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Biomedical subjects

Yoshikazu Kaji

Publications and source records attributed to Yoshikazu Kaji.

At least 19 recordsLinked to original sources

Purified human hematopoietic stem cells contribute to the generation of cardiomyocytes through cell fusion.

To obtain insights into the cardiomyogenic potential of hematopoietic tissue, we intravenously (i.v.) injected purified hematopoietic stem/progenitor cells into newborn recipients that may fully potentiate the developmental plasticity of stem cells. Transplantation of mouse bone marrow (BM) lineage antigen-negative (Lin-) cells resulted in the generation of the cells that displayed cardiomyocyte-specific antigenic profiles and contractile function when transplanted into syngeneic newborn recipients. To clarify the mechanism underlying the cardiomyogenic potential, green fluorescent protein (GFP)-labeled BM Lin-ScaI+ hematopoietic progenitors were transplanted into neonatal mice constitutively expressing cyan fluorescence protein (CFP). Lambda image acquisition and linear unmixing analysis using confocal microscopy successfully separated GFP and CFP, and revealed that donor GFP+ cardiomyocytes coexpressed host-derived CFP. We further reconstituted human hemopoietic- and immune systems in mice by injecting human cord blood (CB)-derived Lin-CD34+CD38- hematopoietic stem cells (HSCs) into neonatal T cell(-)B cell(-)NK cell- immune-deficient NOD/SCID/IL2rgamma(null) mice. Fluoroescence in situ hybridization analysis of recipient cardiac tissues demonstrated that human and murine chromosomes were colocalized in the same cardiomyocytes, indicating that cell fusion occurred between human hematopoietic progeny and mouse cardiomyocytes. These syngeneic- and xenogeneic neonatal transplantations provide compelling evidence that hematopoietic stem/progenitor cells contribute to the postnatal generation of cardiomyocytes through cell fusion, not through transdifferentiation.

Animals↗

Effects of ultrasound energy application on cardiac performance in open-chest Guinea pigs.

BACKGROUND: Although ultrasound (US) is widely used in cardiology, little is known about the effects of US energy on cardiac performance. This study aimed to investigate the mechanical effects of high-intensity continuous US energy (1.0 MHz with 3 different intensities) on cardiac performance. METHODS AND RESULTS: Either left ventricular (LV) pressure or aortic blood flow (ABF) was evaluated in open-chest guinea pigs (n=30) under surface ECG monitoring. LV systolic pressure and ABF increased significantly (ie, maximum percent increases in these parameters were 2.5%, 3.1% and 7.1% for LV systolic pressure and 9.4%, 4.9% and 8.8% for mean ABF at intensities of 0.06, 0.67 and 2.90 W/cm2, respectively). LV end-diastolic pressure was reduced significantly by US (5.3+/-0.9 to 4.8+/-0.8, 5.5 +/-1.3 to 4.8+/-1.0 and 5.8+/-2.0 to 5.0+/-1.2 mmHg, respectively), indicating positive inotropic and lusitropic effects and resultant ABF augmentation. Local temperature was not significantly changed. ECG showed neither chronotropic action nor arrhythmogenesis. CONCLUSIONS: Although the basic mechanisms of these phenomena remain unclear, this pilot study of the short-term effects of US energy on cardiac performance suggests the possibility of physical therapy for heart failure.

Animals↗

Successful treatment of tachycardia-induced cardiomyopathy with LVAD in a 12-year-old boy.

Tachycardia-induced cardiomyopathy is an unusual cardiac disease that is life-threatening if tachycardia is not controlled. We report a 12-year-old boy who suffered from ectopic left atrial tachyarrhythmia that was refractory to medications and caused tachycardia-induced cardiomyopathy with severe heart failure. The patient required a left ventricular assist device (ABIOMED BVS5000 [ABIOMED Inc, Danvers, MA]) as a bridge to recovery. Tachycardia was finally controlled with flecainide while the patient was on left ventricular assist device support. The device was successfully explanted after 28 days of support. The temporary use of a left ventricular assist device was necessary to maintain a good hemodynamic status during the treatment of pharmacological refractory tachycardia, and it allowed a successful bridge to recovery.

Anti-Arrhythmia Agents↗

Influence of interferon therapy on signal-averaged and ambulatory electrocardiograms in patients with chronic active hepatitis.

