Interplay between temporal and spatial dispersion of repolarization in the initiation and perpetuation of Torsades de Pointes in the chronic AV-block dog

Author(s):  
Agnieszka Smoczynska ◽  
Errol W. Aarnink ◽  
Albert Dunnink ◽  
Alexandre Bossu ◽  
Valerie Y.H. van Weperen ◽  
...  

Ventricular arrhythmias, consisting of single ectopic beats (sEB), multiple EB (mEB), and Torsades de Pointes (TdP, defined as >5 beats with QRS vector twisting around isoelectric line) can be induced in the anesthetized chronic AV-block (CAVB) dog by dofetilide (IKr-blocker). The interplay between temporal dispersion of repolarization, quantified as short-term variability (STV), and spatial dispersion of repolarization (SDR) in the initiation and perpetuation of these arrhythmias remains unclear. Five inducible (>3 TdPs/10') CAVB dogs were observed for 10' from the start of dofetilide infusion (0.025mg/kg, 5'). An intracardiac decapolar electrogram (EGM) catheter and 30 intramural cardiac needles in the left ventricle (LV) were introduced. STVARI was derived from 31 consecutive activation recovery intervals (ARI) on the intracardiac EGM, using the formula: . The mean SDR3D in the LV was determined as the three-dimensional repolarization time differences between the intramural cardiac needles. Moments of measurement included baseline (BL) and after dofetilide infusion prior to first 1) sEB (occurrence at 100±35"), 2) mEB (224±96"), and 3) non self-terminating TdP (454±298"). STVARI increased from 2.15±0.32ms at BL to 3.73±0.99ms* prior to the first sEB and remained increased without further significant progression to mEB (4.41±0.45ms*) and TdP (5.07±0.84ms*) (*p<0.05 compared to BL). SDR3D did not change from 31±11ms at BL to 43±13ms prior to sEB, but increased significantly prior to mEB (68±7ms*) and to TdP (86±9ms*+) (+p<0.05 compared to sEB). An increase in STV contributes to the initiation of sEB whereas an increase in SDR is important for the perpetuation of non self-terminating TdPs.

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Long Yu ◽  
Qi Jin ◽  
Zhaoye Zhou ◽  
Liqun Wu ◽  
Bin He

Introduction: Ventricular arrhythmias have been a major threat to human health in developed countries. Each year, more than 300,000 sudden cardiac death cases have been reported in the U.S. alone. The aim of this study is to evaluate a novel Cardiac Electrical Sparse Imaging technique (CESI) for noninvasive mapping and localizing the origin of ventricular arrhythmias in patients undergoing cardiac catheter ablation. Method: Pre-surgical ECG mapping and CT scans were performed in patients (n=13) with symptomatic Premature Ventricular Contraction (PVC, >10,000 beats /24h). Data analysis was performed upon the ectopic beats (n=130) to image the foci and propagation pattern. The imaged activation patterns were compared with the Local Activation Time (LAT) determined from CARTO 3 system and the CESI imaged initiation sites were compared with the last ablation sites. Results: Good correlation was obtained between the CESI imaged activation and the measured LAT with an averaged Correlation Coefficient of 0.79±0.04 and Relative Error of 0.23±0.05 over 130 beats analyzed. The Relative Temporal Shrinkage was as low as 0.01±0.01, indicating 99% of the temporal resolution was preserved. PVCs were found to originate from RV, RVOT and LV. The focal mechanism was well captured with the foci localized 8±0.9 mm away from the last successful ablation sites. In each individual patient, the activation sequence could be imaged with only one beat and the propagation pattern remained stable among all recorded beats. Conclusion: The present results indicate that CESI is feasible to image the activation pattern and localize the ectopic foci in both RV and LV. The imaged activation patterns are in good agreement with the intra-cardiac measured ones over the endocardial surface, and the localized initiators showed concordance with the real ablation outcome. The present promising results suggest the CESI technique can potentially assist clinical management of ventricular arrhythmias.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Smoczynska ◽  
V Loen ◽  
A.A Hernandez ◽  
H.D.M Beekman ◽  
M Meine ◽  
...  

