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Biomedical subjects

M Hiroe

Publications and source records attributed to M Hiroe.

At least 55 records · Page 3Linked to original sources
PubMed1998

The Fas/Fas ligand system is involved in the pathogenesis of autoimmune myocarditis in rats.

The mechanisms responsible for myocardial injury and cell death in myocarditis are still unclear. We examined whether myocardial cell death occurs via apoptosis in myosin-induced autoimmune myocarditis in rats and whether the Fas/Fas ligand (FasL) system plays a role in this apoptosis. On days 14, 17, 21, and 35 after immunization with porcine heart myosin, some cardiomyocytes and infiltrating lymphocytes were found to be apoptotic on in situ terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay, but none was on day 60 and in control rats. Apoptotic indices peaked at day 17, and laddering of genomic DNA from the affected myocardium was observed on days 17 and 21 on agarose gel electrophoresis. The expression of Fas mRNA and protein was detected on days 17 and 21 in some cardiomyocytes and infiltrating lymphocytes by Northern blot analysis and immunohistochemistry, respectively. In addition, FasL was detected in some infiltrating lymphocytes on days 14, 17, and 21 by both in situ hybridization and immunostaining, and FasL-positive lymphocytes were mainly CD4+ cells. Some rats were injected with anti-Fas Ab (0.1 mg/kg) or anti-FasL Ab (0.1 mg/kg), and subsequently, inflammatory lesions exhibited less severe than did untreated rats with myocarditis. These findings suggest that cell death via apoptosis of cardiomyocytes and lymphocytes is one of the mechanisms of myocardial injury in autoimmune myocarditis, and that the Fas/FasL system might play a role in the induction of this apoptosis.

Acute Disease↗
PubMed1998

Comparison of clinical features and prognosis of cardiac sarcoidosis and idiopathic dilated cardiomyopathy.

In the present study, clinical findings of 15 patients with cardiac sarcoidosis presenting as dilated cardiomyopathy were compared with those of 30 consecutive patients with idiopathic dilated cardiomyopathy. The sarcoidosis patients had different clinical features, including female predominance, a high incidence of grave conduction disturbance and abnormal wall thickness, uneven wall motion abnormalities, and perfusion defects preferentially affecting the anteroseptal and apical regions, and poor prognosis compared with those with idiopathic dilated cardiomyopathy.

Adult↗
PubMed1998

Levels of soluble Fas ligand in myocarditis.

Serum levels of soluble Fas ligand (sFasL) increased with the severity of congestive heart failure (p <0.01), and the percentages of apoptotic myocytes detected by in situ DNA nick-end labeling were significantly higher in the patients with increased levels of sFasL than in those with normal levels of sFasL (p <0.05). These findings indicated that sFasL may play an important role in pathogenesis of myocarditis.

Adult↗
PubMed1998

Levels of soluble Fas in patients with myocarditis, heart failure of unknown origin, and in healthy volunteers.

This study showed that serum levels of sFas were elevated in patients with myocarditis, and that this elevation was correlated with sIL-2R level as a marker of T-cell activation. Therefore, sFas levels may be associated with T-cell activation in patients with myocarditis, and elevation of sFas may inhibit apoptosis in activated T cells, leading to persistent cell-mediated destruction of myocytes in myocarditis.

Adult↗
PubMed1998

Expression of costimulatory molecules B7-1, B7-2, and CD40 in the heart of patients with acute myocarditis and dilated cardiomyopathy.

BACKGROUND: In patients with acute myocarditis and dilated cardiomyopathy (DCM), we previously reported that antigen-specific T cells infiltrate the heart and play an important role in the myocardial damage involved. For antigen-specific T-cell activation to occur, it is necessary for T cells to receive a costimulatory signal provided by costimulatory molecules expressed on antigen-presenting cells (APCs) as well as the main signal provided by binding of T-cell receptors to the antigen. METHODS AND RESULTS: To investigate the roles of the costimulatory molecules B7-1, B7-2, and CD40 in the development of acute myocarditis and DCM, we analyzed the expression of these antigens in the myocardial tissues of patients with acute myocarditis and DCM. We also examined the expression of a cytolytic factor, perforin, in the infiltrating cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, because both killer lymphocytes are thought to damage B7-1-expressing APCs. We found that B7-1, B7-2, and CD40 were moderately to strongly expressed in the cardiac myocytes of patients with acute myocarditis. Weak to moderate expression of these antigens was also found in the cardiac myocytes of patients with DCM. There was infiltration of perforin-expressing CTLs and NK cells in the myocardial tissues of patients with acute myocarditis and DCM. CONCLUSIONS: Our findings strongly suggest that expression of B7-1, B7-2, and CD40 antigens on cardiac myocytes may make them APCs for CTLs and NK cells and that they may play an important role in the direct myocardial damage by these killer cells in acute myocarditis and DCM.

