The Ithildin library for efficient numerical solution of anisotropic reaction-diffusion problems in excitable media.

Ithildin is an open-source library and framework for efficient parallelized simulations of excitable media, written in the C++ programming language. It uses parallelization on multiple CPU processors via the message passing interface (MPI). We demonstrate the library's versatility through a series of simulations in the context of the monodomain description of cardiac electrophysiology, including the S1S2 protocol, spiral break-up, and spiral waves in ventricular geometry.

Functional Epicardial Conduction Disturbances Due to a SCN5A Variant Associated With Brugada Syndrome.

Background: Brugada syndrome is a significant cause of sudden cardiac death (SCD), but the underlying mechanisms remain hypothetical.

Objectives: This study aimed to elucidate this knowledge gap through detailed ex vivo human heart studies.

Methods: A heart was obtained from a 15-year-old adolescent boy with normal electrocardiogram who experienced SCD.

Asthmatic bronchial smooth muscle increases rhinovirus replication within the bronchial epithelium.

Rhinovirus (RV) infection of the bronchial epithelium is implicated in the vast majority of severe asthma exacerbations. Interestingly, the susceptibility of bronchial epithelium to RV infection is increased in persons with asthma. Bronchial smooth muscle (BSM) remodeling is an important feature of severe asthma pathophysiology, and its reduction using bronchial thermoplasty has been associated with a significant decrease in the exacerbation rate.

A Population Pharmacokinetic Modeling Approach to Determine the Efficacy of Intravenous Amikacin in Children with Cystic Fibrosis.

Background: In children with cystic fibrosis (CF), the currently recommended amikacin dose ranges between 30 and 35 mg/kg/d; however, data supporting this dosing efficacy are lacking. In this article, the objectives were to develop a nonparametric pharmacokinetic population model for amikacin in children with CF and investigate the efficacy and toxicity at different dose rates for distinct minimum inhibitory concentration (MIC) clinical breakpoints using Monte Carlo simulations.

Methods: Data from 94 children with CF (613 serum concentrations) from the Bordeaux University Hospital's CF-centre were analyzed.

Population pharmacokinetics of ceftazidime in critically ill children: impact of cystic fibrosis.

Background: Pharmacokinetics data on ceftazidime are sparse for the paediatric population, particularly for children with cystic fibrosis (CF) or severe infections.

Objectives: To characterize the population pharmacokinetics of ceftazidime in critically ill children, identify covariates that affect drug disposition and evaluate the current dosing regimens.

Methods: The study was registered with Clinicaltrials.

In vitro study of carbon black nanoparticles on human pulmonary artery endothelial cells: effects on calcium signaling and mitochondrial alterations.

Human exposure to manufactured nanoparticles (NPs) is a public health concern. Endothelial cells lining the inner surface of arteries could be one of the primary targets for inhaled nanoparticles. Moreover, it is well known that alteration in calcium signaling is a critical event involved in the physiopathology of cardiovascular diseases.

Lung Antioxidant Depletion: A Predictive Indicator of Cellular Stress Induced by Ambient Fine Particles.

Regulations on ambient particulate matter (PM) are becoming more stringent because of adverse health effects arising from PM exposure. PM-induced oxidant production is a key mechanism behind the observed health effects and is heavily dependent on PM composition. Measurement of the intrinsic oxidative potential (OP) of PM could provide an integrated indicator of PM bioreactivity and could serve as a better metric of PM hazard exposure than PM mass concentration.

Highlights from the ERS International Congress 2018: Assembly 13 - Pulmonary Vascular Diseases.

The 2018 European Respiratory Society (ERS) International Congress in Paris, France, highlighted the subject of pulmonary vascular disease (PVD). 2018 was an exciting year for the PVD community as it was the first ERS International Congress since the formation of Assembly 13, which is dedicated to PVD, pulmonary embolism and the right ventricle. This article aims to summarise the high-quality studies presented at the 2018 Congress into four subject areas: the use of risk stratification in pulmonary arterial hypertension, the molecular mechanisms and treatment of pulmonary hypertension (PH), understanding and improving the right ventricle in PH, and finally, advances in the field of acute pulmonary embolus.

K 3.1 protein is expressed as a transmural gradient across the rat left ventricular free wall.

Introduction: K 3.1, also known as TASK-1, is a twin-pore acid-sensitive repolarizing K channel, responsible for a background potassium current that significantly contributes to setting the resting membrane potential of cardiac myocytes. Inhibition of I alters cardiac repolarization and is proarrhythmogenic.

Cardiac electrical dyssynchrony is accurately detected by noninvasive electrocardiographic imaging.

Background: Poor identification of electrical dyssynchrony is postulated to be a major factor contributing to the low success rate for cardiac resynchronization therapy.

Objective: The purpose of this study was to evaluate the sensitivity of body surface mapping and electrocardiographic imaging (ECGi) to detect electrical dyssynchrony noninvasively.

Methods: Langendorff-perfused pig hearts (n = 11) were suspended in a human torso-shaped tank, with left bundle branch block (LBBB) induced through ablation.

A technical review of optical mapping of intracellular calcium within myocardial tissue.

Optical mapping of Ca(2+)-sensitive fluorescence probes has become an extremely useful approach and adopted by many cardiovascular research laboratories to study a spectrum of myocardial physiology and disease conditions. Optical mapping data are often displayed as detailed pseudocolor images, providing unique insight for interpreting mechanisms of ectopic activity, action potential and Ca(2+) transient alternans, tachycardia, and fibrillation. Ca(2+)-sensitive fluorescent probes and optical mapping systems continue to evolve in the ongoing effort to improve therapies that ease the growing worldwide burden of cardiovascular disease.

Percolation as a mechanism to explain atrial fractionated electrograms and reentry in a fibrosis model based on imaging data.

Background: Complex fractionated atrial electrograms (CFAEs) have long been associated with proarrhythmic alterations in atrial structure or electrophysiology. Structural alterations disrupt and slow smoothly propagating wavefronts, leading to wavebreaks and electrogram (EGM) fractionation, but the exact nature and characteristics for arrhythmia remain unknown. Clinically, in atrial fibrillation (AF) patients, increases in frequency, whether by pacing or fibrillation, increase EGM fractionation and duration, and reentry can occur in relation with the conduction disturbance.

Forward problem of electrocardiography: is it solved?

Background: The relationship between epicardial and body surface potentials defines the forward problem of electrocardiography. A robust formulation of the forward problem is instrumental to solving the inverse problem, in which epicardial potentials are computed from known body surface potentials. Here, the accuracy of different forward models has been evaluated experimentally.

Quantification of the transmural dynamics of atrial fibrillation by simultaneous endocardial and epicardial optical mapping in an acute sheep model.

Background: Therapy strategies for atrial fibrillation based on electric characterization are becoming viable personalized medicine approaches to treat a notoriously difficult disease. In light of these approaches that rely on high-density surface mapping, this study aims to evaluate the presence of 3-dimensional electric substrate variations within the transmural wall during acute episodes of atrial fibrillation.

Methods And Results: Optical signals were simultaneously acquired from the epicardial and endocardial tissue during acute fibrillation in ovine isolated left atria.

Influence of the Purkinje-muscle junction on transmural repolarization heterogeneity.

Aims: To elucidate the properties of the PMJ and myocardium underlying these effects. Transmural heterogeneity of action potential duration (APD) is known to play an important role in arrhythmogenesis. Regions of non-uniformities of APD gradients often overlap considerably with the location of Purkinje-muscle junctions (PMJs).