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Biomedical subjects

Takanori Ikeda

Publications and source records attributed to Takanori Ikeda.

At least 19 recordsLinked to original sources
PubMed2006

Predictive value of microvolt T-wave alternans for sudden cardiac death in patients with preserved cardiac function after acute myocardial infarction: results of a collaborative cohort study.

OBJECTIVES: We conducted a collaborative cohort study to evaluate the predictive power of microvolt T-wave alternans (TWA) in patients with preserved left ventricular ejection fraction (LVEF) after myocardial infarction (MI). BACKGROUND: There is little information available about the prognostic value of risk stratification markers in this population. Although these patients have a relatively good prognosis, identifying high-risk patients is important in clinical practice. METHODS: This study enrolled 1,041 post-MI patients with an LVEF > or =40% (average 55 +/- 10%). Microvolt TWA testing was performed 48 +/- 66 days after acute MI, and 10 other risk variables were also evaluated. The end points were prospectively defined as sudden cardiac death or life-threatening arrhythmic events. RESULTS: During a follow-up of 32 +/- 14 months, 38 patients (3.7%) died of nonarrhythmic causes and were not considered for analysis. Of the 1,003 evaluable patients, 18 (1.8%) reached an end point. Microvolt TWA was positive in 169 patients (17%), negative in 747 (74%), and indeterminate in 87 (9%). A positive microvolt TWA test, nonsustained ventricular tachycardia, and ventricular late potentials were predictors of events, and percutaneous coronary intervention decreased the risk rate. On multivariate analysis, a positive microvolt TWA test was the most significant predictor, with a hazard ratio of 19.7 (p < 0.0001). This marker had the highest sensitivity and negative predictive value for events. CONCLUSIONS: In patients with preserved cardiac function, the incidence of indeterminate results of microvolt TWA is low, and a positive test result is associated with arrhythmic events. Microvolt TWA could be used for risk stratification in this low-risk population.

Aged↗
PubMed2006

The full stomach test as a novel diagnostic technique for identifying patients at risk of Brugada syndrome.

INTRODUCTION: Autonomic modulation, particularly high vagal tone, plays an important role in the occurrence of ventricular tachyarrhythmias in the Brugada syndrome. Food intake modulates vagal activity. We assessed the usefulness of a novel diagnostic technique, the "full stomach test," for identifying a high-risk group in patients with a Brugada-type electrocardiogram (ECG). METHODS AND RESULTS: In 35 patients with a Brugada-type ECG, we assessed 12-lead ECGs before and after a large meal, a pilsicainide pharmacological test, spontaneous ST-segment change, late potentials by signal-averaged ECG, microvolt T-wave alternans, and four other ECG parameters. These patients were divided into two groups (i.e., high-risk group [n = 17] and indeterminate risk group [n = 18]). The full stomach test was defined as positive when augmentation of characteristic ECG abnormalities was observed after meals. Thirteen patients had a prior history of life-threatening events such as aborted sudden death and syncope, with a total of 30 episodes. These episodes had a circadian pattern, at night and after meals. The full stomach test was positive in 17 of the study patients (49%). A positive test outcome was characterized by a higher incidence of a history of life-threatening events than a negative test outcome (P = 0.015, odds ratio = 7.1). In comparison between the two groups, the incidence (82%) of positive outcomes in the high-risk group was significantly higher than that (17%) in the indeterminate risk group (P = 0.0002). CONCLUSIONS: Characteristic ECG changes diagnostic of Brugada syndrome are augmented by a large meal. These data are associated with a history of life-threatening events in Brugada syndrome.

Adult↗
PubMed2005

Can microvolt T-wave alternans testing reduce unnecessary defibrillator implantation?

The Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) have established that patients with a reduced ejection fraction gain an overall mortality benefit from prophylactic implantable cardioverter-defibrillator therapy. Only a small proportion of the patients in these studies, however, have received life-saving therapy from the defibrillator. Because defibrillator therapy is invasive and expensive, patients with a low ejection fraction would benefit from effective risk stratification so that defibrillator therapy was used only in those at significant risk. In this review, we analyze prospective clinical trials that have evaluated microvolt T-wave alternans (MTWA) testing as a predictor of ventricular tachyarrhythmic events in populations of patients similar to those studied in MADIT II or SCD-HeFT; that is, patients with a reduced ejection fraction who were not selected on the basis of a history of ventricular tachyarrhythmias. In these studies, the average annual rate of fatal and nonfatal ventricular tachyarrhythmic events among the patients who tested negative for MTWA was around 1%. This rate is so low that it is unlikely that such patients would benefit from implantable cardioverter-defibrillator therapy. The mortality, moreover, was lower among MTWA-negative patients who did not receive implantable defibrillators than that observed in the MADIT II and SCD-HeFT patients who received implantable cardioverter-defibrillators. In response, patients with a low ejection fraction who are being considered for implantable cardioverter-defibrillator therapy should undergo MTWA testing as part of their evaluation.

Clinical Trials as Topic↗
PubMed2005

Noninvasive risk stratification of subjects with a Brugada-type electrocardiogram and no history of cardiac arrest.

