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Biomedical subjects

Masaomi Chinushi

Publications and source records attributed to Masaomi Chinushi.

At least 19 recordsLinked to original sources
PubMed2006

Human cardiac ryanodine receptor mutations in ion channel disorders in Japan.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by adrenergic induced bidirectional or polymorphic ventricular tachycardias. Some of CPVT families were reported to be associated with cardiac ryanodine receptor gene (RyR2) mutations. However, association between RyR2 and other arrhythmogenic disorders is not clarified. In this study, we analyzed 83 Japanese patients including patients with long-QT syndrome, Brugada syndrome, idiopathic ventricular fibrillation, arrhythmogenic right ventricular cardiomyopathy and CPVT. Genetic screening of RyR2 revealed 3 distinct mutations among 4 families with CPVT (75% of incidence). However, no mutation was found in other groups. This is the first report to demonstrate prevalence of RyR2 mutations in various arrhythmogenic disorders in Japan. RyR2 mutations were detected frequently in CPVT but not in other diseases.

Arrhythmias, Cardiac↗
PubMed2006

Over-expression of Kv1.5 in rat cardiomyocytes extremely shortens the duration of the action potential and causes rapid excitation.

BACKGROUND: Genetically abnormal action potential duration (APD) can be a cause of arrhythmias that include long and short QT interval syndrome. PURPOSE: The aim of this study was to evaluate the arrhythmogenic effect of short QT syndrome induced by the over-expression of Kv1.5 in rat. METHODS: From Sprague-Dawley rats on fetal days 18-19, cardiomyocytes were excised and cultured with and without transfection with the Kv-1.5 gene using an adenovirus vector. The expression of Kv1.5 was proven by immunohistochemistry and Western blot analysis. In the culture dish and in the whole cells, the electrical activities were recorded using the whole-cell patch-clamp technique and the effects of 4-AP and verapamil were tested. RESULTS: After transfection with Kv1.5 for 12h, immunohistochemical staining and Western blot analysis were positive for Kv1.5 while they were negative in the control transfected with only Lac-Z. In the culture dish, the myocytes showed spontaneous beating at 115beats/min (bpm) just prior to the transfection with Kv1.5 and increased to 367bpm at 24h. The control myocytes showed stable beating rates during culturing. 4-AP at 200microM slowed down the rate and verapamil abolished the beating. In the whole cells, the maximal resting membrane potential was slightly depolarized and APD was extremely abbreviated both at 50% and 90% of repolarization compared with those of the control. Rapid spontaneous activities were found in a single myocyte with Kv1.5 transfection and 4-AP slowed down the frequency of the activities with a reversal of the shortened APD. CONCLUSION: The over-expression of Kv1.5 induced short APD and triggered activities in rat cardiomyocytes. This model can be used to study the arrhythmogenic substrate of short QT syndrome.

Action Potentials↗
PubMed2006

Tumor necrosis factor-alpha inhibits the cardiac delayed rectifier K current via the asphingomyelin pathway.

Tumor necrosis factor-alpha (TNF-alpha) affects contractility and ionic currents in the heart. However, the electrophysiological effects, especially on delayed rectifier K currents (IK), have not yet been fully elucidated. We examined the effects of TNF-alpha on IK. Using a voltage-clamp method, IK was measured in guinea pig ventricular myocytes in the basal state and after pharmacological intervention. To specify the site of the action of TNF-alpha, the myocytes were incubated with pertussis toxin or N-oleoylethanolamine, a ceramidase inhibitor, and IK was measured. TNF-alpha suppressed IK when it was enhanced by isoproterenol, histamine or forskolin but not in the basal state or when IK was augmented by an internal application of cyclic AMP. Both pre-incubation with pertussis toxin and N-oleoylethanolamine abolished the inhibitory action of TNF-alpha on isoproterenol-augmented IK. TNF-alpha inhibits IK, mainly IKs, when it is augmented by PKA as a result of the generation of sphingosine.

Amidohydrolases↗
PubMed2006

Shortening of the ventricular fibrillatory intervals after administration of verapamil in a patient with Brugada syndrome and vasospastic angina.

