scholarly journals Bi-atrial high-density mapping reveals inhibition of wavefront turning and reduction of complex propagation patterns as main antiarrhythmic mechanisms of vernakalant

EP Europace ◽  
2021 ◽  
Author(s):  
Arne van Hunnik ◽  
Stef Zeemering ◽  
Piotr Podziemski ◽  
Pawel Kuklik ◽  
Marion Kuiper ◽  
...  
Keyword(s):  
Flow Line ◽  
Drug Effects ◽  
Density Mapping ◽  
Channel Inhibition ◽  
Turning Behaviour ◽  
Number Flow ◽  
Complex Propagation ◽  
Excitable Gap ◽  
Activation Times ◽  
Unipolar Electrograms

Abstract Aims Complex propagation patterns are observed in patients and models with stable atrial fibrillation (AF). The degree of this complexity is associated with AF stability. Experimental work suggests reduced wavefront turning as an important mechanism for widening of the excitable gap. The aim of this study was to investigate how sodium channel inhibition by vernakalant affects turning behaviour and propagation patterns during AF. Methods and results Two groups of 8 goats were instrumented with electrodes on the left atrium, and AF was maintained by burst pacing for 3 or 22 weeks. Measurements were performed at baseline and two dosages of vernakalant. Unipolar electrograms were mapped (249 electrodes/array) on the left and right atrium in an open-chest experiment. Local activation times and conduction vectors, flow lines, the number of fibrillation waves, and local re-entries were determined. At baseline, fibrillation patterns contained numerous individual fibrillation waves conducting in random directions. Vernakalant induced conduction slowing and cycle length prolongation and terminated AF in 13/15 goats. Local re-entries were strongly reduced. Local conduction vectors showed increased preferential directions and less beat-to-beat variability. Breakthroughs and waves were significantly reduced in number. Flow line curvature reduced and waves conducted more homogenously in one direction. Overall, complex propagation patterns were strongly reduced. No substantial differences in drug effects between right and left atria or between goats with different AF durations were observed. Conclusions Destabilization of AF by vernakalant is associated with a lowering of fibrillation frequency and inhibition of complex propagation patterns, wave turning, local re-entries, and breakthroughs.

scholarly journals The Use of Electrocardiographic Imaging in Localising the Origin of Arrhythmias During Catheter Ablation of Ventricular Tachycardia

2021 ◽  
Vol 10 (3) ◽  
pp. 211-217
Author(s):  
Adam J Graham ◽  
Richard J Schilling
Keyword(s):  
Inverse Problem ◽  
Ventricular Arrhythmia ◽  
Clinical Tool ◽  
Electrocardiographic Imaging ◽  
Surface Electrodes ◽  
Non Invasive ◽  
Large Target ◽  
The Us ◽  
Activation Times ◽  
Unipolar Electrograms

Non-invasive electrocardiographic imaging (ECGI) is a novel clinical tool for mapping ventricular arrhythmia. Using multiple body surface electrodes to collect unipolar electrograms and conventional medical imaging of the heart, an epicardial shell can be created to display calculated electrograms. This calculation is achieved by solving the inverse problem and allows activation times to be calculated from a single beat. The technology was initially pioneered in the US using an experimental torso-shaped tank. Accuracy from studies in humans has varied. Early data was promising, with more recent work suggesting only moderate accuracy when reproducing cardiac activation. Despite these limitations, the system has been successfully used in pioneering work with non-invasive cardiac radioablation to treat ventricular arrhythmia. This suggests that the resolution may be sufficient for treatment of large target areas. Although untested in a well conducted clinical study it is likely that it would not be accurate enough to guide more discreet radiofrequency ablation.

Increased ventricular repolarization heterogeneity in patients with ventricular arrhythmia vulnerability and cardiomyopathy: a human in vivo study

2006 ◽  
Vol 290 (1) ◽  
pp. H79-H86 ◽  
Author(s):  
Vijay S. Chauhan ◽  
Eugene Downar ◽  
Kumaraswamy Nanthakumar ◽  
John D. Parker ◽  
Heather J. Ross ◽  
...  
Keyword(s):  
Ventricular Arrhythmia ◽  
Ventricular Arrhythmias ◽  
Conduction Block ◽  
Left Ventricular ◽  
Ventricular Repolarization ◽  
Similar Patient ◽  
T Wave Alternans ◽  
Activation Times ◽  
Unipolar Electrograms

