Vector Field Heterogeneity for the Assessment of Locally Disorganised Cardiac Electrical Propagation Wavefronts From High-Density Multielectrodes.

High-density multielectrode catheters are becoming increasingly popular in cardiac electrophysiology for advanced characterisation of the cardiac tissue, due to their potential to identify impaired sites. These are often characterised by abnormal electrical conduction, which may cause locally disorganised propagation wavefronts. To quantify it, a novel heterogeneity parameter based on vector field analysis is proposed, utilising finite differences to measure direction changes between adjacent cliques. The proposed Vector Field Heterogeneity metric has been evaluated on a set of simulations with controlled levels of organisation in vector maps, and a variety of grid sizes. Furthermore, it has been tested on animal experimental models of isolated Langendorff-perfused rabbit hearts. The proposed parameter exhibited superior capturing ability of heterogeneous propagation wavefronts compared to the classical Spatial Inhomogeneity Index, and simulations proved that the metric effectively captures gradual increments in disorganisation in propagation patterns. Notably, it yielded robust and consistent outcomes for [Formula: see text] grid sizes, underscoring its suitability for the latest generation of orientation-independent cardiac catheters.

Evaluation and assessment of clique arrangements for the estimation of omnipolar electrograms in high density electrode arrays: an experimental animal model study.

High-density catheters combined with Orientation Independent Sensing (OIS) methods have emerged as a groundbreaking technology for cardiac substrate characterisation. In this study, we aim to assess the arrangements and constraints to reliably estimate the so-called omnipolar electrogram (oEGM). Performance was evaluated using an experimental animal model. Thirty-eight recordings from nine retrospective experiments on isolated perfused rabbit hearts with an epicardial HD multielectrode were used. We estimated oEGMs according to the classic triangular clique (4 possible orientations) and a novel cross-orientation clique arrangement. Furthermore, we tested the effects of interelectrode spacing from 1 to 4 mm. Performance was evaluated by means of several parameters that measured amplitude rejection ratios, electric field loop area, activation pulse width and morphology distortion. Most reliable oEGM estimations were obtained with cross-configurations and interelectrode spacings [Formula: see text] mm. Estimations from triangular cliques resulted in wider electric field loops and unreliable detection of the direction of the propagation wavefront. Moreover, increasing interelectrode distance resulted in increased pulse width and morphology distortion. The results prove that current oEGM estimation techniques are insufficiently accurate. This study opens a new standpoint for the design of new-generation HD catheters and mapping software.

Modifications of short-term intrinsic pacemaker variability in diet-induced metabolic syndrome: a study on isolated rabbit heart.

Metabolic syndrome (MetS) describes a condition associated with multiple diseases concomitantly such as diabetes, hypertension, obesity, and dyslipidemia. It has been linked with higher prevalence of cardiovascular disease, atrial fibrillation, and sudden cardiac death. One of the underlying mechanisms could be altered automaticity, which would reflect modifications of sinus node activity. These phenomena can be evaluated analyzing the components of heart rate variability (HRV). Our aim was to examine the modifications of sinus node variability in an isolated heart model of diet-induced obesity and MetS. Male NZW rabbits were randomly assigned to high-fat (HF, n = 8), control (HF-C, n = 7), high-fat, high-sucrose (HFHS, n = 9), and control (HFHS-C, n = 9) groups, fed with their respective diets during 18/28 weeks. After euthanasia, their hearts were isolated in a Langendorff system. We recorded 10-15 min of spontaneous activity. Short RR time series were analyzed, and standard HRV parameters were determined. One-way ANOVA, Kruskal-Wallis test, and bivariate correlation were used for statistical analysis (p < 0.05). We did find an increase in the complexity and irregularity of intrinsic pacemaker activity as shown by modifications of approximate entropy, sample entropy, minimum multiscale entropy, and complexity index in HFHS animals. Even though no differences were found in standard time and frequency-domain analyses, spectral heterogeneity increased in HFHS group. Animal weight and glucose intolerance were highly correlated with the modifications of intrinsic pacemaker variability. Finally, modifications of intrinsic HRV seemed to be reliant on the number of components of MetS present, given that only HFHS group showed significant changes towards an increased complexity and irregularity of intrinsic pacemaker variability.

Effect of chronic exercise on myocardial electrophysiological heterogeneity and stability. Role of intrinsic cholinergic neurons: A study in the isolated rabbit heart.

