Background
Sinus node dysfunction because of abnormal impulse generation or sinoatrial conduction block causes bradycardia that can be difficult to differentiate from high parasympathetic/low ...sympathetic modulation (HP/LSM).
Hypothesis
Beat‐to‐beat relationships of sinus node dysfunction are quantifiably distinguishable by Poincaré plots, machine learning, and 3‐dimensional density grid analysis. Moreover, computer modeling establishes sinoatrial conduction block as a mechanism.
Animals
Three groups of dogs were studied with a diagnosis of: (1) balanced autonomic modulation (n = 26), (2) HP/LSM (n = 26), and (3) sinus node dysfunction (n = 21).
Methods
Heart rate parameters and Poincaré plot data were determined median (25%‐75%). Recordings were randomly assigned to training or testing. Supervised machine learning of the training data was evaluated with the testing data. The computer model included impulse rate, exit block probability, and HP/LSM.
Results
Confusion matrices illustrated the effectiveness in diagnosing by both machine learning and Poincaré density grid. Sinus pauses >2 s differentiated (P < .0001) HP/LSM (2340; 583‐3947 s) from sinus node dysfunction (8503; 7078‐10 050 s), but average heart rate did not. The shortest linear intervals were longer with sinus node dysfunction (315; 278‐323 ms) vs HP/LSM (260; 251‐292 ms; P = .008), but the longest linear intervals were shorter with sinus node dysfunction (620; 565‐698 ms) vs HP/LSM (843; 799‐888 ms; P < .0001).
Conclusions
Number and duration of pauses, not heart rate, differentiated sinus node dysfunction from HP/LSM. Machine learning and Poincaré density grid can accurately identify sinus node dysfunction. Computer modeling supports sinoatrial conduction block as a mechanism of sinus node dysfunction.
Electrically based therapies for terminating atrial fibrillation (AF) currently fall into 2 categories: antitachycardia pacing and cardioversion. Antitachycardia pacing uses low-intensity pacing ...stimuli delivered via a single electrode and is effective for terminating slower tachycardias but is less effective for treating AF. In contrast, cardioversion uses a single high-voltage shock to terminate AF reliably, but the voltages required produce undesirable side effects, including tissue damage and pain. We propose a new method to terminate AF called far-field antifibrillation pacing, which delivers a short train of low-intensity electric pulses at the frequency of antitachycardia pacing but from field electrodes. Prior theoretical work has suggested that this approach can create a large number of activation sites ("virtual" electrodes) that emit propagating waves within the tissue without implanting physical electrodes and thereby may be more effective than point-source stimulation.
Using optical mapping in isolated perfused canine atrial preparations, we show that a series of pulses at low field strength (0.9 to 1.4 V/cm) is sufficient to entrain and subsequently extinguish AF with a success rate of 93% (69 of 74 trials in 8 preparations). We further demonstrate that the mechanism behind far-field antifibrillation pacing success is the generation of wave emission sites within the tissue by the applied electric field, which entrains the tissue as the field is pulsed.
AF in our model can be terminated by far-field antifibrillation pacing with only 13% of the energy required for cardioversion. Further studies are needed to determine whether this marked reduction in energy can increase the effectiveness and safety of terminating atrial tachyarrhythmias clinically.
The Belle II experiment searches for beyond-the-standard-model physics using the Belle II detector and SuperKEKB collider. The silicon vertex detector (SVD) is crucial for particle tracking. After ...the 1.5-year shutdown from June 2022, Run 2 began in January 2024; Run 2 operation shows stable noise levels, high signal-to-noise ratios, and hit efficiency over 99%. To manage higher beam background from increased luminosity, new techniques such as hit-time selection and cluster grouping are being developed. These methods increase the acceptable level of occupancy by distinguishing hits from triggered collisions and other sources.
Several different types of rapid cardiac rhythm disorders, including atrial and ventricular fibrillation, are likely caused by multiple, rapidly rotating, action potential (AP) waves. Thus, an ...electrical pacing therapy, whose effectiveness is based on being delivered with a particular timing relative to one of these waves, is unlikely to be useful in terminating the remaining waves. Here, we develop pacing protocols that are designed to terminate rotating waves independently of when the sequences of stimuli are imposed or where each wave is in its rotation at the time the sequences are initiated. These protocols are delivered as far-field stimuli, and therefore are capable of simultaneously influencing all the waves present. The pacing intervals for these protocols are, in general, of unequal duration and are determined through examination of the dynamics of AP propagation in a 1-D ring model. Series of two or three stimuli with interstimulus intervals chosen in this way are shown to be effective in terminating these waves over a wide range of ring circumferences and AP dynamical parameters. Stimulus sequences of this type may form the basis for developing new defibrillation protocols to test in experiments or more realistic models of the electrical heart.
The beat-to-beat alternation in action potential durations (APDs) in the heart, called APD alternans, has been linked to the development of serious cardiac rhythm disorders, including ventricular ...tachycardia and fibrillation. The length of the period between action potentials, called the diastolic interval (DI), is a key dynamical variable in the standard theory of alternans development. Thus, methods that control the DI may be useful in preventing dangerous cardiac rhythms. In this study, we examine the dynamics of alternans during controlled-DI pacing using a series of single-cell and one-dimensional (1D) fiber models of alternans dynamics. We find that a model that combines a so-called memory model with a calcium cycling model can reasonably explain two key experimental results: the possibility of alternans during constant-DI pacing and the phase lag of APDs behind DIs during sinusoidal-DI pacing. We also find that these results can be replicated by incorporating the memory model into an amplitude equation description of a 1D fiber. The 1D fiber result is potentially concerning because it seems to suggest that constant-DI control of alternans can only be effective over only a limited region in space.
