Ionic Determinants of Functional Reentry in a 2-D Model of Human Atrial Cells During Simulated Chronic Atrial Fibrillation

¹ SUNY Upstate Medical University
² Montclair state university
³ University of Montreal

^* To whom correspondence should be addressed. E-mail: pandits{at}upstate.edu.

Submitted on January 31, 2005
Revised on March 2, 2005
Accepted on 10 March 2005

	Abstract

Recent studies suggest that atrial fibrillation (AF) is maintained by fibrillatory conduction emanating from a small number of high-frequency reentrant sources (rotors). Our goal was to study the ionic correlates of a rotor during simulated chronic AF conditions. We utilized a two-dimensional (2-D), homogeneous, isotropic sheet (5'5 cm2) of human atrial cells (Courtemanche et al., model) to create a chronic AF substrate, which was able to sustain a stable rotor (dominant frequency ~5.7 Hz, rosette-like tip meander ~2.6 cm). Doubling the magnitude of the inward rectifier K+ current (IK1) increased rotor frequency (~8.4 Hz), and reduced tip meander (~1.7 cm). This rotor stabilization was due to a shortening of the action potential duration and an enhanced cardiac excitability. The latter was caused by a hyperpolarization of the diastolic membrane potential, which increased the availability of the Na+ current (INa). The rotor was terminated by reducing the maximum conductance (by 90%) of the atrial-specific ultra-rapid delayed rectifier K+ current (IKur), or the transient outward K+ current (Ito), but not the fast or slow delayed rectifier K+ currents (IKr/IKs). Importantly, blockade of IKur/Ito prolonged the atrial action potential at the plateau, but not at the terminal phase of repolarization, which led to random tip meander and wavebreak, resulting in rotor termination. Altering the rectification profile of IK1 also slowed down or abolished reentrant activity. In combination, these simulations results provide novel insights into the ionic bases of a sustained rotor in a 2-D chronic AF substrate.

Key Words: Atrial Fibrillation, Modeling, Spiral Dynamics

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