Abnormalities in repolarization and its rate dependence are known to be related increased proarrhythmic risk. A number of repolarization-related electrophysiological properties commonly used as preclinical biomarkers arrhythmic However, the variability complexity mechanisms make use cellular predict risk preclinically challenging. Our goal is investigate role ionic current their modulating improve stratification identification humans. systematic investigation into sensitivity main changes...

The most common sustained cardiac arrhythmias in humans are atrial tachyarrhythmias, mainly fibrillation. Areas of complex fractionated electrograms and high dominant frequency have been proposed as critical regions for maintaining fibrillation; however, there is a paucity data on the relationship between characteristics propagation pattern underlying them. In this study, realistic 3D computer model human atria has developed to investigate relationship. includes geometry with fiber...

Background Heart failure is a final common pathway or descriptor for various cardiac pathologies. It associated with sudden death, which frequently caused by ventricular arrhythmias. Electrophysiological remodeling, intercellular uncoupling, fibrosis and autonomic imbalance have been identified as major arrhythmogenic factors in heart etiology progression. Objective In this study we investigate silico the role of electrophysiological structural remodeling on modulation key elements...

Anatomically based procedures to ablate atrial fibrillation (AF) are often successful in terminating paroxysmal AF. However, the ability terminate persistent AF remains disappointing. New mechanistic approaches use multiple-electrode basket catheter mapping localize and target drivers form of rotors but significant concerns remain about their accuracy. We aimed evaluate how electrode-endocardium distance, far-field sources inter-electrode distance affect accuracy localizing rotors. Sustained...

Preclinical assessment of drug-induced proarrhythmicity is typically evaluated by the potency drug to block potassium human ether-à-go-go-related gene (hERG) channels, which currently quantified IC50. However, channel depends on experimental conditions. Our aim improve evaluation blocking drugs designing stimulation protocols measure IC50 that will help decide whether representative enough. We used state-of-the-art mathematical models cardiac electrophysiological activity design three...

Background/Objectives: Overcoming an oncological process has a significant impact on lower-extremity sarcoma survivors’ quality of life, due to the deterioration in their physical and functional state. This study evaluated effects six-month multicomponent training program function life mesenchymal chondrosarcoma survivor. Methods: The survivor was subjected internal hemipelvectomy including right hemipelvis plus femoral joint resection proximal femur followed by chemotherapy radiotherapy...

Accurate diagnosis of predisposition to long QT syndrome is crucial for reducing the risk cardiac arrhythmias. In recent years, drug-induced provocative tests have proved useful unmask some latent mutations linked this study we expanded concept by developing a prototype computational screening test reveal genetic acquired long-QT (aLQTS). We developed approach pharmacological properties IKr blocking drugs that are most likely cause aLQTS in setting subtle alterations channel gating would be...

Background: Atrial fibrillation (AF), the most common cardiac arrhythmia, is characterized by alteration of action potential (AP) propagation. Under persistent AF, myocytes undergo electrophysiological and structural remodeling, which involves fibroblast proliferation differentiation, modifying substrate for AP The aim this study was to analyze effects on fibroblast-myocyte coupling during AF its propagation in different regions atria. Methods: Isolated were coupled numbers fibroblasts using...

Drug-induced proarrhythmicity is a major concern for regulators and pharmaceutical companies. For novel drug candidates, the standard assessment involves evaluation of potassium hERG channels block in vivo prolongation QT interval. However, this method known to be too restrictive stop development potentially valuable therapeutic drugs. The aim work create an silico tool early detection drug-induced proarrhythmic risk. system based on simulations how different compounds affect action...

Drug-induced torsade de pointes (TdP) is a life-threatening ventricular arrhythmia responsible for the withdrawal of many drugs from market. Although currently used TdP risk-assessment methods are effective, they expensive and prone to produce false positives. In recent years, in silico cardiac simulations have proven be valuable tool prediction drug effects. The objective this work evaluate different biomarkers drug-induced proarrhythmic risk develop an classifier. Cellular were performed...

Ischaemic heart disease is considered as the single most frequent cause of death, provoking more than 7 000 deaths every year worldwide. A high percentage patients experience sudden cardiac caused in cases by tachyarrhythmic mechanisms associated to myocardial ischaemia and infarction. These diseases are difficult study using solely experimental means due their complex dynamics unstable nature. In past decades, integrative computational simulation techniques have become a powerful tool...

Abnormal intracellular Ca2+ handling is the major contributor to depressed cardiac contractility observed in heart failure. The electrophysiological remodeling associated with this pathology alters both action potential and dynamics, leading a defective excitation-contraction coupling that ends mechanical dysfunction. importance of maintaining correct concentration requires better understanding its regulation by ionic mechanisms. To study electrical activity homeostasis failing myocytes,...

Drug-induced action potential (AP) prolongation leading to Torsade de Pointes is a major concern for the development of anti-arrhythmic drugs. Nevertheless improved agents, some which may block different channels, remains an important opportunity. Partial late sodium current (I(NaL)) has emerged as novel mechanism. It can be effective in settings free radical challenge or hypoxia. In addition, this approach attenuate pro-arrhythmic effects blocking rapid delayed rectifying K(+) (I(Kr)). The...

The QT interval is a phase of the cardiac cycle that corresponds to action potential duration (APD) including cellular repolarization (T-wave). In both clinical and experimental settings, prolongation electrocardiogram (ECG) related proarrhythmia have been so strongly associated prolonged largely accepted as surrogate marker for proarrhythmia. Accordingly, drugs prolong are not considered further preclinical development resulting in removal many promising from development. While reduction...

During the last year, approaches that use ontologies, backbone of Semantic Web technologies, for different purposes in assessment domain e-Learning have emerged.One these is ontologies as a mean providing structure to guide automated design assessments.The most deal with this problem proposed individual model only part domain.The main contribution paper an ontology network, called AONet, conceptualizes e-assessment aim supporting semi-automatic generation it.The advantage network it enriched...

Assessment of drug cardiac safety is critical in the development new compounds and commonly addressed by evaluating half-maximal blocking concentration potassium human ether-à-go-go related gene (hERG) channels. However, recent works have evidenced that modelling drug-binding dynamics to hERG can help improve early assessment. Our goal develop a methodology automatically generate Markovian models drug-hERG channel interactions.The training test sets consisted 20800 5200 virtual drugs,...

Assessment of drug cardiotoxicity is critical in the development new compounds and modeling drug-binding dynamics to hERG can improve early assessment. We previously developed a methodology generate Markovian models reproducing preferential state-dependent binding properties, trapping onset IKr block using simple voltage clamp protocols. Here, we test this with real blockers investigate impact on action potential prolongation. Experiments were performed HEK cells stably transfected Nanion...

Long QT syndrome is a repolarization disorder characterized by marked prolongation of interval. A clear consequence long the occurrence polymorphic ventricular tachycardia called Torsade de Pointes, which has been related to early after depolarizations (EADs) formation. This repolarizing observed under pathological situations, such as heart failure, oxidative stress, hypertrophy and/or in presence pure class III antiarrhythmics. Under pathologies electrophysiological changes affect...