OBJECTIVE: Atrial fibrosis and autonomic remodelling are proposed pathophysiological mechanisms in atrial fibrillation (AF). Their impact on conduction velocity (CV) dynamics and wavefront propagation was evaluated.
RESULTS: Local activation times (LATs), voltage, and geometry data were obtained from patients undergoing ablation for persistent AF. LATs were obtained at three pacing intervals (PIs) in sinus rhythm (SR). LATs were used to determine CV dynamics and their relationship to local voltage amplitude. The impact of autonomic modulation- pharmacologically and with ganglionated plexi (GP) stimulation, on CV dynamics, wavefront propagation, and pivot points (change in wavefront propagation of ≥90°) was determined in SR. Fifty-four patients were included. Voltage impacted CV dynamics whereby at non-low voltage zones (LVZs) (≥0.5 mV) the CV restitution curves are steeper [0.03 ± 0.03 m/s ΔCV PI 600-400 ms (PI1), 0.54 ± 0.09 m/s ΔCV PI 400-250 ms (PI2)], broader at LVZ (0.2-0.49 mV) (0.17 ± 0.09 m/s ΔCV PI1, 0.25 ± 0.11 m/s ΔCV PI2), and flat at very LVZ (<0.2 mV) (0.03 ± 0.01 m/s ΔCV PI1, 0.04 ± 0.02 m/s ΔCV PI2). Atropine did not change CV dynamics, while isoprenaline and GP stimulation resulted in greater CV slowing with rate. Isoprenaline (2.7 ± 1.1 increase/patient) and GP stimulation (2.8 ± 1.3 increase/patient) promoted CV heterogeneity, i.e. rate-dependent CV (RDCV) slowing sites. Most pivot points co-located to RDCV slowing sites (80.2%). Isoprenaline (1.3 ± 1.1 pivot increase/patient) and GP stimulation (1.5 ± 1.1 increase/patient) also enhanced the number of pivot points identified.
CONCLUSIONS: Atrial CV dynamics is affected by fibrosis burden and influenced by autonomic modulation which enhances CV heterogeneity and distribution of pivot points. This study provides further insight into the impact of autonomic remodelling in AF.

OBJECTIVE: to investigate the early consequences of type 1 diabetes (T1D) on the neural strategies of muscle force production.
METHODS: motor unit (MU) activity was recorded from the vastus lateralis muscle with High-Density surface Electromyography during isometric knee extension at 20 and 40% of maximum voluntary contraction (MVC) in 8 T1D (4 males, 4 females, 30.5 ± 3.6 years) and 8 matched control (4 males, 4 females, 27.3 ± 5.9 years) participants. Muscle biopsies were also collected from vastus lateralis for fiber type analysis, including myosin heavy chain (MyHC) isoform content via protein and mRNA expression.
RESULTS: MVC was comparable between groups as well as MU conduction velocity, action potentials\' amplitude and proportions of MyHC protein isoforms. Nonetheless, MU discharge rate, relative derecruitment thresholds and mRNA expression of MyHC isoform I were lower in T1D.
CONCLUSIONS: young people with uncomplicated T1D present a different neural control of muscle force production. Furthermore, differences are detectable non-invasively in absence of any functional manifestation (i.e., force production and fiber type distribution). These novel findings suggest that T1D has early consequences on the neuromuscular system and highlights the necessity of a better characterization of neural control in this population.

Myocardial ischemia-reperfusion arrhythmia after cardiac surgery is common and seriously affects quality of life. Remote ischemic preconditioning can reduce the myocardial damage caused by severe ischemia. However, the underlying mechanism is not well understood. This study aimed to investigate the effects of exosomes derived from C2C12 mouse myoblasts after hypoxic preconditioning (HP) on ventricular conduction in hypothermic ischemia-reperfusion hearts. Myocardial ischemia-reperfusion model rats were established using the Langendorff cardiac perfusion system. Exosomes derived from normoxic (ExoA) and hypoxia-preconditioned (ExoB) C2C12 cells were injected into the jugular vein of the model rats. The time to heartbeat restoration, arrhythmia type and duration, and heart rate were recorded after myocardial ischemia-reperfusion. Conduction velocity on the surface of left ventricle was measured using a microelectrode array after 30 min of balanced perfusion, 15 min of reperfusion, and 30 min of reperfusion. Immunohistochemistry and western blotting were performed to determine the distribution and relative expression of connexin 43 (Cx43). ExoB contained more exosomes than ExoA, showing that HP stimulated the release of exosomes. The IR + ExoB group showed faster recovery of ventricular myocardial activity, a lower arrhythmia score, faster conduction velocity, and better electrical conductivity than the IR group. ExoB increased the expression of Cx43 and reduced its lateralization in the ventricular muscle. Our study showed that exosomes induced by hypoxic preconditioning can improve ventricular myocardial conduction and reperfusion arrhythmia in isolated hearts after hypothermic ischemia-reperfusion.
UNASSIGNED:

