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Effects of mechano-electrical feedback on cardiac dynamics: Pro- and anti-arrhythmic effects during alternans
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- Author / Creator
- Hazim, Azzam
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Contraction of the heart has been shown to affect the propagation of action potential (AP). In fact, the electrical waves of the heart propagate through the cardiac tissue and initiate its contraction via excitation-contraction coupling (ECC) while contraction of the heart causes deformations in the cardiac tissue that feedback on the process of wave propagation and affect electrophysiological properties through the mechanism of the so-called mechano-electrical feedback (MEF). The effects of MEF on cardiac electrophysiology may have both anti-arrhythmic and arrhythmogenic actions, however, the underlying mechanisms remain to be completely understood. Moreover, very little work has been done to study the effects of MEF on cardiac alternans. The later is a disturbance in heart rhythm, that manifests as a sequence of alternating long and short AP duration (APD). The APD alternans is linked to the onset of lethal cardiac arrhythmias. The focus of this thesis is to conduct a study on the effects of MEF on cardiac wave dynamics, particularly its effects on the dynamics of alternans, and to develop control algorithms to suppress alternans via MEF in real size of cardiac tissue. Therefore, in this thesis, which is based on computational study, electromechanical (EM) models that couple the cardiac excitation with the mechanical properties of the heart are used to perform numerical and theoretical investigations. The thesis contributions can be summarized as follows:
First, we show that the critical basic cycle length (BCL) corresponding to the onset of alternans along a one-dimensional (1D) cable of cardiac cells may be decreased in the presence of MEF. This antiarrhythmic effect of MEF close to the alternans bifurcation is due to the stretch-activated current (Isac), which is the main effect of MEF, that can modulate APDs in response to stretching. When studying the effects of MEF on the onset of alternans a restriction is put on the strength of Isac, so that its effects on the velocity of the pulse wave can be neglected, and only a certain range of BCLs, that are closed to the critical BCL, is chosen. Second, we show that MEF may play a role in arrhythmogenesis when a 1D cable is paced at a BCL, that is not very close to the critical BCL. It is illustrated that Isac can increase the dispersion of repolarization via its influence on the dispersion of conduction velocity. In particular, it is shown that MEF can convert a spatially concordant alternans (SCA), where APDs alternate in phase along the tissue, into a spatially discordant alternans (SDA), which is more arrhythmogenic, where APDs alternate out of phase in different regions of tissue. In addition, it is shown that for some values of the Isac model parameters, Isac gives rise to a large spatial dispersion of repolarization that can result in blocking AP propagation. Third, a control algorithm that combines the electrical pacing with the mechanical perturbation methods is developed. In this algorithm, the electrical pacing is realized by shortening or lengthening the BCL at the pacing site, and the novel mechanical perturbation strategy is realized by perturbing a small region within the heart tissue. Finally, a novel theoretical framework of 2D iterative maps, that incorporate the effects of MEF, and numerical simulations are presented to demonstrate successful suppression of alternans in cardiac tissue of relevant size using the proposed control algorithm and employing a simple EM model, namely the Nash-Panfilov model and two realistic EM models. In summary, in this thesis, the pro- and anti-arrhythmic effects of MEF during alternans are described and discussed, and a novel method that can manipulate MEF in order to suppress alternans is proposed, thus overcoming the limitations of tissue size that earlier alternans control methods have. -
- Graduation date
- Spring 2020
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- Type of Item
- Thesis
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- Degree
- Doctor of Philosophy
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- License
- Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.