Modelagem de extrassístole associada a transiente de cálcio estocástico

Abstract

The electrical propagation of the heart is a complex phenomenon that results in the contraction of the organ. There are several factors that operate in a normal propagation to ensure cellular homeostasis and the entire myocardium. An abnormal propagation can arise due to several factors, one of which is extrasystole, which can be the precursor of fatal arrhythmias. This work aims to develop a mathematical model capable of describing some mechanisms associated with ventricular extrasystoles. One of the focuses of this study is on understanding the genesis of a Spontaneous Action Potential after the occurrence of a Spontaneous Calcium Pulse, which occurs due to the Spontaneous Calcium Release by the Sarcoplasmic Reticulum at the cellular level. Furthermore, we studied the conditions necessary for a cellular Spontaneous Potential to propagate in a cardiac tissue and in fact generate an extrasystole. Several simulations are presented to represent electrical activity with stochastic characteristics, both at the level of a single cell and at the tissue level. The results suggest that, at the cellular level, Spontaneous Potentials were only observed in response to a beta-adrenergic and under conditions of increased activity of the sodium-calcium exchanger. In tissue, action potential propagation only occurred when we increased cellular excitability, for example via decreased expression of type IK1 ion channels. Furthermore, we only observed the propagation of Spontaneous Potentials in the tissue under particular conditions, where active cells were surrounded by nonconductive tissue (fibrosis or necrosis), forming a structural configuration that we called a sealed funnel. Finally, we observed that all these conditions for the generation of an extrasystole can be satisfied in well-described and known cardiopathies, such as infarction and hypertrophic cardiomyopathy, particularly at the edges of fibrotic or necrotic regions. Thus, our studies result in a better understanding of the complex mechanisms that contribute to the genesis of fatal arrhythmias that are commonly observed in these cardiopathies.