Although interferon (IFN) shows cardiotoxicity and arrhythmogenesis, the influence of IFN on signal-averaged electrocardiography remains to be clarified. The aim of this study was to test a clinical hypothesis that IFN therapy for hepatitis C virus may induce ventricular late potentials (LPs) and related arrhythmias in patients with chronic active hepatitis. Signal-averaged and ambulatory electrocardiograms were recorded sequentially in patients with chronic active hepatitis C (n = 22) throughout the entire period of IFN therapy. The filtered QRS duration (fQRS) and low amplitude (< 40 microV) signal duration (LAS40) were significantly increased (95.5 +/- 8.5 to 99.6 +/- 9.4 msec, P < 0.0001, and 32.8 +/- 3.1 to 36.3 +/- 3.0 msec, P < 0.0001, respectively), whereas the root mean square voltage in the terminal 40 msec of the fQRS (RMS40) was significantly decreased (25.5 +/- 5.4 to 22.3 +/- 5.2 microV, P < 0.005) 1 month after starting the IFN therapy. The ventricular LP was negative in all subjects before starting therapy, but became positive in 7 patients after the therapy commenced. There were no differences in clinical baseline characteristics between the LP-positive (n = 7) and LP-negative (n = 15) groups. Significant increases in mean heart rate, fQRS, and LAS40 were observed after starting the therapy, irrespective of the appearance of the ventricular LP, whereas a decrease in RMS40 was observed only in the LP-positive group. No sustained ventricular arrhythmias were documented in the ambulatory electrocardiography and no cardiac events were encountered in the follow-up period. Therefore, the results indicate a reversible and subclinical risk of IFN-induced arrhythmogenesis.

Adult↗

A unipolar coronary sinus mapping study of patients with left-sided atrioventricular accessory pathways.

So-called unipolar 'PQS pattern' is widely accepted as a hallmark of successful catheter ablation of the left-sided atrioventricular accessory pathway. However, the unipolar nature of the electrogram and the site-dependent appearance of this characteristic pattern are poorly understood. Therefore, unipolar coronary sinus (CS) mapping was performed using a multipolar fine electrode in patients with Wolff-Parkinson-White (WPW) syndrome associated with an antegrade left-sided accessory pathway (case group) and those with a concealed left-sided accessory pathway or atrioventricular nodal reentrant tachycardia (control group) under sinus rhythm and fixed high right atrial, CS ostial, and distal pacing. In both groups, the unipolar CS atrial electrogram showed intrinsic negative deflection (initial positive followed by negative parts) with considerable variation depending on the recording site. This unipolar configuration of the atrial electrogram was not influenced by different activation sequences during pacing at various sites. The case group exhibited a unipolar 'PQS pattern' at successful ablation sites for the left lateral to anterolateral accessory pathway. However, this was not true for the left posteroseptal accessory pathway, possibly because the negative part of the atrial electrogram distorted the 'PQS pattern' as an intervening dip. In conclusion, the site-dependent variations of the unipolar CS atrial electrogram underlie the limited usefulness of the 'PQS pattern' in left posteroseptal accessory pathway localization.

Adolescent↗

[A case of metabolic syndrome with coronary artery disease advanced over 13 years. Case report].

A 61-year-old man was diagnosed with obesity, diabetes mellitus, and hyperlipidemia associated with insulin resistance in 1988. His condition was complicated with asymptomatic coronary artery disease in 1992. His coronary artery disease gradually progressed during the subsequent 13 years of observation, and he underwent percutaneous coronary intervention four times and also received a coronary artery bypass graft. This is a case of metabolic syndrome with multiple risk factors for arteriosclerosis as visceral obesity, insulin resistance, diabetes, hypertension and hyperlipidemia, in which the recent rapid progression of coronary artery disease might be associated with the discontinuation of statin after coronary artery bypass graft, accompanied with hyper-LDL-choleterolemia. Patients with metabolic syndrome require most comprehensive and strict therapies against multiple risk factors.

Coronary Disease↗

Recurrence of cervical carcinoma manifesting as cardiac metastasis three years after curative resection.

