Publications by authors named "Yoshiyuki Hirayama"

13 Publications

  • Page 1 of 1

Noninvasive diagnosis of cardiac sarcoidosis using microvolt T-wave alternans.

Int Heart J 2009 Nov;50(6):731-9

Division of Cardiology, Department of Internal Medicine, Nippon Medical School, Tama Nagayama Hospital, Tama, Tokyo, Japan.

Sarcoidosis is a systemic granulomatous disorder whose prognosis worsens when the heart is involved, and early diagnosis is important. Endomyocardial biopsy is the most helpful diagnostic examination, but suffers from low sensitivity and low specificity. Microvolt T wave alternans (MVTWA) is utilized in noninvasive examinations to detect beat-to-beat changes in the shape of the T wave at the microvolt level. Such beat-to-beat T wave changes arise from beat-to-beat changes in the transmural gradient of action potential duration. We speculate that the granulomatous changes of cardiac sarcoidosis produce cell-to-cell uncoupling and augment the transmural gradients of action potential duration. To examine the clinical significance of MVTWA in the prediction of cardiac involvement in sarcoidosis patients, we obtained MVTWA in a total of 35 sarcoidosis patients with and without cardiac involvement. All patients underwent electrocardiography (ECG), ambulatory electrocardiography, chest radiography, transthoracic echocardiography, and MVTWA examination using a CH 2000 system. We diagnosed cardiac sarcoidosis in 7 patients according to the accepted diagnostic criteria. MVTWA was detected in 6 out of 7 cardiac sarcoidosis patients (85.7%) as opposed to in 2 out of 28 patients without cardiac involvement (7.1%). The difference between the two groups was statistically significant (P < 0.001). The sensitivity and specificity of MVTWA in cardiac sarcoidosis detection were 85.7% and 92.8%, respectively. The positive and negative predictive values were 75% and 96.3%, respectively, with an overall accuracy of 91.4%. Noninvasive examination of MVTWA using a CH 2000 is a useful diagnostic tool for detecting cardiac involvement in patients with sarcoidosis.
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http://dx.doi.org/10.1536/ihj.50.731DOI Listing
November 2009

lipopolysaccharide induces atrial arrhythmogenesis via down-regulation of L-type Ca2+ channel genes in rats.

Int Heart J 2009 May;50(3):353-63

Department of Internal Medicine, Division of Cardiology, Hepatology, Geriatrics and Integrated Medicine, Nippon Medical School, Tokyo, Japan.

Septic shock has been reported as an independent risk factor for atrial fibrillation (AF), however, the mechanism remains unknown. We investigated whether lipopolysaccharide (LPS) could alter cardiac ion channel gene expression, thereby leading to atrial arrhythmogenesis. LPS (2.5 mg/kg) was injected intraperitoneally into 10 week old Sprague-Dawley rats (n = 5). Hemodynamic data were obtained and the atrial appendages were removed after LPS injection (0, 3, 6, 12, and 24 hours) for an RNase protection assay for alpha1C, beta2, alpha1G, and SCN5A. An electrophysiological study in isolated perfused hearts was performed before and 12 hours after the LPS injection. Heart rate and body temperature were significantly increased (P < 0.05) and mean blood pressure was slightly decreased (P < 0.1) at 12 hours after LPS injection. The mRNA levels of the L-type calcium channel gene (beta2 and alpha1C) were significantly decreased at 6 and 12 hours after LPS injection. Atrial ERP became significantly shortened and the number of repetitive atrial responses induced by an extrastimulus were significantly increased after LPS injection. LPS induced the down-regulation of L-type calcium channel gene expression and ERP shortening, which might be a mechanism underlying sepsis-induced AF.
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http://dx.doi.org/10.1536/ihj.50.353DOI Listing
May 2009

Long-term effects of upstream therapy on paroxysmal atrial fibrillation in patients without overt heart diseases.

Int Heart J 2009 Mar;50(2):141-51

Department of Internal Medicine, Nippon Medical School, Japan.