Abstract Background The anesthetized, chronic complete atrioventricular block (CAVB) dog model allows reproducible inducibility of Torsade de Pointes (TdP) arrhythmias due to ventricular remodeling and after a challenge with an IKr-blocker. High rate pacing (HRP) prevents ventricular arrhythmias, but has long-term detrimental effects on cardiac function when applied continuously. Temporal dispersion of repolarization, quantified as short-term variability (STV), increases prior to ventricular arrhythmias and has been proposed as a marker to guide HRP. Purpose A proof-of-principle study to show STV determined automatically and in real-time by an ICD can guide HRP to prevent imminent ventricular arrhythmias. Methods Eight CAVB dogs were implanted with an ICD (Medtronic, lead in the right ventricular (RV) apex), with software to automatically determine STV online (STV-ICD). STV was determined from the activation recovery interval (ARI) of 31 consecutive beats with the formula: STV = Σ|ARI(n+1) − ARI(n)|/(N*√2). The CAVB dogs were challenged twice with dofetilide (0.025 mg/kg i.v. in 5 minutes or until the first TdP). In the first experiment, the individual STV-ICD threshold was determined prior to the first arrhythmic event and programmed into the ICD. In a serial experiment, HRP was initiated automatically once the STV-ICD threshold was reached, by gradually increasing the heart rate to 100 bpm. Occurrence of TdPs was monitored for 10 minutes from the start of dofetilide infusion in both experiments. During HRP, STV was measured offline from RV electrograms (EGM) and left ventricular (LV) monophasic action potential durations (MAPD) (STV-offline). Results During the inducibility experiment, 8/8 dogs had repetitive TdPs and STV-ICD increased from 0.96±0.42 to 2.10±1.26 ms* (*p&lt;0.05). During the prevention experiment, all dogs reached the STV threshold. HRP decreased STV-offline from 2.02±1.12 to 0.78±0.28 ms*, which was accompanied by prevention of TdPs in 7/8 dogs* (Figure 1). Conclusion Temporal dispersion of repolarization, quantified as STV, can guide HRP automatically by an ICD to prevent ventricular arrhythmias. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Dutch Heart Foundation Public Private Partnership


2021 ◽  
Vol 12 ◽  
Author(s):  
Valerie Y. H. van Weperen ◽  
Albert Dunnink ◽  
Alexandre Bossu ◽  
Jet D. M. Beekman ◽  
Veronique M. F. Meijborg ◽  
...  

IntroductionTorsade de pointes arrhythmias (TdP) in the chronic atrioventricular block (CAVB) dog model result from proarrhythmic factors, which trigger TdP and/or reinforce the arrhythmic substrate. This study investigated electrophysiological and arrhythmogenic consequences of severe bradycardia for TdP.MethodsDofetilide (25 μg/kg per 5 min) was administered to eight anesthetized, idioventricular rhythm (IVR) remodeled CAVB dogs in two serial experiments: once under 60 beats per minute (bpm), right ventricular apex paced (RVA60) conditions, once under more bradycardic IVR conditions. Recordings included surface electrocardiogram and short-term variability (STV) of repolarization from endocardial unipolar electrograms. TdP inducibility (three or more episodes within 10 min after start of dofetilide) and arrhythmic activity scores (AS) were established. Mapping experiments in 10 additional dogs determined the effect of lowering rate on STV and spatial dispersion of repolarization (SDR) in baseline.ResultsIVR-tested animals had longer baseline RR-interval (1,403 ± 271 ms) and repolarization intervals than RVA60 animals. Dofetilide increased STV similarly under both rhythm strategies. Nevertheless, TdP inducibility and AS were higher under IVR conditions (6/8 and 37 ± 27 vs. 1/8 and 8 ± 12 in RVA60, respectively, both p &lt; 0.05). Mapping: Pacing from high (128 ± 10 bpm) to middle (88 ± 10 bpm) to experimental rate (61 ± 3 bpm) increased all electrophysiological parameters, including interventricular dispersion, due to steeper left ventricular restitution curves, and intraventricular SDR: maximal cubic dispersion from 60 ± 14 (high) to 69 ± 17 (middle) to 84 ± 22 ms (p &lt; 0.05 vs. high and middle rate).ConclusionIn CAVB dogs, severe bradycardia increases the probability and severity of arrhythmic events by heterogeneously causing electrophysiological instability, which is mainly reflected in an increased spatial, and to a lesser extent temporal, dispersion of repolarization.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Frommeyer ◽  
J Brandt ◽  
C Ellermann ◽  
J Wolfes ◽  
L Eckardt

