Multiscale modelling for the calcium dynamics in cardiac electrophysiology

Abstract

A critical component for the cardiac cells to perform its primary function, the shortening of the cardiac organ, is regulating the intracellular calcium concentration. The calcium ion is the key element in the cardiac cells’ contractility, and its intracellular dynamics involve several physical and chemical activities. The whole process is named the Calcium-Induced Calcium Release (CICR) process. The activities composing the CICR process are of high-order complexity and involve spatial and temporal multiscale phenomena. In this way, a computational model capable of reproducing this crucial process for the correct cardiac function in these scales might contribute to understanding the relation between the micro scale activities and the effects they cause on a whole organ behavior. So, this thesis proposes a novel spatial-temporal computational model for the human left ventricle myocyte capable of reproducing the stochasticity present in the micro scale nature of the cell and determining the effects of these local phenomena in the macro scale cellular behavior. The development of this multiscale model was based on a well-accepted cellular model. This base model was modified by incorporating random variables in its formulation. It enabled the updated version of the model to replicate phenomena occurring at a subcellular level, such as the stochastic behavior of ionic channels and spontaneous calcium sparks. Besides, the multiscale feature was implemented by introducing two parameters in the CICR formulations that allow the usage of the model to reproduce the outputs in both subcellular and cellular scales. The proposed model presented satisfactory results; simulated under the micro scale condition, the model were capable of reproducing the spontaneous calcium sparks while that, under a macro scale viewing, it reproduced the deterministic expected outputs. Furthermore, this new proposition might enable further studies in understanding heart pathologies and their association with the subcellular structure.