Most paroxysmal atrial fibrillation (PAF) ultimately becomes chronic atrial fibrillation (CAF), even in the presence of antiarrhythmic drugs. Upstream therapies such as calcium channel blockers (CCB), angiotensin-converting enzyme inhibitors (ACEI), or statins have attracted attention for treating AF patients. We have previously reported that ACEI inhibited the progression of PAF to CAF. CCB and statins were also reported to inhibit the development of AF, but the follow-up periods in several of the papers appeared to be too short to allow a clear verdict on the antiarrhythmic effects. We therefore conducted a retrospective analysis of the relationship between long-term treatment (over 5 years) with an ACEI, CCB, or statin and outcome in patients with PAF (n = 125).The follow-up period was 7.7 +/- 3.1 years. Class I antiarrhythmic drugs were prescribed for 76.6% of the patients, ACEI for 36.0%, CCB for 47.2%, and statins for 20.0%. We assessed the cardiac rhythm from the medical records or electrocardiograms and determined the time from the first visit to the development of CAF. Kaplan-Meier analysis showed that the use of an ACEI significantly decreased the cumulative probability of CAF, while class I antiarrhythmics, CCB, and statins did not inhibit progression to CAF. Multivariate analysis showed that only ACEI was related to a reduced progression to CAF (odds ratio, 0.112; 95% confidence interval, 0.034 to 0.374, P = 0.001). Class I antiarrhythmic drugs, CCBs, and statins showed no such association.ACEI thus appear to be superior to CCB or statins with respect to upstream therapy.
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http://dx.doi.org/10.1536/ihj.50.141DOI Listing
March 2009

Osborn waves: history and significance.

Indian Pacing Electrophysiol J 2004 Jan 1;4(1):33-9. Epub 2004 Jan 1.

First Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1501063PMC
January 2004

ATP autocrine/paracrine signaling induces calcium oscillations and NFAT activation in human mesenchymal stem cells.

Cell Calcium 2006 Apr 30;39(4):313-24. Epub 2006 Jan 30.

Department of Cardiovascular Diseases, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Japan.

Human bone marrow-derived mesenchymal stem cells (hMSCs) have the potential to differentiate into several types of cells. Calcium ions (Ca(2+)) play an important role in the differentiation and proliferation of hMSCs. We have demonstrated that spontaneous [Ca(2+)](i) oscillations occur without agonist stimulation in hMSCs. However, the precise mechanism of its generation remains unclear. In this study, we investigated the mechanism and role of spontaneous [Ca(2+)](i) oscillations in hMSCs and found that IP(3)-induced Ca(2+) release is essential for spontaneous [Ca(2+)](i) oscillations. We also found that an ATP autocrine/paracrine signaling pathway is involved in the oscillations. In this pathway, an ATP is secreted via a hemi-gap-junction channel; it stimulates the P(2)Y(1) receptors, resulting in the activation of PLC-beta to produce IP(3). We were able to pharmacologically block this pathway, and thereby to completely halt the [Ca(2+)](i) oscillations. Furthermore, we found that [Ca(2+)](i) oscillations were associated with NFAT translocation into the nucleus in undifferentiated hMSCs. Once the ATP autocrine/paracrine signaling pathway was blocked, it was not possible to detect the nuclear translocation of NFAT, indicating that the activation of NFAT is closely linked to [Ca(2+)](i) oscillations. As the hMSCs differentiated to adipocytes, the [Ca(2+)](i) oscillations disappeared and the translocation of NFAT ceased. These results provide new insight into the molecular and physiological mechanism of [Ca(2+)](i) oscillations in undifferentiated hMSCs.
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http://dx.doi.org/10.1016/j.ceca.2005.11.008DOI Listing
April 2006

Inhibition of the reverse mode of the Na+/Ca2+ exchange by KB-R7943 augments arrhythmogenicity in the canine heart during rapid heart rates.

J Electrocardiol 2005 Jul;38(3):218-25

The First Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.