Abstract Background Dexmedetomidine is increasingly employed for conscious sedation during electrophysiological procedures. Recent experimental data have suggested direct effects of dexmedetomidine on cardiac electrophysiology. The aim of the present study was to assess the effects of dexmedetomidin on drug-induced QT-prolongation. Methods and results In 12 isolated rabbit hearts the macrolide antibiotic erythromycin (300μM) was infused as a potent Ikr blocker after obtaining baseline data. Eight endo- and epicardial monophasic action potentials and a simultaneously recorded 12-lead ECG showed a significant prolongation of QT-interval (+25ms, p&lt;0.05) accompanied by a moderate increase of action potential duration (APD, +5ms, p=ns) after infusion of erythromycin as compared with baseline. Effective refractory period (ERP) was also elevated (+33ms, p&lt;0.05). Erythromycin (+26ms, p&lt;0.05) also significantly increased spatial dispersion of repolarisation. Additional infusion of dexmedetomidine (3μM) resulted in a rather stable QT-interval (+7ms, p=ns) and APD (+7ms, p=ns) as compared with sole erythromycin treatment. Of note, a significant decrease of spatial dispersion (−24ms, p&lt;0.05) was observed while ERP was moderately increased (+13ms, p=ns). Lowering of potassium concentration in bradycardic AV-blocked hearts resulted in the occurrence of early afterdepolarizations (EAD) and drug induced proarrhythmia with torsade de pointes in 6 of 12 erythromycin-treated hearts (40 episodes). Additional infusion of dexmedetomidine reduced the occurrence of torsade de pointes (4 of 12 hearts, 9 episodes). Conclusion Infusion of dexmedetomidine resulted in a reduction of spatial dispersion of repolarization in the presence of a prolonged repolarization period. This resulted in a reduction of torsade de pointes with dexmedetomidine. Furthermore, an increase of ventricular refractory periods reduced inducibility of ventricular arrhythmias. Thus, in an experimental setting dexmedetomidine shows significant antiarrhythmic effects, which may influence electrophysiologic findings during clinical electrophysiologic studies. This needs to be studied in the clinical setting. Funding Acknowledgement Type of funding source: None


2021 ◽  
Vol 12 ◽  
Author(s):  
Lukáš Nalos ◽  
Dagmar Jarkovská ◽  
Jitka Švíglerová ◽  
Annabell Süß ◽  
Jakub Záleský ◽  
...  

Metabolic syndrome is associated with hypercholesterolemia, cardiac remodeling, and increased susceptibility to ventricular arrhythmias. Effects of diet-induced hypercholesterolemia on susceptibility to torsades de pointes arrhythmias (TdP) together with potential indicators of arrhythmic risk were investigated in three experimental groups of Carlsson’s rabbit model: (1) young rabbits (YC, young control, age 12–16 weeks), older rabbits (AC, adult control, age 20–24 weeks), and older age-matched cholesterol-fed rabbits (CH, cholesterol, age 20–24 weeks). TdP was induced by α-adrenergic stimulation by methoxamine and IKr block in 83% of YC rabbits, 18% of AC rabbits, and 21% of CH rabbits. High incidence of TdP was associated with high incidence of single (SEB) and multiple ectopic beats (MEB), but the QTc prolongation and short-term variability (STV) were similar in all three groups. In TdP-susceptible rabbits, STV was significantly higher compared with arrhythmia-free rabbits but not with rabbits with other than TdP arrhythmias (SEB, MEB). Amplitude-aware permutation entropy analysis of baseline ECG could identify arrhythmia-resistant animals with high sensitivity and specificity. The data indicate that the TdP susceptibility in methoxamine-sensitized rabbits is affected by the age of rabbits but probably not by hypercholesterolemia. Entropy analysis could potentially stratify the arrhythmic risk and identify the low-risk individuals.


