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Biomedical subjects

Yukio Hosaka

Publications and source records attributed to Yukio Hosaka.

At least 19 recordsLinked to original sources
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

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↗
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

Phosphatidylinositol 3,4,5-trisphosphate and Ca2+/calmodulin competitively bind to the regulators of G-protein-signalling (RGS) domain of RGS4 and reciprocally regulate its action.

RGS (regulators of G-protein signalling) are a diverse group of proteins, which accelerate intrinsic GTP hydrolysis on heterotrimeric G-protein a subunits. They are involved in the control of a physiological behaviour known as 'relaxation' of G-protein-gated K+ channels in cardiac myocytes. The GTPase-accelerating activity of cardiac RGS proteins, such as RGS4, is inhibited by PtdIns(3,4,5)P3 (phosphatidylinositol 3,4,5-trisphosphate) and this inhibition is cancelled by Ca2+/calmodulin (CaM) formed during membrane depolarization. G-protein-gated K+ channel activity decreases on depolarization owing to the facilitation of GTPase-activating protein activity by RGS proteins and vice versa on hyperpolarization. The molecular mechanism responsible for this reciprocal control of RGS action by PtdIns(3,4,5)P3 and Ca2+/CaM, however, has not been fully elucidated. Using lipid-protein co-sedimentation assay and surface plasmon resonance measurements, we show in the present study that the control of the GTPase-accelerating activity of the RGS4 protein is achieved through the competitive binding of PtdIns(3,4,5)P3 and Ca2+/CaM within its RGS domain. Competitive binding occurs exclusively within the RGS domain and involves a cluster of positively charged residues located on the surface opposite to the Ga interaction site. In the RGS proteins conserving these residues, the reciprocal regulation by PtdIns(3,4,5)P3 and Ca2+/CaM may be important for their physiological regulation of G-protein signalling.

Acetylcholine↗
PubMed2005

Unsuccessful internal defibrillation in Brugada syndrome: focus on refractoriness and ventricular fibrillation cycle length.

INTRODUCTION: In patients with Brugada syndrome, implantable cardioverter defibrillator (ICD) is the only reliable treatment to prevent sudden death though, in some cases, internal defibrillation may be unsuccessful. The aim of this study was to examine the determinants of defibrillation failure, with a focus on electrophysiologic characteristics. METHODS: The study included 51 patients treated with ICD: 22 with Brugada syndrome and 29 with structural heart disease (SHD). The prevalence of defibrillation energy requirement precluding the programming of a 10-J safety margin, the mean right ventricular effective refractory period (ERP), and mean induced ventricular fibrillation cycle length (VFCL) from the stored ICD electrograms, were compared between the two patient groups. RESULTS: High defibrillation requirements were observed in 18% of patients with Brugada syndrome versus 0% of patients with SHD. However, the patients with SHD had larger heart size than those with Brugada syndrome. Mean VFCL and mean ERP were both significantly shorter in patients with Brugada syndrome than in patients with SHD, and ERP and VFCL were significantly correlated. CONCLUSION: Patients with Brugada syndrome have a high prevalence of high defibrillation energy requirement, and short ventricular ERP and VFCL.

Bundle-Branch Block↗
PubMed2005

Genomic and non-genomic regulation of L-type calcium channels in rat ventricle by thyroid hormone.

Hyperthyroidism is associated with low exercise tolerance despite high cardiac output and sometimes with the development of heart failure. L-type calcium channels may play a role in the mechanism, but this has not been fully understood. We examined the effects of thyroid hormone on gene expression and function of L-type calcium channels in rat ventricles by the ribonuclease protection assay and whole-cell patch-clamp technique, respectively. The effects of bisoprolol, beta-blocking agent, on the regulation of calcium channel by thyroid hormone was also studied. In hyperthyroid animals, the mRNA of the calcium channel alpha1c subunit was reduced on day 4, compared with that in euthyroid animals, and remained low on day 8. Bisoprolol did not affect the thyroid hormone mediated decrease in alpha1c subunit mRNA. While L-type calcium current was greater in hyperthyroid than euthyroid myocytes on day 4, it was smaller on day 8. In addition, the isoproterenol-induced increase in calcium current in euthyroid rats was attenuated in hyperthyroid rats. Acetylcholine decreased calcium current in hyperthyroid myocytes, but not in euthyroid myocytes. In conclusion, L-type calcium current was increased by thyroid hormone in rat ventricular myocytes by the activation of the adenylate cyclase cascade, despite a decreased calcium channel gene expression. These genomic and non-genomic modifications may play an important role in the association of high cardiac output with low exercise tolerance, and in the development of heart failure in hyperthyroidism.

