Electrophysiological Characterization of Human Atria: The understated Role of Temperature

Ambient temperature has a profound influence on cellular electrophysiology through direct control over the gating mechanisms of different ion channels. In the heart, low temperature is known to favor prolongation of the action potential. However, not much is known about the influence of temperature on other important characterization parameters such as the resting membrane potential (RMP), excitability, morphology and characteristics of the action potential (AP), restitution properties, conduction velocity (CV) of signal propagation, etc. Here we present the first, detailed, systematic in silico study of the electrophysiological characterization of cardiomyocytes from different regions of the normal human atria, based on the effects of ambient temperature (5−50°C). We observe that RMP decreases with increasing temperature. At ~ 48°C, the cells lose their excitability. Our studies show that different parts of the atria react differently to the same changes in temperature. In tissue simulations a drop in temperature correlated positively with a decrease in CV, but the decrease was region-dependent, as expected. In this article we show how this heterogeneous response can provide an explanation for the development of a proarrhythmic substrate during mild hypothermia. We use the above concept to propose a treatment strategy for atrial fibrillation that involves severe hypothermia in specific regions of the heart for a duration of only ~ 200 ms. © Copyright © 2021 Majumder, Mohamed Nazer, Panfilov, Bodenschatz and Wang.This work was supported by the Max Planck Society and the German Center for Cardiovascular Research. Research at Sechenov University was financed by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers Digital biodesign and personalized healthcare No. 075-15-2020-926

Influence of magnetic field on paramagnetic-ferromagnetic transition in La1−x_{1-x}Cax_{x}MnO3_{3} (x≈0.25x\approx 0.25) crystal: ultrasonic and transport studies

The ultrasonic properties of La$_{1-x}$Ca$_{x}$MnO$_{3}$ ($x\approx 0.25$) with the Curie temperature $T_C$ about 200 K are studied. Temperature dependences of longitudinal and transverse sound velocities were measured in zero magnetic field and for different constant magnetic fields as well. The ultrasonic study is supported by magnetic, resistive, magnetoresistive, structural and other measurements of the sample that facilitate interpretation of the results obtained. The magnetic field influence on sound properties found in this study presents some new features of the interplay between the elastic and magnetic properties of these compounds. It is shown that the paramagnetic-ferromagnetic transition in the sample studied is first order, but can become second order under the influence of applied magnetic field.Comment: submitted to Phys. Rev.

BAIKAL experiment: status report

We review the present status of the Baikal Neutrino Project and present the results obtained with the deep underwater neutrino telescope NT-200.Comment: 4 pages, 3 figures. Presented at TAUP 2001 (7th international workshop on Topics in Astroparticle and Underground Physics), Sep. 2001, Laboratori Nazionali del Gran Sasso, Assergi, Ital

Novel non-invasive algorithm to identify the origins of re-entry and ectopic foci in the atria from 64-lead ECGs: A computational study.

Atrial tachy-arrhytmias, such as atrial fibrillation (AF), are characterised by irregular electrical activity in the atria, generally associated with erratic excitation underlain by re-entrant scroll waves, fibrillatory conduction of multiple wavelets or rapid focal activity. Epidemiological studies have shown an increase in AF prevalence in the developed world associated with an ageing society, highlighting the need for effective treatment options. Catheter ablation therapy, commonly used in the treatment of AF, requires spatial information on atrial electrical excitation. The standard 12-lead electrocardiogram (ECG) provides a method for non-invasive identification of the presence of arrhythmia, due to irregularity in the ECG signal associated with atrial activation compared to sinus rhythm, but has limitations in providing specific spatial information. There is therefore a pressing need to develop novel methods to identify and locate the origin of arrhythmic excitation. Invasive methods provide direct information on atrial activity, but may induce clinical complications. Non-invasive methods avoid such complications, but their development presents a greater challenge due to the non-direct nature of monitoring. Algorithms based on the ECG signals in multiple leads (e.g. a 64-lead vest) may provide a viable approach. In this study, we used a biophysically detailed model of the human atria and torso to investigate the correlation between the morphology of the ECG signals from a 64-lead vest and the location of the origin of rapid atrial excitation arising from rapid focal activity and/or re-entrant scroll waves. A focus-location algorithm was then constructed from this correlation. The algorithm had success rates of 93% and 76% for correctly identifying the origin of focal and re-entrant excitation with a spatial resolution of 40 mm, respectively. The general approach allows its application to any multi-lead ECG system. This represents a significant extension to our previously developed algorithms to predict the AF origins in association with focal activities

Finding Type and Location of the Source of Cardiac Arrhythmias from the Averaged Flow Velocity Field Using the Determinant-trace Method

Life threatening cardiac arrhythmias result from abnormal propagation of nonlinear electrical excitation waves in the heart. Finding the locations of the sources of these waves remains a challenging problem. This is mainly due to the low spatial resolution of electrode recordings of these waves. Also, these recordings are subjected to noise. In this paper, we develop a different approach: the AFV-DT method based on an averaged flow velocity (AFV) technique adopted from the analysis of optical flows and the determinant-trace (DT) method used for vector field analysis of dynamical systems. This method can find the location and determine all important types of sources found in excitable media such as focal activity, spiral waves, and waves rotating around obstacles. We test this method on in silico data of various wave excitation patterns obtained using the Luo-Rudy model for cardiac tissue. We show that the method works well for data with low spatial resolutions (up to 8×8) and is stable against noise. Finally, we apply it to two clinical cases and show that it can correctly identify the arrhythmia type and location. We discuss further steps on the development and improvement of this approach. © 2021 American Physical Society.This work was supported by the National Natural Science Foundation of China under Grants No. 12075203 and No. 11975194, and research at Sechenov University was financed by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers “Digital biodesign and personalized healthcare” (Grant No. 075-15-2020-926)

