In Silico Modeling and Validation of the Effect of Calcium-Activated Potassium Current on Ventricular Repolarization in Failing Myocytes.

Objective: The pathophysiological role of the small conductance calcium-activated potassium (SK) channels in human ventricular myocytes remains unclear. Experimental studies have reported upregulation of in pathological states, potentially contributing to ventricular arrhythmias. In heart failure (HF) patients, the upregulation of SK channels could be an adaptive physiological response to shorten the action potential duration (APD) under conditions of reduced repolarization reserve.

Cardiac cells stimulated with an axial current-like waveform reproduce electrophysiological properties of tissue fibers.

Background And Objective: In silico electrophysiological models are generally validated by comparing simulated results with experimental data. When dealing with single-cell and tissue scales simultaneously, as occurs frequently during model development and calibration, the effects of inter-cellular coupling should be considered to ensure the trustworthiness of model predictions. The hypothesis of this paper is that the cell-tissue mismatch can be reduced by incorporating the effects of conduction into the single-cell stimulation current.

The heterogeneous effects of the great recession on informal care to the elderly.

This paper studies the role of unobserved factors to measure the impact of the economic downturn on informal care availability to the elderly in Europe. We use the Survey of Health, Ageing and Retirement in Europe (SHARE), which allows controlling for socio-demographic variables. Our results show that the impact of the Great Recession on care receipt depends not only on observed, but also on unobserved characteristics.

DENIS: Solving cardiac electrophysiological simulations with volunteer computing.

Cardiac electrophysiological simulations are computationally intensive tasks. The growing complexity of cardiac models, together with the increasing use of large ensembles of models (known as populations of models), make extensive simulation studies unfeasible for regular stand-alone computers. To address this problem, we developed DENIS, a cardiac electrophysiology simulator based on the volunteer computing paradigm.

A response surface optimization approach to adjust ionic current conductances of cardiac electrophysiological models. Application to the study of potassium level changes.

Cardiac electrophysiological computational models are often developed from previously published models. The new models may incorporate additional features to adapt the model to a different species or may upgrade a specific ionic formulation based on newly available experimental data. A relevant challenge in the development of a new model is the estimation of certain ionic current conductances that cannot be reliably identified from experiments.

Limitations in electrophysiological model development and validation caused by differences between simulations and experimental protocols.

Models of ion channel dynamics are usually built by fitting isolated cell experimental values of individual parameters while neglecting the interaction between them. Another shortcoming regards the estimation of ionic current conductances, which is often based on quantification of Action Potential (AP)-derived markers. Although this procedure reduces the uncertainty in the calculation of conductances, many studies evaluate electrophysiological AP-derived markers from single cell simulations, whereas experimental measurements are obtained from tissue preparations.

In silico simulations of experimental protocols for cardiac modeling.

A mathematical model of the AP involves the sum of different transmembrane ionic currents and the balance of intracellular ionic concentrations. To each ionic current corresponds an equation involving several effects. There are a number of model parameters that must be identified using specific experimental protocols in which the effects are considered as independent.

A human ventricular cell model for investigation of cardiac arrhythmias under hyperkalaemic conditions.

In this study, several modifications were introduced to a recently proposed human ventricular action potential (AP) model so as to render it suitable for the study of ventricular arrhythmias. These modifications were driven by new sets of experimental data available from the literature and the analysis of several well-established cellular arrhythmic risk biomarkers, namely AP duration at 90 per cent repolarization (APD(90)), AP triangulation, calcium dynamics, restitution properties, APD(90) adaptation to abrupt heart rate changes, and rate dependence of intracellular sodium and calcium concentrations. The proposed methodology represents a novel framework for the development of cardiac cell models.