Differences in sympathetic and vagal effects on paroxysmal atrial fibrillation: a simulation study

The incidence of paroxysmal atrial fibrillation (AF) is affected by circadian variations in the vago-sympathetic balance. It is well known that both sympathetic and vagal effects increase the onset of paroxysmal AF, due to the shortened action potential duration. However, the reason why the vagally-mediated paroxysmal AF is maintained more than the adrenergically-mediated paroxysmal AF has remained unclear. In order to clarify this, we performed the following computer simulations. First, we constructed a homogeneous two-dimensional myocardial sheet (4.5 x 2.25 cm), using a bidomain ion channel model. The sympathetic and vagal effects were achieved by modifications of the ion channel conductance (Sympathetic effect: increased gSI and increased gK. Vagal effect: increased gK and increased gK1 with or without the dispersion of refractoriness). We found that the sympathetic effect shortened the action potential duration and flattened the restitution slope; therefore, this effect promoted spiral wave induction and restrained the spiral wave breakup. On the other hand, we found that the vagal effect also shortened the action potential duration and flattened the restitution slope; however, this effect promoted spiral wave breakup, due to the increase in both the IK1 and the dispersion of refractoriness. Overall, the differences between the sympathetic and vagal effects on the tendency toward spiral wave break-up may explain the reason why adrenergically-mediated paroxysmal AF terminates spontaneously and vagally-mediated paroxysmal AF tends to be maintained. In conclusion, our results may be helpful in understanding the difference in the action of sympathetic and vagal effects on paroxysmal AF.