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Heart failure constitutes a major public health problem worldwide. The electrophysiological remodeling of failing hearts sets the stage for malignant arrhythmias, in which the role of the late Na(+) current (I(NaL)) is relevant and is currently under investigation. In this study we examined the role of I(NaL) in the electrophysiological phenotype of(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)
BACKGROUND Heart failure is a final common pathway or descriptor for various cardiac pathologies. It is associated with sudden cardiac death, which is frequently caused by ventricular arrhythmias. Electrophysiological remodeling, intercellular uncoupling, fibrosis and autonomic imbalance have been identified as major arrhythmogenic factors in heart failure(More)
Several mathematical models of rabbit ventricular action potential (AP) have been proposed to investigate mechanisms of arrhythmias and excitation-contraction coupling. Our study aims at systematically characterizing how ionic current properties modulate the main cellular biomarkers of arrhythmic risk using two widely-used rabbit ventricular models, and(More)
In this study, we have used computer simulations to study the mechanisms of extracellular K+ accumulation during acute ischemia. A modified version of the Luo-Rudy phase II action potential model was used to simulate the electrical behavior of one ventricular myocyte during 14 min of simulated ischemia. Our results show the following: 1) only the integrated(More)
The goal of this modeling research is to provide mechanistic insight into the effect of altered membrane kinetics associated with 5-12 min of acute global ischemia on the upper limit of cardiac vulnerability (ULV) to electric shocks. We simulate electrical activity in a finite-element bidomain model of a 4-mm-thick slice through the canine ventricles that(More)
Ischaemic heart disease is considered as the single most frequent cause of death, provoking more than 7 000 000 deaths every year worldwide. A high percentage of patients experience sudden cardiac death, caused in most cases by tachyarrhythmic mechanisms associated to myocardial ischaemia and infarction. These diseases are difficult to study using solely(More)
AIMS This computational modelling work illustrates the influence of hyperkalaemia and electrical uncoupling induced by defined ischaemia on action potential (AP) propagation and the incidence of reentry at the Purkinje-ventricle interface in mammalian hearts. METHODS AND RESULTS Unidimensional and bidimensional models of the Purkinje-ventricle subsystem,(More)
During acute myocardial ischemia, reentrant episodes may lead to ventricular fibrillation (VF), giving rise to potentially mortal arrhythmias. VF has been traditionally related to dispersion of refractoriness and more recently to the source-sink relationship. Our goal is to theoretically investigate the relative role of dispersion of refractoriness and(More)