Effects Of Chronic Heart Failure On Cardiomyocyte Kinetics

The occurrence of heart failure(CHF)is often associated with sinus tachycardia and other cardiac arrhythmias(CA).Studies have shown that tachycardia may be associated with stable or wandering spiral waves in the process of myocardial cell excitability.However,the phenomenon and mechanism of the occurrence and development of spiral wave in the pathological condition of heart failure remain unclear.So it is of great significance to study the mechanism and rules of the occurrence of spiral wave in heart failure,which is helpful for the prevention and treatment of heart failure.The purpose of this paper is to study the dynamic characteristics of myocardial cells and the difference during the development of spiral waves in normal and heart failure condition by model method.Firstly,the Tusscher-Panfilov(TP06)model was successfully used to simulate the human ventricular myocytes.Then the of excitation-contraction coupling model(ECC)of a single human cell was established by coupling the TNNP06 model with Niederer-Smith(NS08).In this study,the dependence of the activity of human ventricular myocytes on the cell length was studied by using transient(1 ms)mechanical stretch(induced 1% cell length changes).And the interaction of active force induced by calcium and stretch during myocardial contraction was also discussed.Besides,the model of human ventricular myocytes was further established based on the ECC and the existing experimental data,and the data in normal and heart failure condition was compared including the electrophysiological and mechanical properties of human ventricular myocytes,the recovery curve of action potential duration(APD)and early after depolarization(EAD)in the paper.Finally the action potential conduction model of two-dimensional monolayer in myocardial tissue was successfully constructed by adding coupling between cells,and the dynamic characteristics of the spiral wave were compared in normal and heart failure condition induced by the ‘tangent wave method’.The results suggested that the normal contraction of the heart resulted from the combined action of calcium and stretch activation,human cardiac contractility depends on sarcomere length and intracellular calcium concentration,the contractile force was positively correlated with sarcomere length and calcium ion concentration,and the contractile force was resulated by the concentration of calcium ionsin the ECC.Compared with normal condition,abnormal electrophysiological characteristics of ventricular myocytes occurred in heart failure condition,with action potential prolonged,the peak value and decay rate of calcium ion and contractile force decreased,and transmural potential gradient of action potential increased.And heart failure would lead to a increase of the stimulus frequency threshold of early depolarization(EAD)than normal condition.Compared with normal data,dynamic characteristics of spiral waves turned abnormal,and the spiral waves were more likely to be induced,with faster rotating speed,larger functional blocking area and irregular circle.The presence of spiral waves in heart failure would bring about more irregular changes in the electrical activity of the cardiac tissue.Above all,all the results can provide some theoretical basis for the explanation of the phenomenon of arrhythmia associated with heart failure,and supply some useful information to identify and treat arrhythmias for the clinical treatment in heart failure condition.