Acetylcholine↗
PubMed2005

Electrophysiologic study-guided therapy with sotalol for life-threatening ventricular tachyarrhythmias.

The aim of this study was to investigate the long-term efficacy and safety of electrophysiologic study (EPS)-guided sotalol administration combined with implantable cardioverter defibrillators (ICD) for ventricular tachyarrhythmias (VTA). This study enrolled 92 patients with both structural heart disease and sustained VTA. Sotalol was administered to 57 patients, and its efficacy was assessed by EPS. Long-term treatment was continued in combination with ICD in 31 patients (57%) whose VTA was no longer inducible (responder group) and in 16 patients whose VTA remained inducible (nonresponder group). The long-term outcomes were compared among the responder group, the nonresponder group, and 35 ICD recipients untreated with antiarrhythmic drugs (ICD-only group). During a mean follow-up of 44 +/- 33 months, the recurrence of VTA was not significantly different between all patients treated with sotalol (30%) and patients in the ICD-only group (46%). However, the recurrence of VTA was significantly lower in the responder (13%) than in the nonresponder (63%) or the ICD-only groups (46%). There was no significant difference in VTA recurrence between the nonresponder and the ICD-only groups. One patient each in the responder and the ICD-only groups died suddenly, and all-cause mortality was similar in the three groups. The incidence of inappropriate ICD discharges was less in the sotalol than in the ICD-only groups. No patient had to discontinue long-term sotalol treatment because of the adverse effects. In conclusion, sotalol reduced VTA recurrence in the responding patients and inappropriate ICD discharge. EPS may predict the efficacy of sotalol for VTA recurrence.

Aged↗
PubMed2005

Variable electrocardiographic effects of short-term quinidine sulfate administration in Brugada syndrome.

Quinidine, a class I antiarrhythmic agent with blocking property of transient outward current, is a possible candidate for the suppression of ventricular fibrillation in patients with Brugada syndrome; although there is a concern that its ability to these effects may be proarrhythmic. Therefore, we evaluated the effect of quinidine sulfate on ST-segment elevation in Brugada syndrome. In 8 patients with Brugada syndrome, the magnitude of ST-elevation at the J-point (ST(J)), and the ST-segment configuration in leads V1-V3, were compared before and on day 2 after the initiation of quinidine administration. In 3 patients, quinidine attenuated ST(J) by > or = 0.1 mV. Of these 3 patients, ST-segment elevation was normalized in 2 patients, while the ST-segment configuration was unchanged in another. In another 3 patients, quinidine augmented ST(J) by > or = 0.1 mV without any change of ST-segment configuration, and the augmentation was returned to baseline after the discontinuation of quinidine. Quinidine exhibited no effect on the ST-segment in the remaining 2 patients. The favorable effects of quinidine on the ST-segment tended to be more pronounced in patients with prominent ST-elevation at baseline. In 1 patient, quinidine was effective in eliminating both ST-segment elevation and repetitive tachyarrhythmia episodes. In conclusion, the effects of quinidine on ST-segment elevation were variable. Quinidine may potentially augment the ST-segment elevation in some patients with Brugada syndrome.

Adult↗
PubMed2005

Nifekalant hydrochloride suppresses severe electrical storm in patients with malignant ventricular tachyarrhythmias.

