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Computer simulation turns out to be beneficial when clinical data lack spatio-temporal resolution or parameters cannot be measured at all. To derive trustworthy results, these in-silico models have to thoroughly parameterized and validated. In this work we present data from a simplified in-vitro setup for characterizing ventricular electromechanics. Right ventricular papillary muscles from New Zealand rabbits were isolated and stretched from slack length to lmax, i.e. the muscle length at maximum active force development. Active stress development showed an almost linear increase for moderate strain (90–100% of lmax) and a significant decrease for larger strain (100–105% of lmax). Passive strain development showed a nonlinear increase. Conduction velocity CV showed an increase of ≈10% between low and moderate strain and no significant decrease beyond. Fitting active active stress-strain relationship using a 5th-order polynomial yielded adequate results for moderate and high strain values, whereas fitting using a logistic function yielded more reasonable results for low strain values. Passive stress-strain relationship was satisfactorily fitted using an exponential function.

Significant advancements in imaging technology and the dramatic increase in computer power over the last few years broke the ground for the construction of anatomically realistic models of the heart at an unprecedented level of detail. To effectively make use of high-resolution imaging datasets for modeling purposes, the imaged objects have to be discretized. This procedure is trivial for structured grids. However, to develop generally applicable heart models, unstructured grids are much preferable. In this study, a novel image-based unstructured mesh generation technique is proposed. It uses the dual mesh of an octree applied directly to segmented 3-D image stacks. The method produces conformal, boundary-fitted, and hexahedra-dominant meshes. The algorithm operates fully automatically with no requirements for interactivity and generates accurate volume-preserving representations of arbitrarily complex geometries with smooth surfaces. The method is very well suited for cardiac electrophysiological simulations. In the myocardium, the algorithm minimizes variations in element size, whereas in the surrounding medium, the element size is grown larger with the distance to the myocardial surfaces to reduce the computational burden. The numerical feasibility of the approach is demonstrated by discretizing and solving the monodomain and bidomain equations on the generated grids for two preparations of high experimental relevance, a left ventricular wedge preparation, and a papillary muscle. Index Terms--Bidomain model, individualized medicine, in silico heart model, mesh generation, multiscale modeling, octree method.

Electrical loading by ventricular myocardium modulates conduction system repolarization near Purkinje-ventricular junctions (PVJs). We investigated how that loading suppresses and facilitates early afterdepolarizations (EADs) under conditions where there is a high degree of functional coupling between tissue types, which is consistent with the anatomic arrangement at the peripheral conduction system-myocardial interface. Experiments were completed in eight rabbit right ventricular (RV) free wall preparations. Free-running Purkinje strands were locally superfused, and action potentials were recorded from strands. RV free walls were bathed in normal solution. Surface electrograms were recorded near strand insertions into downstream free wall myocardium. Detailed histology was performed to assemble a computer model with interspersed Purkinje and ventricular myocytes weakly coupled throughout the region. Delays from Purkinje upstrokes to downstream peripheral conduction system and myocardial activation were comparable between experiments and simulations, supporting model node-to-node electrical coupling, i.e., the functional coupling. Purkinje action potential duration (APD) prolongation with localized isoproterenol in experiments and calcium current enhancement in simulations failed to establish EADs. With myocardial APD prolongation by delayed rectifier potassium current inhibition or L-type calcium current enhancement accompanying Purkinje APD prolongation in simulations, however, EAD-induced triggered activity developed. Collectively, our findings suggest competing contributions of the myocardial sink when there is a high degree of functional coupling between tissue types, with the transition from suppression to facilitation of EAD-induced triggered activity depending critically upon myocardial APD prolongation. Index Terms--Extracellular mapping, functional coupling, isoproterenol, source-sink interactions, specialized conduction system.

A high-resolution recording and mapping system helps study the excitation spread in ventricular heart preparation and suggests that the multidimensional spread of excitation at a microscopic level is irregular in two dimension. The recording of high waveforms explains propagation events at a small scale in various cardiac tissues under various conditions. A UNIX-based computer system with a custom-designed data acquisition and software program controls the instruments and manages experimental data.

Advanced medical imaging technologies provide a wealth of information on cardiac anatomy and structure at a paracellular resolution, allowing to identify microstructural discontinuities which disrupt the intracellular matrix. Current state-of-the-art computer models built upon such datasets account for increasingly finer anatomical details, however, structural discontinuities at the paracellular level are typically discarded in the model generation process, owing to the significant costs which incur when using high resolutions for explicit representation. In this study, a novel discontinuous finite element (dFE) approach for discretizing the bidomain equations is presented, which accounts for fine-scale structures in a computer model without the need to increase spatial resolution. In the dFE method, this is achieved by imposing infinitely thin lines of electrical insulation along edges of finite elements which approximate the geometry of discontinuities in the intracellular matrix. Simulation results demonstrate that the dFE approach accounts for effects induced by microscopic size scale discontinuities, such as the formation of microscopic virtual electrodes, with vast computational savings as compared to high resolution continuous finite element models. Moreover, the method can be implemented in any standard continuous finite element code with minor effort. [ABSTRACT FROM PUBLISHER]