Transmural Ultrasound-based Visualization of Patterns of Action Potential Wave Propagation in Cardiac Tissue

The pattern of action potential propagation during various tachyarrhythmias is strongly suspected to be composed of multiple re-entrant waves, but has never been imaged in detail deep within myocardial tissue. An understanding of the nature and dynamics of these waves is important in the development of appropriate electrical or pharmacological treatments for these pathological conditions. We propose a new imaging modality that uses ultrasound to visualize the patterns of propagation of these waves through the mechanical deformations they induce. The new method would have the distinct advantage of being able to visualize these waves deep within cardiac tissue. In this article, we describe one step that would be necessary in this imaging process—the conversion of these deformations into the action potential induced active stresses that produced them. We demonstrate that, because the active stress induced by an action potential is, to a good approximation, only nonzero along the local fiber direction, the problem in our case is actually overdetermined, allowing us to obtain a complete solution. Use of two- rather than three-dimensional displacement data, noise in these displacements, and/or errors in the measurements of the fiber orientations all produce substantial but acceptable errors in the solution. We conclude that the reconstruction of action potential-induced active stress from the deformation it causes appears possible, and that, therefore, the path is open to the development of the new imaging modality

Evaluation of Directed Graph-Mapping in Complex Atrial Tachycardias

Objectives: Directed graph-mapping (DGM) is a novel operator-independent automatic tool that can be applied to the identification of the atrial tachycardia (AT) mechanism. In the present study, for the first time, DGM was applied in complex AT cases, and diagnostic accuracy was evaluated. Background: Catheter ablation of ATs still represents a challenge, as the identification of the correct mechanism can be difficult. New algorithms for high-density activation mapping (HDAM) render an easier acquisition of more detailed maps; however, understanding of the mechanism and, thus, identification of the ablation targets, especially in complex cases, remains strongly operator-dependent. Methods: HDAMs acquired with the latest algorithm (COHERENT version 7, Biosense Webster, Irvine, California) were interpreted offline by 4 expert electrophysiologists, and the acquired electrode recordings with corresponding local activation times (LATs) were analyzed by DGM (also offline). Entrainment maneuvers (EM) were performed to understand the correct mechanism, which was then confirmed by successful ablation (13 cases were centrifugal, 10 cases were localized re-entry, 22 cases were macro–re-entry, and 6 were double-loops). In total, 51 ATs were retrospectively analyzed. We compared the diagnoses made by DGM were compared with those of the experts and with additional EM results. Results: In total, 51 ATs were retrospectively analyzed. Experts diagnosed the correct AT mechanism and location in 33 cases versus DGM in 38 cases. Diagnostic accuracy varied according to different AT mechanisms. The 13 centrifugal activation patterns were always correctly identified by both methods; 2 of 10 localized reentries were identified by the experts, whereas DGM diagnosed 7 of 10. For the macro–re-entries, 12 of 22 were correctly identified using HDAM versus 13 of 22 for DGM. Finally, 6 of 6 double-loops were correctly identified by the experts, versus 5 of 6 for DGM. Conclusions: Even in complex cases, DGM provides an automatic, fast, and operator-independent tool to identify the AT mechanism and location and could be a valuable addition to current mapping technologies. © 2021 The Authors.Dr. Lorenzo is an employee of Biosense Webster. Dr. Goedgebeur is funded with a research grant of the Research Foundation Flanders/Fonds voor Wetenschappelijk Onderzoek (FWO). Dr. Strisciuglio is supported by a research grant from the Cardiopath PhD program. Dr. el Haddad is a consultant for Biosense Webster. Dr. Duytschaever is a consultant for Biosense Webster. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose

Superconductivity-induced Resonance Raman Scattering in Multi-layer High-Tc Superconductors

Resonant Raman scattering below Tc has been discovered in several Bi-, Hg-, Tl-based high-Tc superconductors with three or four CuO2-layers. For Bi2Si2Ca2Cu3O10+d, we found an unexpected crossover of the pair-breaking peak in the A1g-spectrum from a broad bump at hw = 6kBTc for Eexc = 2.54eV to a sharp peak at hw = 8kBTc for Eexc = 2.18eV, together with a strong enhancement of the Ca-phonons. Under resonant conditions, the relative positions of the pair breaking peaks in A1g, B1g, and B2g channels are 2Delta(A1g) = 2Delta(B1g) > 2Delta(B2g). This relation implies that the A1g Raman channel is free from the Coulomb screening effect, just as predicted theoretically for a d-wave multi-layer superconductor but have never been observed experimentally thus far. The observed resonance effect is the evidence that the electronic state in the inner CuO2-planes is different from that of the outer CuO2-planes.Comment: 16 pages, 6 figures. submitted to Phys.Rev.