Biomedical subjects

Takashi Ashihara

Publications and source records attributed to Takashi Ashihara.

11 recordsLinked to original sources

PubMed2006

Left ventricular involvement in arrhythmogenic right ventricular cardiomyopathy demonstrated by multidetector-row computed tomography.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a condition in which the right ventricle is partially or totally replaced by the adipose tissue. Pathological abnormalities affect the left ventricle as well as the right ventricle, particularly the epimyocardium. Multidetector-row computed tomography, which allowed excellent visualization of not only the coronary arteries but also the myocardium with submillimeter spatial resolution and high signal-to-noise ratio, would be more suitable for the assessment of the extent of adipose tissue involvement in the right and left ventricular myocardium. We present a patient who was diagnosed as having ARVC with left ventricular involvement and underwent cardioverter defibrillator implantation.

Adult↗

PubMed2006

Gender and age effects on ventricular repolarization abnormality in Japanese general carriers of a G643S common single nucleotide polymorphism for the KCNQ1 gene.

BACKGROUND: The KCNQ1 single nucleotide polymorphism (SNP), G643S, is known to be associated with secondary long QT syndrome (LQTS) and to cause a mild reduction in KCNQ1 current. However, the precise incidence and its association with QT intervals remain unknown in the greater cohort of the population in Japan. METHODS AND RESULTS: The genotype was screened at codon 643 of KCNQ1 in 992 residents of a farming community. Eighty-eight individuals (female/male =52/36, 8.9%) were found to have a heterozygous G643S SNP. Matching both gender and age, we randomly selected 243 control (G643G) cases and compared the electrocardiogram parameters in both groups; QT, QTf (QT corrected by Fridericia's formula) intervals, the peak and the end of the T wave (Tpe) interval, and the Tpe/QT ratio. The latter 2 reflect the transmural dispersion of ventricular repolarization (TDR). In G643S carriers, both Tpe and Tpe/QT were significantly longer than in non-carriers, without significant QT prolongation. Both genders showed a tendency for an increase in QTf with aging. In females, both Tpe and Tpe/QT showed a similar significant increase with age, which was not observed in males. CONCLUSIONS: In elderly females, G643S might be an independent risk factor for secondary LQTS by causing a greater TDR.

Adult↗

PubMed2005

Cell and tissue responses to electric shocks.

AIM: Existing models of myocardial membrane kinetics have not been able to reproduce the experimentally-observed negative bias in the asymmetry of transmembrane potential changes (DeltaV(m)) induced by strong electric shocks. The goals of this study are (1) to demonstrate that this negative bias could be reproduced by the addition, to the membrane model, of electroporation and an outward current, I(a), part of the K(+) flow through the L-type Ca(2+)-channel, and (2) to determine how such modifications in the membrane model affect shock-induced break excitation in a 2D preparation. METHODS AND RESULTS: We conducted simulations of shocks in bidomain fibres and sheets with membrane dynamics represented by the Luo-Rudy dynamic model (LRd'2000), to which electroporation (LRd + EP model) and the outward current, I(a), activated upon strong shock-induced depolarization (aLRd model) was added. Assuming I(a) is a part of K(+) flow through the L-type Ca(2+)-channel enabled us to reproduce both the experimentally observed rectangularly-shaped positive DeltaV(m) and the value of near 2 of the negative-to-positive DeltaV(m) ratio. In the sheet, I(a) not only contributed to the negative bias in DeltaV(m) asymmetry at sites polarized by physical and virtual electrodes, but also restricted positive DeltaV(m). Electroporation, in its turn, was responsible for the decrease in cathode-break excitation threshold in the aLRd sheet, compared with the other two cases, as well as for the occurrence of the excitation after the shock-end rather than during the shock. CONCLUSIONS: The incorporation of electroporation and I(a) in a membrane model ensures match between simulation results and experimental data. The use of the aLRd model results in a lower threshold for shock-induced break excitation.

