System biological modeling of circulation: from cells to system

A new multi-scale simulation model covering from cells to system is proposed to analyze hemodynamics of cardiovascular system. Electrophysiology of a cardiac cell is numerically approximated using the previous model of human ventricular myocyte. Ion transports across cell membrane initiated by action potential induce excitation-contraction mechanism in the cell via cross bridge dynamics. Negroni and Lascano model (NL model) is employed to compute the tension of cross bridge closely related to ion dynamics in cytoplasm. To convert the tension in cell level into contraction force of cardiac muscle, we introduce a simple geometric model of ventricle with a thin-walled hemispheric shape. It is assumed that cardiac tissue is composed of set of cardiac myocytes and its orientation on the hemispheric surface of ventricle remains constant throughout all the domain. Application of Laplace law to the ventricle model enables us to obtain a ventricular pressure that induces blood circulation in body. A lumped parameter model with 6 compartments is utilized to compute systemic circulation interacting with the cardiac cell mechanism via NL model and Laplace law. Numerical simulation shows that ion transports in cell level eventually generates blood hemodynamics in system level via cross bridge dynamics and Laplace law. Computed results using the present multi-scale model are well compared with the existing ones. Especially it is shown that the typical characteristics of heart mechanics, such as pressure volume relation, stroke volume and ejection fraction, can be generated by the present multi-scale cardiovascular model covering from cardiac cells to circulation system.