A study has been made of the effect of chronic exercise on myocardial electrophysiological heterogeneity and stability, as well as of the role of cholinergic neurons in these changes. Determinations in hearts from untrained and trained rabbits on a treadmill were performed. The hearts were isolated and perfused. A pacing electrode and a recording multielectrode were located in the left ventricle. The parameters determined during induced VF, before and after atropine (1µM), were: fibrillatory cycle length (VV), ventricular functional refractory period (FRPVF), normalized energy (NE) of the fibrillatory signal and its coefficient of variation (CV), and electrical ventricular activation complexity, as an approach to myocardial heterogeneity and stability. The VV interval was longer in the trained group than in the control group both prior to atropine (78±10 vs. 68±10 ms) and after atropine (76±8 vs. 67±10 ms). Likewise, FRPVF was longer in the trained group than in the control group both prior to and after atropine (53±8 vs. 42±7 ms and 50±6 vs. 40±6 ms, respectively), and atropine did not modify FRPVF. The CV of FRPVF was lower in the trained group than in the control group prior to atropine (12.5±1.5% vs. 15.1±3.8%) and, decreased after atropine (15.1±3.8% vs. 12.2±2.4%) in the control group. The trained group showed higher NE values before (0.40±0.04 vs. 0.36±0.05) and after atropine (0.37±0.04 vs. 0.34±0.06; p = 0.08). Training decreased the CV of NE both before (23.3±2% vs. 25.2±4%; p = 0.08) and after parasympathetic blockade (22.6±1% vs. 26.1±5%). Cholinergic blockade did not modify these parameters within the control and trained groups. Activation complexity was lower in the trained than in the control animals before atropine (34±8 vs. 41±5), and increased after atropine in the control group (41±5 vs. 48±9, respectively). Thus, training decreases the intrinsic heterogeneity of the myocardium, increases electrophysiological stability, and prevents some modifications due to muscarinic block.

Effects of S-Nitrosoglutathione on Electrophysiological Manifestations of Mechanoelectric Feedback.

Electromechanical coupling studies have described the intervention of nitric oxide and S-nitrosylation processes in Ca2+ release induced by stretch, with heterogeneous findings. On the other hand, ion channel function activated by stretch is influenced by nitric oxide, and concentration-dependent biphasic effects upon several cellular functions have been described. The present study uses isolated and perfused rabbit hearts to investigate the changes in mechanoelectric feedback produced by two different concentrations of the nitric oxide carrier S-nitrosoglutathione. Epicardial multielectrodes were used to record myocardial activation at baseline and during and after left ventricular free wall stretch using an intraventricular device. Three experimental series were studied: (a) control (n = 10); (b) S-nitrosoglutathione 10 µM (n = 11); and (c) S-nitrosoglutathione 50 µM (n = 11). The changes in ventricular fibrillation (VF) pattern induced by stretch were analyzed and compared. S-nitrosoglutathione 10 µM did not modify VF at baseline, but attenuated acceleration of the arrhythmia (15.6 ± 1.7 vs. 21.3 ± 3.8 Hz; p < 0.0001) and reduction of percentile 5 of the activation intervals (42 ± 3 vs. 38 ± 4 ms; p < 0.05) induced by stretch. In contrast, at baseline using the 50 µM concentration, percentile 5 was shortened (38 ± 6 vs. 52 ± 10 ms; p < 0.005) and the complexity index increased (1.77 ± 0.18 vs. 1.27 ± 0.13; p < 0.0001). The greatest complexity indices (1.84 ± 0.17; p < 0.05) were obtained during stretch in this series. S-nitrosoglutathione 10 µM attenuates the effects of mechanoelectric feedback, while at a concentration of 50 µM the drug alters the baseline VF pattern and accentuates the increase in complexity of the arrhythmia induced by myocardial stretch.

Heterogeneidades inducidas en el intervalo QT mediante enfriamiento/calentamiento epicárdico local. Estudio experimental / QT interval heterogeneities induced through local epicardial warming/cooling. An experimental study

Introducción y objetivos. La duración anormal del intervalo QT o su dispersión se han asociado con un incremento en el riesgo de arritmias ventriculares. Se analiza el posible efecto arritmogénico de sus variaciones inducidas mediante enfriamiento y calentamiento local epicárdico. Métodos. En 10 corazones aislados de conejo, se modificó escalonadamente la temperatura de una región epicárdica del ventrículo izquierdo (22 a 42 °C), registrando simultáneamente los electrogramas en dicha zona y en otra del mismo ventrículo. En ritmo sinusal, se determinó el QT y el intervalo de recuperación de la activación y, mediante estimulación programada, la velocidad de conducción y la inducción de arritmias ventriculares. Resultados. En la zona modificada respecto al valor basal (37 °C), el QT se prolongó en hipotermia máxima (195 ± 47 frente a 149 ± 12 ms; p < 0,05) y se acortó en hipertermia (143 ± 18 frente a 152 ± 27 ms; p < 0,05). El intervalo de recuperación de la activación tuvo el mismo comportamiento. La velocidad de conducción disminuyó en hipotermia y aumentó en hipertermia. No hubo cambios en la otra zona. Se observaron respuestas repetitivas en cinco experimentos, pero no se encontró dependencia entre su aparición y las condiciones de hipotermia e hipertermia inducidas (p > 0,34). Conclusiones. En el modelo experimental empleado, las variaciones locales de la temperatura epicárdica modulan el intervalo QT, el intervalo de recuperación de la activación y la velocidad de conducción. Las heterogeneidades inducidas no han favorecido la inducción de arritmias ventriculares (AU)