Animals↗

PubMed2005

Refractory gradient is responsible for the increase in ventricular vulnerability under sodium channel blockade.

BACKGROUND: Previous studies have shown that sodium channel (I(Na)) blockade increases ventricular vulnerability; however, there were differences in the degree of the increase. Because the vulnerable window (VW) is altered by the type of preshock refractory gradient (RG), the hypothesis was that the differences in the arrhythmogenesis of I(Na) blockade result from the different types of preshock RG employed. METHODS AND RESULTS: Simulations of regio(Na)l electric shock following constant pacing stimuli in 2-dimensional bidomain myocardial sheets under I(Na) blockade were conducted using 3 types of preshock RG: longitudinally tilted (LRG), transversely tilted (TRG), and non-tilted RG (NRG). The increase in the degree of I(Na) blockade almost linearly decreased the conduction velocity. The action potential duration in the LRG and TRG cases was non-linearly shortened with the increase in INa blockade because of electrotonic influences, whereas in the case of NRG it was slightly prolonged. In both LRG and TRG cases, the VW for reentry induction by electric shock was considerably widened by the INa blockade; however, this was not the case for NRG in which the VW was rather narrowed by the INa blockade. CONCLUSION: The type of preshock RG alters the degree of the increase in ventricular vulnerability under INa blockade.

Action Potentials↗

PubMed2004

Mechanisms of myocardial capture and temporal excitable gap during spiral wave reentry in a bidomain model.

BACKGROUND: Recent studies have demonstrated that regional capture during cardiac fibrillation is associated with an elevated capture threshold. It is typically assumed that the temporal excitable gap (capture window) during fibrillation reflects the size of the spatial excitable gap (excitable tissue between fibrillation waves). Because capture threshold is high, virtual electrode polarization is expected to be involved in the process. However, little is known about the underlying mechanisms of myocardial capture during fibrillation. METHODS AND RESULTS: To clarify these issues, we conducted altogether 3168 simulations of single spiral wave capture in a bidomain sheet. Unipolar stimuli of strengths 4, 8, 16, and 24 mA and 2-ms duration were delivered at 99 locations in the sheet. We found that cathode-break rather than cathode-make excitation was the dominant mechanism of myocardial capture. When the stimulation site was located diagonally with respect to the core (upper left or lower right if the spiral wave rotates counterclockwise), the cathode-break excitation easily invaded the spatial excitable gap and resulted in a successful capture as a result of the formation of virtual anodes in the direction of the myocardial fibers. Thus, the spatial distribution of the temporal excitable gap did not reflect the spatial excitable gap. CONCLUSIONS: The areas exhibiting wide temporal excitable gaps were areas in which the cathode-break excitation wave fronts easily invaded the spatial excitable gap via the virtual anodes. This study provides mechanistic insight into myocardial capture.

Atrial Fibrillation↗

PubMed2004

Spiral wave control by a localized stimulus: a bidomain model study.

INTRODUCTION: It has been reported that electrical stimulation can control spiral wave (SW) reentry. However, previous research does not account for the effects of stimulus-induced virtual electrode polarization (VEP) and the ensuing cathode-break (CB) excitation. The aim of the present study was to examine the interaction of VEP with SW reentry in a bidomain model of electrical stimulation and thus provide insight into the mechanistic basis of SW control. METHODS AND RESULTS: We conducted 3,168 simulations of localized stimulation during SW reentry in an anisotropic bidomain sheet. Unipolar cathodal 2-ms stimuli of strengths 4, 8, 16, and 24 mA were delivered at 99 locations in the sheet. The interaction between stimulus-induced VEP and SW reentry resulted in 1 of 3 possible outcomes: SW shift, SW breakup, or no effect. SW shift, which could be instrumental in SW termination at an anatomic or functional line of block, resulted from CB rather than cathode-make excitation. Stimulus timing, site, and strength all were important factors in VEP-mediated SW control. Furthermore, we found that the number of episodes of SW shift across the fibers was more sensitive to stimulus strength than that of SW shift along the fibers. SW shift can be explained by the interaction between the four VEP-induced wavebreaks and the wavebreak of the SW, ultimately resulting in termination of the original SW and the survival of one of the VEP-induced wavebreaks. This establishes a new SW reentry. CONCLUSION: This study provides new mechanistic insight into SW control.

