Spatial phase discontinuity at the center of moving cardiac spiral waves.

BACKGROUND: Precise analysis of cardiac spiral wave (SW) dynamics is essential for effective arrhythmia treatment. Although the phase singularity (PS) point in the spatial phase map has been used to determine the cardiac SW center for decades, quantitative detection algorithms that assume PS as a point fail to trace complex and rapid PS dynamics. Through a detailed analysis of numerical simulations, we examined our hypothesis that a boundary of spatial phase discontinuity induced by a focal conduction block exists around the moving SW center in the phase map. METHOD: In a numerical simulation model of a 2D cardiac sheet, three different types of SWs (short wavelength; long wavelength; and low excitability) were induced by regulating ion channels. Discontinuities of all boundaries among adjacent cells at each instance were evaluated by calculating the phase bipolarity (PB). The total amount of phase transition (PTA) in each cell during the study period was evaluated. RESULTS: Pivoting, drifting, and shifting SWs were observed in the short-wavelength, low-excitability, and long-wavelength models, respectively. For both the drifting and shifting cases, long high-PB edges were observed on the SW trajectories. In all cases, the conduction block (CB) was observed at the same boundaries. These were also identical to the boundaries in the PTA maps. CONCLUSIONS: The analysis of the simulations revealed that the conduction block at the center of a moving SW induces discontinuous boundaries in spatial phase maps that represent a more appropriate model of the SW center than the PS point.

ECG QT-I nterval Measurement Using Wavelet Transformation.

Wavelet transformation, with its markedly high time resolution, is an optimal technique for the analysis of non-stationary waveform signals, such as physiological signals. Therefore, wavelet transformation is widely applied to electrocardiographic (ECG) signal processing. However, an appropriate application method for automated QT-interval measurement has yet to be established. In this study, we developed an ECG recognition technique using wavelet transformation and assessed its efficacy and functionality. The results revealed that the difference between the values obtained using our algorithm and the visually measured QT interval was as low as 4.8 ms. Our technique achieves precise automated QT-interval measurement, as well as Te recognition, that is difficult to accomplish even by visual examination under the electromyography noise environment.

Interaction of phase singularities on the spiral wave tail: reconsideration of capturing the excitable gap.

The action mechanism of stimulation toward spiral waves (SWs) owing to the complex excitation patterns that occur just after point stimulation has not yet been experimentally clarified. This study sought to test our hypothesis that the effect of capturing excitable gap of SWs by stimulation can also be explained as the interaction of original phase singularity (PS) and PSs induced by the stimulation on the wave tail (WT) of the original SW. Phase variance analysis was used to quantitatively analyze the postshock PS trajectories. In a two-dimensional subepicardial layer of Langendorff-perfused rabbit hearts, optical mapping was used to record the excitation pattern during stimulation. After a SW was induced by S1-S2 shock, single biphasic point stimulation S3 was applied. In 70 of the S1-S2-S3 stimulation episodes applied on 6 hearts, the original PS was clearly observed just before the S3 point stimulation in 37 episodes. Pairwise PSs were newly induced by the S3 in 20 episodes. The original PS collided with the newly induced PSs in 16 episodes; otherwise, they did not interact with the original PS. SW shift occurred most efficiently when the S3 shock was applied at the relative refractory period, and PS shifted in the direction of the WT. In conclusion, quantitative tracking of PS clarified that stimulation in desirable conditions induces pairwise PSs on WT and that the collision of PSs causes SW shift along the WT. The results of this study indicate the importance of the interaction of shock-induced excitation with the WT for effective stimulation. NEW & NOTEWORTHY The quantitative analysis of spiral wave dynamics during stimulation clarified the action mechanism of capturing the excitable gap, i.e., the induction of pairwise phase singularities on the wave tail and spiral wave shift along the wave tail as a result of these interactions. The importance of the wave tail for effective stimulation was revealed.

Detection Algorithm of Phase Singularity Using Phase Variance Analysis for Epicardial Optical Mapping Data.

OBJECTIVE: Spiral reentry is a recognized cause of tachycardia. Detection and tracking of the spiral core are essential for understanding the spiral wave dynamics. The core of the spiral corresponds to a phase singularity (PS), which can be identified in an optical mapping image by a kernel convolution method. However, because of a large number of false positives, this method cannot automatically and stably track the core of sustaining spiral reentry in optical mapping data. METHOD: We developed a new PS detection algorithm that quantifies the variance of phase values in a phase map and identifies the position of PS as its peak. RESULTS: In comparison with the kernel convolution method, our method improved the precision of detecting a single sustaining spiral wave core from 73.1% to 99.8%. The precision of the proposed method for virtual-electrode-polarization-induced multiple PSs detections was also higher than the convolutional method. CONCLUSION: The proposed method detects PS by finding the peaks in the phase variance distribution of cardiac optical mapping image. It improved the precision of the core detection of the spiral wave in cardiac optical mapping images in comparison with the conventional kernel convolution method. SIGNIFICANCE: The proposed method will reveal the spiral wave dynamics in optical mapping images better than existing approaches. The objective analysis method of a spiral wave is important for understanding the mechanisms and dynamics of serious heart arrhythmias.