Background Ventricular tachyarrhythmias are often preceded by short sequences of premature ventricular complexes. In a previous study, a restitution-based computational model predicted which ...sequences of stimulated premature complexes were most likely to induce ventricular fibrillation in canines in vivo. However, the underlying mechanism, based on discordant-alternans dynamics, could not be verified in that study. The current study seeks to elucidate the mechanism by determining whether the spatiotemporal evolution of action potentials and initiation of ventricular fibrillation in in vitro experiments are consistent with model predictions. Methods and Results Optical mapping voltage signals from canine right-ventricular tissue (n=9) were obtained simultaneously from the entire epicardium and endocardium during and after premature stimulus sequences. Model predictions of action potential propagation along a 1-dimensional cable were developed using action potential duration versus diastolic interval data. The model predicted sign-change patterns in action potential duration and diastolic interval spatial gradients with posterior probabilities of 91.1%, and 82.1%, respectively. The model predicted conduction block with 64% sensitivity and 100% specificity. A generalized estimating equation logistic-regression approach showed that model-prediction effects were significant for both conduction block ( P<1×10
, coefficient 44.36) and sustained ventricular fibrillation ( P=0.0046, coefficient, 1.63) events. Conclusions The observed sign-change patterns favored discordant alternans, and the model successfully identified sequences of premature stimuli that induced conduction block. This suggests that the relatively simple discordant-alternans-based process that led to block in the model may often be responsible for ventricular fibrillation onset when preceded by premature beats. These observations may aid in developing improved methods for anticipating block and ventricular fibrillation.
It has been postulated that cardiac cell models accounting for changes in intracellular ion concentrations violate a conservation principle, and, as a result, computed parameters (e.g., ion ...concentrations and transmembrane potential,
V
m) drift in time, never attaining steady state. To address this issue, models have been proposed that invoke the charge conservation principle to calculate
V
m from ion concentrations (“algebraic” method), rather than from transmembrane current (“differential” method). The aims of this study are to compare model behavior during prolonged periods of pacing using the algebraic and differential methods, and to address the issue of model drift. We pace the Luo–Rudy dynamic model of a cardiac ventricular cell and compare the time-dependent behavior of computed parameters using the algebraic and differential methods. When ions carried by the stimulus current are taken into account, the algebraic and differential methods yield identical results and neither shows drift in computed parameters. The present study establishes the proper pacing protocol for simulation studies of cellular behavior during long periods of rapid pacing. Such studies are essential for mechanistic understanding of arrhythmogenesis, since cells are subjected to rapid periodic stimulation during many arrhythmias.
Three-dimensional scroll waves direct cell movement and gene expression, and induce chaos in the brain and heart. We found an approach to terminate multiple three-dimensional scrolls. A pulse of a ...properly configured electric field detaches scroll filaments from the surface. They shrink due to filament tension and disappear. Since wave emission from small heterogeneities is not used, this approach requires a much lower electric field. It is not sensitive to the details of the excitable medium. It may affect future studies of low-energy chaos termination in the heart.
We propose a solution to a long-standing problem: how to terminate multiple vortices in the heart, when the locations of their cores and their critical time windows are unknown. We scan the phases of ...all pinned vortices in parallel with electric field pulses (E-pulses). We specify a condition on pacing parameters that guarantees termination of one vortex. For more than one vortex with significantly different frequencies, the success of scanning depends on chance, and all vortices are terminated with a success rate of less than one. We found that a similar mechanism terminates also a free (not pinned) vortex. A series of about 500 experiments with termination of ventricular fibrillation by E-pulses in pig isolated hearts is evidence that pinned vortices, hidden from direct observation, are significant in fibrillation. These results form a physical basis needed for the creation of new effective low energy defibrillation methods based on the termination of vortices underlying fibrillation.
Characteristics of type‐1 radar echoes obtained from the E region ionosphere have yet to be conclusively explained. The dynamical properties of the saturated state of the Farley‐Buneman instability ...are widely thought responsible for these type‐1 echoes. In this paper we present a different perspective and new details on a previously proposed three‐wave coupling mechanism (Otani and Oppenheim, 1998) for the saturation of the Farley‐Buneman instability. A novel method is presented for the analysis of general, three‐wave systems with stationary, sinusoidal solutions. Computer simulations of the three‐wave system produce steady states in close agreement with those obtained from the method. Despite the fact that the system only contains three modes, a number of features also agree well with observation, including density fluctuation magnitudes (∣δn∣/n0 = 5%), propagation speeds (clustered around the sound speed), and power falloff as a function of elevation angle. We demonstrate how the spatial distributions of the phases of the electron advection term and electron E × B velocity for the secondary modes lead to the partial cancellation of the destabilizing zero‐order electron drift, thereby saturating the Farley‐Buneman instability. The mechanism is consistent with the one previously advanced, which described saturation of the instability in terms of the diversion of electron flow around density peaks.
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