Simulation Study Of Heart Failure Based On Heart Cell Model

Heart failure (HF) has emerged as one of the largest threats to the public health, which is a primary cardiac disease characterized by decreased myocardial contractility and reduced cardiac output. At the cellular level, heart failure is also accompanied by changes in the expression of proteins governing electrical repolarization and intracellular calcium handling which might cause fatal ventricular arrhythmias. Recent investigations have markedly advanced our understanding of the molecular and ionic alterations that occur in response to HF. However, the relationship between alterations of repolarization and arrhythmia mechanisms in HF remains largely unknown, and effects of heart failure on the mechanical function of the heart are difficult to assess experimentally. Computer simulations in the human heart, as a substitute of experiments can overcome lots of problems. In the past decades, many electrical and mechanical heart models have been developed and used to investigate cardiac properties. The electromechanical mechanism of heart failure, however, is not exactly clear so far.In this paper, firstly, Hunter-McCulloch-ter Keurs (HMT) mechanical cardiac cellular model was modified based on recent research findings, and then integrated with Luo-Rudy phase II model and ten Tusscher model respectively, to simulate the electromechanical properties of both fast and slow contracting myocytes. Secondly, a simulation study of the action potential waveforms of different ventricular cell types was presented based on recent experimental studies of transmural electrophysiological heterogeneities in nonfailing and failing human hearts. By using the modified action potential (AP) model, the AP shapes of different ventricular cell types were simulated, and the changes of transmural heterogeneity of cellular electrophysiology in non-failing and failing hearts were determined. Thirdly, in failing hearts, how major membrane ionic currents influence AP repolarization, and how action potential duration (APD) rate-dependence changes in transmural electrical remodeling wereevaluated. Finally, by means of the changes in intracellular Ca2+ concentration, the changes of mechanical properties of both fast and slow contracting myocytes in heart failure were studies.The results show that: (1) APDs are prolonged to some degree in all the three layers of ventricular cells in heart failure, which induce an increase of peak IcaL current and contribution of NCX (INaca) to Ca2+ removal in repolarizational phase of AP. (2) Heart failure causes transmural electrical remodeling and changes the transmural heterogeneity in APs, and thus results in a reduction of transmural APD gradients. And in M cell, EAD (early afterdepolarization) can be observed when the pulses increase to 2 Hz in failing hearts. (3) At fast rate, APD rate dependence is increased in heart failure compared with controlled heart, which is caused by increased IcaL current and decreased Itoi in heart failure. (4) The changes of IcaL current in epicardial cells compared with other cells cause a significant rise in the transmural APD gradient. (5) 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. 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 both the tissue and the whole organ levels.In conclusion, the model established in this article was mainly used to investigate the transmural electrophysiological heterogeneities of different ventricular cell types in nonfailing and failing human hearts, and also the changes of mechanical properties of failing hearts. In the international cardiac research area, many researchers study one or a few ion channels specially to quantify the changes in electrophysiological prop...