Virtual cell and tissue dynamics of ectopic activation of the ventricles

Abstract

Cardiac ventricular cells and tissues are normally excitable, and are activated by propagating waves of excitation that are initiated in the specialized pacemaking region of the heart. However, isolated or repetitive activity can be initiated at abnormal (ectopic) sites in the ventricles. To trigger an endogenous ectopic beat, there must be a compact focus of cells with changed membrane excitation parameters and kinetics, which initiate activity by after-depolarizations triggered by propagating activity, or that have bifurcated into autorhythmicity. This ectopic focus needs to be large enough, and adequately coupled, to drive the surrounding tissue. We investigate the initiation of ectopic excitation in computational models of human ventricular cells triggered by after-depolarizations and by up/down regulation of specific membrane conductance systems, and the propagation and evolution of ectopic activity in homogeneous or heterogeneous and isotropic, anisotropic, or orthotropic tissues.

Construction and validation of anisotropic and orthotropic ventricular geometries for quantitative predictive cardiac electrophysiology

“…I ion in equation (1.1)) given by the rat ventricular model of Pandit et al [67], for epicardial excitation at a point analogous to that for figure 5. Space steps were 0.2 mm isotropic as defined by the DT-MRI dataset, and equation (1.1) was solved with a forward-time centred-space method using an operator splitting technique and an adaptive time step (see [26,68] for details). The qualitative similarity between the experimental and computed maps-compare figures 5a,b and 6b,c-provides a partial validation for our computational models where geometry and architecture are constructed using data obtained from DT-MRI.…”

Quantifying the effects of ischaemia on electrophysiology and the ST segment of the ECG in human virtual ventricular cells and tissues

“…Integration details for the models can be found in [7]. Figure 1 shows action potentials recorded from single endocardial human cell models at 1 Hz pacing, for control and ischaemic conditions plus the component parts of ischaemia in isolation.…”

“…Parameter changes were made to simulate the individual component changes seen during ischaemia -hyperkalaemia, acidosis and anoxia -as in Shaw & Rudy [6], but with extracellular potassium during hyperkalaemia set to [K + ] o = 10 mM and with an 80% reduction in the maximal conductance of the ATP-sensitive K + current I K(ATP) to ensure realistic changes in resting membrane potential and action potential duration (APD) respectively (see Results). These cell models were incorporated into a heterogeneous 15 mm one-dimensional strand model of the human left ventricular wall [7]. Propagation of electrical excita- tion in such a model of cardiac tissue is described by…”

Reconstruction and Quantification of Diffusion Tensor Imaging-Derived Cardiac Fibre and Sheet Structure in Ventricular Regions used in Studies of Excitation Propagation

“…Such wedge and whole ventricle simulations of cardiac electrophysiology are now tractable and extremely useful, as the data they provide can be dissected in time and space, and by parameters. This allows a detailed examination of the effects of cardiac structure on propagation of excitation [9], the elucidation of mechanisms underlying arrhythmias [7,8,15], and gives an additional means of interpreting the results from experimental studies [59]. Propagation of electrical excitation in cardiac tissue can be described by the non-linear cable equation, a reaction-diffusion-type partial differential equation:…”