The ionic expression gradients affect paroxysmal atrial fibrillation dynamics: A simulation study

Ionic expression gradients could determine the paroxysmal atrial fibrillation (pAF) dynamics. Recently, it has been demonstrated that the acetylcholine (ACh)-activated potassium current (IKACh) and the inward rectifier K⁺ current (I_K1) densities are ≈2-fold larger in the left atrium (LA) versus right atrium (RA) during pAF, which may result in a greater increase in LA than RA rotor frequency. We investigated how the ionic expression gradients may affect the pAF dynamics. Experimental LA-RA I_K1 and I_KACh gradients were incorporated in a cellular atrial kinetics to simulate pAF in a 3D model of the human atria. pAF episodes were generated by a burst of 6 ectopic beats. In pAF model (with I_K1 and I_KACh gradients) action potential duration (APD) gradient was observed. However, without I_K1 gradient or without I_KACh gradient the APD gradient was decreased. In the pAF model, single rotor and then figure-of-eight reentry sustained in the LA maintained the AF, without reentrant activity in RA. When one of the two ionic expression gradients was not present, the pAF was maintained by multiple reentrant waves that collided and fragmented in the RA. In conclusion, LA-RA gradients in both I_KACh and I_K1 expression are important in establishing APD and frequency gradients, and LA reentrant activity maintaining pAF.