Increased repolarization heterogeneity can provide the substrate for reentrant ventricular arrhythmias in animal models of cardiomyopathy. We hypothesized that ventricular repolarization heterogeneity is also greater in patients with cardiomyopathy and ventricular arrhythmia vulnerability (inducible ventricular tachycardia or positive microvolt T wave alternans, VT/TWA) compared with a similar patient population without ventricular arrhythmia vulnerability (no VT/TWA). Endocardial and epicardial repolarization heterogeneity was measured in patients with ( n = 12) and without ( n = 10) VT/TWA by using transvenous 26-electrode catheters placed along the anteroseptal right ventricular endocardium and left ventricular epicardium. Local activation times (AT), activation-recovery intervals (ARI), and repolarization times (RT) were measured from unipolar electrograms. Endocardial RT dispersion along the apicobasal ventricle was greater ( P < 0.005) in patients with VT/TWA than in those without VT/TWA because of greater ARI dispersion ( P < 0.005). AT dispersion was similar between the two groups. Epicardial RT dispersion along the apicobasal ventricle was greater ( P < 0.05) in patients with VT/TWA than in those without VT/TWA because of greater ARI dispersion ( P < 0.05). AT dispersion was similar between the two groups. A plot of AT as a function of ARI revealed an inverse linear relationship for no VT/TWA such that progressively later activation was associated with progressively shorter ARI. The AT-ARI relationship was nonlinear in VT/TWA. In conclusion, patients with cardiomyopathy and VT/TWA have greater endocardial and epicardial repolarization heterogeneity than those without VT/TWA without associated conduction slowing. The steep repolarization gradients in VT/TWA may provide the substrate for functional conduction block and reentrant ventricular arrhythmias.

Quantification of spatial inhomogeneity in conduction and initiation of reentrant atrial arrhythmias

1990 ◽  
Vol 259 (4) ◽  
pp. H1254-H1263 ◽  
Author(s):  
W. J. Lammers ◽  
M. J. Schalij ◽  
C. J. Kirchhof ◽  
M. A. Allessie
Keyword(s):  
Spatial Distribution ◽  
Spatial Inhomogeneity ◽  
Density Mapping ◽  
Preparation Phase ◽  
Myocardial Substrate ◽  
Rapid Pacing ◽  
Activation Times ◽  
Premature Beats ◽  
Inhomogeneity Index ◽  
Phase Differences

In isolated superfused left atria of the rabbit, inhomogeneity in conduction was quantified using the activation times measured with a high-density mapping system. At each recording site, the maximal difference with neighboring activation times (i.e., phase difference) was calculated. Local phase differences were plotted in a phase map, revealing the spatial distribution of inhomogeneities in conduction, and from each map a total index of inhomogeneity was calculated. During slow pacing (2 Hz) local differences in conduction velocity, depending on the direction of propagation, were found already. Inhomogeneity in conduction increased significantly during single early premature beats (inhomogeneity index increased from 2.3 to 3.1; P less than 0.001). The application of multiple premature beats further increased inhomogeneity in conduction, whereas rapid pacing induced the highest level of inhomogeneity (inhomogeneity index 5.3; P less than 0.001). An analysis of the spatial distribution of maximal phase differences revealed that during premature beats inhomogeneities in conduction were limited to an area of 6 mm around the point of origin of the premature impulse, whereas during rapid pacing inhomogeneities in conduction were found throughout the whole preparation. Phase maps constructed during the initiation of reentrant tachyarrhythmias showed that reentry occurred at sites with the highest phase differences. Quantification of spatial inhomogeneities in conduction is a useful tool to evaluate the vulnerability of the myocardial substrate for reentrant arrhythmias.

Opposite effects of lidocaine and diltiazem on electrophysiologic alterations in acutely ischemic porcine myocardium

1989 ◽  
Vol 67 (7) ◽  
pp. 697-703 ◽  
Author(s):  
René Cardinal ◽  
D. Leigh Carson ◽  
Chantal Lambert ◽  
Jafar Shenasa ◽  
Robert Parent ◽  
...  
Keyword(s):  
Ventricular Arrhythmias ◽  
St Segment ◽  
St Elevation ◽  
The Difference ◽  
Activation Times ◽  
Electrical Alternans ◽  
Transmembrane Currents ◽  
Ischemic Arrhythmias ◽  
Unipolar Electrograms ◽  
T Waves

To investigate the actions of lidocaine and diltiazem on the ischemic alterations associated with the onset of acute ischemic arrhythmias, the left anterior descending coronary artery was occluded for 6-min periods separated by 30 min of reperfusion, under control conditions and after injection of lidocaine (2.4–3.8 μg/mL of plasma) or diltiazem (390–510 ng/mL) in open–chest anesthetized pigs. Sixty-one unipolar electrograms were continuously recorded in the ischemic zone. Isochronal maps and isopotential maps were determined by computer analysis. The magnitude of beat-to-beat alternation of unipolar waveforms was described by the difference between the time integrals subtended by electrograms of consecutive beats. Activation times were prolonged by ischemia and the ST segment became elevated. Delay and ST elevation developed at a faster rate in the presence of lidocaine than under control conditions, but were reduced by diltiazem. ST-T alternation was not significantly different between control and lidocaine occlusions, but the incidence of negative T waves and that of ventricular tachycardia degenerating to fibrillation were higher in lidocaine occlusions than in control occlusions. In contrast, unipolar waveform alternation and negative T waves were virtually abolished by diltiazem, even at fast pacing rates (180–210 beats/min) at which diltiazem did not reduce ST elevation. Ventricular arrhythmias also were abolished by diltiazem. Thus, lidocaine and diltiazem produce opposite effects on the ischemic alterations most closely associated with the initiating mechanism of tachycardia. This could be related to differences between these drugs with regard to their actions on transmembrane currents during repolarization.Key words: acute myocardial ischemia, lidocaine, diltiazem, ventricular arrhythmias, electrical alternans.