Acute Disease↗
PubMed1998

Skeletal and smooth muscle alpha-actin mRNA in endomyocardial biopsy samples of dilated cardiomyopathy patients.

Skeletal or smooth muscle alpha-actin isoform is reexpressed in hypertrophied or failing heart in experimental animals, however, it has been unknown whether there is a switching of these genes in the human heart. In this study, we assessed alpha-actin isoform mRNA in biopsied specimens from the left ventricle of patients with dilated cardiomyopathy (DCM). The biopsy was performed in 21 patients (DCM; 16, normal; 5). Skeletal and smooth muscle alpha-actin mRNA levels were assessed by quantitative reverse transcriptase-polymerase chain reaction using a synthetic RNA as internal control. The level of both alpha-actin mRNAs correlated well with the mean cardiomyocyte diameter as an index of cardiac hypertrophy. Further, there was a clear correlation between the expression of skeletal alpha-actin mRNA or smooth muscle alpha-actin mRNA and the ejection fraction. These results suggested that mRNAs for skeletal and smooth muscle alpha-actin isoforms are increased in the hypertrophic and/or failing heart. These mRNAs may be an useful marker for the pathological state of cardiomyopathy.

Actins↗
PubMed1998

Delayed kinetics of oxygen uptake during recovery after exercise in cardiac patients.

PURPOSE: Little is known about cardiovascular responses during recovery from exercise in patients with cardiovascular disease. The aim of this study was to determine the time constants of the kinetics of oxygen uptake and heart rate during recovery from exercise and to evaluate the influence of resting cardiac function on these kinetics in patients with left ventricular dysfunction. METHODS: A moderate exercise test was performed by 40 patients (57+/-10 yr old) with prior myocardial infarction at a constant work rate (40+/-8 W) for 6 min on a cycle ergometer. The time constants of oxygen uptake and heart rate during 6 min of recovery were compared in patients whose left ventricular ejection fractions were > or =35% (group 1, N = 20) and those with ejection fractions <35% (group 2, N = 20). RESULTS: The time constant of the decrease in oxygen uptake during exercise recovery was significantly prolonged (oxygen requirement was increased) in group 2 compared with group 1. Heart rate during recovery was consistently higher, and its time constant was prolonged in group 2 compared with group 1. The time constant of oxygen uptake was positively correlated with the time constant of heart rate. CONCLUSION: The recovery of oxygen uptake after exercise was significantly delayed, associated with delayed recovery of heart rate, in patients with severely impaired left ventricular function.

Aged↗
PubMed1998

Effects of isosorbide dinitrate on oxygen uptake kinetics in cardiac patients.

PURPOSE: Although nitrates are known to improve indices of exercise capacity in patients with coronary artery disease, their effects on oxygen uptake kinetics during the onset of exercise have not been clarified. We evaluated the acute effects of isosorbide dinitrate on the kinetics of oxygen uptake during the onset of exercise at a constant work rate in patients with coronary artery disease. METHODS: We studied 14 patients with coronary artery disease who performed 6 min of low-intensity exercise at a constant work rate on a cycle ergometer 30 min after oral administration of 10 mg of isosorbide dinitrate or placebo in a double-blind, crossover manner. Oxygen uptake was calculated from breath-by-breath analysis of respired gases. The time constant of oxygen uptake kinetics during the onset of exercise was determined by fitting a single exponential function to the oxygen uptake response. RESULTS: Heart rate was significantly increased at rest, and systolic blood pressure was significantly decreased both at rest and during exercise after administration of isosorbide dinitrate. The time constant of oxygen uptake was significantly shorter (the kinetics were faster) after administration of isosorbide dinitrate (39.4+/-10.1 vs 44.5+/-10.5 s, P = 0.038). CONCLUSIONS: Isosorbide dinitrate was found to speed the kinetics of the increase in oxygen uptake during constant work-rate exercise. The time constant of oxygen uptake, which reflects the rapidity of cardiovascular adaptation at the onset of exercise, seems to be a useful parameter of the effectiveness of therapy in patients with coronary artery disease.

