Abstract 20773: Contribution of Ox-CaMKII and CaMKII-Phosphorylated Nav1.5 to Atrial Fibrillation Substrate Development in the Failing Heart

Introduction: Substrate for atrial fibrillation (AF) in heart failure (HF) is thought to be mediated by slow conduction and conduction inhomogeneity (CI). Among various contributors, oxidative stress (OS) plays an important role in formation of AF substrate, especially in the setting of HF. However, the precise mechanisms by OS create electrophysiological substrate for AF in HF atrium has not been explained. One of the major signaling pathways for OS is oxidized-CaMKII (Ox-CaMKII), which regulates virtually all known ion channels and Ca2+ handling proteins, including Nav1.5. Thus, we postulate that increased manifestation and inhomogeneous distribution of Ox-CaMKII and CaMKII phosphorylated Nav1.5 at S571 (p-Nav1.5) contribute to slow and inhomogeneous conduction in HF atrium. Methods: HF was induced in dogs by ventricular pacing at 240 bpm for 3 weeks. In both HF (n = 6) and control animals (n = 4), CI and conduction velocity (CV) was assessed in the posterior left atrium (PLA) by high density mapping (1...