Transmural cellular heterogeneity in myocardial electromechanics

Area of Science:

• Cardiovascular Physiology
• Computational Biology
• Cardiac Electrophysiology

Background:

• Myocardial heterogeneity, regional differences in cardiac cell properties, is a fundamental characteristic of the healthy heart.
• Understanding the cellular basis of this heterogeneity is crucial for comprehending intact heart function.

Purpose of the Study:

• To develop integrative computational models of subendocardial (ENDO) and subepicardial (EPI) ventricular cardiomyocytes.
• To simulate and explain regional differences in intracellular electromechanical coupling using experimental data from guinea pig hearts.

Main Methods:

• Development of integrative computational models for ENDO and EPI cardiomyocytes.
• Incorporation of experimental data on regional features of intracellular electromechanical coupling.
• Simulation of action potential and contraction profiles, calcium (Ca2+) transients, and mechanical load sensitivity.

Main Results:

• Models successfully simulate experimental differences in action potential and contraction between ENDO and EPI cells.
• Heterogeneity in calcium handling and myofilament mechanics are predicted as essential for observed Ca2+ transients and contraction profiles.
• Mechano-calcium-electric feedback mechanisms are implicated in producing these cellular differences.
• ENDO cells demonstrate greater sensitivity to mechanical load variations compared to EPI cells.

Conclusions:

• Regional differences in calcium handling and myofilament properties are critical drivers of myocardial heterogeneity.
• Cooperative feedback mechanisms significantly contribute to transmural electrical and mechanical differences.
• These findings enhance the understanding of cardiomyocyte behavior within the intact heart and their response to mechanical stress.