Mechanoelectric feedback as a trigger mechanism for cardiac electrical remodeling: a model study

Area of Science:

• Cardiovascular Physiology
• Computational Biology
• Cardiac Electrophysiology

Background:

• Regional differences in ionic membrane currents lead to action potential duration (APD) variability and proarrhythmia.
• Ventricular pacing causes electrical remodeling, altering the transient outward potassium current (Ito) and L-type calcium current (ICa,L), but the underlying mechanism remains unclear.

Purpose of the Study:

• Investigate the hypothesis that electrical remodeling is triggered by mechanical load.
• Model cardiac muscle as electrically and mechanically coupled segments to explore remodeling mechanisms.

Main Methods:

• Simulated cardiac cycle to determine stroke work for each segment.
• Modeled electrical remodeling by adapting ICa,L kinetics to achieve homogeneous stroke work distribution.
• Assessed changes in fiber shortening, APD heterogeneity, and repolarization wave behavior.

Main Results:

• Electrical remodeling resulted in more homogeneous fiber shortening.
• APD heterogeneity increased, and the repolarization wave reversed.
• Findings align with experimental observations of mechanical homogeneity and electrophysiological heterogeneity.

Conclusions:

• Electrical remodeling is a potential mechanism to mitigate cardiomechanical heterogeneity induced by ventricular pacing.
• The study provides insights into the interplay between mechanical load and electrical remodeling in the heart.