We report a rare case of cardiac metastasis from carcinoma of the uterine cervix. A 58-year-old woman presented with multiple pulmonary emboli, disseminated intravascular coagulation, and right heart failure 43 months after a curative resection of cervical carcinoma (stage IB1). Transthoracic echocardiography and computed tomography revealed large tumors in the right ventricle and right main pulmonary artery. No evidence of recurrence was obtained in the pelvis and abdomen. Surgical removal of the tumors remarkably improved her general condition, which had been declining progressively. The patient declined further treatment, including adjuvant chemotherapy, and was followed in the outpatient clinic. The right ventricular tumor recurred 4 months later and she died of heart failure. The possibility of late recurrence of cervical carcinoma in the heart should be considered even after curative resection.

Female↗

Verapamil prevents impairment in filterability of human erythrocytes exposed to oxidative stress.

Effects of oxidative stress on intact human erythrocytes were investigated using tert-butyl hydroperoxide (tBHP). Exposure of erythrocytes to tBHP caused a marked decrease in filterability in a time-dependent manner. Erythrocytes exposed to tBHP also show an increase in mean corpuscular volume and a remarkable formation of methemoglobin (met-Hb) without any appearance of hemichromes that form Heinz bodies. High performance liquid chromatography demonstrated that the tBHP-treated erythrocytes exhibited an apparent decrease in the membrane phospholipid, phosphatidylethanolamine (PE). The decrease in PE was inhibited by pretreatment with ascorbate, but not with verapamil. SDS-polyacrylamide gel electrophoresis of the tBHP-treated erythrocyte membrane showed a degradation of spectrin, band 3, band 4.2, and band 4.5, accompanied by the appearance of low-molecular-weight products. The degradation of the membrane proteins was not prevented by pretreatment with verapamil or ascorbate. However, the pretreatment with verapamil but not with ascorbate revealed significant inhibition of the tBHP-induced impairment in filterability in the presence of extracellular Ca2+. Thus, the present study shows that verapamil, a potent drug in reperfusion therapy, plays an important role in protection against oxidative injury, based on a close linkage among decreased filterability, met-Hb formation, and impaired membrane integrity.

Calcium Channel Blockers↗

Extracellular potassium dependent negative dromotropic action of nicorandil in guinea pig myocardium.

Although the antiarrhythmic action of nicorandil is drawing an increasing attention, dromotropic effect of this agent is unclear. Therefore, this was investigated by microelectrode technique to the superfused guinea pig papillary muscle to record the action potential and extracellular potential during conduction. The correlation of myocardial internal longitudinal resistance (r1) assumed to reflect the global gap junctional resistance, maximum rate of rise of the action potential upstroke (Vmax), and conduction velocity was examined under the alterations of external potassium concentrations ([K+]e; ranging from 3.0 to 12.0 mM) in the presence or absence of 100 microM nicorandil. In the minimum [K+]e, nicorandil caused significant (p < 0.05) hyperpolarization and reduction in Vmax. Negative dromotropic action of nicorandil was slight but significant (p < 0.05) in low (3.0 mM) [K+]e but was not evident in physiologic (5.4 mM) or elevated (9.0 to 12.0 mM)[K+]e. In conclusion, nicorandil exerts negative dromotropic action as [K+]e decreased, which was accounted for by the cable analysis and may contribute to the prevention of low [K+]e-induced arrhythmia.

Animals↗

Bezold-Jarisch-like reflex during Brockenbrough's procedure for radiofrequency catheter ablation of focal left atrial fibrillation: report of two cases.

Brockenbrough's puncture technique has been widely conducted in the electrophysiologic laboratory. We report here two cases exhibiting a rare complication of this procedure, which arose during the conduct of catheter ablation using radiofrequency energy delivered to the pulmonary vein for the treatment of focal left atrial fibrillation. These cases exhibited marked sinus bradycardia and profound hypotension, suggestive of a Bezold-Jarisch-like reflex, observed immediately after Brockenbrough's procedure but before radiofrequency application. ST elevation in the inferior leads was also observed in spite of normal coronary angiograms. This unanticipated transient complication was treated by intravenous administration of atropine, which had no influence on the ablation procedure or prognosis. This is speculated to be attributable to the elevation of vagal tone caused by the mechanical effects of transseptal puncture on the interatrial vagal network.

Adult↗

Reentrant atrial tachycardia originating from the superior vena cava.