BACKGROUND: Some patients with an implantable cardioverter-defibrillator (ICD) suffer from burst of inappropriate multiple discharges (severe electrical storm), and because the current therapeutic options are limited, the effect of nifekalant hydrochloride, a new class III drug, on severe electrical storm was investigated in the present study. METHODS AND RESULTS: Ninety-one consecutive patients treated with ICD were included in the study (M 70; mean age 58 years; left ventricular ejection fraction 45+/-15%). Severe electrical storm was defined as more than 10 ICD discharges within 1 h. During a mean follow-up period of 30+/-13 months, 41/91 (45%) patients had appropriate ICD therapy for arrhythmias and severe electrical storm occurred in 11 of them (12%) at 20+/-18 months after ICD implantation. The mean number of ICD discharges/h during severe electrical storm was 18+/-12. In 4 of 10 patients, severe electrical storm was successfully suppressed by a combination of deep sedation and beta-blocking agent; 6 other patients were refractory to this treatment, but severe electrical storm was successfully suppressed by intravenous administration of nifekalant hydrochloride with no adverse effects. CONCLUSIONS: Nifekalant hydrochloride is an effective and safe treatment for severe electrical storm.

Adolescent↗
PubMed2004

Postprandial variations in ST-segment in a patient with Brugada syndrome and partial gastrectomy.

A 74-year-old man with a history of partial gastrectomy presented with an electrocardiogram consistent with Brugada syndrome and marked meal related fluctuations in the ST segment. ST-segment elevation was prominently attenuated at 30 minutes and increased at 120 minutes after meals. Analysis of heart rate variability revealed a relationship between postprandial heightened parasympathetic activity and increase in Brugada-type ECG abnormality. A rapid postprandial increase in blood glucose may initially stimulate sympathetic nervous activity and secondarily increase parasympathetic tone. Food intake can be associated with fluctuations in ST-segment elevation in patients with the Brugada syndrome.

Aged↗
PubMed2003

Thyroid hormone regulates mRNA expression and currents of ion channels in rat atrium.

Atrial fibrillation is one of the common arrhythmias associated with hyperthyroidism. This study examined the effects of thyroid hormone (T3) on mRNA expression and currents of major ionic channels determining the action potential duration (APD) in the rat atrium using the RNase protection assay and the whole-cell patch-clamp technique, respectively. T3 increased the Kv1.5 mRNA expression and decreased the L-type calcium channel mRNA expression, while the Kv4.2 mRNA expression did not change. APD was shorter in hyperthyroid than in euthyroid myocytes. The ultrarapid delayed rectifier potassium currents were remarkably increased in hyperthyroid than in euthyroid myocytes, whereas the transient outward potassium currents were unchanged. L-type calcium currents were decreased in hyperthyroid than in euthyroid myocytes. T3 shifted the current-voltage relationship for calcium currents negatively. In conclusion, T3 increased the outward currents and decreased the inward currents. The resultant changes of ionic currents shortened APD, providing a substrate for atrial fibrillation.

Action Potentials↗
PubMed2003

Function, subcellular localization and assembly of a novel mutation of KCNJ2 in Andersen's syndrome.

Andersen's syndrome (AS) (which is characterized by periodic paralysis, cardiac arrhythmias and dysmorphic features), a hereditary disease, and missense mutations of KCNJ2 (which encodes an inward rectifying potassium channel) have been reported recently. We performed clinical and molecular analyses of a patient with AS, and found a novel mutation (G215D) of KCNJ2. Twelve-lead electrocardiography revealed a long QT interval and frequent premature ventricular contractions, and polymorphic ventricular tachycardia was induced by programmed electrical stimulation. Use of a conventional whole-cell patch-clamp system with COS7 cells demonstrated that the G215D mutant was non-functional, and that co-expression of wild type (WT)- and mutant-KCNJ2 shows a dominant negative effect on both inward and outward currents. We performed confocal laser scanning microscopy to assess the cellular trafficking of WT- and mutant-KCNJ2 subunits tagged with yellow fluorescent protein (YFP) and cyan fluorescent protein (CFP), respectively. Tagging with the YFP did not affect the channel function of WT-KCNJ2 and both proteins showed similar plasma membrane fluorescence patterns. Furthermore, the result of fluorescence resonance energy transfer (FRET) studies at the plasma membrane region suggested that both YFP-tagged WT- and CFP-tagged mutant-KCNJ2 combine to construct a hetero-multimer of the potassium channel. In conclusion, the G215D mutant of KCNJ2 is distributed normally in the plasma membrane, but exhibits a dominant-negative effect and reduces the Kir2.1 current, presumably due to hetero-multimer construction.

