Amr Al Abed

Erratum to “Optimisation of a Generic Ionic Model of Cardiac Myocyte Electrical Activity”.

A generic cardiomyocyte ionic model, whose complexity lies between a simple phenomenological formulation and a biophysically detailed ionic membrane current description, is presented.Themodel provides a user-defined number of ionic currents, employing two-gate Hodgkin-Huxley type kinetics. Its generic nature allows accurate reconstruction of action potential waveforms recorded experimentally from a range of cardiac myocytes. Using a multiobjective optimisation approach, the generic ionic model was optimised to accurately reproduce multiple action potential waveforms recorded from central and peripheral sinoatrial nodes and right atrial and left atrial myocytes from rabbit cardiac tissue preparations, under different electrical stimulus protocols and pharmacological conditions. When fitted simultaneously to multiple datasets, the time course of several physiologically realistic ionic currents could be reconstructed. Model behaviours tend to be well identified when extra experimental information is incorporated into the optimisation.

A computational model of direct brain excitation induced by electroconvulsive therapy: Comparison among three conventional electrode placements

BACKGROUND Electroconvulsive therapy (ECT) is a highly effective treatment for severe depressive disorder. Efficacy and cognitive outcomes have been shown to depend on variations in electrode placement and other stimulus parameters, presumably because of differences in the pattern of neuronal activation. This latter effect, however, is poorly understood. OBJECTIVE In this study, we present an anatomically accurate human head computational model to stimulate neuronal excitation during ECT, to better understand the effects of varying electrode placement and stimulus parameters. METHODS Electric field and current density throughout the head, as well as direct neural activation within the brain, were computed using the finite element method. Regions representing passive volume conductors (skin, skull, cerebrospinal fluid) were extracellularly coupled to an excitable neural continuum region representing the brain. The skull was modeled with anistropic electrical conductivity. RESULTS Simulation results indicated that direct activation of the brain occurred immediately beneath the electrodes on the scalp, consistent with existing imaging studies. In addition, we found that the brainstem was also activated using a right unilateral electrode configuration. Simulation also demonstrated that a reduction in stimulus amplitude or pulse width led to a reduction in the spatial extent of brain activation. CONCLUSIONS The novel model described in this study was able to simulate direct excitation of the brain during ECT, was useful in characterizing differences in neuronal activation as electrode placement, pulse width, and amplitude were altered, and is proposed as a tool for further exploring the effects of variations in ECT stimulation approaches. Results from the simulations assist in understanding recently described clinical phenomena, in particular, the reduction in cognitive side effects with ultrabrief pulse width stimulation, and greater effects of the ECT stimulus on cardiovascular function with unilateral electrode placement.

Numerical investigation of the effect of cannula placement on thrombosis

Despite the rapid advancement of left ventricular assist devices (LVADs), adverse events leading to deaths have been frequently reported in patients implanted with LVADs, including bleeding, infection, thromboembolism, neurological dysfunction and hemolysis.Cannulation forms an important component with regards to thrombus formation in assisted patients by varying the intraventricular flow distribution in the left ventricle (LV). To investigate the correlation between LVAD cannula placement and potential for thrombus formation, detailed analysis of the intraventricular flow field was carried out in the present study using a two way fluid structure interaction (FSI), axisymmetric model of a passive LV incorporating an inflow cannula. Three different cannula placements were simulated, with device insertion near the LV apex, penetrating one-fourth and mid-way into the LV long axis. The risk of thrombus formation is assessed by analyzing the intraventricular vorticity distribution and its associated vortex intensity, amount of stagnation flow in the ventricle as well as the level of wall shear stress. Our results show that the one-fourth placement of the cannula into the LV achieves the best performance in reducing the risk of thrombus formation. Compared to cannula placement near the apex, higher vortex intensity is achieved at the one-fourth placement, thus increasing wash out of platelets at the ventricular wall. One-fourth LV penetration produced negligible stagnation flow region near the apical wall region, helping to reduce platelet deposition on the surface of the cannula and the ventricular wall.

Optimisation of Ionic Models to Fit Tissue Action Potentials: Application to 3D Atrial Modelling

A 3D model of atrial electrical activity has been developed with spatially heterogeneous electrophysiological properties. The atrial geometry, reconstructed from the male Visible Human dataset, included gross anatomical features such as the central and peripheral sinoatrial node (SAN), intra-atrial connections, pulmonary veins, inferior and superior vena cava, and the coronary sinus. Membrane potentials of myocytes from spontaneously active or electrically paced in vitro rabbit cardiac tissue preparations were recorded using intracellular glass microelectrodes. Action potentials of central and peripheral SAN, right and left atrial, and pulmonary vein myocytes were each fitted using a generic ionic model having three phenomenological ionic current components: one time-dependent inward, one time-dependent outward, and one leakage current. To bridge the gap between the single-cell ionic models and the gross electrical behaviour of the 3D whole-atrial model, a simplified 2D tissue disc with heterogeneous regions was optimised to arrive at parameters for each cell type under electrotonic load. Parameters were then incorporated into the 3D atrial model, which as a result exhibited a spontaneously active SAN able to rhythmically excite the atria. The tissue-based optimisation of ionic models and the modelling process outlined are generic and applicable to image-based computer reconstruction and simulation of excitable tissue.