A 52-years old man with a previous pericardiotomy for idiopathic constrictive pericarditis underwent catheter ablation for drug-resistant atrial tachycardia (AT). The mechanism of the AT was considered as reentry because of resetting response and the entrainment phenomenon during AT. We introduced a 64-electrode basket catheter into the superior vena cava (SVC) during AT to obtain precise mapping. A fractionated potential preceding local atrial electrogram was recorded in the SVC. The earliest activation site of the potential was located at the anterior aspect of the SVC, 2 cm above the SVC-right atrium junction determined fluoroscopically. The fractionated potential at this site preceded the onset of the P wave by 115 msec. Radiofrequency catheter ablation at this site eliminated the tachycardia. At 6 months follow-up, the patient is free of AT. Reentrant AT involving the SVC is a candidate of RF ablation. Multielectrode basket catheter is useful for a detailed mapping of the SVC.

Catheter Ablation↗

High-cholesterol diets induce changes in lipid composition of rat erythrocyte membrane including decrease in cholesterol, increase in alpha-tocopherol and changes in fatty acids of phospholipids.

Effects of high dietary cholesterol on erythrocyte membrane lipids were studied. Feeding rats with a diet containing 0.5% cholesterol and 0.15% sodium cholate for two weeks induced changes in erythrocyte membrane lipids including a decrease in cholesterol, an increase in alpha-tocopherol (alpha-Toc) and changes in the fatty acid composition of phospholipids. Oleic acid and linoleic acid increased, while arachidonic acid decreased in phosphatidylcholine. Saturated fatty acids decreased and unsaturated fatty acids increased in phosphatidylethanolamine. Almost the same changes in membrane lipids were also noted after six weeks of feeding rats with the diet. A diet containing 0.5% cholesterol but without sodium cholate caused a decrease in erythrocyte cholesterol and an increase in erythrocyte alpha-Toc after two weeks of feeding, as compared to the basal diet, indicating that high dietary cholesterol, but not sodium cholate, was responsible for these changes in the erythrocyte membrane.

Animals↗

Surgical resection of malignant lymphoma in the right atrium after systemic chemotherapy.

A 74-year-old man was referred to us for evaluation of a tumor in the right atrium (RA). Transesophageal echocardiography (TEE) showed an unmovable 50x60 mm mass in the RA. Based on histological findings of subcutaneous tumors in the right abdominal wall, he was diagnosed as malignant lymphoma (ML), and treated with a THP-COP regimen. Upon completion of first THO-COP therapy, TEE showed marked regression of the mass and division into 3 masses, one of which showed marked floating movement with a small stalk. To prevent the risk of embolic events, surgical resection was performed. Resected tumors were necrotic tissues. Serial imaging of cardiac tumor and surgical resection is desirable to decrease the possibility of embolic complication.

Aged↗

Overexpression of Polycomb-group gene rae28 in cardiomyocytes does not complement abnormal cardiac morphogenesis in mice lacking rae28 but causes dilated cardiomyopathy.

The Polycomb-group genes (PcG) are widely conserved from Drosophila to mammals and are required for maintaining positional information during development. The rae28 gene (rae28) is a member of the mouse PcG. Mice deficient in rae28 (rae28(-/-)) demonstrated that rae28 has a role not only in anteroposterior patterning but also in cardiac morphogenesis. In this study we generated transgenic mice with ubiquitous or cardiomyocyte-specific exogenous rae28 expression. Genetic complementation experiments with these transgenic mice showed that ubiquitous expression of rae28 could reverse the cardiac anomalies in rae28(-/-), whereas cardiomyocyte-specific expression of rae28 could not, suggesting that rae28 is involved in cardiac morphogenesis through a noncardiomyocyte pathway. Interestingly, however, cardiomyocyte-specific overexpression of rae28 caused dilated cardiomyopathy, which was associated with cardiomyocyte apoptosis, abnormal myofibrils, and severe heart failure. Cardiac expression of rae28 was predominant in the early embryonic stage, whereas that of the other PcG members was relatively constitutive. Because rae28 forms multimeric complexes with other PcG proteins in the nucleus, it is presumed that constitutive cardiomyocyte-specific rae28 overexpression impaired authentic PcG functions in the heart. rae28-induced dilated cardiomyopathy may thus provide a clue for clarifying the direct role of PcG in the maintenance of cardiomyocytes.

