Air Pollution and Cardiac Diseases: A Review of Experimental Studies.

Air pollution is associated with around 6.5 million premature deaths annually, which are directly related to cardiovascular diseases, and the most dangerous atmospheric pollutants to health are as follows: NO2, SO2, CO, and PM. The mechanisms underlying the observed effects have not yet been clearly defined. This work aims to conduct a narrative review of experimental studies to provide a more comprehensive and multiperspective assessment of how the effect of atmospheric pollutants on cardiac activity can result in the development of cardiac diseases. For this purpose, a review was carried out in databases of experimental studies, excluding clinical trials, and epidemiological and simulation studies. After analyzing the available information, the existence of pathophysiological effects of the different pollutants on cardiac activity from exposure during both short-term and long-term is evident. This narrative review based on experimental studies is a basis for the development of recommendations for public health.

Characterization of airborne particulate matter and its toxic and proarrhythmic effects: A case study in Aburrá Valley, Colombia.

Particle matter (PM) is a complex mixture of particles suspended in the air, mainly caused by fuel combustion from vehicles and industry, and has been related to pulmonary and cardiovascular diseases. The Metropolitan Area of Aburrá Valley in Colombia is the second most populous urban agglomeration in the country and the third densest in the world, composed of ten municipalities. Examining the physicochemical properties of PM is crucial in comprehending its composition and its effects on human health, as it varies based on the socioeconomic dynamics specific to each city. This study characterized the PM collected from the north, south, and central zones to evaluate its chemical composition and morphology. Different elements such as silicon, carbon, aluminum, potassium, calcium, sodium, iron, magnesium, and copper and the presence of unburned fuel, motor oil, and silicon fibers were identified. In vitro and in silico studies were conducted to evaluate the toxicity of the PM, and it was found that the PM collected from the central zone had the greatest impact on cell viability and caused DNA damage. The in silico study demonstrated that PM has concentration-dependent proarrhythmic effects, reflected in an action potential duration shortening and an increased number of reentries, which may contribute to the development of cardiac arrhythmias. Overall, the results suggest that the size and chemical composition of ambient PM can induce toxicity and play an important role in the generation of arrhythmias.

The Effects of Fibrotic Cell Type and Its Density on Atrial Fibrillation Dynamics: An In Silico Study.

Remodeling in atrial fibrillation (AF) underlines the electrical and structural changes in the atria, where fibrosis is a hallmark of arrhythmogenic structural alterations. Fibrosis is an important feature of the AF substrate and can lead to abnormal conduction and, consequently, mechanical dysfunction. The fibrotic process comprises the presence of fibrotic cells, including fibroblasts, myofibroblasts and fibrocytes, which play an important role during fibrillatory dynamics. This work assesses the effect of the diffuse fibrosis density and the intermingled presence of the three types of fibrotic cells on the dynamics of persistent AF. For this purpose, the three fibrotic cells were electrically coupled to cardiomyocytes in a 3D realistic model of human atria. Low (6.25%) and high (25%) fibrosis densities were implemented in the left atrium according to a diffuse fibrosis representation. We analyze the action potential duration, conduction velocity and fibrillatory conduction patterns. Additionally, frequency analysis was performed in 50 virtual electrograms. The tested fibrosis configurations generated a significant conduction velocity reduction, where the larger effect was observed at high fibrosis density (up to 82% reduction in the fibrocytes configuration). Increasing the fibrosis density intensifies the vulnerability to multiple re-entries, zigzag propagation, and chaotic activity in the fibrillatory conduction. The most complex propagation patterns were observed at high fibrosis densities and the fibrocytes are the cells with the largest proarrhythmic effect. Left-to-right dominant frequency gradients can be observed for all fibrosis configurations, where the fibrocytes configuration at high density generates the most significant gradients (up to 4.5 Hz). These results suggest the important role of different fibrotic cell types and their density in diffuse fibrosis on the chaotic propagation patterns during persistent AF.

Atrial proarrhythmic effect of lead as one of the PM10 metal components of air pollution. An in-silico study.

Particulate matter (PM) is considered the most severe environmental pollution problem due to its serious effects on human health associated with an increased risk of cardiovascular morbidity and mortality. In this work, a physicochemical characterization of PM10 from the city of Medellin was developed. The results evince that lead (Pb) is one of the most abundant elements since it is present in all analyzed samples. Therefore, Pb was chosen to perform an in-silico study to assess its effects on atrial arrhythmias generation. For this purpose, we developed a model representing the Pb2+ blocking effect on the L-type calcium channel. This formulation was incorporated in a human atrial cell mathematical model and in 2D and 3D models of human atria. The simulations showed a proarrhythmic effect at high Pb2+ concentrations, through shortening of action potential duration inducing the generation of reentrant activity and atrial flutter. The results contribute to the knowledge about the cardiac physiopathological processes, triggered by lead as one of the main PM10 metal components of air pollution, that yields the generation of arrhythmias.

