Asymmetry in dynamics of action potential duration transition between steady states: A simulation study

Ventricular fibrillation (VF) contributes importantly to sudden cardiac death, however, exact mechanisms of VF remain elusive. Action potential duration (APD) restitution is widely used to predict dynamics of VF. Restitution of APD is a multi-modal phenomenon, with contributions from previous diastolic intervals (DI), as well as from activation history. We investigated dynamics of change in APD with contributions from memory by using a feedback-based protocol. A Luo-Rudy ionic model of cardiac activation was used to simulate activation. We used four levels of DI, 150, 450, 700, and 1000 msec, to compose a DI sequence which included all possible switches among these DIs. By abruptly changing the DI after APD reached a steady state, we analyzed the transient dynamics of change in APD. As expected, our results showed that for sufficiently long activation, the steady state of APD was unique for each DI. Transient changes in APD showed an asymmetric pattern that was dependent on direction of change in DI, the absolute level of change and the operating level of APD. These results further support the notion that restitution of APD is a multi-modal phenomenon, and that multiple factors need to be considered in using restitution to predict activation dynamics.