Atrial Fibrillation↗

PubMed2004

Asymmetry in membrane responses to electric shocks: insights from bidomain simulations.

Models of myocardial membrane dynamics have not been able to reproduce the experimentally observed negative bias in the asymmetry of transmembrane potential changes (DeltaVm) induced by strong electric shocks delivered during the action potential plateau. The goal of this study is to determine what membrane model modifications can bridge this gap between simulation and experiment. We conducted simulations of shocks in bidomain fibers and sheets with membrane dynamics represented by the LRd'2000 model. We found that in the fiber, the negative bias in DeltaVm asymmetry could not be reproduced by addition of electroporation only, but by further addition of hypothetical outward current, Ia, activated upon strong shock-induced depolarization. Furthermore, the experimentally observed rectangularly shaped positive DeltaVm, negative-to-positive DeltaVm ratio (asymmetry ratio) = approximately 2, electroporation occurring at the anode only, and the increase in positive DeltaVm caused by L-type Ca2+-channel blockade were reproduced in the strand only if Ia was assumed to be a part of K+ flow through the L-type Ca2+-channel. In the sheet, Ia not only contributed to the negative bias in DeltaVm asymmetry at sites polarized by physical and virtual electrodes, but also restricted positive DeltaVm. Inclusion of Ia and electroporation is thus the bridge between experiment and simulation.

Action Potentials↗

PubMed2003

Widening of the excitable gap and enlargement of the core of reentry during atrial fibrillation with a pure sodium channel blocker in canine atria.

BACKGROUND: This study aimed to assess the effects of pilsicainide, a pure sodium channel blocker, on electrophysiological action and wavefront dynamics during atrial fibrillation (AF). METHODS AND RESULTS: In a newly developed model of isolated, perfused, and superfused canine atria (n=12), the right and left endocardia were mapped simultaneously by use of a computerized mapping system. AF was induced with 1 to 5 micromol/L acetylcholine. The antifibrillatory actions of pilsicainide on AF cycle length (AFCL), refractory period (RP), conduction velocity (CV), excitable gap (EG), and the core of the mother rotor were studied. The RP was defined as the shortest coupling interval that could capture the fibrillating atrium. The EG was estimated as the difference between the AFCL and RP. At baseline, multiple wavefronts were observed. After 2.5 microg/mL infusion of pilsicainide, all preparations showed irregular activity, and AF was terminated in 2 preparations. The AFCL and RP were prolonged, and CV was decreased significantly. The EG was widened (147%; P<0.01), and the core perimeter was increased (100%; P<0.01). Increasing the dosage either terminated AF (6 preparations) or converted to organized activity (ie, atypical atrial flutter) (4 preparations). On the maps, all "unorganized" AFs were terminated with the excitation of the core of the mother rotor by an outside wavefront, whereas in preparations with atrial flutter, pilsicainide did not terminate its activity. CONCLUSIONS: Widening of the EG by pilsicainide facilitates the excitation of the core of the mother rotor, leading to the termination of AF. In some experiments, pilsicainide converts AF to persistent atrial flutter.

Acetylcholine↗

PubMed2003

Vortex cordis as a mechanism of postshock activation: arrhythmia induction study using a bidomain model.

