Biomedical subjects

Kiyoshi Nakazawa

Publications and source records attributed to Kiyoshi Nakazawa.

At least 19 recordsLinked to original sources

PubMed2006

Population pharmacokinetic and pharmacodynamic analysis of a class IC antiarrhythmic, pilsicainide, in patients with cardiac arrhythmias.

Population pharmacokinetics (PK) of a sodium channel-blocking antiarrhythmic, pilsicainide, was studied using the nonlinear mixed-effects modeling technique in 91 patients with cardiac arrhythmias (80 suspected Brugada syndrome [BrS] and 11 with atrial fibrillation) who received an intravenous infusion of 10 mg of the drug. Population pharmacodynamic (PD) analysis was also performed using an effect compartment model. PD responses were assessed by changes in electrocardiogram (ECG) pattern (BrS-like elevation of ST-segment) and conduction parameters. The final PK model showed that gender (values were 50% lower in women than in men) and creatinine clearance were significant (P < .01) covariates of weight-normalized systemic clearance of pilsicainide. Patients who showed a BrS-like ECG pattern after the drug administration also showed a significantly (P < .01) greater prolongation in His-Purkinje conduction compared to the remaining patients. In conclusion, female gender, renal dysfunction, and the drug-induced BrS-like ECG morphology may be associated with augmented ECG responses to pilsicainide.

Adult↗

PubMed2006

Molecular and electrophysiological differences in the L-type Ca2+ channel of the atrium and ventricle of rat hearts.

BACKGROUND: Many pathological conditions induce electrical remodeling, possibly through intracellular Ca2+ overload, but the currently available L-type Ca2+ channel blockers may be detrimental because of their global negative inotropic effects. METHODS AND RESULTS: To determine whether the L-type Ca2+ channel is identical throughout the heart, the distribution of the mRNAs and proteins comprising the L-type Ca2+ channel and its electrophysiological properties were analyzed in rat atria and ventricles. The mRNA of alpha2delta-2 (Cacna2d2) was more abundantly expressed in the atrium (approximately 5-fold) than in the ventricle. In contrast, alpha1C (Cacna1c) (Cav1.2) mRNA was significantly less abundant in the atrium. The level of the alpha1C (Cacna1c) (Cav1.2) protein was decreased (approximately 0.5-fold) and that of alpha2 delta-1 (Cacna2d1) was increased (approximately 2-fold) in the atrium compared with the ventricle. Although the peak ICa,L density showed no significant differences, voltage dependence of inactivation and activation of the current showed a more depolarized shift in the atrium than in the ventricle. CONCLUSION: These results indicate that in the rat heart the L-type Ca2+ channel differs between the atrium and ventricle with regard to gene expression and electrophysiological properties.

Animals↗

PubMed2006

Continuous administration of nicorandil decreases QT dispersion during the chronic phase of acute myocardial infarction.

We previously reported that continuous intravenous (IV) administration of nicorandil (NIC) inhibits QT dispersion (QTd). However, no prior study has evaluated the efficacy of NIC when administered orally to acute myocardial infarction (AMI) patients following continuous IV administration. Thirty patients with anteroseptal infarction in whom revascularization was performed successfully within 6 hours of AMI onset were included in the study and assigned to one of 3 groups: group A (continuous IV administration of NIC), group B (continuous IV and oral administration of NIC), and group C (no treatment with NIC). After 24 hours, QTd in groups A and B was significantly decreased compared to QTd in group C (P < 0.01) (group A, 58.1; group B, 58.2; and group C, 81.3). The QTd obtained 3 months later was significantly shorter in group B subjects who were orally administered NIC, and QTd before percutaneous coronary intervention (PCI) was restored in group A, in which no NIC had been administered orally [group A, 66.7; group B, 54.1; and group C, 73.9; P < 0.05 (group A versus group B) and P < 0.01 (group B versus group C)]. The effects were evaluated by comparing different routes of administration. Continuous IV and subsequent oral administration of NIC inhibited prolongation of QTd, suggesting that these effects may prevent the occurrence of cardiac events during both the acute and chronic phases of AMI.

Administration, Oral↗

PubMed2005

Tests of the homogeneous nucleation theory with molecular-dynamics simulations. I. Lennard-Jones molecules.