P1389Periodicity and Spatial Stability of Complex Propagation Patterns in Atrial Fibrillation

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
M Pope ◽  
P Kuklik ◽  
A Briosa E Gala ◽  
M Mahmoudi ◽  
J Paisey ◽  
...  
Keyword(s):  
Surface Area ◽  
Left Atrial ◽  
Moving Average ◽  
Temporal Stability ◽  
Low Frequency ◽  
Kappa Statistic ◽  
Spatial Stability ◽  
Density Mapping ◽  
Complex Propagation ◽  
The Stability

Abstract Introduction Non-contact charge density mapping identifies complex wavefront propagation including localised rotational activation (LRA), localised irregular activation (LIA) and focal firing (FF). However, the duration of mapping required to reveal underlying patterns and their temporal stability is unknown. Purpose We sought to evaluate the variability in propagation patterns over increasing durations of recordings up to 30 seconds and examine the stability of these patterns between 2 separate maps with the aim of identifying the minimum duration required to reveal underlying patterns and how they represent the stable arrhythmia substrate. Methods Patients undergoing first time AcQMap guided catheter ablation were studied. 30s recordings of left atrial propagation were analysed. LIA, LRA, and FF were quantified for frequency, percentage time present and percentage surface area affected (for FF only frequency was assessed) at increasing durations up to 30s in 1s increments. At each incremental recording duration the percentage change in each variable was calculated. For occurrence frequency the results for every possible combination of maps of increasing duration within the 30s recording were compared whilst for occurrence time and surface area a 5s moving average at 1s increments was calculated. The point at which variability was seen to plateau represents the minimum optimal mapping duration. Spatial stability was assessed by correlating the frequency of patterns at each vertex of the anatomy over 2 separate 30s recordings. Stability of regions with the most repetitive patterns were compared using Cohen’s kappa statistic. Results 15 patients were analysed (age 63 ± 9, 10 male, BMI 30 ± 5, CHA2DS2Vasc 1 ± 1.3, ejection fraction 54 ± 12%, left atrial diameter 46 ± 7mm, paroxysmal 1, persistent 14) with 11 included in the spatial stability analysis due to availability of recordings of sufficient duration. LRA demonstrated most variability followed by LIA and FF. Variability in LIA, LRA and FF decrease at increasing durations. LIA and FF variability plateau by 13 and 17s respectively. LRA plateaus at 23s. Variability of &lt;10% is reached in all parameters at 18s. LIA demonstrated the greatest stability with average R2 of 0.76 ± 0.14 (figure). Average R2 for LRA and FF were 0.45 ± 0.16 and 0.47 ± 0.12.  Low frequency focal firings were widely distributed across the atrial surface. For FF occurring at a frequency ≥10 over the 30s, average R2 value was 0.65 ± 0.14. Cohen kappa statistic was 0.70 for LIA and 0.45 for LRA. Conclusion Mapping durations of ≥23s are required to identify all temporally variable propagation patterns although shorter durations will identify less variable LIA and FF.  LIA demonstrates high spatiotemporal stability and may best reflect disrupted conduction caused by the underlying atrial substrate and tissue architecture. Regions of high frequency FF are temporally stable and may represent important targets for ablation. Abstract Figure 1

scholarly journals Ventricular Electrical Heterogeneity in Experimental Diabetes Mellitus: Effect of Myocardial Ischemia

2016 ◽  
pp. 437-445 ◽  
Author(s):  
K. A. SEDOVA ◽  
M. A. VAYKSHNORAYTE ◽  
A. O. OVECHKIN ◽  
P. KNEPPO ◽  
O. G. BERNIKOVA ◽  
...  
Keyword(s):  
Body Surface ◽  
Ventricular Myocardium ◽  
Progressive Increase ◽  
The Body ◽  
Significant Prolongation ◽  
Diabetic Rabbits ◽  
Activation Times ◽  
And Control ◽  
Global And Local ◽  
Unipolar Electrograms