A 43-year-old man presented with electrocardiographic findings consistent with Brugada syndrome. Though the baseline coronary angiogram was normal, intracoronary infusion of ergonovine maleate caused complete occlusion of the left anterior descending and a 99% occlusion of the proximal right coronary artery, each relieved by intracoronary isosorbide dinitrate. Double extrastimuli delivered at the right ventricular outflow tract induced ventricular fibrillation terminated by a 200-J shock. Verapamil, 10 mg IV, increased ST-segment elevation and programmed stimulation repeated after the drug induced ventricular fibrillation with shorter F-F intervals and lower amplitude signals, which was not terminated by 200 J and required an additional 360-J shock. Ca2+ antagonism may have been adverse in this patient with Brugada syndrome because the drug has the potential to increase the voltage gradient through the right ventricle and to slow intraventricular conduction at very fast heart rates.

Adult↗
PubMed2006

Ventricular tachycardia late after repair of congenital heart disease: efficacy of combination therapy with radiofrequency catheter ablation and class III antiarrhythmic agents and long-term outcome.

OBJECTIVE: This study investigated the treatment of ventricular tachycardia (VT) after repair of tetralogy of Fallot or double outlet of the right ventricle. BACKGROUND: The ideal antiarrhythmic therapy for VT in patients after repair of congenital heart disease, especially without left ventricular dysfunction, has not yet been established. METHODS: Seven consecutive patients (2 women and 5 men) with stable monomorphic sustained VT were investigated. The mean age was 25 +/- 7 years (range, 16-35 years). Four patients had undergone surgical repair of tetralogy of Fallot, and 3 had surgical correction of double outlet of the right ventricle at the mean age of 18 +/- 7 years (range, 9-27 years) before documentation of the arrhythmia. RESULTS: The mean ejection fraction of the left ventricle was 60% +/- 8% (range, 50-72). Fourteen sustained monomorphic VTs were induced in 7 patients using programmed electrical stimulation. The mean cycle length of tachycardia was 346 +/- 77 milliseconds (range, 260-480 seconds). The site of the surgical correction of the right ventricle was associated with the origin of VT in all patients. Radiofrequency catheter ablation was attempted in 8 VTs in 7 patients: 7 clinical and 1 nonclinical VTs. In 6 patients, class III antarrhythmic agents were added because VT remained inducible after ablation. During a follow-up of 61 +/- 29 months (range, 15-110 months), there were no recurrences of VT. CONCLUSION: In patients with drug-refractory VT originating from the right ventricle late after congenital heart disease, and when their left ventricular function do not deteriorate, combined therapy for radiofrequency catheter ablation with class III antiarrhythmic agents might effective and should be considered as a therapeutic option.

Adolescent↗
PubMed2006

Role of autonomic nervous activity in the antiarrhythmic effects of magnesium sulfate in a canine model of polymorphic ventricular tachyarrhythmia associated with prolonged QT interval.

This study was performed to examine the role played by the autonomic nervous system in the antiarrhythmic effects of magnesium sulfate (Mg) in a canine model of polymorphic ventricular tachyarrhythmia facilitated by anthopleurin-A and a slower heart rate induced QT interval prolongation. In 6 experiments, complete atrioventricular block was created to control the heart rate and bradycardia at 800- to 1500-ms cycle lengths was applied for 60 sec before and after drug-induced autonomic block. Transmural unipolar electrograms were recorded from multipolar needle electrodes, and activation-recovery intervals (ARI) were measured. Before drug-induced autonomic block, polymorphic ventricular tachyarrhythmia developed in all 6 experiments during bradycardia before but not after the administration of Mg (0.2 ml/kg intravenous bolus). During drug-induced autonomic block, triggered premature activity decreased without significant changes in underlying dispersion of repolarization and polymorphic ventricular tachyarrhythmia developed during bradycardia in 1 experiment. Administration of Mg during drug-induced autonomic block eliminated premature activity and polymorphic ventricular tachyarrhythmia during bradycardia. The distribution of left ventricular (LV) and right ventricular repolarization and dispersion of transmural repolarization were analyzed before and 60 sec after Mg administration during ventricular pacing at 80 bpm. Mg caused a modest shortening of ARI at all sites before and after drug-induced autonomic block. Since ARI shortening was greater at the mid-myocardial sites than at other LV sites, Mg decreased transmural ARI dispersion from 77 +/- 16 to 46 +/- 21 ms before drug-induced autonomic block and from 79 +/- 7 to 51 +/- 16 ms after drug-induced autonomic block. The antiarrhythmic effects of Mg in this model of long QT syndrome were attributable to its direct pharmacological properties and not to changes in ambient autonomic nervous activity. The blockade of sympathetic activity decreased the incidence of premature events and partially suppressed polymorphic ventricular tachyarrhythmia in this model.

