refractory period
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Author(s):  
Yuzhen Zhao ◽  
Yuping Liu ◽  
Xiyu Liu ◽  
Minghe Sun ◽  
Feng Qi ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Mattias Karlsson ◽  
Frida Sandberg ◽  
Sara R. Ulimoen ◽  
Mikael Wallman

During atrial fibrillation (AF), the heart relies heavily on the atrio-ventricular (AV) node to regulate the heart rate. Thus, characterization of AV-nodal properties may provide valuable information for patient monitoring and prediction of rate control drug effects. In this work we present a network model consisting of the AV node, the bundle of His, and the Purkinje fibers, together with an associated workflow, for robust estimation of the model parameters from ECG. The model consists of two pathways, referred to as the slow and the fast pathway, interconnected at one end. Both pathways are composed of interacting nodes, with separate refractory periods and conduction delays determined by the stimulation history of each node. Together with this model, a fitness function based on the Poincaré plot accounting for dynamics in RR interval series and a problem specific genetic algorithm, are also presented. The robustness of the parameter estimates is evaluated using simulated data, based on clinical measurements from five AF patients. Results show that the proposed model and workflow could estimate the slow pathway parameters for the refractory period, RminSP and ΔRSP, with an error (mean ± std) of 10.3 ± 22 and −12.6 ± 26 ms, respectively, and the parameters for the conduction delay, Dmin,totSP and ΔDtotSP, with an error of 7 ± 35 and 4 ± 36 ms. Corresponding results for the fast pathway were 31.7 ± 65, −0.3 ± 77, 17 ± 29, and 43 ± 109 ms. These results suggest that both conduction delay and refractory period can be robustly estimated from non-invasive data with the proposed methodology. Furthermore, as an application example, the methodology was used to analyze ECG data from one patient at baseline and during treatment with Diltiazem, illustrating its potential to assess the effect of rate control drugs.


2021 ◽  
pp. 174702182110547
Author(s):  
Thomas Spalek ◽  
Hayley Lagroix ◽  
Vincent Di Lollo

When the visual system is busy processing one stimulus it has problems processing a subsequent stimulus if it arrives soon after the first. Laboratory studies of this second-stimulus impairment – known as ¬attentional blink (AB) – have employed two targets (T1, T2) presented in rapid sequence, and have found identification accuracy to be nearly perfect for T1 but impaired for T2. It is commonly believed that the magnitude of the AB is related directly to the difficulty of T1: the greater the T1 difficulty, the larger the AB. A survey of the experimental literature disconfirms that belief showing it to have arisen from artificial constraints imposed by the 100% limit of the response scale. Removal of that constraint, either by using reaction time (RT) instead of accuracy as the dependent measure, or in experiments in which the functions of T2 accuracy over lags do not converge to the limit of the response scale, reveals parallel functions for the easy-T1 and the hard-T1 conditions, consistent with the idea that T1 difficulty does not modulate AB magnitude. This finding is problematic for all but the Boost-and-Bounce and the Locus Coeruleus-Norepinephrine theories in which T1 acts merely as a trigger for an eventual refractory period that leads to the failure to process T2, rendering T1 difficulty and its relationship to the AB an irrelevant consideration.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
P Adragao ◽  
D Nascimento Matos ◽  
F Costa ◽  
P Galvao Santos ◽  
G Rodrigues ◽  
...  

Abstract Introduction Twenty years ago, pulmonary veins (PV) ostia were identified as the left atrium (LA) areas with the shortest refractory period during sinus rhythm. Pulmonary veins isolation (PVI) became standard of care, but clinical results are still suboptimal. Today, a special tool using the Carto® electroanatomical mapping (EAM) allows for AF cycle length mapping (CLM), to identify the areas in the left atria with shortest refractory period, during atrial fibrillation. Using this EAM tool, our study aimed to find the LA areas with the shortest refractory period to better recognize electrical targets for catheter ablation. Methods Retrospective analysis of an unicentric registry of individuals with symptomatic drug-refractory AF who underwent PVI with Carto® EAM. CLM was performed with a high-density mapping Pentaray® catheter before and after PVI and in 4 redo procedures. We assessed areas of short cycle length (SCL) (defined as 120 to 250ms), and their relationships with complex fractionated atrial electrograms (CFAE), and low-voltage zones (from 0.1 to 0.3mV). Results A total of 18 patients (8 men, median age 63 IQR 58–71 years) were included. Most patients presented with persistent AF (n=12, 67%), and 4 patients (22%) had a previous PVI. The mean shortest measured cycle length in AF was 140ms (SD ±27ms). All patients presented areas of SCL located in the PVs or their insertion, 70% in the posterior/roof region adjacent to the left superior pulmonary vein (LSPV) (figure 1) and 60% in the anterior region of the right superior pulmonary vein (RSPV). These two areas remained the fastest even after PVI. The anterior mitral region rarely presented SCL (17%). SCL were related to low-voltage areas in 94% and were adjacent to CFAE. Low-voltage areas and CFAE were more frequent and had a larger LA dispersion than SCL. Conclusion We confirmed in 3D mapping that PVs are the LA zones with shortest refractory period, not only in sinus rhythm but also during AF. The persistence of SCL areas in the border zones of the PVI lines suggest the benefit of a more extensive CLM guided ablation. Larger studies are needed. FUNDunding Acknowledgement Type of funding sources: None. Short cycle length mapping


Author(s):  
Yasunobu Yamagishi ◽  
Yasushi Oginosawa ◽  
Yoshihisa Fujino ◽  
Keishiro Yagyu ◽  
Taro Miyamoto ◽  
...  

