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

Area of Science:

• Computational Biology and Physiology
• Cardiac Electrophysiology
• Mathematical Modeling

Background:

• Cardiac electrical-excitatory-coupling (EC coupling) stability is crucial for regular heartbeats.
• Variability in heart rhythm affects action potential duration (APD) and calcium transient amplitude (CTA), influencing beating stability.
• Understanding the interplay between APD and CTA dynamics under variable pacing is essential.

Purpose of the Study:

• To investigate whether APD and CTA oscillations under variable pacing align with coupled harmonic oscillator dynamics.
• To compare a human ventricular action potential model (OR) with a mass-spring (MS) model.
• To determine the leading mechanism in EC coupling dynamics during variable heart rates.

Main Methods:

• Utilized sinusoidal-varying pacing rates on a human ventricular action potential model (OR).
• Developed and analyzed a two-degree-of-freedom mass-spring (MS) model.
• Fitted the MS model to the OR model's behavior to assess consistency and key features.

Main Results:

• APD and CTA oscillations in the OR model are consistent with the dynamics of the coupled MS model.
• The MS model accurately replicates the dependence of APD and CTA oscillation amplitudes on average pacing rate and beat-to-beat changes.
• The MS model captures the phase relationship between APD and CTA oscillations.

Conclusions:

• The mass-spring model provides a valid representation of cardiac electromechanical interactions under variable pacing.
• Calcium cycling, influenced by SR calcium release, appears to be the leading mechanism driving EC coupling dynamics.
• This modeling approach offers a compact representation of electromechanical coupling relevant for whole-organ level analysis and clinical applications.