Animals↗
PubMed2006

Multiple premature beats triggered ventricular arrhythmias during pilsicainide infusion in a patient with inferior ST-segment elevation.

A 17-year-old man was referred to our hospital for treatment of common paroxysmal atrial flutter. His electrocardiogram at rest showed subtle ST-segment elevation in leads II, III, and aV(F). Intravenous pilsicainide caused further ST-segment elevation in the inferior leads, new ST-segment depression in leads V2-V6, two distinct forms of premature ventricular complexes (PVCs) triggering short runs of polymorphic ventricular tachycardia (VT). An infusion of isoproterenol suppressed these arrhythmias and normalized the ST-segment. Pilsicainide may induce PVCs and polymorphic VT in atypical Brugada syndrome.

Adolescent↗
PubMed2006

Japanese randomized trial for investigation of a combined therapy of amiodarone and implantable cardioverter defibrillator in patients with ventricular tachycardia and fibrillation: the Nippon ICD Plus Pharmachologic Option Necessity study design.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are the most effective therapy in reducing the mortality of patients with life-threatening ventricular tachyarrhythmias. However, the ICD cannot prevent the recurrence of tachycarida attacks and that limits the clinical usefulness of them. The Nippon ICD Plus Pharmachologic Option Necessity (NIPPON) trial was designed as the first prospective randomized study to test the hypothesis whether amiodarone could improve the patient's clinical outcome by reducing the amount of ICD therapy in the Japanese patient population. METHODS AND RESULTS: Approximately 400 patients with organic heart disease and spontaneous episode(s) of sustained ventricular tachycardia/fibrillation (VT/VF) will be randomly assigned to one of 2 groups; the amiodarone group and non-amiodarone group. Both groups of patients will be followed at least for 24 months. The end-point committee will adjudicate events in a blinded fashion. The primary end-points of this study are determination of the appropriate therapy from the ICD and alteration of the assigned treatment because of its harmful effects and/or frequent ICD therapies. CONCLUSION: The NIPPON study is expected to confirm our understanding of the prognostic and therapeutic usefulness of adjuvant amiodarone therapy for patients with an ICD and with a history of sustained VT/VF.

Amiodarone↗
PubMed2006

Comparison of efficacy of sotalol and nifekalant for ventricular tachyarrhythmias.

BACKGROUND: Suppression of implantable defibrillator discharges associated with ventricular tachyarrhythmia (VTA) has been reported for sotalol. This study aimed to investigate the efficacy of intravenous nifekalant hydrochloride in predicting the effects of oral sotalol. METHODS AND RESULTS: The present study included 14 patients who had sustained VTA associated with structural heart disease. All patients also had inducible VTA. To compare the effects of nifekalant and sotalol, programmed electrical stimulation was performed, in the basal state, after nifekalant administration, and after sotalol administration. Nifekalant and sotalol similarly prolonged the corrected QT interval and ventricular effective refractory periods, but the heart rate was slowed by sotalol only. In 4 of 5 patients whose VTA became non-inducible by nifekalant, subsequent treatment with sotalol also suppressed the inducible VTA. In all of the 9 patients non-responding to nifekalant, VTA remained inducible during sotalol treatment. Nifekalant accurately predicted the response to sotalol during electrophysiologic study in 13 of 14 patients. Of 11 patients who remained on sotalol, VTA recurred in 3 non-responders during a follow-up of 46 +/- 11 months. CONCLUSIONS: Nifekalant and sotalol had similar effects on inducible VTA. The response of inducible VTA to nifekalant may predict the clinical efficacy of sotalol.

Adult↗
PubMed2006

Amiodarone therapy in patients implanted with cardioverter-defibrillator for life-threatening ventricular arrhythmias.

