Key result
In a computational model of human ventricular action potentials, periodically beat-to-beat changing cycle lengths stabilized repolarization more effectively than random changes.
Short-term action potential memory, stored in APD rather than diastolic interval, plays a stabilizing role on cardiac repolarization under dynamic pacing perturbations, particularly with periodic cycle length variability.
Periodic cycle length variability may guide pacing protocols for repolarization; leaves open translation beyond computational models.
Electrical restitution (ER) is a major determinant of repolarization stability and, under fast pacing rate, it reveals memory properties of the cardiac action potential (AP), whose dynamics have never been fully elucidated, nor their ionic mechanisms. Previous studies have looked at ER mainly in terms of changes in AP duration (APD) when the preceding diastolic interval (DI) changes and described dynamic conditions where this relationship shows hysteresis which, in turn, has been proposed as a marker of short-term AP memory and repolarization stability. By means of numerical simulations of a non-propagated human ventricular AP, we show here that measuring ER as APD versus the preceding cycle length (CL) provides additional information on repolarization dynamics which is not contained in the companion formulation. We focus particularly on fast pacing rate conditions with a beat-to-beat variable CL, where memory properties emerge from APD vs CL and not from APD vs DI and should thus be stored in APD and not in DI. We provide an ion-currents characterization of such conditions under periodic and random CL variability, and show that the memory stored in APD plays a stabilizing role on AP repolarization under pacing rate perturbations. The gating kinetics of L-type calcium current seems to be the main determinant of this safety mechanism. We also show that, at fast pacing rate and under otherwise identical pacing conditions, a periodically beat-to-beat changing CL is more effective than a random one in stabilizing repolarization. In summary, we propose a novel view of short-term AP memory, differentially stored between systole and diastole, which opens a number of methodological and theoretical implications for the understanding of arrhythmia development.
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Massimiliano Zaniboni (2018) studied Cardiac repolarization stability. Periodic beat-to-beat cycle length variability vs. Random cycle length variability or constant pacing was evaluated on Repolarization stability (number of beats to resume unperturbed APD sequence). In a computational model of human ventricular action potentials, periodically beat-to-beat changing cycle lengths stabilized repolarization more effectively than random changes.
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