UNASSIGNED: Ventricular tachycardia (VT) is a life-threatening heart condition commonly seen in patients with myocardial infarction (MI). Although personalized computational modeling has been used to understand VT and its treatment noninvasively, this approach can be computationally intensive and time consuming. Therefore, finding a balance between mesh size and computational efficiency is important. This study aimed to find an optimal mesh resolution that minimizes the need for computational resources while maintaining numerical accuracy and to investigate the effect of mesh resolution variation on the simulation results.
UNASSIGNED: We constructed ventricular models from contrast-enhanced magnetic resonance imaging data from six patients with MI. We created seven different models for each patient, with average edge lengths ranging from 315 to 645 µm using commercial software, Mimics. Programmed electrical stimulation was used to assess VT inducibility from 19 sites in each heart model.
UNASSIGNED: The simulation results in the slab model with adaptive tetrahedral mesh (same as in the patient-specific model) showed that the absolute and relative differences in conduction velocity (CV) were 6.1 cm/s and 7.8% between average mesh sizes of 142 and 600 µm, respectively. However, the simulation results in the six patient-specific models showed that average mesh sizes with 350 µm yielded over 85% accuracy for clinically relevant VT. Although average mesh sizes of 417 and 478 µm could also achieve approximately 80% accuracy for clinically relevant VT, the percentage of incorrectly predicted VTs increases. When conductivity was modified to match the CV in the model with the finest mesh size, the overall ratio of positively predicted VT increased.
UNASSIGNED: The proposed personalized heart model could achieve an optimal balance between simulation time and VT prediction accuracy when discretized with adaptive tetrahedral meshes with an average edge length about 350 µm.

Neurons have high energy demands. In a recent study, Looser et al. identified oligodendrocyte Kir4.1 as the activity-dependent driver of oligodendrocyte glycolysis that ensures that lactate is supplied to active neurons. Given that oligodendrocyte Kir4.1 also influenced axonal glucose consumption and uptake, oligodendrocytes may play a broader role in neuronal metabolic regulation.

BACKGROUND: Understanding the dynamics of conduction velocity (CV) and voltage amplitude (VA) is crucial in cardiac electrophysiology, particularly for substrate-based catheter ablations targeting slow conduction zones and low voltage areas. This study utilizes ultra-high-density mapping to investigate the impact of heart rate and pacing location on changes in the wavefront direction, CV, and VA of healthy pig hearts.
METHODS: We conducted in vivo electrophysiological studies on four healthy juvenile pigs, involving various pacing locations and heart rates. High-resolution electroanatomic mapping was performed during intrinsic normal sinus rhythm (NSR) and electrical pacing. The study encompassed detailed analyses at three levels: entire heart cavities, subregions, and localized 5-mm-diameter circular areas. Linear mixed-effects models were used to analyze the influence of heart rate and pacing location on CV and VA in different regions.
RESULTS: An increase in heart rate correlated with an increase in conduction velocity and a decrease in voltage amplitude. Pacing influenced conduction velocity and voltage amplitude. Pacing also influenced conduction velocity and voltage amplitude, with varying effects observed based on the pacing location within different heart cavities. Pacing from the right atrium (RA) decreased CV in all heart cavities. The overall CV and VA changes in the whole heart cavities were not uniformly reflected in all subregions and subregional CV and VA changes were not always reflected in the overall analysis. Overall, there was a notable variability in absolute CV and VA changes attributed to pacing.
CONCLUSIONS: Heart rate and pacing location influence CV and VA within healthy juvenile pig hearts. Subregion analysis suggests that specific regions of the heart cavities are more susceptible to pacing. High-resolution mapping aids in detecting regional changes, emphasizing the substantial physiological variations in CV and VA.

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One hundred years ago, Erlanger and Gasser demonstrated that conduction velocity is correlated with the diameter of a peripheral nerve axon. Later, they also demonstrated that the functional role of the axon is related to its diameter: touch is signalled by large-diameter axons, whereas pain and temperature are signalled by small-diameter axons. Certain discoveries in recent decades prompt a modification of this canonical classification. Here, we review the evidence for unmyelinated (C) fibres signalling touch at a slow conduction velocity and likely contributing to affective aspects of tactile information. We also review the evidence for large-diameter Aβ afferents signalling pain at ultrafast conduction velocity and likely contributing to the rapid nociceptive withdrawal reflex. These discoveries imply that conduction velocity is not as clear-cut an indication of the functional role of the axon as previously thought. We finally suggest that a future taxonomy of the peripheral afferent nervous system might be based on the combination of the axońs molecular expression and electrophysiological response properties.

BACKGROUND: Atrial arrhythmogenic substrate is a key determinant of atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI), and reduced conduction velocities have been linked to adverse outcome. However, a noninvasive method to assess such electrophysiologic substrate is not available to date.
OBJECTIVE: This study aimed to noninvasively assess regional conduction velocities and their association with arrhythmia-free survival after PVI.
METHODS: A consecutive 52 patients scheduled for AF ablation (PVI only) and 19 healthy controls were prospectively included and received electrocardiographic imaging (ECGi) to noninvasively determine regional atrial conduction velocities in sinus rhythm. A novel ECGi technology obviating the need of additional computed tomography or cardiac magnetic resonance imaging was applied and validated by invasive mapping.
RESULTS: Mean ECGi-determined atrial conduction velocities were significantly lower in AF patients than in healthy controls (1.45 ± 0.15 m/s vs 1.64 ± 0.15 m/s; P < .0001). Differences were particularly pronounced in a regional analysis considering only the segment with the lowest average conduction velocity in each patient (0.8 ± 0.22 m/s vs 1.08 ± 0.26 m/s; P < .0001). This average conduction velocity of the \"slowest\" segment was independently associated with arrhythmia recurrence and better discriminated between PVI responders and nonresponders than previously proposed predictors, including left atrial size and late gadolinium enhancement (magnetic resonance imaging). Patients without slow-conduction areas (mean conduction velocity <0.78 m/s) showed significantly higher 12-month arrhythmia-free survival than those with 1 or more slow-conduction areas (88.9% vs 48.0%; P = .002).
CONCLUSIONS: This is the first study to investigate regional atrial conduction velocities noninvasively. The absence of ECGi-determined slow-conduction areas well discriminates PVI responders from nonresponders. Such noninvasive assessment of electrical arrhythmogenic substrate may guide treatment strategies and be a step toward personalized AF therapy.

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