Abstract 16781: Dyssynchronous Ca Removal in Atrial Cardiac Myocytes From Failing Hearts

Abstract

In heart failure atrial remodeling (AR) leads to impaired contractility and relaxation as well as, atrial fibrillation and contributes to negative clinical outcomes. In myocytes cytosolic Ca removal after systolic release is primarily achieved by SERCA pump and Na/Ca exchange (NCX) activity, allowing atrial relaxation. In atrial myocytes that lack a transverse tubule system, NCX is located exclusively in the cell periphery where it is exposed to high concentrations of Ca during the cardiac cycle. Previously we found that the relative contribution of NCX to Ca removal was increased in AR and was associated with a higher propensity of arrhythmogenic Ca waves, i.e. Ca waves that triggered action potentials (APs). We hypothesize that dyssynchrony of Ca removal globally (whole cell) and locally (peripheral subsarcolemmal (SS) and central (CT) domains) is responsible for impaired relaxation and increased arrhythmogenicity. We used confocal line scan imaging and Ca sensitive dyes (Fluo-4/AM) to investigate Ca removal in remodeled atrial myocytes from a rabbit left ventricular volume-pressure overload systolic heart failure model. In control atrial myocytes Ca removal (assessed by the time constant of decay (TAU) of local SS and CT AP-induced Ca transients) is faster in the cell center (CT region) compared to the SS domain (342±32 vs. 393±31 ms, n=10 cells). In AR myocytes however, CT TAU was not different from SS TAU (196±11 vs. 190+14 ms, n=10 cells). In addition, in AR cells local dyssynchrony (defined as the standard deviation of TAU divided by mean TAU) in the CT domain was significantly increased compared to control (0.11±0.03 vs. 0.04±0.01, n=10 AR and CTRL cells). However despite the increased dyssynchrony, CT Ca removal was 50% and SS Ca removal 56% faster in AR myocytes as compared to control cells (n=10 AR and CTRL cells). In summary, AR myocytes show accelerated but dyssynchronous diastolic Ca removal that may result in impaired relaxation and increased susceptibility to rhythm disorders.