Cellular Level Electromechanical Modeling and Simulation of Heart Failure

Effects of heart failure on the mechanical function of the heart are difficult to assess experimentally, yet they pose a serious physiological challenge. By integrating modified cellular action potential model based on experimental data of heart failure with modified Hunter-McCulloch-ter Keurs (HMT) mechanical heart cell model, an electromechanical cardiac cell model was constructed and used to study cellular mechanical properties of both fast and slow contracting myocytes in heart failure. The simulation results show that the differences of the electrical responses between failing cells and normal cells can cause slowing relaxation of the Ca²⁺ transient, and the difference of the Ca²⁺-TnC concentrations between fast and slow myocytes in failing hearts is much reduced than in nonfailing hearts. It results in a decrease of force, which might diminish the role of mechanoelectric feedback (MEF), then induce an increase of transmural action potential duration (APD) gradients. It might cause arrhythmia in heart failure. These results are in good accordance with experimental findings reported in the literatures and might motivate further research on modeling and simulation of heart failure at the tissue and the whole organ levels