variability time-domain measure RR-corrected SDNN was attenuated (CTL: 11.3 ± 1.1 ms, n=10; DSS A : 8.2 ± 0.7 ms, n=16; p < 0.05). The latter is an indicator for an attenuated vagal tone in DSS A mice and coincided with an increased sensitivity to the vagal agonist Carbachol in-vivo (CCh 150 ng/g, change in HR: CTL: -3.8 ± 4.4 %, n=6; DSS A : -42.2 ± 4.8 %, n=10; p < 0.0001). After burst pacing DSS A hearts exhibited a prolonged RR-corrected sinus node recovery time (CTL: 11.2 ± 1.4 ms, n=3; DSS A : 25.5 ± 2.1 ms, n=4; p < 0.0001), an increased AF propensity, and prolonged duration of AF episodes (CTL: 0.8 ± 0.17 s, n=3; DSS A : 2.4 ± 0.31 s, n=4; p < 0.05) even in the absence of CCh. No changes in atrial myocyte Ca handling properties were determined. After remission HR, P-wave duration, and HRV in DSS R returned to control values. Conclusions: The data suggests that acute UC increases the risk for AF likely as a consequence of an attenuated sinus rhythm and atrial conduction velocity where vagal stimuli could exacerbate the risk for reentry of excitation. If these changes are the direct consequence of the attenuated vagal tone remains to be determined.