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Myocardial ischemia is one of the main causes of sudden cardiac death, with 80% of victims suffering from coronary heart disease. In acute myocardial ischemia, the obstruction of coronary flow leads to the interruption of oxygen flow, glucose, and washout in the affected tissue. Cellular metabolism is impaired and severe electrophysiological changes in(More)
Abnormalities in repolarization and its rate dependence are known to be related to increased proarrhythmic risk. A number of repolarization-related electrophysiological properties are commonly used as preclinical biomarkers of arrhythmic risk. However, the variability and complexity of repolarization mechanisms make the use of cellular biomarkers to predict(More)
Fluorescent photon scattering is known to distort optical recordings of cardiac transmembrane potentials; however, this process is not well quantified, hampering interpretation of experimental data. This study presents a novel model, which accurately synthesizes fluorescent recordings over the irregular geometry of the rabbit ventricles. Using the model,(More)
Cardiac modelling is the area of physiome modelling where the available simulation software is perhaps most mature, and it therefore provides an excellent starting point for considering the software requirements for the wider physiome community. In this paper, we will begin by introducing some of the most advanced existing software packages for simulating(More)
The sodium-potassium pump is widely recognized as the principal mechanism for active ion transport across the cellular membrane of cardiac tissue, being responsible for the creation and maintenance of the transarcolemmal sodium and potassium gradients, crucial for cardiac cell electrophysiology. Importantly, sodium-potassium pump activity is impaired in a(More)
a r t i c l e i n f o a b s t r a c t Chaste ('Cancer, heart and soft-tissue environment') is a software library and a set of test suites for computational simulations in the domain of biology. Current functionality has arisen from modelling in the fields of cancer, cardiac physiology and soft-tissue mechanics. It is released under the LGPL 2.1 licence.(More)
This paper presents methods to build histo-anatomically detailed individualized cardiac models. The models are based on high-resolution three-dimensional anatomical and/or diffusion tensor magnetic resonance images, combined with serial histological sectioning data, and are used to investigate individualized cardiac function. The current state of the art is(More)
Enhanced temporal and spatial variability in cardiac repolarization has been related to increased arrhythmic risk both clinically and experimentally. Causes and modulators of variability in repolarization and their implications in arrhythmogenesis are however not well understood. At the ionic level, the slow component of the delayed rectifier potassium(More)
Many experimental studies have pointed out the controversy involving the arrhythmogenic effects of potassium channel openers (KCOs) in ischemia. KCOs activate the ATP-sensitive potassium current [IK(ATP)], resulting in action potential duration (APD) shortening, especially under pathological conditions such as ischemia. Acute myocardial ischemia leads to(More)
Optical mapping of arrhythmias and defibrillation provides important insights; however, a limitation of the technique is signal distortion due to photon scattering. The goal of this experimental/simulation study is to investigate the role of three-dimensional photon scattering in optical signal distortion during ventricular tachycardia (VT) and(More)