Key result
Computational simulations demonstrated that a higher degree of fibrosis and larger patch size were associated with increased strength of virtual electrodes during defibrillation, while increased fibroblast-myocyte coupling reduced virtual electrode strength.
Why the study?
Defibrillation is an established therapy for atrial and ventricular arrhythmia, but its effects in the fibrotic heart required further evaluation.
Does extracellular current application cause virtual electrodes at boundaries of fibrotic patches in computational models of rabbit ventricular tissue?
Does extracellular current application cause virtual electrodes at boundaries of fibrotic patches in computational models of rabbit ventricular tissue?
Computational modeling demonstrates that fibrosis degree, patch size, and geometry significantly influence virtual electrode strength during defibrillation, highlighting the importance of tissue structure in defibrillation efficacy.
May alter defibrillation thresholds in fibrotic hearts; hypothesis-generating modeling leaves clinical translation open.
Defibrillation is a well-established therapy for atrial and ventricular arrhythmia. Here, we shed light on defibrillation in the fibrotic heart. Using the extended bidomain model of electrical conduction in cardiac tissue, we assessed the influence of fibrosis on the strength of virtual electrodes caused by extracellular electrical current. We created one-dimensional models of rabbit ventricular tissue with a central patch of fibrosis. The fibrosis was incorporated by altering volume fractions for extracellular, myocyte and fibroblast domains. In our prior work, we calculated these volume fractions from microscopic images at the infarct border zone of rabbit hearts. An average and a large degree of fibrosis were modeled. We simulated defibrillation by application of an extracellular current for a short duration (5 ms). We explored the effects of myocyte-fibroblast coupling, intra-fibroblast conductivity and patch length on the strength of the virtual electrodes present at the borders of the normal and fibrotic tissue. We discriminated between effects on myocyte and fibroblast membranes at both borders of the patch. Similarly, we studied defibrillation in two-dimensional models of fibrotic tissue. Square and disk-like patches of fibrotic tissue were embedded in control tissue. We quantified the influence of the geometry and fibrosis composition on virtual electrode strength. We compared the results obtained with a square and disk shape of the fibrotic patch with results from the one-dimensional simulations. Both, one- and two-dimensional simulations indicate that extracellular current application causes virtual electrodes at boundaries of fibrotic patches. A higher degree of fibrosis and larger patch size were associated with an increased strength of the virtual electrodes. Also, patch geometry affected the strength of the virtual electrodes. Our simulations suggest that increased fibroblast-myocyte coupling and intra-fibroblast conductivity reduce virtual electrode strength. However, experimental data to constrain these modeling parameters are limited and thus pinpointing the magnitude of the reduction will require further understanding of electrical coupling of fibroblasts in native cardiac tissues. We propose that the findings from our computational studies are important for development of patient-specific protocols for internal defibrillators.
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Bragard et al. (2019) studied Cardiac fibrosis and defibrillation. Extracellular electrical current (defibrillation) vs. Varying degrees of fibrosis and coupling was evaluated on Virtual electrode strength (change in transmembrane voltage). Computational simulations demonstrated that a higher degree of fibrosis and larger patch size were associated with increased strength of virtual electrodes during defibrillation, while increased fibroblast-myocyte coupling reduced virtual electrode strength.
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