Spontaneous onset of atrial fibrillation

Abstract

Most commonly, atrial fibrillation is triggered by rapid bursts of electrical impulses originating in the myocardial sleeves of pulmonary veins (PVs). However, the nature of such bursts remains poorly understood. Here, we propose a mechanism of bursting consistent with the extensive empirical information about the electrophysiology of the PVs. The mechanism is essentially non-local and involves the spontaneous initiation of non-sustained spiral waves in the distal end of the muscle sleeves of the PVs. It reproduces the experimentally observed dynamics of the bursts, including their frequency, their intermittent character, and the unusual shape of the electrical signals in the pulmonary veins that are reminiscent of so-called early afterdepolarizations (EADs).

Figure 1

Simulation of electrical propagation in the myocardial sleeves. A: Location of the pulmonary veins in the left atrium of the heart. B: A single pulmonary vein (marked in Panel A) Dashed rectangle shows the approximate location of the simulated region (see Panel C) C: Spatial distribution of electrophysiological properties in our model. Gray levels indicate the local conductivity (the conductivity tensor g is isotropic, g_x(x,y)=g_y(x,y)). Dashed line indicates the boundary of vagally innervated tissue. Dotted line marks the pacemaker region. D: Action potentials from different cell types.

Figure 2

Bursting in the pulmonary veins triggered by a sudden reduction in heart rate. A-F: Initiation of a spiral wave by an ectopic beat originating in the pacemaker region. Black lines are isochrones, spaced 5 ms apart, arrows indicate the direction of wave propagation. A: Sinus activation. B: Ectopic wave originated in the pacemaker region is blocked at the interface of the areas with reduced (medium gray) and normal (light gray) coupling . C: The ectopic beat penetrates into the normally conducting region, collides with the next sinus front, and reenters the low conduction region (upward arrow) forming a spiral wave. D-F: Subsequent evolution of the spiral wave. a-c: Transmembrane voltage signal at three different locations (marked in Panel A). Three sinus stimulations, followed by two high-frequency bursts. Bursting starts after a slowdown in the pacing rate from 500 ms to 800 ms.

Figure 3

Action potentials resembling early afterdepolarizations (EADs) during spiral wave reentry in the pulmonary veins. A: Area in which EAD-like APs occur. a-b: Electrical and intracellular calcium signals recorded from the points marked in the upper Panel.

Figure 4

Vagal stimulation induces conduction block at coupling heterogeneities. A: Propagation during normal vagal tonus. For g_min=0.11 and Δg=0.69, a wave initiated in the distal end penetrates into the proximal PV. B: Increased vagal tonus, modeled by doubling I_K1, leads to conduction block at the interface between normal and reduced conduction.

Figure 5

Conditions needed for spiral reentry induction. A: Dependence of the critical ratio g_max / g_min, at which block occurs, on g_K1. B: Dependence of critical block length on g_min (g_max was kept constant).

Figure 6

The natural distribution of ion channel densities. Reentry induction is inhibited for a. A: Action potentials for ion channel densities typical in the PV region, the atria, and densities halfway between these two cases. B: The first stimulus applied to the distal PV does not produce reentry.