Population of human ventricular cell models calibrated with in vivo measurements unravels ionic mechanisms of cardiac alternans

Cardiac alternansis an important risk factor in cardiac physiology, and is related to the initiation of many pathophysiological conditions. However, the mechanisms underlying the generation of alternans remain unclear. In this study, we used a population of computational human ventricle models based onthe O’Hara model [1] to explore the effect of 11 key factors experimentally reported to be related to alternans. In vivo experimental datasets coming from patients undergoing cardiac surgery were used in the calibration of our in silico population of models. The calibrated models in the population were divided into two groups (Normal and Alternans) depending on alternans occurrence. Our results showed that there were significant differences in the following 5 ionic currents between the two groups: fast sodium current, sodium calcium exchanger current, sodium potassium pump current, sarcoplasmic reticulum (SR) calcium release flux and SR calcium reuptake flux. Further analysis indicated that fast sodium current and SR calcium uptake were the two most significant currents that contributed to voltage and calcium alternans generation, respectively

Fractional diffusion models of cardiac electrical propagation: role of structural heterogeneity in dispersion of repolarization

Structural heterogeneity constitutes one of the main substrates influencing impulse propagation in living tissues. In cardiac muscle, improved understanding on its role is key to advancing our interpretation of cell-to-cell coupling, and how tissue structure modulates electrical propagation and arrhythmogenesis in the intact and diseased heart. We propose fractional diffusion models as a novel mathematical description of structurally heterogeneous excitable media, as a mean of representing the modulation of the total electric field by the secondary electrical sources associated with tissue inhomogeneities. Our results, validated against in-vivo human recordings and experimental data of different animal species, indicate that structural heterogeneity underlies many relevant characteristics of cardiac propagation, including the shortening of action potential duration along the activation pathway, and the progressive modulation by premature beats of spatial patterns of dispersion of repolarization. The proposed approach may also have important implications in other research fields involving excitable complex media

On the eigenvalues and eigenvectors of nonsymmetric saddle point matrices preconditioned by block triangular matrices

Block lower triangular and block upper triangular matrices are popular preconditioners for nonsymmetric saddle point matrices. In this note we show that a block lower triangular preconditioner gives the same spectrum as a block upper triangular preconditioner and that the eigenvectors of the two preconditioned systems are related

Computational modeling of human atrial cardiomyocytes: integration of electro-mechanical & mechano-electric feedback pathways

The cardiomyocytes are very complex consisting of many interlinked non-linear regulatory mechanisms between electrical excitation and mechanical contraction. Thus given a integrated electromechanically coupled system it becomes hard to understand the individual contributor of cardiac electrics and mechanics under both physiological and pathological conditions. Hence, to identify the causal relationship or to predict the responses in a integrated system the use of computational modeling can be beneficial. Computational modeling is a powerful tool that provides complete control of parameters along with the visibility of all the individual components of the integrated system. The advancement of computational power has made it possible to simulate the models in a short timeframe, providing the possibility of increased predictive power of the integrated system. My doctoral thesis is focused on the development of electromechanically integrated human atrial cardiomyocyte model with proper consideration of feedforward and feedback pathways

Singular inextensible limit in the vibrations of post-buckled rods: analytical derivation and role of boundary conditions

In-plane vibrations of an elastic rod clamped at both extremities are studied. The rod is modeled as an extensible planar Kirchhoff elastic rod under large displacements and rotations. Equilibrium configurations and vibrations around these configurations are computed analytically in the incipient post-buckling regime. Of particular interest is the variation of the first mode frequency as the load is increased through the buckling threshold. The loading type is found to have a crucial importance as the first mode frequency is shown to behave singularly in the zero thickness limit in case of prescribed axial displacement, whereas a regular behavior is found in the case of prescribed axial load

Interfacial deflection and jetting of a paramagnetic particle-laden fluid: theory and experiment

We describe the results of experiments and mathematical analysis of the deformation of a free surface by an aggregate of magnetic particles. The system we study is differentiated from ferrofluid systems because it contains regions rich with magnetic material as well as regions of negligible magnetic content. In our experiments, the magnetic force from a spherical permanent magnet collects magnetic particles to a liquid–air interface, and deforms the free surface to form a hump. The hump is composed of magnetic and non-magnetic regions due to the particle collection. When the magnet distance falls below a threshold value, we observe the transition of the hump to a jet. The mathematical model we develop, which consists of a numerical solution and an asymptotic approximation, captures the shape of the liquid–air interface during the deformation stage and a scaling prediction for the critical magnet distance for the hump to become a jet

A lattice Boltzmann model for natural convection in cavities

We study a multiple relaxation time lattice Boltzmann model for natural convection with moment–based boundary conditions. The unknown primary variables of the algorithm at a boundary are found by imposing conditions directly upon hydrodynamic moments, which are then translated into conditions for the discrete velocity distribution functions. The method is formulated so that it is consistent with the second–order implementation of the discrete velocity Boltzmann equations for fluid flow and temperature. Natural convection in square cavities is studied for Rayleigh numbers ranging from 103 to 106. An excellent agreement with benchmark data is observed and the flow fields are shown to converge with second order accuracy

Rivulet flow round a horizontal cylinder subject to a\ud uniform surface shear stress

The steady flow of a slowly varying rivulet with prescribed flux in the azimuthal direction round a large stationary horizontal cylinder subject to a prescribed uniform azimuthal surface shear stress is investigated. In particular, we focus on the case where the volume flux is downwards but the shear stress is upwards, for which there is always a solution corresponding to a rivulet flowing down at least part of one side of the cylinder. We consider both a rivulet with constant non-zero contact angle but slowly varying width (i.e. de-pinned contact lines) and a rivulet with constant width but slowly varying contact angle (i.e. pinned contact lines), and show that they have qualitatively different behaviour. When shear is present, a rivulet with constant non-zero contact angle can never run all the way from the top to the bottom of the cylinder, and so we consider the scenario in which an infinitely wide two-dimensional film of uniform thickness covers part of the upper half of the cylinder and “breaks” into a single rivulet with constant non-zero contact angle. In contrast, a sufficiently narrow rivulet with constant width can run all the way from the top to the bottom of the cylinder, whereas a wide rivulet can do so only if its contact lines de-pin, and so we consider the scenario in which the contact lines of a wide rivulet de-pin on the lower half of the cylinder