Background: In terms of the pulmonary vein (PV), atrial fibrillation (AF) patients have a shorter effective refractory period (ERP) and a larger dispersion of the ERP than patients without AF. Although the frequency of AF from the superior vena cava (SVC) was the highest among non-PV foci, the characteristics of the ERP in the SVC (SVC-ERP) were unclear. The purpose of this study was to elucidate the relationship between SVC-ERP and the inducibility of AF after pulmonary vein isolation (PVI). Methods and Results: Consecutive 28 patients who underwent PVI were included. After successful PVI, the SVC-ERP was measured at three positions in SVC. Rapid electrical stimuli were delivered at the shortest SVC-ERP to induce AF. Patients in whom AF was induced were assigned to the SVC-induced group (SIG) and the remaining patients were the non-SVC-induced group (non-SIG). The size of the SVC sleeve was evaluated using three-dimensional electroanatomic mapping. The SIG had a significantly shorter average SVC-ERP (236.0±25.2 vs. 294.8±36.8 ms, p<0.001), while SVC-ERP dispersion was not significantly different (30.0±25.4 vs. 33.3±20.1 ms, p=0.56). Although the longer SVC diameter was significantly longer in the SIG (27.4±4.3 vs. 22.9±4.6 mm, p=0.03), the SVC-ERP was significantly associated with pacing inducibility of AF after adjustment for the longer SVC diameter (odds ratio: 0.96 [1-ms increments], p=0.01). Conclusions: The SIG had a shorter SVC-ERP, while the dispersion was not significantly different between the two groups. The SVC-ERP can be one of the mechanisms of arrhythmogenicity for AF originating from the SVC.


2021 ◽  
Vol 153 (10) ◽  
Author(s):  
Jacob M. Kemp ◽  
Dominic G. Whittaker ◽  
Ravichandra Venkateshappa ◽  
ZhaoKai Pang ◽  
Raj Johal ◽  
...  

Human Ether-à-go-go (hERG) channels contribute to cardiac repolarization, and inherited variants or drug block are associated with long QT syndrome type 2 (LQTS2) and arrhythmia. Therefore, hERG activator compounds present a therapeutic opportunity for targeted treatment of LQTS. However, a limiting concern is over-activation of hERG resurgent current during the action potential and abbreviated repolarization. Activators that slow deactivation gating (type I), such as RPR260243, may enhance repolarizing hERG current during the refractory period, thus ameliorating arrhythmogenicity with reduced early repolarization risk. Here, we show that, at physiological temperature, RPR260243 enhances hERG channel repolarizing currents conducted in the refractory period in response to premature depolarizations. This occurs with little effect on the resurgent hERG current during the action potential. The effects of RPR260243 were particularly evident in LQTS2-associated R56Q mutant channels, whereby RPR260243 restored WT-like repolarizing drive in the early refractory period and diastolic interval, combating attenuated protective currents. In silico kinetic modeling of channel gating predicted little effect of the R56Q mutation on hERG current conducted during the action potential and a reduced repolarizing protection against afterdepolarizations in the refractory period and diastolic interval, particularly at higher pacing rates. These simulations predicted partial rescue from the arrhythmic effects of R56Q by RPR260243 without risk of early repolarization. Our findings demonstrate that the pathogenicity of some hERG variants may result from reduced repolarizing protection during the refractory period and diastolic interval with limited effect on action potential duration, and that the hERG channel activator RPR260243 may provide targeted antiarrhythmic potential in these cases.


2021 ◽  
Vol 8 ◽  
Author(s):  
Baozhen Qi ◽  
Shimo Dai ◽  
Yu Song ◽  
Dongli Shen ◽  
Fuhai Li ◽  
...  

SCN10A/NaV1.8 may be associated with a lower risk of ventricular fibrillation in the setting of acute myocardial infarction (AMI), but if and by which mechanism NaV1.8 impacts on ventricular electrophysiology is still a matter of debate. The purpose of this study was to elucidate the contribution of NaV1.8 in ganglionated plexi (GP) to ventricular arrhythmias in the AMI model. Twenty beagles were randomized to either the A-803467 group (n = 10) or the control group (n = 10). NaV1.8 blocker (A-803467, 1 μmol/0.5 mL per GP) or DMSO (0.5 mL per GP) was injected into four major GPs. Ventricular effective refractory period, APD90, ventricular fibrillation threshold, and the incidence of ventricular arrhythmias were measured 1 h after left anterior descending coronary artery occlusion. A-803467 significantly shortened ventricular effective refractory period, APD90, and ventricular fibrillation threshold compared to control. In the A-803467 group, the incidence of ventricular arrhythmias was significantly higher compared to control. A-803467 suppressed the slowing of heart rate response to high-frequency electrical stimulation of the anterior right GP, suggesting that A-803467 could inhibit GP activity. SCN10A/NaV1.8 was readily detected in GPs, but was not validated in ventricles by quantitative RT-PCR, western blot and immunohistochemistry. While SCN10A/NaV1.8 is detectible in canine GPs but not in ventricles, blockade of NaV1.8 in GP increases the incidence of ventricular arrhythmias in AMI hearts. Our study shows for the first time an influence of SCN10A/NaV1.8 on the regulation of ventricular arrhythmogenesis via modulating GP activity in the AMI model.


Author(s):  
Roni Vardi ◽  
Yael Tugendhaft ◽  
Shira Sardi ◽  
Ido Kanter
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