INTRODUCTION: The ventricular apex has a helical arrangement of myocardial fibers called the "vortex cordis." Experimental studies have demonstrated that the first postshock activation originates from the ventricular apex, regardless of the electrical shock outcome; however, the related underlying mechanism is unclear. We hypothesized that the vortex cordis contributes to the initiation of postshock activation. To clarify this issue, we numerically studied the transmembrane potential distribution produced by various electrical shocks. METHODS AND RESULTS: Using an active membrane model, we simulated a two-dimensional bidomain myocardial tissue incorporating a typical fiber orientation of the vortex cordis. Monophasic or biphasic shock was delivered via two line electrodes located at opposite tissue borders. Transmembrane potential distribution during the monophasic shock at the center of the vortex cordis showed a gradient high enough to initiate postshock activation. The postshock activation from the center of the vortex cordis was not suppressed, regardless of the initiation of spiral wave reentry. Spiral wave reentry was induced by the monophasic shock when the center area of the vortex cordis was partially excited by the nonuniform virtual electrode polarization. Postshock activation following the biphasic shock also originated from the center of the vortex cordis, but it tended to be suppressed due to the narrower excitable gap around the center of the vortex cordis. The electroporation effect, which was maximal at the center of the vortex cordis, is another possible mechanism of postshock activation. CONCLUSION: Our simulations suggest that the vortex cordis may cause postshock activation.

Arrhythmias, Cardiac↗

PubMed2002

Differences in sympathetic and vagal effects on paroxysmal atrial fibrillation: a simulation study.

The incidence of paroxysmal atrial fibrillation (AF) is affected by circadian variations in the vago-sympathetic balance. It is well known that both sympathetic and vagal effects increase the onset of paroxysmal AF, due to the shortened action potential duration. However, the reason why the vagally-mediated paroxysmal AF is maintained more than the adrenergically-mediated paroxysmal AF has remained unclear. In order to clarify this, we performed the following computer simulations. First, we constructed a homogeneous two-dimensional myocardial sheet (4.5 x 2.25 cm), using a bidomain ion channel model. The sympathetic and vagal effects were achieved by modifications of the ion channel conductance (Sympathetic effect: increased gSI and increased gK. Vagal effect: increased gK and increased gK1 with or without the dispersion of refractoriness). We found that the sympathetic effect shortened the action potential duration and flattened the restitution slope; therefore, this effect promoted spiral wave induction and restrained the spiral wave breakup. On the other hand, we found that the vagal effect also shortened the action potential duration and flattened the restitution slope; however, this effect promoted spiral wave breakup, due to the increase in both the IK1 and the dispersion of refractoriness. Overall, the differences between the sympathetic and vagal effects on the tendency toward spiral wave break-up may explain the reason why adrenergically-mediated paroxysmal AF terminates spontaneously and vagally-mediated paroxysmal AF tends to be maintained. In conclusion, our results may be helpful in understanding the difference in the action of sympathetic and vagal effects on paroxysmal AF.

Action Potentials↗

PubMed2002

Afterdepolarizations promote the transition from ventricular tachycardia to fibrillation in a three-dimensional model of cardiac tissue.

Recent experimental results regarding the action potential duration restitution curve have explained the transition from ventricular tachycardia (VT) to fibrillation (VF) in terms of spiral wave (SW) meandering and breakup. However, it remains unclear whether VF always has a steep restitution curve. The present study was designed to test the hypothesis that afterdepolarizations occur at excitable gaps during VF and affect the SW dynamics, even if the restitution curve is gentle. Homogeneous and isotropic 3-dimensional tissue was simulated with a LRd model. Because of the gentle restitution curve, it was not expected that SW instabilities would occur in this condition. In the tissue, a stationary SW reentry was initially observed; however, afterdepolarizations erupted from the excitable gap near the SW tip, and the SW then meandered widely. Following that, afterdepolarizations erupted far from the SW tip, resulting in SW breakup. In this manner, the wave dynamics degenerated into a chaotic state within a few seconds. Furthermore, not only triggered activity but also subthreshold afterdepolarizations were found to cause SW instabilities. These results suggest that afterdepolarizations may play an important role in the transition to VF and that the mechanism is independent of restitution properties.

Computer Simulation↗