Psychosocial factors are preventive against coronary events in Japanese men with coronary artery disease: The Eastern Collaborative Group Study 7.7-year follow-up experience.

BACKGROUND: The Japanese Coronary-prone Behaviour Scale (JCBS) is a questionnaire developed by the Eastern Collaborative Group Study (ECGS), a multi-centre study of coronary-prone behaviour among Japanese men. Subscale C of the JCBS consists of 9 items that have been independently associated with the presence of coronary artery disease (CAD) in patients undergoing coronary angiography (CAG). There have been no reports of a relationship between any behavioural factor and the prognosis of CAD in Japan. The purpose of the current study was to investigate behavioural correlations with the prognosis of CAD as a part of the ECGS. METHODS: We examined the mortality and coronary events of 201 men (58 ± 10, 27-86 years) enrolled in the ECGS from 1990 to 1995, who underwent diagnostic coronary angiography and were administered the JCBS and the Japanese version of the Jenkins Activity Survey (JAS) Form C. Their health information after CAG was determined by a review of their medical records and by telephone interviews that took place from 2002 to 2003. RESULTS: Cardiac events during the follow-up period (7.7 ± 4.2 years) included 13 deaths from CAD, 25 cases of new-onset myocardial infarction, 26 cases of percutaneous coronary intervention, and 19 cases of coronary artery bypass graft surgery. There was no difference in established risk factors between groups with and without cardiac events. Seven factors were extracted by principal component analysis in order to clarify which factors were measured by the JCBS. Stepwise multivariate Cox-hazard regression analysis, in which 9 standard coronary risk factors were forced into the model, showed that Factor 4 from the JCBS (namely, the Japanese spirit of 'Wa') was independently associated with coronary events (hazard ratio: 0.21; p = 0.01). By other Cox-hazards regression analyses of coronary events using each set of JAS scores and the JCBS Scale C score instead of Factor 4 as selectable variables, the JAS scores or the JCBS Scale C score were not entered into the models. CONCLUSION: The Japanese spirit of 'Wa' is a preventive factor against coronary events for Japanese men with CAD.

Importance of gradients in membrane properties and electrical coupling in sinoatrial node pacing.

The sinoatrial node (SAN) is heterogeneous in terms of cell size, ion channels, current densities, connexins and electrical coupling. For example, Nav1.5 (responsible for INa) and Cx43 (responsible for electrical coupling) are absent from the centre of the SAN (normally the leading pacemaker site), but present in the periphery (at SAN-atrial muscle junction). To test whether the heterogeneity is important for the functioning of the SAN, one- and two-dimensional models of the SAN and surrounding atrial muscle were created. Normal functioning of the SAN (in terms of cycle length, position of leading pacemaker site, conduction times, activation and repolarization sequences and space constants) was observed when, from the centre to the periphery, (i) cell characteristics (cell size and ionic current densities) were changed in a gradient fashion from a central-type (lacking INa) to a peripheral-type (possessing INa) and (ii) coupling conductance was increased in a gradient fashion. We conclude that the heterogeneous nature of the node is important for its normal functioning. The presence of Nav1.5 and Cx43 in the periphery may be essential for the node to be able to drive the atrial muscle: Nav1.5 provides the necessary depolarizing current and Cx43 delivers it to the atrial muscle.

Simulation study of complex action potential conduction in atrioventricular node.

The atrioventricular (AV) node, which is located between the atria and ventricles of the heart, acts as important roles in cardiac excitation conduction between the two chambers. Although there are multiple conduction pathways in the AV node, the structure of the AV node has not been clarified. In this study, we constructed a one-dimensional model of the AV node and simulated excitation conduction between the right atrium and the bundle of His via the AV node. We also investigated several characteristics of the AV node: (1) responses of the AV node to high-rate excitation in the right atrium, (2) the AV nodal reentrant beat induced by premature stimulus, and (3) ventricular rate control during atrial fibrillation with various methods. Our simulation results suggest that multiple conduction pathways act as important roles in controlling the ventricular rate. The one-dimensional model constructed in this study may be useful to analyze complex conduction patterns in the AV node.

Single camera system for multi-wavelength fluorescent imaging in the heart.

