Basic/Translational Science -> Whole Animal Electrophysiology and Pharmacology (includes Neurohumoral Modulation) D-PO05 - Poster Session V (ID 39) Poster

D-PO05-054 - Increased Oxidative Stress Causes Ion Channel Remodeling In Obesity-mediated Atrial Fibrillation (ID 1253)


Background: Recent studies have established obesity as an independent risk factor for atrial fibrillation (AF). While both are independently associated with increased mitochondrial oxidative stress and compromised redox balance, the underlying mechanisms by which obesity and increased atrial oxidation are linked with AF remain unclear.
Objective: We hypothesized that increased oxidative stress causes cardiac ion channel remodeling in obesity-mediated AF.
Methods: To elucidate the underlying electrophysiologic (EP) mechanisms of obesity-mediated AF we used a diet induced obese (DIO) mouse model. Weight, BP, plasma glucose, and F2-isoprostanes were measured in DIO mice and compared to controls. Invasive electrophysiology (EP), immunohistochemistry, Western blotting, cellular patch clamping and optical mapping studies were performed.
Results: DIO (56%) mice were heavier than controls (P<0.001). AF burden was 284±295 sec in DIO mice vs. 13±26 sec (controls; P<0.001). DIO mice showed significantly increased mitochondrial reactive oxygen species (ROS) production compared to controls. Cardiac Na+ and Ca2+ current (INa, ICa,L) were reduced while K+ current (IKur) was increased shortening the atrial action potential duration (APD) and reducing conduction velocity (CV). Chronic treatment with a mitochondrial antioxidant (MitoTEMPO) reduced ROS production, normalized ion channel remodeling, restored the APD and reduced AF burden.
Conclusion: Mice with acquired obesity are more prone to develop AF and this risk is mediated in part by increased mitochondrial oxidative stress causing remodeling of cardiac ion channels, shortening of atrial APD and reduced CV.