The Antimalarial Chloroquine Reduces the Burden of Persistent Atrial Fibrillation.

In clinical practice, reducing the burden of persistent atrial fibrillation by pharmacological means is challenging. We explored if blocking the background and the acetylcholine-activated inward rectifier potassium currents (IK1 and IKACh) could be antiarrhythmic in persistent atrial fibrillation. We thus tested the hypothesis that blocking IK1 and IKACh with chloroquine decreases the burden of persistent atrial fibrillation. We used patch clamp to determine the IC50 of IK1 and IKACh block by chloroquine and molecular modeling to simulate the interaction between chloroquine and Kir2.1 and Kir3.1, the molecular correlates of IK1 and IKACh. We then tested, as a proof of concept, if oral chloroquine administration to a patient with persistent atrial fibrillation can decrease the arrhythmia burden. We also simulated the effects of chloroquine in a 3D model of human atria with persistent atrial fibrillation. In patch clamp the IC50 of IK1 block by chloroquine was similar to that of IKACh. A 14-day regimen of oral chloroquine significantly decreased the burden of persistent atrial fibrillation in a patient. Mathematical simulations of persistent atrial fibrillation in a 3D model of human atria suggested that chloroquine prolonged the action potential duration, leading to failure of reentrant excitation, and the subsequent termination of the arrhythmia. The combined block of IK1 and IKACh can be a targeted therapeutic strategy for persistent atrial fibrillation.

IDENTIFICACIÓN DE ZONAS SUSCEPTIBLES DE ABLACIÓN EN FIBRILACIÓN AURICULAR PERMANENTE IMPLEMENTANDO ENTROPÍA APROXIMADA EN UN MODELO 2D / IDENTIFICATION OF TARGET SITES FOR ABLATION DURING PERMANENT ATRIAL FIBRILLATION IMPLEMENTING APPROXIMATE ENTROPY IN A 2D MODEL / IDENTIFICAÇÃO DE ÁREAS SUSCETÍVEIS DE ABLAÇÃO PERMANENTE DE FIBRILAÇÃO ATRIAL NA IMPLEMENTAÇÃO ENTROPY APROXIMADO UM MODELO 2D

La fibrilación auricular (FA) es la arritmia cardiaca más común. La ablación con catéter se ha convertido en la principal estrategia terapéutica para el tratamiento de la FA paroxística, sin embargo, los resultados en FA permanente no son completamente satisfactorios. Se propone la ablación de los electrogramas auriculares complejos fragmentados (CFAE) para la terminación de un rotor como mecanismo de mantenimiento de FA permanente. El objetivo de este trabajo es caracterizar los CFAE mediante la implementación de entropía aproximada (ApEn) y correlacionarlos con el tip de un rotor simulado. Para esto, se desarrolló un modelo 2D de tejido de aurícula humana bajo condiciones de FA permanente; se registraron electrogramas unipolares durante la actividad del rotor y se desarrolló un algoritmo para la medida de ApEn. La ApEn permitió localizar los CFAE con una alta precisión y relacionarlos con el tip del rotor. Por lo que este índice podría ser muy eficaz en la identificación de zonas susceptibles de ablación.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Catheter ablation has become the main therapeutic strategy for the treatment of paroxysmal AF, however, results in permanent AF are not completely satisfactory. Ablation of complex fractionated atrial electrograms (CFAE) is proposed for the termination of a rotor as mechanism of permanent AF maintenance. The aim of this work is to characterize the CFAE by implementing approximate entropy (ApEn) and to correlate with the tip of a simulated rotor. For this, a 2D model of human atrial tissue under permanent FA conditions was developed. Unipolar electrograms were recorded during the rotor activity and an algorithm to measure ApEn was developed. The ApEn allowed locate the CFAE with high precision and relate them to the tip of the rotor. So this index could be very effective in identifying target sites for ablation.

A fibrilação atrial (FA) é a arritmia cardíaca mais comum. A ablação por cateter tornou-se a principal estratégia terapêutica para o tratamento da fibrilação atrial paroxística, no entanto, resulta em FA permanente não são completamente satisfatórios. Ablação de fones de ouvido eletrocardiogramas complexos fragmentada (CFAE) para a conclusão de um rotor como um mecanismo de manutenção da FA permanente, é proposto. O objetivo deste trabalho é caracterizar o CFAE através da implementação de entropia aproximada (ApEn) e correlacioná-los com a ponta de um rotor simulado. Para isso, um modelo em 2D do tecido atrial humano sob condições de FA permanente desenvolvido; unipolares electrogramas foram registados durante a actividade do rotor e um algoritmo para medir ApEn desenvolvido. O ApEn permitido CFAE localizar com precisão elevada e relacioná-los com a ponta do rotor. Portanto, esta taxa pode ser muito eficaz na identificação de áreas suscetíveis a ablação.