Adult↗
PubMed2003

Historical view of schistosomiasis japonica in Japan: implementation and evaluation of disease-control strategies in Yamanashi Prefecture.

We summarized historical aspects of disease control activities targeting schistosomiasis japonica in Kofu basin, Yamanashi Prefecture, Japan. Kofu Basin was one of the biggest endemic foci of schistosomiasis japonica in Japan, and the last place where transmission of Schistosoma japonicum was confirmed in Japan. Because of the most severe endemic situations in Yamanashi, intensive control measures had been implemented by the central as well as the local government. The last human case in Japan was in 1977, which is just before praziquantel being available. Therefore, the main efforts were focused on snail control. Mass examination and mass chemotherapy were implemented, however, the compliance was not so good because of the severe side effects due to the available therapeutics, Stibnal. Along with socioeconomic development after World War II, big changes in land use, life style, and farming led drastic reduction in the disease prevalence in Kofu Basin in the 1960s. A large amount of budget was also used for disease control. Cementing water canals covered more than 95% of paddy fields in Kofu Basin, and this resulted in ecological changes. After elimination of schistosomiasis, environmental repair is the urgent subject in Kofu Basin. Our experiences in Yamanashi contain both good influences and also a lot of reflection. It is important to evaluate each activity in our history before we give intensive cooperation with countries where endemic foci is still present.

Animals↗
PubMed2003

Suppression of electrical storm by biventricular pacing in a patient with idiopathic dilated cardiomyopathy and ventricular tachycardia.

This study presents a patient with idiopathic dilated cardiomyopathy who had suffered from multiple ICD shocks. Amiodarone and a beta-blocker failed to suppress ventricular tachycardia. His ECG showed a very wide QRS complex with an intraventricular conduction delay, so biventricular (BV) pacing was attempted. The BV pacing successfully prevented the multiple ICD shocks accompanied with an improvement in left ventricular systolic function and physical activity.

Cardiac Pacing, Artificial↗
PubMed2003

Ventricular tachyarrhythmias in a canine model of LQT3: arrhythmogenic effects of sympathetic activity and therapeutic effects of mexiletine.

The ventricular tachyarrhythmias associated with the LQT3 syndrome are typically bradycardia-dependent. However, some episodes can be associated with exercise or emotional stress, suggesting a different arrhythmogenic mechanism when sympathetic activity predominates. This study examined the potential arrhythmogenic mechanisms during periods of autonomically mediated transient heart rate acceleration in a canine anthopleurin-A model of LQT3 syndrome. Using plunge needle electrodes, transmural unipolar electrograms of the left ventricle were recorded from endocardial (Endo), mid-myocardial (Mid) and epicardial (Epi) sites. The activation-recovery interval (ARI) was measured to estimate local refractoriness. The cardiac cycle length was gradually shortened by cessation of vagal stimulation (vagal stimulation protocol (VSP)), and intramural electrograms and onset mode of ventricular tachyarrhythmias were analyzed in 7 experiments. The VSP was performed 8 times before and 5 times after administration of mexiletine in each experiment. Before mexiletine, vagal stimulation slowed the heart rate and created large transmural ARI dispersion because of a greater ARI prolongation at Mid rather than Epi/Endo sites. After cessation of vagal stimulation, unipolar electrograms started to show ARI alternans and ventricular premature beats developed sporadically. Sustained ventricular tachyarrhythmias were induced in 12 of the 56 trials of the VSP. Initiation of ventricular tachyarrhythmias was associated with delayed conduction at Mid/Endo sites. Mexiletine attenuated transmural ARI dispersion, and neither ARI alternans nor ventricular tachyarrhythmias was observed during all 35 trials of the VSP after mexiletine administration. Heart rate acceleration induced by an abrupt shift to a state of predominant sympathetic activity enhances arrhythmias in this LQT3 model. Mexiletine homogenizes ventricular repolarization, suppresses premature complexes and was antiarrhythmic during ventricular tachyarrhythmias induced by the VSP.