To test the hypothesis that the reverse mode of the Na+/Ca2+ exchange augmented by a rapid heart rate has an antiarrhythmic effect by shortening the action potential duration, we examined the effects of KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl] isothiourea methanesulfonate), a selective inhibitor of the reverse mode of the Na+/Ca2+ exchange, to attenuate this effect. We recorded the electrocardiogram, monophasic action potential (MAP), and left ventricular pressure in canine beating hearts. In comparison to the control, KB-R7943 significantly increased the QTc value and MAP duration. MAP alternans and left ventricular pressure alternans were observed after changing the cycle length to 300 milliseconds in the control studies. KB-R7943 magnified both types of alternans and produced spatially discordant alternans between right and left ventricles. Early after-depolarizations and nonsustained ventricular tachycardia occurred in the presence of KB-R7943. Our data suggest that the reverse mode of the Na+/Ca2+ exchange may contribute to suppression of arrhythmias by abbreviating action potential duration under pathophysiological conditions. This conclusion is based on further confirmation by future studies of the specificity of KB-R7943 for block of the reverse mode of the Na+/Ca2+ exchange.
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http://dx.doi.org/10.1016/j.jelectrocard.2004.12.001DOI Listing
July 2005

Angiotensin-converting enzyme inhibitor therapy inhibits the progression from paroxysmal atrial fibrillation to chronic atrial fibrillation.

Circ J 2005 Jun;69(6):671-6

First Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.

Background: Atrial fibrillation is a progressive disease, which in the paroxysmal form (PAF) becomes more frequent and finally becomes chronic (CAF). A retrospective analysis of patients with PAF was conducted to examine the hypothesis that angiotensin-converting enzyme inhibitors (ACEI) will prevent the progression to CAF.

Methods And Results: On the basis of their treatment, 95 patients with PAF were divided into 2 groups: 42 patients treated with ACEI for hypertension throughout the period of treatment and follow-up (ACEI group) and 53 patients not given ACEI (non-ACEI group). Cardiac rhythms were assessed either from the medical records or the electrocardiograms recorded every 2-4 weeks at follow-up visits. The mean follow-up time was 8.3+/-3.5 years. There was no significant difference in the use of antiarrhythmic drugs, left atrial diameter or left ventricular ejection fraction between the 2 groups. The Kaplan-Meier curve for the time to occurrence of CAF showed a lower incidence of CAF in the ACEI group and demonstrated that the 5-year probability for persistence of PAF without progression to CAF was 88.3%, but 47.5% in the non-ACEI group.

Conclusions: These results indicate that ACEI will prevent progression from PAF to CAF.
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http://dx.doi.org/10.1253/circj.69.671DOI Listing
June 2005

Na+/K+ ATPase and its functional coupling with Na+/Ca2+ exchanger in mouse embryonic stem cells during differentiation into cardiomyocytes.

Cell Calcium 2005 Feb;37(2):137-51

Department of Cardiovascular Diseases, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.

Cardiomyocytes derived from mouse embryonic stem (mES) cells have been demonstrated to exhibit a time-dependent expression of ion channels and signal transduction pathways in electrophysiological studies. However, ion transporters, such as Na+/K+ ATPase (Na+ pump) or Na+/Ca2+ exchanger, which play crucial roles for cardiac function, have not been well studied in this system. In this study, we investigated the functional expression of Na+/K+ ATPase and Na+/Ca2+ exchanger in mES cells during in vitro differentiation into cardiomyocytes, as well as the functional coupling between the two transporters. By measuring [Na+]i and Na+ pump current (Ip), it was shown that an ouabain-high sensitive Na+/K+ ATPase was expressed functionally in undifferentiated mES cells and these activities increased during a time course of differentiation. Using RT-PCR, the expression of mRNA for alpha1-subunit and alpha3-subunit of the Na+/K+ ATPase could be detected in both undifferentiated mES cells and derived cardiomyocytes. In contrast alpha2-subunit mRNA could be detected only in derived cardiomyocytes but not in undifferentiated mES cells. mRNA for the Na+/Ca2+ exchanger 1 isoform (NCX1) could be detected in undifferentiated mES cells and its expression levels seemed to gradually increase throughout the differentiation accompanied by increasing its Ca2+ extrusion function. At the middle stages of differentiation (after 10-day induction), more than 75% derived cardiomyocytes exhibited [Ca2+]i oscillations by blocking of Na+/K+ ATPase, suggesting the functional coupling with Na+/Ca2+ exchanger. From these results and RT-PCR analysis, we conclude that alpha2-subunit Na+/K+ ATPase mainly contributes to establish the functional coupling with NCX1 at the middle stages of differentiation of cardiomyocytes.
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http://dx.doi.org/10.1016/j.ceca.2004.08.004DOI Listing
February 2005

Functional expression of Ca2+ signaling pathways in mouse embryonic stem cells.