Introduction and objectives. Abnormal QT interval durations and dispersions have been associated with increased risk of ventricular arrhythmias. The present study examines the possible arrhythmogenic effect of inducing QT interval variations through local epicardial cooling and warming. Methods. In 10 isolated rabbit hearts, the temperatures of epicardial regions of the left ventricle were modified in a stepwise manner (from 22 °C to 42 °C) with simultaneous electrogram recording in these regions and in others of the same ventricle. QT and activation-recovery intervals were determined during sinus rhythm, whereas conduction velocity and ventricular arrhythmia induction were determined during programmed stimulation. This multicenter retrospective study involved patients from the UMBRELLA national registry who underwent replacement due to defibrillator battery depletion. The incidence of ventricular arrhythmias was determined via remote monitoring. Risk factors for sustained ventricular arrhythmia after replacement were analyzed. Results. In the area modified from baseline temperature (37 °C), the QT (standard deviation) was prolonged with maximum hypothermia (195 [47] vs 149 [12] ms; P < .05) and shortened with hyperthermia (143 [18] vs 152 [27] ms; P < .05). The same behavior was displayed for the activation-recovery interval. The conduction velocity decreased with hypothermia and increased with hyperthermia. No changes were seen in the other unmodified area. Repetitive responses were seen in 5 experiments, but no relationship was found between their occurrence and hypothermia or hyperthermia (P > .34). Conclusions. In the experimental model employed, local variations in the epicardial temperature modulate the QT interval, activation-recovery interval, and conduction velocity. Induction of heterogeneities did not promote ventricular arrhythmia occurrence (AU)

QT interval heterogeneities induced through local epicardial warming/cooling. An experimental study.

INTRODUCTION AND OBJECTIVES: Abnormal QT interval durations and dispersions have been associated with increased risk of ventricular arrhythmias. The present study examines the possible arrhythmogenic effect of inducing QT interval variations through local epicardial cooling and warming. METHODS: In 10 isolated rabbit hearts, the temperatures of epicardial regions of the left ventricle were modified in a stepwise manner (from 22°C to 42°C) with simultaneous electrogram recording in these regions and in others of the same ventricle. QT and activation-recovery intervals were determined during sinus rhythm, whereas conduction velocity and ventricular arrhythmia induction were determined during programmed stimulation. RESULTS: In the area modified from baseline temperature (37°C), the QT (standard deviation) was prolonged with maximum hypothermia (195 [47] vs 149 [12] ms; P<.05) and shortened with hyperthermia (143 [18] vs 152 [27] ms; P<.05). The same behavior was displayed for the activation-recovery interval. The conduction velocity decreased with hypothermia and increased with hyperthermia. No changes were seen in the other unmodified area. Repetitive responses were seen in 5 experiments, but no relationship was found between their occurrence and hypothermia or hyperthermia (P>.34). CONCLUSIONS: In the experimental model employed, local variations in the epicardial temperature modulate the QT interval, activation-recovery interval, and conduction velocity. Induction of heterogeneities did not promote ventricular arrhythmia occurrence.

New epicardial mapping electrode with warming/cooling function for experimental electrophysiology studies.

Cardiac electrical activity is influenced by temperature. In experimental models, the induction of hypothermia and/or hyperthermia has been used for the study of mechanisms of cardiac arrhythmia. A system that allows for localized, controlled induction, besides simultaneously recording electrical activity in the same induced area, needs to be developed ad hoc. This article describes the construction and application of a new system capable of locally modifying the epicardial temperature of isolated hearts and of carrying out cardiac mapping with sufficient spatial resolution. The system is based on a thermoelectric refrigerator and an array of 128 stainless steel unipolar electrodes in encapsulated epoxy of good thermal conductivity. The surface of the electrode is shaped to match the ventricular curvature. The electrode-device was tested on 7 isolated perfused rabbit hearts following the Langendorff technique. Quality recordings were obtained for the left ventricle at temperatures of 37° C, 22° C and 42° C. The effects of temperature were explored in relation to two electrophysiological parameters: the QT interval during sinus rhythm and the VV interval during ventricular fibrillation. The results indicate that this is a suitable method for creating and analyzing electrophysiological heterogeneities induced by temperature in the experimental model.

Analyzing the electrophysiological effects of local epicardial temperature in experimental studies with isolated hearts.

As a result of their modulating effects upon myocardial electrophysiology, both hypo- and hyperthermia can be used to study the mechanisms that generate or sustain cardiac arrhythmias. The present study describes an original electrode developed with thick-film technology and capable of controlling regional temperature variations in the epicardium while simultaneously registering its electrical activity. In this way, it is possible to measure electrophysiological parameters of the heart at different temperatures. The results obtained with this device in a study with isolated and perfused rabbit hearts are reported. An exploration has been made of the effects of local temperature changes upon the electrophysiological parameters implicated in myocardial conduction. Likewise, an analysis has been made of the influence of local temperature upon ventricular fibrillation activation frequency. It is concluded that both regional hypo- and hyperthermia exert reversible and opposite effects upon myocardial refractoriness and conduction velocity in the altered zone. The ventricular activation wavelength determined during constant pacing at 250 ms cycles is not significantly modified, however. During ventricular fibrillation, the changes in the fibrillatory frequency do not seem to be transmitted to normal temperature zones.