Electrical loading by ventricular myocardium modulates conduction system repolarization near Purkinje-ventricular junctions (PVJs). We investigated how that loading suppresses and facilitates early afterdepolarizations (EADs) under conditions where there is a high degree of functional coupling between tissue types, which is consistent with the anatomic arrangement at the peripheral conduction system-myocardial interface. Experiments were completed in eight rabbit right ventricular (RV) free wall preparations. Free-running Purkinje strands were locally superfused, and action potentials were recorded from strands. RV free walls were bathed in normal solution. Surface electrograms were recorded near strand insertions into downstream free wall myocardium. Detailed histology was performed to assemble a computer model with interspersed Purkinje and ventricular myocytes weakly coupled throughout the region. Delays from Purkinje upstrokes to downstream peripheral conduction system and myocardial activation were comparable between experiments and simulations, supporting model node-to-node electrical coupling, i.e., the functional coupling. Purkinje action potential duration (APD) prolongation with localized isoproterenol in experiments and calcium current enhancement in simulations failed to establish EADs. With myocardial APD prolongation by delayed rectifier potassium current inhibition or L-type calcium current enhancement accompanying Purkinje APD prolongation in simulations, however, EAD-induced triggered activity developed. Collectively, our findings suggest competing contributions of the myocardial sink when there is a high degree of functional coupling between tissue types, with the transition from suppression to facilitation of EAD-induced triggered activity depending critically upon myocardial APD prolongation. [ABSTRACT FROM AUTHOR]

Microstructural heterogeneities in cardiac tissue, such as embedded connective tissue secondary to fibrosis, may lead to complex patterns of electrical activation that are reflected in the fractionation of extracellularly recorded electrograms. The decomposition of such electrograms into non-fractionated components is expected to provide additional information to allow a more precise classification of the microstructural properties adjacent to a given recording site. For the sake of this, an analytic signal model is introduced in this study that is capable of reliably identifying extracellular waveforms associated with sites of initiating, free-running, and terminating or colliding activation wavefronts. Using this signal model as a template, a procedure is developed for the automatic decomposition of complex fractionated electrograms into non-fractionated components. The decomposition method has been validated using electrograms obtained from one- and two-dimensional computer simulations in which all relevant intracellular and extracellular quantities are accessible at a very high spatiotemporal resolution and can be manipulated in a controlled manner. Fractionated electrograms were generated in these models by incorporating microstructural obstacles that mimicked inlays of connective tissue. Using this signal model, fractionated electrograms emerging from microstructural heterogeneities in the submillimeter range with latencies between components down to 0.6 ms can be decomposed.

The presence of connective tissue as well as interstitial clefts forms a natural barrier to the electrical propagation in the heart. At a microscopic scale, such uncoupling structures change the pattern of the electrical conduction from uniform towards complex and may play a role in the genesis of cardiac arrhythmias. The anatomical diversity of conduction structures and their topology at a microscopic size scale is overwhelming for experimental techniques. Mathematical models have been often employed to study the behavior of the electrical propagation at a sub-cellular level. However, very fine and computationally expensive meshes are required to capture all microscopic details found in the cardiac tissue. In this work, we present a numerical technique based on the finite element method which allows to reproduce the effects of microscopic conduction barriers caused by the presence of uncoupling structures without actually resolving these structures in a high resolution mesh, thereby reducing the computational costs significantly.

In experiments with cardiac tissue, local conduction is described by waveform analysis of the derivative of the extracellular potential Φ(e) and by the loop morphology of the near-field strength E (the components of the electric field parallel and very close to the tissue surface). The question arises whether the features of these signals can be used to quantify the degree of fibrosis in the heart. A computer model allows us to study the behavior of electric signals at the endocardium with respect to known configurations of microstructure which can not be detected during the electrophysiological experiments. This work presents a 2D-computer model with sub-cellular resolution of atrial micro-conduction in the rabbit heart. It is based on the monodomain equations and digitized histographs from tissue slices obtained post-experimentum. It could be shown that excitation spread in densely coupled regions produces uniform and anisotropic conduction. In contrast, zones with parallel fibers separated by uncoupling interstitial space or connective tissue may show uniform or complex signals depending on pacing site. These results suggest that the analysis of Φ(e) and E combined with multi-site pacing could be used to characterize the type and the size of fibrosis.

Wave fronts of cardiac activation, when propagating oblique to the fiber axis, reveal small fractionations and distortions in extracellular potential waveforms Phi(e) as well as in parameters derived from Phi(e) like dPhi(e)/dt and the gradient of Phi(e), the cardiac near field E. dPhi(e)/dt shows multiple deflections and E changes its morphology forming abnormal or even two or multiple subsequent loops. We analyze segments of such irregular loops of E obtained from in-vitro experiments and from computer simulation of a 2D-tissue sheet with a longitudinal oriented obstacle. In computer simulations we found that the individual sections of E reflect fairly well individual pathways of activation separated and delayed by the presence of a structural obstacle similar to connective tissue embedded longitudinally in heart tissue. Electrophysiological experiments with papillary muscles confirm this near field behavior.

Local velocity and direction of cardiac excitation spread can be estimated from four extra-cellular electric potential waveforms recorded simultaneously by closely-spaced electrodes. In this work, three methods for the determination of these parameters in case of non-fractionated electrograms were compared. Waveforms recorded during in-vitro experiments were analyzed in terms of their noise components. Noise according to the experimental environment was generated and added to noise-free waveforms obtained from computer simulations. For each of the three investigated methods the accuracy of the determined parameters velocity and direction was evaluated for three different noise levels and three types of propagation.