Cell Calcium 2004 Aug;36(2):135-46

Department of Cardiovascular Diseases, Medical Research Institute, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Japan.

Mouse embryonic stem (mES) cells have the potential to differentiate into all types of cells, but the physiological properties of undifferentiated mES cells, including Ca2+ signaling systems, are not fully understood. In this study, we investigated Ca2+ signaling pathways in mES cells by using confocal Ca2+ imaging systems, patch clamp techniques and RT-PCR. The stimulations with ATP and histamine (His) induced a transient increase of intracellular Ca2+ concentration ([Ca2+]i), which were prevented by the pretreatment of 2-amino-ethoxydiphenyl borate (2-APB), a blocker for inositol-1,4,5-triphosphate receptors (InsP3Rs). The application of caffeine (Caff) or ryanodine (Ry) did not change [Ca2+]i. When stores were depleted with Ca2+ -ATPase blocker, thapsigargin (TG), or histamine, the capacitative Ca2+ entry (CCE) was observed. In whole cell patch clamp mode, store-operated Ca2+ currents could be recorded in cells treated with histamine and thapsigargin. On the other hand, voltage-operated Ca2+ channels (VOCCs) could not be elicited. The application of blockers for plasma membrane Ca2+ pump (PMCAs) (carboxeosin or caloxin2A1) induced a large increase of [Ca2+]i. When the Na+/Ca2+ exchangers (NCXs) were blocked by Na+ free solution or KBR7943, [Ca2+]i was also elevated. Using RT-PCR, mRNAs for InsP3Rs type-1, -2, and -3, PMCA-1 and -4, NCX-1, -2, and -3 could be detected. From these results, we conclude that Ca2+ release from ER is mediated by InsP3Rs in mES cells before differentiation and Ca2+ entry through plasma membrane is mainly mediated by the store-operated Ca2+ channels (SOCs). For the Ca2+ extrusion systems, both NCXs and PMCAs play important roles for maintaining the low level of [Ca2+]i.
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http://dx.doi.org/10.1016/j.ceca.2004.01.022DOI Listing
August 2004

Angiotensin-converting enzyme inhibitors are not effective at inhibiting further fibrous changes in the atria in patients with chronic atrial fibrillation: speculation from analysis of the time course of fibrillary wave amplitudes.

Jpn Heart J 2004 Jan;45(1):93-101

First Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.

To examine whether angiotensin-converting enzyme (ACE) inhibitors are effective at inhibiting further fibrous changes in atria in patients with chronic atrial fibrillation, we retrospectively evaluated the time course of fibrillatory wave amplitudes and the effects of an ACE inhibitor on the changes. We reviewed medical records and electrocardiographic files. The patients were eligible for inclusion if they had chronic atrial fibrillation for more than 10 years. The fibrillatory wave with the greatest amplitude was measured in lead V1 of standard electrocardiograms. A total of 31 patients were enrolled and were divided into two groups according to treatment. Twelve patients were classified as the ACE inhibitor group and 19 as the non-ACE inhibitor group. There was no significant difference in the mean value of the fibrillatory wave amplitude at baseline between the 2 groups (ACE inhibitor group, 0.23 +/- 0.02 mV; non-ACE inhibitor group, 0.18 +/- 0.02 mV). The fibrillatory wave amplitude decreased significantly after 10 years in both groups (ACE inhibitor group, 0.10 +/- 0.02 mV; non-ACE inhibitor group, 0.11 +/- 0.01 mV) and the changes in the fibrillatory wave amplitude were similar between the 2 groups. These results suggest that ACE inhibitors are not effective at inhibiting further fibrous changes in atria in patients with chronic atrial fibrillation.
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http://dx.doi.org/10.1536/jhj.45.93DOI Listing
January 2004

Possible contribution of the sarcoplasmic reticulum Ca(2+) pump function to electrical and mechanical alternans.

