Session S43.1

Effects of Intracellular Ca2+ Dynamics on Restitution Properties and Stability of Reentry in a Rabbit Atrial Tissue Model

OV Aslanidi*, MR Boyett, H Zhang

The University of Manchester
Manchester, UK

Atrial fibrillation (AF) is associated with irregular rapid excitation of the atria, but mechanisms of its initiation are unknown. Intracellular Ca2+ dynamics has been shown to affect cell restitution properties and, as a result, patterns of rapid reentrant excitation in the ventricles at early stages of ventricular fibrillation. We study effects of intracellular Ca2+ on restitution properties and stability of reentry in atrial cell and tissue models. The Lindblad et al. (1996) model for an atrial action potential (AP) was updated based on extant voltage-clamp datasets recorded for ionic currents from rabbit right atrial cells, which allowed reproducing feasible AP morphologies. The single cell AP model was incorporated into a 2D tissue model with an intercellular conductance set to produce the AP propagation velocity of 0.5 m/s. Ca2+ dynamics were either described by the full kinetic model, or buffered to a constant level of 73 nM. APs simulated with the full model and buffered Ca2+ model had similar morphologies at a slow pacing cycle length (CL) of 500 ms; neither APs nor Ca2+ transients in the full model showed beat-to-beat variations. However, rapid pacing at CL < 100 ms resulted in alternating Ca2+ transients – as a result, respective APs also had alternating diastolic membrane potential (DMP) and the action potential duration (APD) – whereas APs in the buffered model did not alternate. Ca2+ alternans were transient, followed by accumulation of intracellular Ca2+ after ~500 ms, which produced elevated DMP and shortened APD compared to the buffered model. These APD changes were reflected in detailed restitution curves calculated for both models. A reentrant spiral wave in the tissue model with buffered Ca2+ rotated stably with a period of ~90 ms – whereas in the full model reentry was unstable, breaking up within 500 ms of rotation as Ca2+ and APD alternated. However, break-ups stopped as Ca2+ alternans transited to Ca2+ accumulation; the period of reentry progressively decreased and after ~1000 ms it self-terminated. In summary, Ca2+ dynamics altered electrical activity in both atrial cell and tissue models. Ca2+ and AP alternans were transient and resultant reentry break-ups were reversible, whereas subsequent accumulation of intracellular Ca2+ lead to APD shortening and self-termination of reentry. Thus, other factors such as tissue anisotropy may play more important role in cascading break-up of reentry into AF.

(Abstract Control Number: 137)