Simulation of the influence of voltage level and pulse spacing on the efficiency, aggressiveness and uniformity of the electroporation process in tissues using meshless techniques.

Electroporation is a widely used method consisting of application of high-voltage, short-duration electric pulses to increase cell membrane permeability, allowing cellular internalization of medications. In this work, the influence of two primary parameters, voltage level (V) and pulse spacing (N), on electroporation efficiency, uniformity and aggressiveness, as quantified by the total mass transport to viable cells, intracellular concentration gradients and an aggressiveness factor introduced here, is studied by means of numerical simulations of drug transport in electroporated tissues. The global method of approximate particular solutions (Global MAPS) is used to solve the governing equations, together with domain scaling, singular value decomposition and smoothing algorithms, to address the ill-conditioning of the final system and suppress small scale oscillations. The accuracy of Global MAPS is evaluated by comparing the initial extracellular concentration, Ce , and final intracellular concentration, Ci , with previous finite volume method results, obtaining similar behavior of Ce and Ci along the tissue domain, with some differences for Ci in high-gradient zones. According to the Global MAPS results, the influence of V and N on Ci is only significant over a certain range, within which the largest drug transport to viable cells occurs. In general, both electroporation efficiency and aggressiveness change in nonuniform manner with V and decrease with N, whereas the electroporation uniformity decreases as V increases and N decreases. The contour plots obtained here can be considered useful tools to compare electroporation-based treatments in terms of their efficiency, aggressiveness and uniformity, assisting in the selection of a suitable treatment plan for cancer.

A three-dimensional human atrial model with fiber orientation. Electrograms and arrhythmic activation patterns relationship.

The most common sustained cardiac arrhythmias in humans are atrial tachyarrhythmias, mainly atrial fibrillation. Areas of complex fractionated atrial electrograms and high dominant frequency have been proposed as critical regions for maintaining atrial fibrillation; however, there is a paucity of data on the relationship between the characteristics of electrograms and the propagation pattern underlying them. In this study, a realistic 3D computer model of the human atria has been developed to investigate this relationship. The model includes a realistic geometry with fiber orientation, anisotropic conductivity and electrophysiological heterogeneity. We simulated different tachyarrhythmic episodes applying both transient and continuous ectopic activity. Electrograms and their dominant frequency and organization index values were calculated over the entire atrial surface. Our simulations show electrograms with simple potentials, with little or no cycle length variations, narrow frequency peaks and high organization index values during stable and regular activity as the observed in atrial flutter, atrial tachycardia (except in areas of conduction block) and in areas closer to ectopic activity during focal atrial fibrillation. By contrast, cycle length variations and polymorphic electrograms with single, double and fragmented potentials were observed in areas of irregular and unstable activity during atrial fibrillation episodes. Our results also show: (1) electrograms with potentials without negative deflection related to spiral or curved wavefronts that pass over the recording point and move away, (2) potentials with a much greater proportion of positive deflection than negative in areas of wave collisions, (3) double potentials related with wave fragmentations or blocking lines and (4) fragmented electrograms associated with pivot points. Our model is the first human atrial model with realistic fiber orientation used to investigate the relationship between different atrial arrhythmic propagation patterns and the electrograms observed at more than 43000 points on the atrial surface.

Remodelado estrcctural y de gap junctions en un modelo 3d de aurícula humana / Strctural remodeeling and of gap junctions in a 3d model of human atrial

Introducción: la fibrilación auricular (AF), es la más común de la arritmia cardiaca sostenida y un factor de riesgo para el accidente cerebro vascular y otras morbilidades, si no es tratada. Estudios epidemiológicos muestran que la AF tiende a perpetuarse con el tiempo, generando cambios electrofisiológicos y anatómicos denominados: remodelados auriculares. Se ha demostrado que estos cambios provocan variaciones de la velocidad de conducción (CV), en el tejido auricular. Objetivo: estudiar el efecto del remodelado de gap junctions en la propagación del potencial de acción, implementando un modelo 3D de aurícula humana altamente realista. Materiales y Métodos: se incorporaron los cambios generados por el remodelado eléctrico a un modelo de potencial de acción (AP) de miocito auricular, acoplado con un modelo tridimensional anatómicamente realista de aurícula humana dilatada. Mediante simulaciones de la propagación del AP en condiciones de remodelado eléctrico y anatómico, y de remodelado de gap junctions, se midieron las ventanas vulnerables de generación de reentradas en la base de las venas pulmonares izquierdas de la aurícula. Resultados: los resultados obtenidos indican que la ventana vulnerable en el remodelado de gap junctions, se desplazó 38 ms con relación al modelo dilatado, lo que nos muestra el impacto de la dilatación con remodelado de gap junction. Conclusiones: el remodelado eléctrico generó una disminución del 70 % en la duración del potencial de acción y una disminución de las velocidades de conducción entre un 14.6 y un 26 %, que fueron medidas en diferentes regiones de la aurícula dilatada. El foco disparado en la base de las venas pulmonares izquierdas, generó un frente de onda que mantiene una actividad reentrante debido a la anatomía subyacente de las venas pulmonares.

Introduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a significant risk factor for cerebrovascular accident and other morbidities if left untreated. Epidemiological studies show that AF tends to persist over time, creating electrophysiological and anatomical changes called atrial remodeling. It has been shown that these changes result in variations in conduction velocity (CV) in the atrial tissue. Objective: to study the effect of remodeling of gap junctions in the propagation of the action potential by implementing a highly realistic 3D human atrial model. Materials and methods: the changes caused by electrical remodeling were incorporated in an atrial myocyte action potential (AP) model coupled with an anatomically realistic three-dimensional model of dilated human atria. Through simulations of the AP spread in variations of anatomical and electrical remodeling and of gap junctions remodeling, vulnerable windows of reentry generation were measured at the base of the atrium left pulmonary veins. Results: the results obtained indicate that vulnerable window in the gap junctions remodeling moved 38 ms in relation with the expanded model which shows the impact of the dilatation gap junction remodeling. Conclusions: the electrical remodeling produced 70% decrease in action potential duration and decreased conduction velocities between 14.6 and 26 %, which were measured in different regions of the dilated atrium. The focus shot at the base of the left pulmonary veins created a wave which maintains a reentering activity due to the underlying anatomy of the pulmonary veins.