Two kinds of the homogeneous nucleation theory exist at the present: the classical nucleation theory and the semiphenomenological model. To test them, we performed molecular-dynamics (MD) simulations of nucleation from vapor to liquid with 5000-20,000 Lennard-Jones-type molecules. Simulations were done for various values of supersaturation ratios (from 2 to 10) and temperatures (from 80 to 120 K). We compared the size distribution of clusters in MD simulations with those in the theoretical models because the number density of critical clusters governs the nucleation rate. We found that the semiphenomenological model achieves excellent agreements in size distributions of the clusters with all MD simulations we done. The classical theory underestimates the number density of the clusters in the temperature range of 80-100 K, but overestimates in 100-120 K. The semiphenomenological model also predicts well the nucleation rate in MD simulations, while the classical nucleation theory does not. Our results confirmed the validity of the semiphenomenological model for Lennard-Jones-type molecules.

Journal Article↗

PubMed2005

Automated detection of Brugada-type electrocardiogram using diagnostic criteria of the European Society of Cardiology and the American Heart Association.

The diagnostic criteria of Brugada syndrome were reported from the European Society of Cardiology (ESC) and the American Heart Association in 2002. We examined the automated detection of Brugada-type electrocardiogram (ECG) on 12-lead ECG analysis program by modifying ESC criteria and evaluated it. In ESC criteria, Brugada-type ECG was classified into 3 types of ST-segment abnormalities of V1 to V3 leads. We modified these criteria and determined automated detection criteria as follows: type 1: STj>or=0.2 mV and STj>ST1>ST2 and T<0 mV; type 2: STj>or=0.2 mV and STj>STmin>or=0.1 mV and T>0 mV and T<1.8xR' and S or=0.2 mV and 0.1 mV>STmin>0 mV and T>0 mV and T<1.8xR' and S>or=3.0 mV; STj, ST1, and ST2 are amplitude of the ST segment (STj: J point, ST1: J point +40 milliseconds, ST2: J point +80 milliseconds). We evaluated these criteria with 97 ECGs from 27 patients, which are diagnosed as Brugada syndrome in university hospital. Brugada-type ECGs were detected correctly in 85 of total 97 ECGs (sensitivity, 88.7%, type 1: 32/32, type 2: 50/61, type 3: 4/4). As compared with 5 cardiologists interpretation of Brugada-type ECGs, computer classified incorrectly in 20 ECGs (type 1: 2, type 2: 17, type 3: 1) in 21,524 cases.

American Heart Association↗

PubMed2004

Clinical significance of electrocardiography recordings from a higher intercostal space for detection of the brugada sign.

BACKGROUND: The significance of higher intercostal space electrocardiography (HICS ECG) for the detection of the Brugada sign was investigated. METHODS AND RESULTS: The subjects consisted of 113 cases (108 males, 5 females; mean age, 57+/-17 years) with incomplete right bundle branch block type QRS morphology and ST-segment elevation (>0.10 mV) in the right precordial leads. Obvious structural heart disease was not observed in any of the subjects. The V(1-3) leads of the standard 12-lead ECG and the HICS ECG were recorded in the supine position, and the amplitude of the terminal portion of the QRS (J-point) and ST-segment (80 ms from the J-point) were measured. In the HICS ECG, there was an increase in the area in which the Brugada sign was detectable (47 leads to 66 leads), and in cases with the Brugada sign, the amplitude of the J-point increased. CONCLUSIONS: The HICS ECG may be helpful for the detection of the Brugada sign.

Adult↗

PubMed2004

Brugada syndrome-like ST-segment elevation increase exacerbated by vomiting.

The patient was a 53 year-old male who had 3 syncopal episodes over a 6-month period. In the electrophysiological study, ventricular fibrillation (VF) was repeatedly induced by the ventricular extrastimulus method. Intravenous pilsicainide was administered, and the J-point and ST-segment in the right precordial leads became slightly elevated just following drug administration. Five min later, the patient experienced severe nausea and then vomited twice, at which point the electrocardiogram (ECG) showed increased elevation of the J-point and ST-segment. These ECG changes recovered to normal 30 min later. The cause of his syncope was strongly suspected to be related to the VF associated with Brugada syndrome. An interesting aspect of this case was the particular type of J-point and ST-segment elevation that was induced when the patient experienced nausea and vomiting. It is proposed that this phenomenon originated from the vagal stimulation associated with the nausea and vomiting.

