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Concept: Electrical conduction system of the heart

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Cardiac arrhythmias and conduction disturbances are accompanied by structural remodelling of the specialised cardiomyocytes known collectively as the cardiac conduction system. Here, using contrast enhanced micro-computed tomography, we present, in attitudinally appropriate fashion, the first 3-dimensional representations of the cardiac conduction system within the intact human heart. We show that cardiomyocyte orientation can be extracted from these datasets at spatial resolutions approaching the single cell. These data show that commonly accepted anatomical representations are oversimplified. We have incorporated the high-resolution anatomical data into mathematical simulations of cardiac electrical depolarisation. The data presented should have multidisciplinary impact. Since the rate of depolarisation is dictated by cardiac microstructure, and the precise orientation of the cardiomyocytes, our data should improve the fidelity of mathematical models. By showing the precise 3-dimensional relationships between the cardiac conduction system and surrounding structures, we provide new insights relevant to valvar replacement surgery and ablation therapies. We also offer a practical method for investigation of remodelling in disease, and thus, virtual pathology and archiving. Such data presented as 3D images or 3D printed models, will inform discussions between medical teams and their patients, and aid the education of medical and surgical trainees.

Concepts: Medicine, Heart, Cardiac electrophysiology, Engineering, Operations research, Mathematical model, Image resolution, Electrical conduction system of the heart

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Organ-specific functions of tissue-resident macrophages in the steady-state heart are unknown. Here, we show that cardiac macrophages facilitate electrical conduction through the distal atrioventricular node, where conducting cells densely intersperse with elongated macrophages expressing connexin 43. When coupled to spontaneously beating cardiomyocytes via connexin-43-containing gap junctions, cardiac macrophages have a negative resting membrane potential and depolarize in synchrony with cardiomyocytes. Conversely, macrophages render the resting membrane potential of cardiomyocytes more positive and, according to computational modeling, accelerate their repolarization. Photostimulation of channelrhodopsin-2-expressing macrophages improves atrioventricular conduction, whereas conditional deletion of connexin 43 in macrophages and congenital lack of macrophages delay atrioventricular conduction. In the Cd11b(DTR) mouse, macrophage ablation induces progressive atrioventricular block. These observations implicate macrophages in normal and aberrant cardiac conduction.

Concepts: Heart, Action potential, Circulatory system, Sinoatrial node, Atrioventricular node, Connexin, Resting potential, Electrical conduction system of the heart

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-Risks associated with pediatric reconstructive heart surgery include injury of the sinoatrial node (SAN) and atrioventricular node (AVN), requiring cardiac rhythm management using implantable pacemakers. These injuries are result of difficulties in identifying nodal tissues intraoperatively. Here, we describe an approach based on confocal microscopy and extracellular fluorophores to quantify tissue microstructure and identify nodal tissue.

Concepts: Cardiology, Heart, Cardiac anatomy, Identification, Cardiac pacemaker, Sinoatrial node, Atrioventricular node, Electrical conduction system of the heart

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The anesthetized guinea pig (ANES GP) has proven to be an effective small animal model to evaluate cardiac electrophysiologic effects of drug-candidate molecules during lead optimization. While heart rate (HR) corrected QT interval (QTc) is a key variable to determine test article-dependent repolarization effects, ideal correction methods are an area of constant debate given the potential influence of anesthesia, autonomic tone, species, strain and gender on the QT/HR relationship. The aim of this study was to characterize the ability of common correction formulas to normalize rate-dependent effects on the QT interval in the ketamine/xylazine ANES GP.

Concepts: Cardiology, Model organism, Cardiac electrophysiology, QT interval, Electrical conduction system of the heart

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The purpose of this study was to analyze the effects of four weeks of training cessation (TC) on specific endurance performance, resting and post-exercise heart rate variability (HRV) and neuromuscular capacities of high-level endurance runners.

Concepts: Cardiology, Heart, Muscle, Cardiac muscle, Pulse, Performance, Acetylcholine, Electrical conduction system of the heart

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Late sodium channel current (late INa) is considered to be an anti-arrhythmic target. The prime anti-arrhythmic mechanisms of late INa inhibition have been suggested to be 1) suppression of intracellular calcium [Cai]-mediated rhythmic activity (via reduction of Cai secondary to the decrease of intracellular sodium [Nai]) and 2) normalization of repolarization. Endogenous late INa is a small current and acceleration of heart rate decreases late INa density. Late INa influx may significantly contribute to Nai loading, but it appears to largely occur in the combined conditions of augmented late INa density, bradycardia, and prolonged repolarization. At the same time, the relative contribution of late INa (including endogenous) in any types of prolonged cardiac repolarization is critical. Sodium channel blockers inhibit both late INa and peak INa, and a specific block of late INa might be achieved at slow and normal but seems not at rapid activation rates, at which peak INa, a much greater current, is likely to be inhibited also. The anti-arrhythmic potential of a specific inhibition of late INa appears to best fit for, or may be limited to, the prevention of arrhythmias associated with prolonged repolarization, but it seems to be applicable to all types of arrhythmic abnormalities with elongated cardiac repolarization.

Concepts: Water, Electrophysiology, Cardiac arrest, Cardiac electrophysiology, Sodium, Relative density, Antiarrhythmic agents, Electrical conduction system of the heart

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This study addresses whether a unitary cardiac autonomic nervous system index (ANSI), obtained combining multiple metrics from Heart Rate Variability (HRV) into a radar plot could provide an easy appreciation of autonomic performance in a clinical setting.

Concepts: Psychology, Brain, Cardiology, Avicenna, Pulse, Parasympathetic nervous system, Electrical conduction system of the heart

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Cognitive difficulties and autonomic dysfunction have been reported separately in patients with chronic fatigue syndrome (CFS). A role for heart rate variability (HRV) in cognitive flexibility has been demonstrated in healthy individuals, but this relationship has not as yet been examined in CFS. The objective of this study was to examine the relationship between HRV and cognitive performance in patients with CFS.

Concepts: Cardiology, Heart, Avicenna, Pulse, Chronic fatigue syndrome, Heart rate variability, Malaise, Electrical conduction system of the heart

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Epidemiological studies have shown that as ambient air pollution (AP) increases the risk of cardiovascular mortality also increases. The mechanisms of this effect may be linked to alterations in autonomic nervous system function. We wished to examine the effects of industrial AP on heart rate variability (HRV), a measure of subtle changes in heart rate and rhythm representing autonomic input to the heart.

Concepts: Nervous system, Epidemiology, Brain, Medical statistics, Parasympathetic nervous system, Air pollution, Associated Press, Electrical conduction system of the heart