BACKGROUND: Recent studies suggest that the Brugada-type electrocardiogram (ECG) is much more prevalent than the manifest Brugada syndrome. Although invasive electrophysiologic investigations have been proposed as a risk stratifier, their value is controversial, and alternative noninvasive techniques may be preferred. We sought a noninvasive strategy to detect a high-risk group in a long-term follow-up study of subjects with a Brugada-type ECG, and no history of cardiac arrest. METHODS: This study enrolled 124 consecutive subjects with a Brugada-type ECG. Prognostic indices included: age, sex, a family history of sudden death, syncopal episodes, a spontaneous coved-type ST-segment elevation, maximal magnitude of ST-segment elevation, a spontaneous change in ST segment, a mean QRS duration, maximal QT interval, QT dispersion, late potentials (LP) by signal-averaged ECG, and microvolt T-wave alternans. RESULTS: Of the 124 subjects, 20 consenting subjects had an implantable defibrillator before follow-up. During a 40 +/- 19-month follow-up, 12 subjects (9.7%) reached one of the endpoints (sudden death or ventricular tachyarrhythmia). Of the 12 risk indices, a family history of sudden death, syncopal episodes, a spontaneous coved-type ST-segment elevation, a spontaneous change in ST segment, and LP had significant values. In multivariate analysis, a spontaneous change in ST segment had the most significance (a relative hazard, 9.2; P = 0.036). Combined assessment of this index and other significant indices obtained higher positive predictive values (43-71%). CONCLUSIONS: A spontaneous change in ST segment is associated with the highest risk for subsequent events in subjects with a Brugada-type ECG. The presence of syncopal episodes, a history of familial sudden death, and/or LP may increase its value.

Adult↗
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↗
PubMed2003

Time course for resolution of left atrial appendage stunning after catheter ablation of chronic atrial flutter.

OBJECTIVES: This study assessed the time course of resolution of left atrial appendage (LAA) stunning after catheter ablation of chronic atrial flutter (AFL). BACKGROUND: Although the presence of LAA stunning after ablation of chronic AFL calls for anticoagulation in the post-cardioversion period, limited information has been obtained, particularly regarding its duration. METHODS: Sixteen patients who underwent ablation of chronic, pure AFL were studied, only five of whom had structural heart disease and one of whom had a reduced left ventricular ejection fraction. The LAA emptying velocities (LAAEV) and left atrial spontaneous echo contrast (SEC) were assessed using transesophageal echocardiography before, within 24 h after, one week after, and two weeks after ablation. RESULTS: Within 24 h after ablation, the LAAEV decreased from 39 +/- 10 cm/s during AFL to 21 +/- 10 cm/s during sinus rhythm (p < 0.01), with eight patients (50%) having documented SEC. After one week, the LAAEV increased (39 +/- 17 cm/s, p < 0.01 vs. within 24 h) and SEC resolved in five of eight patients. After two weeks, the increase in LAAEV persisted (54 +/- 14 cm/s, p < 0.01 vs. 1 week) and SEC was no longer present in any of the patients. The numbers of patients with LAAEV >30 cm/s and absence of SEC were three within 24 h, 11 at one week, and 16 at two weeks after ablation. CONCLUSIONS: Patients with chronic, pure AFL and preserved left ventricular function who will undergo catheter ablation may not require anticoagulation therapy for more than two weeks after the procedure because of the presence of forceful mechanical LAA contractions and the absence of SEC.

Aged↗
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

Vitamin D3 up-regulated protein-1 regulates collagen expression in mesangial cells.

BACKGROUND: Hyperglycemia is a known risk factor in the pathogenesis of nephropathy, and collagen accumulation due to an increase reactive oxygen species (ROS) has been suspected to be one of the reasons for high glucose-mediated diseases. However, molecular mechanisms that connect glucose stimulation, oxidative stress, and collagen induction are unknown. METHODS: We examined global changes in gene expression patterns following high glucose stimulation by using DNA microarray technology in cultured human mesangial cells. The expression of vitamin D3 up-regulated protein-1 (VDUP-1), our candidate for the molecular mediator, was evaluated in the human mesangial cells, mouse mesangial cell line, and kidneys of diabetic mice by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Truncated VDUP-1 proteins were used to test the effects of VDUP-1 on the biosynthesis of collagen in mesangial cells. RESULTS: Expression of VDUP-1, which was reported as an inhibitor of thioredoxin, was induced rapidly and constantly after exposure to high concentrations of glucose upon analysis with DNA microarray. Overexpression of VDUP-1 gene in cultured mesangial cells resulted in type IV collagen alpha1 chain (COL4A1) mRNA induction and accumulation of type IV collagen protein. However, induction of COL4A1 expression was abolished with a deletion mutant of VDUP-1, which lost thioredoxin-interacting domain. Also, streptozotocin-induced diabetic mice were shown to overexpress VDUP-1 as well as COL4A1. CONCLUSION: VDUP-1 mediates collagen accumulation in mesangial cells and could be the molecular mediator/marker for fibrosis in diabetic nephropathy caused by chronic hyperglycemia such as diabetes.