Animals↗

The Polycomb-group gene Rae28 sustains Nkx2.5/Csx expression and is essential for cardiac morphogenesis.

The Polycomb-group (PcG) gene Rae28 is a mammalian homologue of the Drosophila gene polyhomeotic. PcG genes are known to maintain transcription states, once initiated, probably by regulating chromatin structure. Since homozygous Rae28-deficient (Rae28(-/-)) mice displayed cardiac anomalies similar to congenital heart diseases in humans, we examined the role of Rae28 in cardiac morphogenesis at the molecular level. In Rae28(-/-) embryos, expression of the cardiac selector gene Nkx2.5/Csx (Nkx2.5) was initiated properly but was not sufficiently sustained later in development. This impaired expression of Nkx2.5 in the maintenance phase proved to have a crucial effect on cardiac morphogenesis, as demonstrated by the results of a genetic complementation experiment in which the cardiac anomalies were suppressed by overexpression of human NKX2.5/CSX1 in Rae28(-/-) embryos. Ubiquitous expression of exogenous Rae28 likewise restored the impaired Nkx2.5 expression in Rae28(-/-) embryos, further supporting the notion that Rae28 sustains Nkx2.5 expression in cardiomyocytes. Thus, our data show that a mammalian PcG gene can play a key role in organogenesis by helping to maintain the expression of a selector gene.

Animals↗

Arrhythmogenic and inotropic effects of interferon investigated in perfused and in vivo rat hearts: influences of cardiac hypertrophy and isoproterenol.

Although the arrhythmogenic effects of interferon (IF) have been reported in clinical practice, the experimental data are limited. Therefore, these effects were investigated in in vivo and Langendorff-perfusion studies using 3 different groups of rats (ie, control, aorta-banded, and deoxycorticosterone acetate (DOCA)-salt hypertension groups) in the presence or absence of isoproterenol. In the perfusion study, human recombinant IF-alpha (< or =15,000 U/ml) alone induced irreversible atrioventricular blockade in all groups, whereas this agent (< or =1,500 U/ml) caused negative inotropism and ventricular tachyarrhythmias (arrhythmic score greater in the order of DOCA-salt>aorta-banded = control group) in the preparations pretreated with isoproterenol (10(-9) mol/L). In an in vivo study, IF-alpha (6x10(6) U/kg) resulted in ventricular tachyarrhythmias only in the presence of isoproterenol (10 mg/kg), as in the perfusion study (arrhythmic score; DOCA-salt>aorta-banded>control). In conclusion, the arrhythmogenesis of IF-alpha is potentiated in pathophysiological conditions such as cardiac hypertrophy or elevated sympathetic activity.

Animals↗

Left ventricular diastolic dysfunction induced by cyclophosphamide in blood stem cell transplantation.

Cardiac complications are major limiting factors regarding the success of high-dose chemotherapy supported by blood stem cell transplantation (BSCT). The cardiotoxicity of cyclophosphamide remains obscure relative to that of anthracyclines. The aim of this study was to estimate noninvasively the cardiotoxicity of cyclophosphamide administered during the pretransplant conditioning of BSCT for patients with various hematological diseases. A total of 27 consecutive patients were divided into two groups depending on the conditioning regimen, ie, group A (n=15) which received cyclophosphamide (median dose of 120 mg/kg; range 100 to 200 mg/kg) and group B (n=12) which did not. Ultrasound cardiograms (UCG) and signal-averaged electrocardiograms (SAECG) were recorded in the two groups both preceding and following the BSCT. There were no statistical intergroup or intragroup differences in left ventricular (LV) dimensions or contractile function. Significant (P<0.01) posttransplant increases in interventricular septal wall thickness and Ap/Ep ratio were noted in group A. Moreover, the filtered QRS duration as estimated by SAECG was prolonged (P<0.05) whereas the summated LV voltage (S(V1)+R(V5)) was reduced in the posttransplant period only in group A. These results suggest that early cyclophosphamide cardiotoxicity was characterized by LV diastolic rather than systolic dysfunction. These findings may contribute to acute hemodynamic deterioration observed after cyclophosphamide-containing conditioning chemotherapy.

Adolescent↗