Animals↗
PubMed2003

Different gene expression of potassium channels by thyroid hormone and an antithyroid drug between the atrium and ventricle of rats.

UNLABELLED: Thyroid hormone has been shown to modulate the gene expression of cardiac potassium channels, however, it is not known if gene expression is different between the atrium and the ventricle. The long-term effects of thyroid hormone on nuclear thyroid hormone receptors are also not known. Triiodothyronine (T3) at 25 microg/100 g of body weight or propylthiouracil (PTU) at 4 mg/100 g of body weight was given to adult rats via a gastric tube for 14 days. The levels of mRNA of Kv1.2. Kv1.4, Kv1.5, Kv2.1, Kv4.2, erg, LQT1, and minK were assayed by RNase protection assay. The mRNA of nuclear T3-receptor-al and T3-receptor-beta1 were also assayed for 15 days. After T3 (or PTU), plasma free T3 and free T4 increased (or decreased) significantly. The mRNA levels of Kv1.2 and Kv1.4 were reduced after T3 in the atrium and the ventricle. while PTU increased the levels in both chambers. Kv1.5 was significantly up-regulated by T3 in the atrium and the ventricle (P < 0.02 for both) and PTU decreased its expression in the ventricle (P < 0.02). Kv2.1 and Kv4.2 were not affected by T3 or PTU. mRNA of erg was not affected by T3 in the atrium but decreased in the ventricle (P < 0.01). After PTU, erg mRNA was decreased in the atrium (P < 0.02) but increased in the ventricle (P < 0.01). LQT1 was decreased by T3 in both chambers (P < 0.01) and not affected by PTU. minK was not detectable in the control state and was up-regulated only in the atrium: a peak on the 4th day followed by a decline to the undetectable level on the 10-15th days. During T3 treatment, nuclear T3-receptor-alpha1 and beta1 mRNA were decreased in the initial 3 days but returned to control levels thereafter. CONCLUSIONS: Between the atrium and ventricle of the adult rat heart, the responses of gene expression of voltage-gated potassium channels to T3 or PTU were quantitatively or qualitatively different and the differential responses may explain cardiac manifestations of hyperthyroidism, which is a frequent complication of supraventricular arrhythmia.

Animals↗
PubMed2002

Alpha1-syntrophin-deficient skeletal muscle exhibits hypertrophy and aberrant formation of neuromuscular junctions during regeneration.

Alpha1-syntrophin is a member of the family of dystrophin-associated proteins; it has been shown to recruit neuronal nitric oxide synthase and the water channel aquaporin-4 to the sarcolemma by its PSD-95/SAP-90, Discs-large, ZO-1 homologous domain. To examine the role of alpha1-syntrophin in muscle regeneration, we injected cardiotoxin into the tibialis anterior muscles of alpha1-syntrophin-null (alpha1syn-/-) mice. After the treatment, alpha1syn-/- muscles displayed remarkable hypertrophy and extensive fiber splitting compared with wild-type regenerating muscles, although the untreated muscles of the mutant mice showed no gross histological change. In the hypertrophied muscles of the mutant mice, the level of insulin-like growth factor-1 transcripts was highly elevated. Interestingly, in an early stage of the regeneration process, alpha1syn-/- mice showed remarkably deranged neuromuscular junctions (NMJs), accompanied by impaired ability to exercise. The contractile forces were reduced in alpha1syn-/- regenerating muscles. Our results suggest that the lack of alpha1-syntrophin might be responsible in part for the muscle hypertrophy, abnormal synapse formation at NMJs, and reduced force generation during regeneration of dystrophin-deficient muscle, all of which are typically observed in the early stages of Duchenne muscular dystrophy patients.

Animals↗