High-amplitude electrical stimulation can reduce elicited neuronal activity in visual prosthesis

Retinal electrostimulation is promising a successful therapy to restore functional vision. However, a narrow stimulating current range exists between retinal neuron excitation and inhibition which may lead to misperformance of visual prostheses. As the conveyance of representation of complex visual scenes may require neighbouring electrodes to be activated simultaneously, electric field summation may contribute to reach this inhibitory threshold. This study used three approaches to assess the implications of relatively high stimulating conditions in visual prostheses: (1) in vivo, using a suprachoroidal prosthesis implanted in a feline model, (2) in vitro through electrostimulation of murine retinal preparations, and (3) in silico by computing the response of a population of retinal ganglion cells. Inhibitory stimulating conditions led to diminished cortical activity in the cat. Stimulus-response relationships showed non-monotonic profiles to increasing stimulating current. This was observed in vitro and in silico as the combined response of groups of neurons (close to the stimulating electrode) being inhibited at certain stimulating amplitudes, whilst other groups (far from the stimulating electrode) being recruited. These findings may explain the halo-like phosphene shapes reported in clinical trials and suggest that simultaneous stimulation in retinal prostheses is limited by the inhibitory threshold of the retinal ganglion cells.

Optimisation of a Generic Ionic Model of Cardiac Myocyte Electrical Activity

A generic cardiomyocyte ionic model, whose complexity lies between a simple phenomenological formulation and a biophysically detailed ionic membrane current description, is presented. The model provides a user-defined number of ionic currents, employing two-gate Hodgkin-Huxley type kinetics. Its generic nature allows accurate reconstruction of action potential waveforms recorded experimentally from a range of cardiac myocytes. Using a multiobjective optimisation approach, the generic ionic model was optimised to accurately reproduce multiple action potential waveforms recorded from central and peripheral sinoatrial nodes and right atrial and left atrial myocytes from rabbit cardiac tissue preparations, under different electrical stimulus protocols and pharmacological conditions. When fitted simultaneously to multiple datasets, the time course of several physiologically realistic ionic currents could be reconstructed. Model behaviours tend to be well identified when extra experimental information is incorporated into the optimisation.

A generic ionic model of cardiac action potentials

A generic cardiac ionic model employing membrane currents based on two-gate Hodgkin-Huxley kinetics is presented. Its generic nature allows it to accurately reproduce action potential waveforms in heterogeneous cardiac tissue by optimizing parameters governing ion channel kinetics and magnitudes. The model allows a user-defined number of voltage and time-dependent ion currents to be incorporated, in order to reproduce and predict electrophysiological action potential waveforms from multiple recordings in individual cardiac myocytes.

Sensitivity Analysis of Left Ventricle with Dilated Cardiomyopathy in Fluid Structure Simulation

Dilated cardiomyopathy (DCM) is the most common myocardial disease. It not only leads to systolic dysfunction but also diastolic deficiency. We sought to investigate the effect of idiopathic and ischemic DCM on the intraventricular fluid dynamics and myocardial wall mechanics using a 2D axisymmetrical fluid structure interaction model. In addition, we also studied the individual effect of parameters related to DCM, i.e. peak E-wave velocity, end systolic volume, wall compliance and sphericity index on several important fluid dynamics and myocardial wall mechanics variables during ventricular filling. Intraventricular fluid dynamics and myocardial wall deformation are significantly impaired under DCM conditions, being demonstrated by low vortex intensity, low flow propagation velocity, low intraventricular pressure difference (IVPD) and strain rates, and high-end diastolic pressure and wall stress. Our sensitivity analysis results showed that flow propagation velocity substantially decreases with an increase in wall stiffness, and is relatively independent of preload at low-peak E-wave velocity. Early IVPD is mainly affected by the rate of change of the early filling velocity and end systolic volume which changes the ventriculo:annular ratio. Regional strain rate, on the other hand, is significantly correlated with regional stiffness, and therefore forms a useful indicator for myocardial regional ischemia. The sensitivity analysis results enhance our understanding of the mechanisms leading to clinically observable changes in patients with DCM.

Simplified 2D Bidomain Model of Whole Heart Electrical Activity and ECG Generation

Abstract The aim of this study was the development of a geometrically simple and highly computationally-efficient two dimensional (2D) biophysical model of whole heart electrical activity, incorporating spontaneous activation of the sinoatrial node (SAN), the specialized conduction system, and realistic surface ECG morphology computed on the torso. The FitzHugh-Nagumo (FHN) equations were incorporated into a bidomain finite element model of cardiac electrical activity, which was comprised of a simplified geometry of the whole heart with the blood cavities, the lungs and the torso as an extracellular volume conductor. To model the ECG, we placed four electrodes on the surface of the torso to simulate three Einthoven leads VI, VII and VIII from the standard 12-lead system. The 2D model was able to reconstruct ECG morphology on the torso from action potentials generated at various regions of the heart, including the sinoatrial node, atria, atrioventricular node, His bundle, bundle branches, Purkinje fibers, and ventricles. Our 2D cardiac model offers a good compromise between computational load and model complexity, and can be used as a first step towards three dimensional (3D) ECG models with more complex, precise and accurate geometry of anatomical structures, to investigate the effect of various cardiac electrophysiological parameters on ECG morphology.

A morphologically realistic shell model of atrial propagation and ablation

A three dimensional morphologically realistic model of atrial propagation is developed, based on the male Visible Human dataset and the Fitzhugh-Nagumo equations for cardiac excitation. The atrial shell geometry incorporates eleven different anatomical structures, including the pulmonary veins, and the septum, Bachmann’s bundle and coronary sinus as interatrial conduction pathways. Although the model utilizes a simplified cellular model of cardiac excitation it is able to reproduce a variety of electrophysiological phenomena including: autorhythmicity of the sinoatrial node and its ability to excite surrounding atrial tissue, spiral re-entrant wavefronts, ectopic beats originating in the PV and their termination by circumferential ablation of the PV. The model is an important tool to quantitatively study atrial excitation under normal conditions and during atrial fibrillation.