BACKGROUND: Whether amiodarone can improve the patient's clinical outcome by reducing implantable cardioverter-defibrillator (ICD) therapy deliveries for ventricular tachycardia or fibrillation (VT/VF) has not been clearly evaluated. METHODS AND RESULTS: A total of 507 patients with VT/VF due to organic heart disease who had ICDs implanted were enrolled in this study. The patients were divided into 3 groups: Amiodarone (n=247), Class I anti-arrhythmic drug (n=103) and CONTROL (n=157) groups, and the total cause mortality and arrhythmic event free survival rates were evaluated between the groups. The mean follow-up period was 38+/-27 months. The left ventricular ejection fraction was significantly decreased in the Amiodarone group (Amiodarone: 37+/-15%; Class I: 39+/-16%; CONTROL: 44+/-17%). The mortality and arrhythmic events were significantly higher in the Class I group than the Amiodarone group (p<0.05), but there was no significant difference between the Amiodarone and CONTROL groups (arrhythmic event free rate at 5 years: Amiodarone: 53%; Class I: 35%; CONTROL: 48%; 5 year survival: 86%, 74% and 77%, respectively). Side effects from amiodarone were found in 12% of the patients, but no fatal events were observed. CONCLUSIONS: The present study could not demonstrate the benefit of amiodarone in ICD patients, probably due to a significant clinical bias exerted in selecting this drug.

Adolescent↗
PubMed2006

Decrease in amplitude of intracardiac ventricular electrogram and inappropriate therapy in patients with an implantable cardioverter defibrillator.

Intracardiac electrograms are important for discrimination of tachyarrhythmia by implantable cardioverter defibrillators (ICD). A low R-wave can cause not only undersensing of ventricular tachyarrhythmia but also inappropriate discharges due to oversensing of unexpected signals because of its characteristic sensing algorithm. Therefore, this study aimed to investigate adverse events associated with R-wave amplitude. We included 115 consecutive patients followed-up over one year after implantation of a transvenous ICD system. The status of the ICD was checked every 3 months and intracardiac ventricular electrograms were analyzed. The decrease in R-wave amplitude was high in arrhythmogenic hypertrophy cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy (ARVC), and sarcoidosis. Low R-waves (< 5.0 mV) were observed in 13 patients at a follow-up of 15 +/- 16 months after implantation, and the mean R-wave was 3.0 +/- 0.8 mV. The frequency of low R-waves was high in ARVC (38%), sarcoidosis (33%), and dilated cardiomyopathy (17%). All of the dilated cardiomyopathy patients with low R-waves had severe left ventricular dysfunction. Inappropriate ICD therapy resulting from T-wave oversensing occurred in 7 patients and the R-wave was < 5.0 mV in 6 of the patients. The frequency of inappropriate therapy was high in patients with sarcoidosis. In 3 patients, inappropriate therapy caused ventricular tachyarrhythmia. In conclusion, decreases in R-wave amplitude occurred in some progressive cardiac disorders and caused inappropriate ICD discharges having arrhythmogenicity. Physicians should attempt to obtain a high R-wave amplitude during ICD implantation and careful follow-up is required, especially in patients with ARVC or sarcoidosis.

Adult↗
PubMed2006

Distinct U wave changes in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT).

Although catecholaminergic polymorphic ventricular tachycardia (CPVT) is associated with fatal ventricular arrhythmias and sudden death, the ECG findings are not fully understood. In this paper, we report on alterations in the U-wave. Seven patients from 6 families with CPVT in which bidirectional tachycardia and polymorphic VT were induced by exercise or isoproterenol infusion visited our hospitals. VT was not inducible by programmed electrical stimulation. A novel gene mutation of the ryanodine receptor 2 (RyR2) was confirmed in 2 families. In one of these patients, U-wave alternans was observed following ventricular pacing at 160 beats/min. In the other patient, U-wave alternans was observed during the recovery phase after the exercise stress test, which was terminated because of polymorphic VT. In both cases, leads V3-V5 were the leads showing alternans most clearly. In the third patient, a negative U-wave became positive following a pause from sinus arrest and a change in T-wave was also noted. Since such findings were not found in the other subjects who underwent electrophysiologic study, isoproterenol infusion or exercise stress testing, the phenomenon seems to be relevant to the underlying pathogenesis of CPVT. The genesis and significance of U-wave alteration need to be determined.

Adolescent↗
PubMed2006

Transient left ventricular apical ballooning developing after the Central Niigata Prefecture Earthquake: two case reports.

