**5. Effect of the ANS on action potential duration restitution**

Following electrical and ischemic instability, ANS also have a direct effect on action potential duration restitution. The destabilization of activation wavefronts is associated with the alteration in action potential duration (APD) resulting from the alteration of the previous diastolic interval, called restitution. Steepened APD restitution curve slope has been associated with complex, unstable dynamics, while a decrease of the steepness of the curve by drugs may suppress ventricular arrhythmia [17–19]. A study in porcine models by Taggart et al. has shown that sympathetic stimulation with adrenaline (α – and β-adrenergic agonist) steepens the APD restitution curve [20]. The same effect was confirmed in humans with normal ventricles by a more recent study using isoprenaline (β-adrenergic agonist) and adrenaline, demonstrating that both adrenaline and isoprenaline steepen the APD restitution curve at the minimum range of 40 ms. This evidence suggests a mechanism in which the sympathetic nervous system is contributed to inducing arrhythmia and ventricular fibrillation [16]. Additionally, a study conducted in an isolated rabbit heart model demonstrated that parasympathetic activation exerts a contradictory effect, reducing the steepness of the slope, thereby suppressing ventricular fibrillation [21].
