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Long QT syndrome is a repolarization disorder characterized by marked prolongation of QT interval. A clear consequence of long QT syndrome is the occurrence of a polymorphic ventricular tachycardia called Torsade de Pointes, which has been related to early after depolarizations (EADs) formation. This repolarizing disorder has been observed under pathological situations, such as heart failure, oxidative...
Experimental studies of pro-arrhythmic mechanisms are scarcely performed in humans due to the limited availability of human cardiomyocytes. Subsequently, extrapolation of animal experimental research to humans is widely extended. Our aim is to systematically compare the ionic mechanisms of the main cellular biomarkers of arrhythmic risk between human and rabbit using computer simulations. For this...
The prolongation of action potential duration (APD) is usually related to conditions of low repolarization reserve and leads to long QT syndrome. In these situations, an unbalance between currents can fire early after depolarizations (EADs). This repolarizing disorder has been observed in heart failure situations, where the late sodium current (INaL) has an important role. In this work we evaluate...
The aim of this study was to investigate interactions between acquired long QT syndrome by dofetilide and reduced repolarization reserve in simulated human ventricular cells using prolongation of APD and triangulation of action potential. A Markovian model of hERG capable of reproducing a wild type as well an acquired long QT syndrome by dofetilide was developed and was included into a ventricular...
Cardiac proarrhythmic risk can be estimated considering several biomarkers based on electrophysiological properties. The aim of this work is to identify the key ionic mechanisms predicting arrhythmia generation in rabbit hearts at the cellular level. For this purpose, the sensitivity of action potential (AP) duration (APD), AP triangulation, AP rate dependence and intracellular calcium and sodium...
Torsades de pointes (TdP) is a life-threatening ventricular tachycardia associated to reduction of the rapid delayed rectifier potassium current (IKr) and prolongation of ventricular action potential duration (APD) and long QT (LQT) syndrome. An abnormal increase of the late sodium current (INaL) is also associated to susceptibility to TdP. In this work, a mathematical model of INaL has been proposed...
During the acute phase of myocardial ischemia, electrophysiological changes and heterogeneities predispose the heart to arrhythmogenic reentrant excitation. In this computational work we analyze the role of dispersion of refractoriness on reentry generation in a two-dimensional sheet of ischemic tissue at different stages after the onset of ischemia. A realistic model of regional ischemia was used...
Traditionally, VF has been directly related to dispersion of refractoriness. However, further theoretical studies relating refractoriness and reentry generation would be helpful to understand their implication. Recently, the safety factor for conduction (SF) has been proposed as a useful parameter to analyze propagation of action potential (AP) and conduction block. In this work, the relative role...
Ventricular tachycardia and ventricular fibrillation are known to be two types of cardiac arrhythmias that usually take place during acute ischemia and frequently lead to sudden death. In this work, we have studied the different patterns of activation displayed in a virtual ventricular slab preparation after premature stimulation during acute ischemia. Furthermore, we also have analyzed the vulnerable...
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