Two patients presented with transient left ventricular apical ballooning (takotsubo cardiomyopathy) induced by emotional stress caused by the Central Niigata Prefecture Earthquake in 2004. These patients complained of chest pain immediately after the earthquake. In patient 1, electrocardiography (ECG) showed slight ST elevation in leads V5 to V6 and 1 mm ST depression in lead III. Serial ECG revealed inverted giant T waves in leads V3 to V6 and inverted T waves in leads I, II, aVL and aVF 13 days after the earthquake occurred. Patient 2 also complained of chest pain right after the earthquake, but consulted a doctor 15 days after the earthquake occurred. ECG showed inverted giant T wave in leads V1 to V6 and inverted T waves in leads I, II and aVL. Transthoracic echocardiography showed hypokinesis of the apical area of the left ventricle with normokinesis in the basal area in both patients. Coronary angiography showed no stenotic segments and coronary spasms were not induced by provocative testing. Serial cardiac radionuclide single photon emission computed tomography of myocardial functional sympathetic innervation using iodine-123-metaiodobenzyl-guanidine (MIBG) and thiallium-201 (201Tl) showed an MIBG uptake defect and increased wash-out in the apical area, but only mild decrease of apical 201Tl uptake. Due to strong emotional stress, earthquakes may induce transient left ventricular apical ballooning (takotsubo cardiomyopathy).

Aged↗
PubMed2005

Elimination of late potentials by quinidine in a patient with Brugada syndrome.

The beneficial effects of quinidine on ST-segment elevation, inducible ventricular tachyarrhythmias, and episodes of ventricular tachyarrhythmia have been reported in Brugada syndrome. This is the first report describing quinidine-induced elimination of the late potential, which is considered one of the parameters for an arrhythmic event, in a patient with Brugada syndrome.

Anti-Arrhythmia Agents↗
PubMed2005

A novel mutation in FKBP12.6 binding region of the human cardiac ryanodine receptor gene (R2401H) in a Japanese patient with catecholaminergic polymorphic ventricular tachycardia.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an autosomal dominant inherited disorder characterized by adrenergic induced polymorphic ventricular tachycardias and associated with sudden cardiac death. The human cardiac ryanodine receptor gene (RyR2) was linked to CPVT. A 20-year-old male was referred to our hospital because of recurrent syncope after physical and emotional stress. Routine cardiac examinations including catheterization revealed no structural abnormality. Exercise on treadmill induced premature ventricular contraction in bigeminy and bidirectional ventricular tachycardia was induced during isoproterenol infusion. Beta-blocking drug was effective in suppressing the arrhythmias. We performed genetic screening by PCR-SSCP method followed by DNA sequencing, and a novel missense mutation R2401H in RyR2 located in FKBP12.6 binding region was identified. This mutation was not detected in 190 healthy controls. Since FKBP12.6 plays a critical role in Ca channel gating, the R2401H mutation can be expected to alter Ca-induced Ca release and E-C coupling resulting in CPVT. This is the first report of RyR2 mutation in CPVT patient from Asia including Japan.

Adrenergic beta-Agonists↗
PubMed2005

Similarities between Brugada syndrome and ischemia-induced ST-segment elevation. Clinical correlation and synergy.

Vasospastic angina (VSA) and Brugada syndrome (BS) are classified into different categories of cardiac disease, but both can be causes of sudden cardiac death from ventricular fibrillation (VF). The coexistence of VSA and BS in the same patient is possible, and this raises several questions: (1) what is the incidence of the coexistence of BS and VSA in the same patient? (2) is susceptibility to VF enhanced by the coexistence of the 2 diseases? and (3) is there any possibility of Ca-antagonists being used for the treatment of VSA-aggravated BS? In our institution, VSA coexisted in 5 of the 38 patients with BS (13.1%). Anginal episodes were confirmed clinically in 4 of the 5 patients, and syncope attack occurred after the symptom of chest pain in 2 patients. However, VF did not develop during the coronary vasospasm in any of the patients. Treatment with Ca-antagonist was effective for VSA, and neither aggravation of Brugada-type electrocardiographic abnormality nor an increase in the incidence of syncope attack was observed. Although the coexistence of BS and VSA in the same patient is not rare, neither enhanced susceptibility to VF nor the proarrhythmic effect of Ca-antagonist has been confirmed in our experience. However, careful attention is required in such patients because the influence of myocardial ischemia and/or the effect of Ca-antagonist may be different in each patient with BS.

Aged↗