Acetylcholine↗

PubMed2004

New holter monitoring analysis system: a calculation of the lead vectors.

BACKGROUND: A new system of synthesizing a 12-lead electrocardiogram (Syn-ECG) with practically identical waveforms to the standard 12-lead ECG (Stn-ECG) from 3-channel ECGs recorded by Holter monitoring has been developed. METHODS AND RESULTS: The study group comprised 16 healthy individuals and 13 patients with abnormal ECGs. The bipolar eV1, eV5 and eVF leads were recorded using digital Holter monitoring and nine Syn-ECGs, corresponding to each lead of the Stn-ECG, were synthesized. The 9 ECGs consisted of a theoretical Syn-ECG and 8 Syn-ECGs positioned around the theoretical Syn-ECG at 3 cm intervals on the Frank's image surface. Of the 9 ECGs, the Syn-ECG with the maximum product of the cross-correlation coefficient of the QRS wave and that of the T wave, was automatically selected as the optimal Syn-ECG. The amplitude data from the QRS wave, R wave, T wave, and ST level, and also the amplitude ratio of the R wave, T wave to the QRS wave, were significantly well correlated between the Syn-ECG and Stn-ECG. CONCLUSIONS: A practically identical ECG morphology, comparable with a Stn-ECG, was successfully created using this system.

Adult↗

PubMed2004

Transvenous catheter cryoablation of the atrioventricular node and visual assessment of freezing of cardiac tissue using intracardiac echocardiography.

We investigated the use of a catheter-based cryoablation system on atrioventricular (AV) junction ablation in dogs. In five dogs, the cryoablation catheter was introduced to the AV junction area in order to create transient high degree or complete AV block. Cryo-freezing energy was applied by lowering the temperature to -75 degrees C for five minutes as a single cycle. This cycle was repeated until significant impairment of the AV conduction appeared. Transient high degree and complete AV block was obtained in all five dogs without any adverse effects. The iceball formation was identified by intracardiac echocardiography. Ablation of the AV junction is effective with several freeze-thaw cycles using a transvenous catheter cryoablation system.

Animals↗

PubMed2004

Efficacy of steroid therapy for pacing failure in a patient with chronic myocarditis.

A 66-year-old man had a progressive increase in the pacing threshold over a one-year period, resulting from chronic myocarditis. Following steroid therapy, the pacing threshold decreased and became stabilized, and was accompanied by a decrease in the serum creatine kinase, cardiac myosin light chains and pro-collagen III peptide values, but cardiac function did not improve. Endocardial biopsy showed that there was no progression in the fibrosis. The pacing failure improved, but the cardiac function did not. It was believed that the steroid therapy suppressed the progression of the inflammation and fibrosis caused by the chronic myocarditis.

Aged↗

PubMed2004

Left ventricular rupture associated with Takotsubo cardiomyopathy.

A 70-year-old woman was admitted to the hospital with chest discomfort after quarreling with her neighbors. Electrocardiography revealed ST-segment elevation in leads I, II, III, aVL, aVF, and V2 through V6. Coronary angiography demonstrated normal arteries, but left ventriculography showed apical akinesis and basal hyperkinesis. Takotsubo cardiomyopathy was diagnosed on the basis of these characteristic findings. The creatine kinase and creatine kinase-MB concentrations were elevated at admission and reached maximum levels 6 hours after admission. The plasma level of brain natriuretic peptide was 10.7 pg/mL (reference range, <18.4 pg/mL) on the first hospital day. ST-segment elevation in leads I, II, III, aVL, aVF, and V2 through V6 persisted at 72 hours after admission. On the third hospital day, sudden rupture of the left ventricle occurred, and despite extensive resuscitation efforts, the patient died. Takotsubo cardiomyopathy presents in a manner similar to that of acute myocardial infarction, but ventricular systolic function usually returns to normal within a few weeks. To our knowledge, this is the first reported case of fatal left ventricular rupture associated with takotsubo cardiomyopathy. We suggest that takotsubo cardiomyopathy may be a newly recognized cause of sudden cardiac death.

Aged↗

PubMed2004

123I-MIBG myocardial scintigraphy in patients with "takotsubo" cardiomyopathy.

