Catálogo de publicaciones - libros

Our aim is to develop a framework to validate 3-D computer models of cardiac electrophysiology using measurements of action potential obtained via optical imaging (based on voltage-sensitive fluorescence), and heart anatomy and fiber directions which are obtained from magnetic resonance imaging (MRI). In this paper we present preliminary results of this novel framework using a healthy porcine heart ex vivo model and the Aliev & Panfilov mathematical model. This experimental setup will facilitate the testing, validation and adjustment of computational models prior to their integration into clinical applications.

We introduce a framework to characterize and visualize the transverse tubular system of cardiac myocytes imaged with confocal microscopy. We imaged rabbit ventricular cells and cell segments with fluorescein linked to dextran. The image datasets were deconvolved with the Richardson-Lucy algorithm using the point spread function extracted from images of fluorescent beads. The transverse tubular system (t-system) was segmented with the methods of digital image processing. We reconstructed single transverse tubules and quantitatively described these in terms of length, cross-sectional area, ellipticity and orientation. These results should yield geometric markers for studies of protein distribution and provide insights into the function of the t-system.

Mathematical models were used to explore sodium (Na) current alterations. Markovian representations were chosen to describe the Na current behavior under pathological conditions, such as genetic defects (Long QT and Brugada syndromes) or acquired diseases (heart failure). These Na current formulations were subsequently introduced in an integrated model of the ventricular myocyte to investigate their effects on the ventricular action potential. This “in silico” approach is a powerful tool, providing new insights into arrhythmia susceptibility due to inherited and/or acquired Na channelopathies.

Atrial fibrillation (AF) induced electrical remodelling of ionic channels shortens action potential duration and reduces atrial excitability. Experimental data of AF-induced electrical remodelling (AFER) from two previous studies on human atrial myocytes were incorporated into a human atrial cell computer model to simulate their effects on atrial electrical behaviour. The dynamical behaviors of excitation scroll waves in an anatomical 3D homogenous model of human atria were studied for control and AF conditions. Under control condition, scroll waves meandered in large area and became persistent when entrapped by anatomical obstacles. In this case, a mother rotor dominated atrial excitation. Action potentials from several sites behaved as if the atrium were paced rapidly. Under AF conditions, AFER increased the stability of re-entrant scroll waves by reducing meander. Scroll wave break up leads to wavelets underpinning sustained chronic AF. Our simulation results support the hypothesis that AF-induced electrical remodelling perpetuates and sustains AF.

In this study, we quantitatively analyze some frequently used markers of recovery time, derived from the transmembrane action potentials and from unipolar extracellular electrograms. To this end, we performed 3D numerical simulations by using the anisotropic bidomain model of normal cardiac tissue, coupled with the Luo-Rudy phase I membrane model. We show that the extracellular markers considered are very accurate estimates of (and very well correlated with) the transmembrane action potential markers of the repolarization phase, irrespective of T-wave polarity, repolarization sequence, and transmural distribution of intrinsic properties of the cell membrane.

Much attention has been drawn to adopt complicated and realistic physiological models for simulating cardiac electrophysiological activities with abundant computing resources for quite a long time. However, to incorporate these physiological meaningful models into the recovery/inverse framework for estimating patient-specific cardiac electrophysiological activities always needs to handle excessive computational loads caused by the complexities of models. Thus, a balance should be found between physiological meaningfulness and computational feasibility for the recovery/inverse framework. In this paper, a novel numerical scheme, combination of meshfree method and BEM (boundary element method), is proposed to simulate intracardiac and extracardiac electrophysiological activities, which is aimed to provide physiological meaningful simulations with feasible computation for our recovery/inverse approaches. In our simulations, intracardiac electrophysiological activities (transmembrane potentials, TMPs) are obtained by solving a modified Fitzhugh-Nagumo (FHN) model using the meshfree method, and then extracardiac electrophysiological activities (body surface potentials, BSPs) are calculated using BEM. Moreover, we demonstrate the ability of our meshfree-BEM framework through favorable results.

Cardiac arrhythmias can develop complex electrophysiological patterns which complexify the planning and control of therapies, especially in the context of radio-frequency ablation. The development of electrophysiology models aims at testing different therapy strategies. However, current models are computationally expensive and often too complex to be adjusted with limited clinical data. In this paper, we propose a real-time method to simulate cardiac electrophysiology on triangular meshes. This model is based on a multi-front integration of the Fast Marching Method. This efficient approach opens new possibilities, including the ability to directly integrate modelling in the interventional room.

Solution in simulation of cardiac excitation anisotropic propagation throughout the ventricular myocardium is computationally very expensive that demands the introduction of a high performance computing techniques. In this study, a canine ventricle model was constructed features a realistic anatomical structure, including intramural fiber rotation and a conduction system. By using operator-splitting scheme, adaptive time step and backward differentiation formulation techniques in a parallel implement, we solved mondomain equation successfully. The stimulation produced isochrone’s map is close to the clinical record that obtained from the non-contact mapping system of Ensite 3000. The results show that the proposed methods can successfully be used to simulate heart excitation anisotropic propagation in three-dimensional anatomical large tissue size.

To investigate the mechanisms underlying the initiation and propagation of intracellular Ca ^2 +  waves, we developed a three-dimensional ventricular E-Cell (3Dv E-Cell), where cell membrane, nucleus, ryanodine receptor clusters, Z-disk, cytoplasm are modeled as spatially distributed structures. For the simulation of Ca ^2 +  sparks and Ca ^2 +  diffusion, a modified Fire-Diffuse-Fire model is used with stochastic rules for triggering Ca ^2 +  release. The 3Dv E-Cell is used to illustrate how stochastic properties of Ca ^2 +  sparks can lead to complex spatio-temporal intracellular wave processes and allows the incorporation of spatial data sets (protein distribution) into the geometry.

We developed an infant circulation model which incorporates an accurate myocardial cell model including a beta adrenergic system. The beta adrenergic system is essential for the response reproduction of the baroreflex control system. The proposed model was constructed by modifying the parameters of a human adult circulation model with the aid of a guinea pig myocardial cell model, whose baseline heart rate is close to that of an infant. The presented model is in good agreement with results obtained in physiological experiments.