Influence of <formula formulatype="inline"><tex Notation="TeX">${I_{Ks}}$</tex></formula> Heterogeneities on the Genesis of the T-wave: A Computational Evaluation

Abstract

Despite the commonly accepted notion that action potential duration (APD) is distributed heterogeneously throughout the ventricles and that the associated dispersion of repolarization is mainly responsible for the shape of the T-wave, its concordance and exact morphology are still not completely understood. This paper evaluated the T-waves for different previously measured heterogeneous ion channel distributions. To this end, cardiac activation and repolarization was simulated on a high resolution and anisotropic biventricular model of a volunteer. From the same volunteer, multichannel ECG data were obtained. Resulting transmembrane voltage distributions for the previously measured heterogeneous ion channel expressions were used to calculate the ECG and the simulated T-wave was compared to the measured ECG for quantitative evaluation. Both exclusively transmural (TM) and exclusively apico-basal (AB) setups produced concordant T-waves, whereas interventricular (IV) heterogeneities led to notched T-wave morphologies. The best match with the measured T-wave was achieved for a purely AB setup with shorter apical APD and a mix of AB and TM heterogeneity with M-cells in midmyocardial position and shorter apical APD. Finally, we probed two configurations in which the APD was negatively correlated with the activation time. In one case, this meant that the repolarization directly followed the sequence of activation. Still, the associated T-waves were concordant albeit of low amplitude.

Action potential duration gradients in the heart ventricles and the cardiac electric field during ventricular repolarization (a model study)

“…Often, the transmural and apicobasal gradients are alternatively considered as a major contributor to the generation of the T-wave. In accordance with the previous simulations [12,16], the present results showed that if equally expressed, the two gradients (as well as the interventricular gradient) produced the similar body surface potential distributions. The analysis of the contribution of the different parts of the ventricles to the resultant repolarization vector revealed that the transmural gradient produced substantial but oppositely directed transversal T-vectors.…”

“…In view of the fact that the mass of the septum is comparable with the left ventricular free wall mass, the septum could contribute much to the resulting repolarization gradient. The experiments, as well as computer simulations, showed that both the transmural and the apicobasal APD gradients can generate concordant T-waves and body surface potential distributions [5,12,16]. However, it remains unclear how the two different gradients can produce the similar electric field.…”

In Silico Organ Modelling in Predicting Efficacy and Safety of New Medicines

“…Three-dimensional anatomical models of the cardiac ventricles and atria have also been constructed. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] Simulations using sophisticated soware and numerical techniques have been conducted to investigate the effect of drugs, disease or mutations at the ionic level on the electrical activity of the human heart. 13,24,27,30,34 10.…”

Science at LLNL with IBM Blue Gene/Q

“…Previous cardiac simulation implementations are limited in biophysical detail of the cellular models, size of the model structure (e.g., rabbit vs. human heart), spatial resolution, and practical length of simulation time. Published scientific studies typically cite spatial resolutions of 0.2 to 0.3 mm and 20 to 32 million active elements [19][20][21][22] and simulation times of at most tens of heartbeats. To address these limitations, we have developed Cardioid, a high-performance cardiac simulation tool with detailed cell representations and support for heart geometries with near-cellular spatial resolution based on full-size human ventricle anatomy [23].…”