Abstract 15159: Heart Failure Contributes to Atrial Fibrillation Substrate by Creating Conditions for the Generation of Triggered Ca2+ Waves in the Posterior Left Atrium and Pulmonary Veins
Introduction: Calcium (Ca2+) dysregulation is thought to contribute to AF substrate, with Ca2+ waves having been shown to underlie arrhythmogenesis in the atrium. Since the pulmonary veins and the posterior left atrium (PLA) have been shown to play a significant role in the genesis of atrial fibrillation (AF), we hypothesized that PLA myocytes in heart failure (HF) are more likely to generate triggered Ca2+ waves than myocytes from the rest of the atrium. We further hypothesized that reactive oxygen species (ROS) - also known to contribute to AF substrate - underlie the formation of triggered Ca2+ waves in the HF atrium.
Methods: PLA and left atrial appendage (LAA) atrial myocytes were separately isolated from 3 failing dog hearts (HF induced by ventricular tachypacing at 240 bpm for 3 weeks), and pre-incubated in either apocynin, which inhibits NADPH oxidase or mito-TEMPO, a mitochondrial ROS scavenger, for 2 to 4 hrs at room temperature. While myocytes, loaded with fluo-4AM, were paced at cycle lengths (CLs) from 1000 ms to 200 ms, line-scan images were taken using Zeiss LSM510 confocal microscope. Amount of superoxide (O2-) from PLA and LAA tissues were measured by lucigenin chemiluminscence assay.
Results: PLA myocytes showed significantly more triggered Ca2+ waves compared to LAA myocytes at a CL of 300 ms (0.23 ± 0.07 vs. 0.02 ± 0.02; p < 0.05; Figure 1A, B). The frequency of triggered Ca2+ waves in PLA myocytes was significantly reduced by mito-TEMPO (Fig1C, 0.23 ± 0.07 vs. 0.04 ± 0.01; p < 0.05), but not by apocynin. Furthermore, O2- content was significantly greater in the HF PLA, compared to the LAA (PLA, 91.75 vs. LAA, 30.13; p < 0.05).
Conclusions: In HF, PLA myocytes are significantly more prone to develop triggered Ca2+ waves than myocytes from the rest of the left atrium. Since these Ca2+ waves appears to be at least partially ROS-mediated and ROS is preferentially elevated in the PLA, anti-oxidant strategies targeted at the PLA may have therapeutic value in AF.
- © 2013 by American Heart Association, Inc.