J Electrocardiol 2003 Apr;36(2):125-35

First Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.

We investigated the role of the sarcoplasmic reticulum's (SR) Ca(2+) pump function of the in the mechanism of alternans. We recorded the surface ECG, monophasic action potential (MAP) and left ventricular pressure (LVP) in the canine beating heart. Alternans was induced with an abrupt shortening of the cycle length from 1000 to 350 ms. After the control studies, we administered propranolol or isoproterenol. In the presence of propranolol, we administered milrinone or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). In the presence of isoproterenol, we administered thapsigargin. Isoproterenol and milrinone attenuated both the electrical and mechanical alternans. Thapsigargin, a specific SR Ca(2+) pump inhibitor, and propranolol magnified both types of alternans. DIDS, a Ca(2+)-activated Cl(-) current (I(Cl(Ca))) inhibitor, attenuated the MAP alternans without an affect on the LVP alternans. Thus, the delayed intracellular Ca(2+) cycling caused by the impaired SR Ca(2+) pump function might produce electrical and mechanical alternans. beta-adrenergic stimulation eliminated these alternans. The I(Cl(Ca)) contributed to the appearance of the electrical alternans.
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http://dx.doi.org/10.1054/jelc.2003.50021DOI Listing
April 2003

Calcium-activated CL- current is enhanced by acidosis and contributes to the shortening of action potential duration in rabbit ventricular myocytes.

Jpn J Physiol 2002 Jun;52(3):293-300

Department of Cardiovascular Diseases, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, 113-8510 Japan.

Ca2+-activated Cl- current (I(Cl(Ca))) is activated by Ca2+ transient via Ca2+-induced Ca2+ release from sarcoplasmic reticulum in cardiac myocytes and is supposed to play an important role in the repolarization of action potential. It is not well understood, however, how I(Cl(Ca)) is modulated to affect action potential in normal or pathological conditions. In this study we examined the effects of external acidosis on I(Cl(Ca)) and action potential. A whole-cell patch clamp was performed to record action potential and I(Cl(Ca)), using isolated rabbit ventricular myocytes. In the standard solution at pH 7.4, action potential duration (APD) was markedly prolonged by lowering the extracellular Cl- concentration ([Cl-](o)) or by applying an anion channel blocker, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). In the low pH solution at 6.4, APD was markedly shortened and the amplitude of I(Cl(Ca)) was increased at all membrane potentials. At pH 6.4, the apparent steady-state inactivation curves of I(Cl(Ca)) were shifted to more positive potentials compared with those at pH 7.4, but no change in inactivation occurred at a holding potential of -60 mV. The apparent activation curves were not changed between the two sets of conditions. When I(Cl(Ca)) was inhibited at low pH, early afterdepolarizations and triggered activities were induced. The amplitude of I(Cl(Ca)) was suggested to be enhanced by the external acidosis, which may have prevented the induction of early afterdepolarization or triggered activity.
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http://dx.doi.org/10.2170/jjphysiol.52.293DOI Listing
June 2002

Systemic lupus erythematosus related transverse myelitis presenting longitudinal involvement of the spinal cord.

Intern Med 2002 Feb;41(2):156-60

First Department of Internal Medicine, Nippon Medical School, Tokyo.

Lupus-related transverse myelitis is a rare but serious complication. A 25-year-old Japanese woman with systemic lupus erythematosus (SLE) was admitted because of numbness of the face and left upper extremity, headache, and intermittent fever. Six days later, she developed tetraplegia. MRI of the spinal cord showed longitudinal high intensity signals from medulla oblongata to C5, and from Th12 to conus medullaris on T2-weighted image. These MRI findings were consistent with acute catastrophic neurological abnormalities. Despite administration of the combination of methylprednisolone and cyclophosphamide pulse therapies, as well as plasmapheresis, her condition did not improve. Any vasculopathy in addition to the autoimmune pathogenesis, and narrow therapeutic window may relate to the present refractory case.
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http://dx.doi.org/10.2169/internalmedicine.41.156DOI Listing
February 2002