Aims of the study were to compare the development of electrocardiographic responses of the ischemia-induced heterogeneities of activation and repolarization in the ventricular myocardium of normal and diabetic animals. Body surface ECGs and unipolar electrograms in 64 epicardial leads were recorded before and during 20 min after the ligation of the left anterior descending artery in diabetic (alloxan model, 4 weeks, n=8) and control (n=8) rabbits. Activation times (ATs), end of repolarization times (RTs) and repolarization durations (activation-recovery intervals, ARIs) were determined in ischemic and periischemic zones. In contrast to the controls, the diabetic rabbits demonstrated the significant prolongation of ATs and shortening of ARIs (P<0.05) during ischemia in the affected region resulting in the development and progressive increase of the ARI and RT gradients across the ischemic zone boundary. The alterations of global and local dispersions of the RTs in diabetics correlated with the Tpeak-Tend interval changes in the limb leads ECGs. In the ischemic conditions, the diabetic animals differed from the controls by the activation delay, significant repolarization duration shortening, and the increase of local repolarization dispersion; the latter could be assessed by the Tpeak-Tend interval measurements in the body surface ECGs.

scholarly journals Non-blocking modulation as the major mechanism of sodium channel inhibition by riluzole

2017 ◽  
Author(s):  
AK Szabo ◽  
K Pesti ◽  
P Lukacs ◽  
MC Földi ◽  
Z Gerevich ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Sodium Channels ◽  
Activity Patterns ◽  
Drug Effects ◽  
Inhibitory Effect ◽  
Major Mechanism ◽  
State Dependent ◽  
Mechanism Of Inhibition ◽  
Channel Inhibition ◽  
Major Factors

ABSTRACTModulated- or guarded receptor hypothesis; Channel block or modulation; “Voltage-sensor block” or “lipophilic block” are some of the questions that arise when drug effects on sodium channels are investigated. Understanding the exact mechanism of action for individual drugs is essential, because it is one of the major factors that determine their therapeutic applicability.In this study we created a kinetic model of sodium channels, which can help us understand the modes of action for individual drugs in the context of these hypotheses. The model was constructed so that it could integrate the above hypotheses.In particular we aimed to understand the mode of action of riluzole, a neuroprotective drug with a peculiar state-dependent inhibition. In experiments the inhibition by 100μM riluzole was full within the first two milliseconds, but it was almost completely removed between 2 and 20 ms post-depolarization. This abrupt loss of inhibition could not be explained by dissociation, which was proceeding with a time constant of ~300 ms. We propose that for sodium channel inhibitors binding without blocking is possible, and riluzole predominantly inhibits by non-blocking modulation. We used lidocaine as a reference compound, and found that non-blocking modulation, although less prominent, also may play a role in its mechanism of inhibition. Non-blocking modulation may selectively inhibit cells with pathological activity patterns, therefore this property may be a good trait to investigate in the development of sodium channel inhibitor drugs.SUMMARYAlthough never actually proven, presence of sodium channel inhibitors at their binding site is assumed to prevent ion conduction. Authors provide evidence from experiments and kinetic simulations that bound riluzole permits conduction and exerts its inhibitory effect almost entirely by modulation.

Reduction in Pain Sensitivity from Pharmacological Elevation of Blood Pressure in Persons with Chronically Low Blood Pressure

2009 ◽  
Vol 23 (3) ◽  
pp. 104-112 ◽  
Author(s):  
Stefan Duschek ◽  
Heike Heiss ◽  
Boriana Buechner ◽  
Rainer Schandry
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Pain Sensitivity ◽  
Pain Threshold ◽  
Pain Perception ◽  
Drug Effects ◽  
Pressure Effects ◽  
Double Blind ◽  
Low Blood Pressure ◽  
Present Trial

Recent studies have revealed evidence for increased pain sensitivity in individuals with chronically low blood pressure. The present trial explored whether pain sensitivity can be reduced by pharmacological elevation of blood pressure. Effects of the sympathomimetic midodrine on threshold and tolerance to heat pain were examined in 52 hypotensive persons (mean blood pressure 96/61 mmHg) based on a randomized, placebo-controlled, double-blind design. Heat stimuli were applied to the forearm via a contact thermode. Confounding of drug effects on pain perception with changes in skin temperature, temperature sensitivity, and mood were statistically controlled for. Compared to placebo, higher pain threshold and tolerance, increased blood pressure, as well as reduced heart rate were observed under the sympathomimetic condition. Increases in systolic blood pressure between points of measurement correlated positively with increases in pain threshold and tolerance, and decreases in heart rate were associated with increases in pain threshold. The findings underline the causal role of hypotension in the augmented pain sensitivity related to this condition. Pain reduction as a function of heart rate decrease suggests involvement of a baroreceptor-related mechanism in the pain attrition. The increased proneness of persons with chronic hypotension toward clinical pain is discussed.

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