Abstract 18212: Weight Loss Reverses Ionic Remodeling Responsible for Increased Atrial Fibrillation Inducibility and Burden in High-Fat Diet Induced Obese Mice
Introduction: Obesity is an accepted major risk factor for atrial fibrillation (AF) and heart disease, with high-fat diets leading to morbid obesity. Using atrial burst pacing I previously demonstrated that diet-induced obese mice (DIO) exhibit increased AF inducibility and burden, which is decreased with weight loss (WL). Still, cellular mechanisms remain unknown.
Hypothesis: I hypothesized that obesity and its comorbidities induce ionic remodeling that increases AF inducibility and burden, and that this ionic remodeling is reversed with WL.
Methods: C57bl6 mice were fed on high-fat diet. I used 3 WL strategies: vertical-sleeve gastrectomy, caloric restriction, and their combination. Applying current-clamp technique, I recorded action potentials (APs) from isolated atrial and ventricular myocytes. I then calculated AP duration at 90% of repolarization (APD90). APs were recorded across 4 groups: DIO, DIO after WL, DIO after weight regain, and control (LEAN) mice. Mean±SEM, 4 mice/group.
Results: APD90 from DIO atrial cells was significantly prolonged vs. APD90 from LEAN atrial cells (40±2.8 vs. 24.2±1.6 ms, n=12 cells/group, p<0.001). Similar results were observed in ventricular myocytes (61.7±3.7 (DIO) vs. 31±1.7 ms (LEAN), n=35 cells/group, p<0.0001). AP upstroke slope was significantly decreased in DIO atrial cells vs. LEAN atrial cells (25.4±1.1 vs. 31.6±1.9 mV/ms respectively, n=12 cells/group, p<0.01). Similar effect was observed in DIO ventricular cells. After 20% WL (all WL strategies showed similar efficacies), DIO showed significantly decreased AF inducibility and burden (88% decrease), atrial APD90 significantly decreased and AP upstroke slope increased back to LEAN values (27.1±2.2 ms and 29±1 mV/ms respectively, n=7 cells). After mice regained weight, AF burden significantly increased and APD90 prolonged.
Conclusions: Prolonged APD90 in DIO atrial myocytes increases dispersion of repolarization and supports ionic remodeling as one mechanism that increases AF inducibility and burden in DIO. Prolonged APD90 and decreased upstroke slope (mainly driven by canonical cardiac sodium current (INa)) suggest that modulation of INa contributes to it. WL decreases AF inducibility and burden by reversing the ionic remodeling.
Author Disclosures: E. Savio-Galimberti: None.
- © 2016 by American Heart Association, Inc.