UNLABELLED: The clinical characteristics of reversible left ventricular dysfunction due to "takotsubo" cardiomyopathy have been described, but the origin of this condition remains unclear. This study investigated (123)I-metaiodobenzlguanidine ((123)I-MIBG) myocardial scintigraphy in patients with takotsubo cardiomyopathy. METHODS: Eight consecutive patients with takotsubo cardiomyopathy were studied. Left ventricular wall motion was monitored by echocardiography until wall motion normalized. (123)I-MIBG myocardial scintigrams were performed within 3 d of admission (0 mo) and after the improvement of left ventricular dysfunction (3 mo). Early images were obtained at 30 min after radioisotope injection and delayed images were obtained after 4 h. The heart-to-mediastinum ratio (H/M ratio) and the washout rate were calculated. RESULTS: The mean left ventricular ejection fraction improved significantly (from 42.8% +/- 8.7% to 66.5% +/- 7.9%; P < 0.0001) and normalized after 19.4 +/- 5.4 hospital days. The early H/M ratio was significantly higher than the late ratio at 0 mo (2.16 +/- 0.25 vs. 1.89 +/- 0.24, respectively; P < 0.05), but not at 3 mo. The washout rate was significantly greater at 0 mo than at 3 mo (39.1% +/- 10.2% vs. 25.4% +/- 6.3%, respectively; P < 0.05). CONCLUSION: In patients with takotsubo cardiomyopathy, initial (123)I-MIBG myocardial scintigraphy depicted a unique pattern of ventricular asynergy and indicated the existence of cardiac sympathetic hyperactivity, although coronary blood flow was maintained. These findings strongly suggest that takotsubo cardiomyopathy could be caused by neurogenic myocardial stunning.

3-Iodobenzylguanidine↗

PubMed2003

Reversible ventricular dysfunction (takotsubo cardiomyopathy) following polymorphic ventricular tachycardia.

A 67-year-old female with recurrent syncope and no obvious heart disease developed ventricular dysfunction, known as takotsubo cardiomyopathy, following a 90 s episode of polymorphic ventricular tachycardia originating from a ventricular extrasystole with a short coupling interval. Cardiac catheterization performed 30 min after the arrhythmic event revealed angiographically normal coronary arteries, and left ventricular apical akinesis and basal hyperkinesis. An intracoronary injection of acetylcholine revealed no inducible coronary spasm, and an electrophysiological study revealed normal atrioventricular conduction and no inducible ventricular arrhythmia. Thirty hours after the arrhythmic event, electrocardiography revealed deeply inverted T waves in leads V3 to V6, I, and aVL, which continued for more than a week. Although no treatment was given to maintain hemodynamic stability, echocardiography revealed normal left ventricular contraction 14 days after the onset of the ventricular dysfunction. The reversible ventricular dysfunction might have been induced by altered catecholamine dynamics due to the persistent syncope during the occurrence of tachycardia.

Aged↗

PubMed2003

Influence of mobile magnetic resonance imaging on implanted pacemakers.

PURPOSE: Mobile magnetic resonance imaging (MRI) systems will be widely used in Japan. When traveling, mobile MRI generate alternating electromagnetic waves which may cause electromagnetic interference (EMI). This study was designed to determine whether this may influence the function of implanted pacemakers (PM). METHODS AND RESULTS: The influence of the static magnetic fields was tested in the first method using a PM-human model (Phantom). Magnetic force was simultaneously measured. The PM was switched to the magnet mode within 90 cm from the vehicle, where the magnetic force was = 2 mT. In the second method, six phantoms were placed on the side of the road, facing in three different directions in X-Y-Z axis orientations, at 1.3 m and 2.0 m above the ground. The mobile MRI passed by at a distance of 1 m from the phantoms at the speed of 20 or 40 km/h. In these experiments, magnet mode switch of the PM was observed for 2 seconds when the vehicle passed close to the phantoms, though no electrical noise was recorded. CONCLUSION: Mobile MRI vehicles can switch a PM to magnet mode when the distance between patient and vehicle is < 90 cm, regardless of whether the vehicle is moving or at a stop. Patients with implanted PM should not approach within < 1 m of a mobile MRI. No other EMI-induced PM dysfunction was detected.

Electromagnetic Fields↗

PubMed2003

Experimental study on the effectiveness and safety of radiofrequency catheter ablation with the cooled ablation system.

