Abstract:

Computer simulations of cardiac force development, based on mathematical models, lead to better understanding of the cardiac contractile function and its pathological behavior. In this work, quantitative data concerning cardiac force development of micro- scopic myocytes and macroscopic specimen were acquired from publications, which report from experiments. A material database quantified by species, e.g. human, mice, and cow, specimen, e.g. left ventricular papillary, and Purkinje myocyte, and pathology, e.g. dilatated cardiomyopathy, and diabetes, was gen- erated. The adaptation of the cardiac force development model using new quan- titative microscopic calcium sensitivity via re-parameterization techniques was accomplished. Force development simulations were also performed, on species- and specimen-specific and pathologic cell models. A species- and specimen- specific method to scale the calculated tension using the generated database was implemented. The species- and specimen-specific scalation of calculated tension was also performed. Through the integration of quantitative informa- tion, a more close-to-reality model of force development was created.In this work, applied methods and materials were also described. Mathematical principles, used for this purpose, i.e. continuum mechanics, numerical optimiza- tion and numerical minimization, are described in the second chapter. A deep insight into the structures of cardiac myocyte, which involve force development and cellular contraction, are provided in the third chapter. The forth chapter describes the electrophysiology of ionic channels, especially the gap junction. The electrophysiological model used for this work was also introduced. The fifth chapter explains in detail how an electrical excitation begins, spreads, and ends up on the triggered contraction of myocyte. The excitation-contraction coupling mechanism of the cardiac force development was described in detail. The sixth chapter shows the measurement construction and the quantifying definition of the experimental data acquisition concerning both calcium sensi- tivity and force generation. The database acquired for this diploma thesis is also displayed in the sixth chapter. In chapter seven, modelings of the force development in myofibrillar level, e.g. calcium triggering and the cross-bridge building, were described. The former and up-to-date cardiac force development models are listed and explained.Finally in the last chapter, results of the integration of calcium sensitivity, simulations with new re-parameterized cellular force development models, and species- and specimen-specific scalation of calculated tension in deformation model are shown. The eighth chapter provides an overview of the improvement history of the force development models.