A two-variable model robust to pacemaker behaviour for the dynamics of the cardiac action potential

Area of Science:

• Computational biology
• Biophysics
• Cardiac electrophysiology

Background:

• Two-state variable ionic models are computationally tractable for patient-specific electrophysiology simulations.
• The Mitchell and Schaeffer (MS) model is widely used for ventricular electrophysiology due to its accuracy in reproducing action potential shapes and restitution properties.
• Unstable parameter combinations in the MS model can lead to unphysiological pacemaker behavior, complicating parameter fitting.

Purpose of the Study:

• To develop a robust adaptation of the Mitchell and Schaeffer (MS) model.
• To eliminate inherent pacemaker behavior across all parameter combinations.
• To enhance the suitability of the MS model for inverse problem applications in electrophysiology.

Main Methods:

• Modification of the existing Mitchell and Schaeffer (MS) ionic model.
• Analysis of parameter space to ensure absence of pacemaker behavior.
• Validation of the adapted model for computational tractability and physiological relevance.

Main Results:

• The adapted MS model demonstrates robustness against pacemaker behavior for all parameter sets.
• The modified model maintains the ability to reproduce action potential characteristics.
• Elimination of a priori criteria for excluding unstable parameters enhances parameter fitting algorithms.

Conclusions:

• The proposed adaptation of the MS model provides a more reliable tool for electrophysiology simulations.
• The absence of pacemaker behavior ensures physiological relevance and simplifies inverse problem applications.
• This robust model facilitates accurate patient-specific simulations and parameter estimation.