Experimental in vitro and in vivo studies were performed to assess the effectiveness and safety of the cooled-tip catheter and the Cooled Ablation System, which enables the creation of deeper and wider burn lesions in the myocardial tissue using radiofrequency current. This system was confirmed to consistently create large burns by cooling the catheter tip with circulating water within the catheter, even under unfavorable conditions. On the other hand, unfavorable effects, as a result of over burning, such as explosive vaporization within the tissue (the 'pop' phenomenon), tissue carbonization, coronary artery injury and lung injury were identified. 'Pop' was difficult to predict, but it is important to know how it can be avoided. No 'Pop' was seen without first observing an impedance decrease, thus it was considered safe to decrease the radiofrequency current if the impedance began to decrease. This system will be very effective for ablation of refractory arrhythmias, such as ventricular tachycardia or atrial flutter, but it is recommended that only experienced electrophysiologists use this system to avoid serious complications.

Animals↗

PubMed2003

Autonomic imbalance as a property of symptomatic Brugada syndrome.

The autonomic properties in 27 patients with the electrocardiographic morphology of Brugada syndrome were investigated using 24-h Holter monitoring: 10 patients had a history of ventricular fibrillation (VF; Br-VF group) and 17 did not (Br-N group); there were 26 healthy subjects enrolled in this study. All subjects underwent normal Holter data monitoring and power spectral analysis. Few extrasystoles were observed in either group, and the mean heart rate (HR), maximum HR, and total heart beats over 24 h were obtained. All of these measurements were significantly lower in the Br-VF group than in the Br-N and healthy subject groups. The RR interval variability was analyzed over 512 beats every 10 min. The high-frequency component (0.15-0.40 Hz; HF), low-frequency component (0.04-0.15 Hz; LF) and the LF/HF ratio were analyzed over 24 h. The HF was significantly higher and LF/HF ratio lower in the Br-VF group than in the healthy subjects. The HF was also significantly higher than in the Br-N group. During the night (00.00-05.00 h), the HF was significantly higher in the Br-VF group, and the LH/HF lower. During the day (12.00-17.00 h), the HF was significantly higher in the Br-VF group, but there was no difference in the LF/HF. These results indicate that high vagal tone and low sympathetic tone are specific properties of symptomatic Brugada syndrome.

Autonomic Nervous System Diseases↗

PubMed2003

Stimulation of glucose uptake in muscle cells by prolonged treatment with scriptide, a histone deacetylase inhibitor.

Glucose incorporation is regulated mainly by GLUT4 in skeletal muscles. Here we report that treatment of L6 myotubes with scriptide, a hydroxamic acid-based histone deacetylase (HDAC) inhibitor, stimulated 2-deoxyglucose uptake. The effect appeared only after 24 hr, resulting in 2.4-fold glucose uptake at treatment day 6. Scriptide acted synergistically with insulin, indicating it stimulated a distinct pathway from the insulin signaling pathway. It was not observed in undifferentiated myoblasts or 3T3-L1 adipocytes, suggesting a muscle-specific effect of scriptide. A five-carbon chain and hydroxamic acid, essential for histone deacetylase inhibition, were indispensable for this effect, and trichostatin A stimulated glucose uptake as well. Scriptide increased the cellular content of GLUT4, and induced GLUT4 translocation, but GLUT4 mRNA level did not change, indicating scriptide functions posttranslationally. Our results indicated a novel function for HDAC inhibitors of increasing GLUT4 content and its translocation in muscle cells, resulting in stimulation of glucose uptake.

3T3-L1 Cells↗

PubMed2003

Reversible ischemic neurological deficit (RIND) due to exercise testing for the diagnosis of angina pectoris.

A 57 year old Japanese male with chest oppression due to exercise is presented. This symptom was likely due to effort angina pectoris. Master's double two-step test revealed ischemic ST segment depression on the electrocardiogram, thus, a Tl201 myocardial stress imaging test using a bicycle ergometer was undertaken. Immediately following the exercise test, the patient experienced dizziness and palsy in his left upper and lower limbs. Cerebral angiography demonstrated 70% stenosis at the right internal carotid artery, but no abnormal findings were demonstrated on a cranial x-ray CT scan and magnetic resonance imaging. His palsy in the left limbs completely recovered within 3 weeks. Thus this event was diagnosed as a reversible ischemic neurological deficit (RIND). Major but non-cardiogenic complications during exercise testing are very rare, and RIND has not been reported thus far to the best of our knowledge.

Angina Pectoris↗