Adult↗
PubMed1998

High energy radiofrequency catheter ablation for common atrial flutter targeting the isthmus between the inferior vena cava and tricuspid valve annulus using a super long tip electrode.

There have been controversies concerning the optimal target sites and approaches in radiofrequency catheter ablation of common atrial flutter. We attempted high energy radiofrequency catheter ablation targeting the isthmus between the inferior vena cava and tricuspid valve annulus (IVC-TV isthmus) with a super long (8 mm) tip electrode, and compared the efficacy of this anatomical approach with the electrophysiological approach targeting the posteroseptal right atrium posterior to the coronary sinus using a standard 4-mm tip electrode. Atrial flutter was successfully ablated in 12 of 12 patients (100%) without recurrence with the anatomical approach, while, in 7 of 9 patients (64%) with 2 recurrences with the electrophysiological approach. In comparison of ablation data between the anatomical and electrophysiological approaches, there were significant differences in the mean number of application pulses (anatomical vs electrophysiological: 2.3 +/- 0.8 vs 9.9 +/- 6.4, P < 0.01), applied wattage (39 +/- 12 W vs 24 +/- 6 W, P < 0.01), applied energy per application (1,986 +/- 426 J vs 659 +/- 323 J, P < 0.01), fluoroscopic time (26 +/- 11 min vs 74 +/- 30 minutes, P < 0.01), and procedure time (59 +/- 8 min vs 181 +/- 53 min, P < 0.01). In conclusion, the anatomical approach is superior to the electrophysiological one with respect to procedure and radiation time, and linear ablation at the IVC-TV isthmus with an 8-mm tip electrode and high energy application is highly effective and safe.

Aged↗
PubMed1998

Retrograde multiple and multifiber accessory pathway conduction in the Wolff-Parkinson-White syndrome: potential precipitating factor of atrial fibrillation.

INTRODUCTION: The determinants of susceptibility to atrial fibrillation (AF) and the existence of accessory pathway conduction have remained unidentified in the Wolff-Parkinson-White (WPW) syndrome. We tested the hypothesis that excitation inputs into the atrium over a retrograde multiple or multifiber accessory pathway during AV reentrant tachycardia (AVRT) could precipitate initiation of AF. METHODS AND RESULTS: Two hundred fifty consecutive patients with WPW syndrome underwent electrophysiologic study and radiofrequency catheter ablation. The patients were classified into two groups according to the study results: 29 with retrograde multiple or multifiber accessory pathway (MP) and 221 with retrograde single accessory pathway (SP). Compared with the SP patients, the MP patients showed a significantly higher incidence of clinical AF (MP vs SP: 19/29 vs 51/221, P < 0.01), induced AF (12/29 vs 32/221, P < 0.01), and initiated AF during ventricular pacing and AVRT (10/12 vs 17/32, P < 0.05). There were no differences between the two groups in incidence of clinical and induced AVRT (24/29 vs 200/221 and 25/29 vs 206/221, respectively), mean cycle length of induced AVRT, or electrophysiologic parameters of the accessory pathway. AF inducibility during AVRT or ventricular pacing was eliminated by partial ablation in 7 of 10 patients with MP. After total ablation, the incidence of induced AF was similar between the two groups (MP vs SP: 1/29 vs 11/221). CONCLUSION: The existence of a retrograde multiple or multifiber accessory pathway in patients with WPW syndrome is associated with a higher incidence of clinical and induced AF. Successful ablation of the retrograde multiple or multifiber accessory pathway can eliminate the induction of both AVRT and AF.

Adult↗
PubMed1998

Essential roles for G1 cyclin-dependent kinase activity in development of cardiomyocyte hypertrophy.

Although cardiomyocytes undergo terminal differentiation soon after birth, irreversibly withdrawing from the cell cycle, growth stimulation induces cell hypertrophy. Such growth stimulation is also responsible for the upregulation of G1 cyclins and cyclin-dependent kinase (CDK) activity in proliferating cells. We sought to determine whether G1 CDK activity is involved in the hypertrophy of rat neonatal cardiomyocytes in culture. We show that serum stimulation promoted the G1 CDK activity without induction of DNA synthesis in cardiomyocytes. Furthermore, overexpression of CDK inhibitors p16(INK4a) and p21(CIP1/WAF1) by use of the adenovirus vector effectively prevented cell enlargement and depressed serum-induced protein synthesis and expression of skeletal alpha-actin and atrial natriuretic factor, genetic markers of cardiac hypertrophy. These results suggest that the G1 CDK activity promoted by serum stimulation is required for the induction of cardiomyocyte hypertrophy and provide novel evidence for understanding the regulation of cardiac hypertrophy by cell cycle regulators.