Optical mapping has been a powerful method to measure the cardiac electrophysiological phenomenon such as membrane potential(V(m)), intracellular calcium(Ca(2+)), and the other electrophysiological parameters. To measure two parameters simultaneously, the dual mapping system using two cameras is often used. However, the method to measure more than three parameters does not exist. To exploit the full potential of fluorescence imaging, an innovative method to measure multiple, more than three parameters is needed. In this study, we present a new optical mapping system which records multiple parameters using a single camera. Our system consists of one camera, custom-made optical lens units, and a custom-made filter wheel. The optical lens units is designed to focus the fluorescence light at filter position, and form an image on camera's sensor. To obtain optical signals with high quality, efficiency of light collection was carefully discussed in designing the optical system. The developed optical system has object space numerical aperture(NA) 0.1, and image space NA 0.23. The filter wheel was rotated by a motor, which allows filter switching corresponding with needed fluorescence wavelength. The camera exposure and filter switching were synchronized by phase locked loop, which allow this system to record multiple fluorescent signals frame by frame alternately. To validate the performance of this system, we performed experiments to observe V(m) and Ca(2+) dynamics simultaneously (frame rate: 125fps) with Langendorff perfused rabbit heart. Firstly, we applied basic stimuli to the heart base (cycle length: 500ms), and observed planer wave. The waveforms of V(m) and Ca(2+) show the same upstroke synchronized with cycle length of pacing. In addition, we recorded V(m) and Ca(2+) signals during ventricular fibrillation induced by burst pacing. According to these experiments, we showed the efficacy and availability of our method for cardiac electrophysiological research.

Development of optical mapping system with real-time feedback stimulation in the heart.

Recent studies showed that electrical stimuli in the excitable gaps during ventricular fibrillation (VF) are important for defibrillation requiring low electrical energy. We developed an optical mapping system that measures action potentials and controls the timings and sites of electrical stimulus to verify the effectiveness of electrical stimulation in the excitable gaps. In this paper, the time delay of feedback algorithms with our optical mapping system was evaluated and the feedback stimulation protocols were operated using isolated rabbit hearts. We optically mapped electrical activity from a surface of Langendorff-perfused rabbit hearts stained with a voltage sensitive dye using high-speed video cameras. Acquiring image data triggered a timing pulse after 5.5ms using LED. In the experiment using isolated rabbit hearts, the timing delay was 10.2 ms. The velocity and direction of wave propagation was calculated in real-time using two reference points on a field of view. The two electrical stimulating points was selected by the action potentials on electrical stimulation points. The electrical shock was delivered on the point that was triggered earlier than the other point.

Pacing-induced spontaneous activity in myocardial sleeves of pulmonary veins after treatment with ryanodine.

BACKGROUND: Recent clinical electrophysiology studies and successful results of radiofrequency catheter ablation therapy suggest that high-frequency focal activity in the pulmonary veins (PVs) plays important roles in the initiation and perpetuation of atrial fibrillation, but the mechanisms underlying the focal arrhythmogenic activity are not understood. METHODS AND RESULTS: Extracellular potential mapping of rabbit right atrial preparations showed that ryanodine (2 micromol/L) caused a shift of the leading pacemaker from the sinoatrial node to an ectopic focus near the right PV-atrium junction. The transmembrane potential recorded from the isolated myocardial sleeve of the right PV showed typical atrial-type action potentials with a stable resting potential under control conditions. Treatment with ryanodine (0.5 to 2 micromol/L) resulted in a depolarization of the resting potential and a development of pacemaker depolarization. These changes were enhanced transiently after an increase in the pacing rate: a self-terminating burst of spontaneous action potentials (duration, 33.6+/-5.0 s; n=32) was induced by a train of rapid stimuli (3.3 Hz) applied after a brief rest period. The pacing-induced activity was attenuated by either depletion of the sarcoplasmic reticulum of Ca2+ or blockade of the sarcolemmal Na+-Ca2+ exchanger or Cl- channels and potentiated by beta-adrenergic stimulation. CONCLUSIONS: PV myocardial sleeves have the potential to generate spontaneous activity, and such arrhythmogenic activity is uncovered by modulation of intracellular Ca2+ dynamics.

A dynamic action potential model analysis of shock-induced aftereffects in ventricular muscle by reversible breakdown of cell membrane.

To elucidate the subcellular mechanism underlying the aftereffects of high-intensity dc shocks, a small pore, which mimics reversible breakdown of the cell membrane (electroporation), was incorporated into the phase-2 Luo-Rudy (L-R) model of ventricular action potentials. The pore size was set to occupy 0.15%-4.25% of the total cell membrane during the 10-ms shock. The pore was assumed to decrease after the shock exponentially with a time constant of 100-1,400 ms to simulate resealing process. In normal myocytes, the pore formation results in a delay of repolarization of the shocked action potential, which is followed by prolonged depolarization and oscillation of membrane potential like early afterdepolarization (EAD). Time- and voltage-dependent changes in the delayed rectifier K+ currents (IKr, IKs) in combination with those of L-type Ca2+ current (ICa,(L)) and ion flux through the pore (I(pore)) are responsible for the potential changes. Spontaneous excitation from the oscillation depends on activation of ICa,(L). In myocytes overloaded with Na+ and Ca2+ secondary to 90% inhibition of Na+-K+ pump, the pore formation results in a delay of repolarization of the shocked action potential, which is followed by slower cyclic depolarization in response to spontaneous release of Ca2+ from the sarcoplasmic reticulum (SR). This delayed afterdepolarization-type oscillation is abolished by complete block of Ca2+ release from the SR. These findings suggest that high-intensity electric field application will cause arrhythmogenic responses through a transient rupture of sarcolemma with different subcellular events in ventricular cells under normal and pathological conditions.