Ventricular Repolarization and Calcium Transient Show Resonant Behavior under Oscillatory Pacing Rate

Abstract

Cardiac EC coupling is triggered by rhythmic depolarizing current fronts originating from the sino-atrial node, and the way variability in rhythm is associated with variability in action potential duration (APD) and, in turn, in the variability of calcium transient amplitude (CTA) and contraction is a key determinant of beating stability. Sinusoidal-varying pacing rate is adopted here in order to establish whether APD and CTA oscillations, elicited in a human ventricular AP model (OR) under oscillatory pacing, are consistent with the dynamics of two coupled harmonic oscillators, e.g., a two-degree-of-freedom system of mass and springs (MS model). I show evidence that this is the case, and that the MS model, preliminarily fitted to OR behavior, retains key features of the physiological system, such as the dependence of APD and CTA oscillation amplitudes from average value and from beat-to-beat changes in pacing rate, and the phase relationship between them. The bi-directionality of coupling between APD and CTA makes it difficult to discriminate which one leads EC coupling dynamics under variable pacing. The MS model suggests that the calcium cycling, with its greater inertia chiefly determined by the SR calcium release, is the leading mechanism. I propose the present approach to also be relevant at the whole organ level, where the need of compact representations of electromechanical interaction, particularly in clinical practice, remains urgent.

The electrical restitution of the non-propagated cardiac ventricular action potential

“…The ER btb has been adopted in experimental and numerical studies. I have measured it with my collaborators in rat ventricular myocytes [ 180 ], and in numerical models of ventricular AP, by means of constantly, sinusoidally, and randomly varying CL sequences [ 180 , 183 , 184 , 186 ]. This type of restitution is used extensively for representing QT versus RR in electrocardiographic recordings.…”

“…A link has been demonstrated between STM and the stability of ventricular AP repolarization, as the increase in the former frequently increases the latter [ 20 , 55 , 173 , 183 – 185 ], and the initiation of ventricular arrhythmias has been reported to be affected by both ER properties and STM [ 20 ]. In the case of CL harmonically oscillating within a given range σ around a constant BCL, and with an angular frequency ω [ 183 – 186 ], the linking mechanism between STM and stability has been related to the hysteretic behavior that ER btb curves assume under these pacing conditions for large ω values [ 1 , 12 , 173 , 183 – 186 ], and which is functional to quench APD oscillations and potentially prevent malignant arrhythmias [ 12 , 183 ]. Under these pacing conditions, in fact, the ER btb goes from a simple monotonic curve for pacing rate constant or oscillating at low ω values, to a hysteretic loop for higher ω values (Fig.…”