Animals↗
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↗
PubMed2003

Relationship between ST-segment morphology and conduction disturbances detected by signal-averaged electrocardiography in Brugada syndrome.

BACKGROUND: Although arrhythmogenesis of Brugada syndrome is still unknown, it has been reported to be associated with conduction disturbances. Two ST-segment morphologies (coved and saddle-back patterns) have been described in this syndrome. No study has sought to determine which morphology has stronger conduction disturbances, thereby associating with life-threatening events. METHODS: Forty-six patients who presented the Brugada-type ECG with either of a characteristic coved (n = 25) or saddle-back (n = 21) pattern of ST-segment morphology underwent signal-averaged ECG (SAECG). SAECG parameters, and the history of life-threatening events defined as syncope or aborted sudden death, were compared between groups. RESULTS: Although filtered QRS duration did not differ between groups, the incidence of late potentials in the coved group was higher than in the saddle-back group (22 patients (88%) versus 4 patients (19%); P < 0.01), showing lower RMS40 and longer LAS40. Life-threatening events occurred in 17 patients (68%) in the coved group and 7 patients (33%) in the saddle-back group (P = 0.02). CONCLUSION: The coved pattern of ST segment was more closely related to conduction disturbances than the saddle-back pattern in patients with Brugada-type ECG. Life-threatening events were more common in patients with the coved ST-segment elevation. Conduction disturbances in the coved pattern of ST segment may reflect a substrate of arrhythmogenesis in Brugada syndrome.

Adult↗
PubMed2003

Pharmacological effects of ivermectin, an antiparasitic agent for intestinal strongyloidiasis: its mode of action and clinical efficacy.

Ivermectin is an oral semi-synthetic lactone anthelmintic agent derived from avermectins isolated from fermentation products of Streptomyces avermitilis. Ivermectin showed a concentration-dependent inhibitory effect on motility of a free-living nematode, Caenorhabditis elegans (C. elegans). There exist specific binding sites having a high affinity for ivermectin in the membrane fraction of C. elegans, and a strong positive correlation was detected between the affinity for these binding sites and the suppressive effect on motility of C. elegans in several ivermectin-related substances. These results suggested that the binding to these binding sites is important for the nematocidal activity of ivermectin. In oocytes of Xenopus laevis injected with the Poly (A)(+) RNA of C. elegans, expression of a chloride channel, which is irreversibly activated by ivermectin, was recognized. The pharmacological properties of this channel suggest that the ivermectin-sensitive channel is a glutamate-activated chloride channel. As to the glutamate-activated chloride channel, two subtypes (GluCl-alpha and GluCl-beta) were cloned, suggesting these subtypes constitute the glutamate-activated chloride channel. These findings suggest that ivermectin binds to glutamate-activated chloride channels existing in nerve or muscle cells of nematode with a specific and high affinity, causing hyperpolarization of nerve or muscle cells by increasing permeability of chloride ion through the cell membrane, and as a result, the parasites are paralyzed to death. In experimental infections in sheep and cattle, ivermectin exhibited potent dose-dependent anthelmintic effects on Haemonchus, Ostertagia, Trichostrongylus, Cooperia, Oesphagostomum, and Dictyocaulus. Anthelmintic effects were reported also in dogs, horses, and humans infected with Strongyloides. In the clinical Phase III trial in Japan, 50 patients infected with Strongyloides stercoralis were administered approx. 200 microg/kg of ivermectin to be given orally twice at an interval of 2 weeks. As a result, the Strongyloides stercoralis-eradicating rate was 98.0% (49/50).

Animals↗
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

Brugada syndrome: current clinical aspects and risk stratification.

Brugada syndrome is a primary electrical disease of the heart that causes sudden cardiac death or life-threatening ventricular arrhythmias, especially in younger men. Genetic analysis supports that this syndrome is a cardiac ion channel disease. A typical electrocardiographic finding consists of a right bundle branch block pattern and ST-segment elevation in the right precordial leads. The higher intercostal space V(1) to V(3) lead electrocardiogram could be helpful in detecting Brugada patients. Although two types of the ST-segment elevation are present, the coved type is more relevant to the syndrome than the saddle-back type. These patterns can be present permanently or intermittently. Recent data suggest that the Brugada-type electrocardiogram is more prevalent than the manifest Brugada syndrome. Asymptomatic individuals have a much lower incidence of future cardiac events than the symptomatic patients. Although risk stratification for the Brugada syndrome is still incomplete, the inducibility of sustained ventricular arrhythmias has been proposed as a good outcome predictor in this syndrome. In noninvasive techniques, some clinical evidence supports that late potentials detected by signal-averaged electrocardiography are a useful index for identifying patients at risk. The available data recommend prophylactic implantation of an implantable cardioverter defibrillator to prevent sudden cardiac death. This review summarizes recent information of the syndrome by reviewing most of new clinical reports and speculates on its risk stratification.

Age Distribution↗
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↗