2002 ◽  
Vol 727 ◽  
Author(s):  
S. Ichikawa ◽  
T. Akita ◽  
M. Okumura ◽  
M. Haruta ◽  
K. Tanaka

AbstractThe catalytic properties of nanostructured gold catalyst are known to depend on the size of the gold particles and to be activated when the size decreases to a few nanometers. We investigated the size dependence of the three-dimensional nanostructure on the mean inner potential of gold catalysts supported on titanium oxide using electron holography and high-resolution electron microscopy (HREM). The contact angle of the gold particles on the titanium oxide tended to be over 90° for gold particles with a size of over 5 nm, and below 90° for a size of below 2 nm. This decreasing change in the contact angle (morphology) acts to increase the perimeter and hence the area of the interface between the gold and titanium oxide support, which is considered to be an active site for CO oxidation. The mean inner potential of the gold particles also changed as their size decreased. The value of the inner potential of gold, which is approximately 25 V in bulk state, rose to over 40 V when the size of the gold particles was less than 2 nm. This phenomenon indicates the existence of a charge transfer at the interface between gold and titanium oxide. The 3-D structure change and the inner potential change should be attributed to the specific electronic structure at the interface, owing to both the “nano size effect” and the “hetero-interface effect.”


1996 ◽  
Vol 118 (2) ◽  
pp. 347-352 ◽  
Author(s):  
R. G. Dominy ◽  
D. A. Kirkham

Interturbine diffusers provide continuity between HP and LP turbines while diffusing the flow upstream of the LP turbine. Increasing the mean turbine diameter offers the potential advantage of reducing the flow factor in the following stages, leading to increased efficiency. The flows associated with these interturbine diffusers differ from those in simple annular diffusers both as a consequence of their high-curvature S-shaped geometry and of the presence of wakes created by the upstream turbine. It is shown that even the simplest two-dimensional wakes result in significantly modified flows through such ducts. These introduce strong secondary flows demonstrating that fully three-dimensional, viscous analysis methods are essential for correct performance modeling.


Author(s):  
Daphne Schönegg ◽  
Raphael Ferrari ◽  
Julian Ebner ◽  
Michael Blumer ◽  
Martin Lanzer ◽  
...  

Abstract Purpose The close topographic relationship between vascular and osseous structures in the condylar and subcondylar region and marked variability in the arterial course has been revealed by both imaging and cadaveric studies. This study aimed to verify the previously published information in a large sample and to determine a safe surgical region. Methods We analyzed the three-dimensional time-of-flight magnetic resonance angiography images of 300 individuals. Results The mean distance between the middle meningeal artery and the apex of the condyle or the most medial point of the condyle was 18.8 mm (range: 11.2–25.9 mm) or 14.5 mm (range: 8.8–22.9 mm) respectively. The course of the maxillary artery relative to the lateral pterygoid muscle was medial in 45.7% of cases and lateral in 54.3%. An asymmetric course was evident in 66 patients (22%). The mean distance between the maxillary artery and condylar process at the deepest point of the mandibular notch was 6.2 mm in sides exhibiting a medial course (range: 3.7–9.8 mm) and 6.6 mm in sides exhibiting a lateral course (range: 3.9–10.4 mm). The distances were significantly influenced by age, gender, and the course of the maxillary artery. Conclusion Our study emphasizes the marked inter- and intra-individual variability of the maxillary and middle meningeal arterial courses. We confirmed the proximity of the arteries to the condylar process. Extensive surgical experience and thorough preparation for each individual case are essential to prevent iatrogenic vascular injury.


Water ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 1718
Author(s):  
Hasan Zobeyer ◽  
Abul B. M. Baki ◽  
Saika Nowshin Nowrin

The flow hydrodynamics around a single cylinder differ significantly from the flow fields around two cylinders in a tandem or side-by-side arrangement. In this study, the experimental results on the mean and turbulence characteristics of flow generated by a pair of cylinders placed in tandem in an open-channel flume are presented. An acoustic Doppler velocimeter (ADV) was used to measure the instantaneous three-dimensional velocity components. This study investigated the effect of cylinder spacing at 3D, 6D, and 9D (center to center) distances on the mean and turbulent flow profiles and the distribution of near-bed shear stress behind the tandem cylinders in the plane of symmetry, where D is the cylinder diameter. The results revealed that the downstream cylinder influenced the flow development between cylinders (i.e., midstream) with 3D, 6D, and 9D spacing. However, the downstream cylinder controlled the flow recirculation length midstream for the 3D distance and showed zero interruption in the 6D and 9D distances. The peak of the turbulent metrics generally occurred near the end of the recirculation zone in all scenarios.


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