Cardiac arrhythmias are irregularities in the heart's rhythm that can range from mild and
asymptomatic to life-threatening conditions. The treatment of cardiac arrhythmias is
individualized and based on the type of arrhythmia, its severity, the individual's health
conditions, as well as the patient's age and lifestyle. Atrial fibrillation (AF) is the most common heart rhythm disorder, characterized by an irregular and rapid heartbeat. It often causes symptoms such as palpitations, fatigue, and shortness of breath and increases the risk of stroke and heart failure.
In recent years, catheter ablation has become the preferred method for treating atrial fibrillation, as reflected in the latest recommendations. The ablation procedure destroys specific areas of heart tissue that cause the arrhythmia or electrically isolates these areas from the rest of the heart. Traditional methods of catheter ablation include radiofrequency ablation (RFA) and cryoablation, which have proven effective in eliminating arrhythmic foci.
Irreversible electroporation is an innovative non-thermal ablation method in cardiac
electrophysiology that uses high-voltage electric pulses to increase the permeability of cell
membranes. The increased permeability disrupts cellular homeostasis, which can lead to the
death of target cells. This process allows the destruction of target cells and has been shown to be effective in treating cardiac arrhythmias. Irreversible electroporation promises a lower risk of damage to surrounding tissues and better safety for patients compared to thermal ablation methods.
However, it is known that around the irreversibly electroporated tissue, there is always a region of reversibly electroporated tissue, in which cells survive exposure to the electric pulses. Reversible electroporation of cardiomyocytes could affect their ability to trigger action potentials in these regions. Therefore, it is necessary to better understand how electroporation affects the function of cardiomyocytes.
The aim of this thesis was to investigate the impact of electroporation on the function of
cardiomyocytes, with a focus on modeling the impact of electroporation on the triggering of
action potentials in isolated cardiomyocytes. The model aimed to clarify how increased membrane permeability and non-selective ionic current across the membrane affect the
functioning of ion channels and transporters in the cell membrane, as well as the dynamics of action potentials and the time course of intracellular calcium associated with cardiomyocyte contraction.
To achieve the research goal, we used two mathematical models that describe the dynamics of action potentials in isolated cardiomyocytes using an equivalent electrical circuit. The selected models were upgraded by including a description of the non-selective ionic current through pores in the membrane created due to electroporation. The model was implemented and simulated in the Matlab environment, and the system of differential equations was solved using the ode15s function.
Our simulations showed that the formation of pores in the membrane significantly affects the triggering of action potentials. As the number of pores increases, the action potential starts to prolong until, at a certain number of pores, cardiomyocytes can no longer repolarize and remain depolarized, becoming incapable of triggering action potentials. When cardiomyocytes become depolarized, the concentration of intracellular calcium also increases. These changes are observed already with a very small number of created pores (less than 20), indicating that even very weak electroporation can significantly affect the ability of cardiomyocytes to trigger action potentials. The results of this research will contribute to better understanding of the changes in intracardiac
electrograms that are observed by cardiologists following cardiac ablation with electroporation,and potentially to the use of these signals for improving the treatment outcome.
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