Animals↗
PubMed1998

Hepatitis C virus infection and heart diseases: a multicenter study in Japan.

As a collaborative research project of the Committees for the Study of Idiopathic Cardiomyopathy, a questionnaire was sent out to 19 medical institutions in Japan in order to examine the possible association between hepatitis C virus (HCV) infection and cardiomyopathies. Hepatitis C virus antibody was found in 74 of 697 patients (10.6%) with hypertrophic cardiomyopathy (mean age, 57.7 years) and in 42 of 663 patients (6.3%) with dilated cardiomyopathy (mean age, 56.5 years); these prevalences were significantly higher than that found in volunteer blood donors in Japan (2.4%, 50-59 years of age, each p<0.0001). The prevalence was significantly higher in patients suffering from hypertrophic cardiomyopathy as opposed to those with dilated cardiomyopathy (p<0.01). The presence of HCV antibody was detected in 650 of 11,967 patients (5.4%) patients seeking care in 5 academic hospitals. Various cardiac abnormalities were found among these patients, arrhythmias being the most frequent. These observations suggest that HCV infection is an important cause of a variety of otherwise unexplained heart diseases.

Cardiomyopathies↗
PubMed1998

National survey of the use of endomyocardial biopsy in Japan.

A national survey of endomyocardial biopsy procedures was conducted in Japan. Questionnaires were mailed to 852 institutions and statistical analysis of the 213 completed questionnaires (25.0% of the total) was performed. Cardiac biopsies were being performed at 134 of these institutions (62.9%), representing a 5.5-fold increase over 1980. A total of 19,964 cardiac biopsies have been performed in Japan. Specimens were obtained from the right ventricle at 113 institutions, and from the left ventricle at 76 centers. The Konno-Sakakibara bioptome was used at 32 institutions, whereas the long sheath method was used at 98 institutions. Sixty of the institutions (44.8%) had encountered ventricular wall perforation. The perforation rate of the two ventricles combined was 0.7% (147 of 19,964 cases), with a mortality rate of 0.05% (10 of 19,964 cases). Endomyocardial biopsy has become widespread in Japan, and its safety was ascertained by this national survey.

Adult↗
PubMed1998

[Use of 99mTc-labeled myocardial perfusion agents in the Kanto-Koshinetsu area].

We sent out a questionnaire to investigate how the 99mTc-labeled myocardial perfusion agents are used in the Kanto-Koshinetsu area. Answers were obtained from 83 laboratories. Examinations using 99mTc-labeled agents were performed more frequently than those using 201T1 only in 10 of 83 laboratories. Main reasons for not using 99mTc-labeled agents were as follows: two injections required in the stress study, superiority of thallium-201 in the assessment of myocardial viability, a large amount of clinical data cumulated in thallium-201 imaging, and problems caused by abdominal uptake of 99mTc-labeled agents. Comparing purposes of the examinations using 201T1 and 99mTc-labeled agents, evaluation of myocardial viability was more common in 201Tl imaging, meanwhile, detection of myocardial ischemia was more common in imaging with 99mTc-labeled agents. It was pointed out that dual isotope imaging using 201Tl and 99mTc-labeled agents and simultaneous evaluation of myocardial perfusion and cardiac function are clinically feasible as new diagnostic procedures.

Heart↗
PubMed1997

Calcitonin gene-related peptide (CGRP) increases cell surface area and induces expression of skeletal alpha-actin ANP mRNA in hypertrophying neonatal cardiomyocytes.

We have reported previously that calcitonin gene-related peptide (CGRP) exerts hypertrophic effects, defined in the broadest sense as increased mass of protein per cell, in adult rat ventricular in vitro. The aim of the present investigation was to determine whether the peptide also increases the cell surface area of, and induces expression of ANP and skeletal alpha-actin mRNA in hypertrophying neonatal rat ventricular cardiomyocytes. Cells cultured in the presence of CGRP were invisibly hypertrophied after 48 h compared to cells cultured in serum-free MEM for the same period. CGRP, 100 pM and 1 nM, increased cell surface area significantly and to values 1.82- and 2.15-fold greater, respectively, than in the absence of peptide (659.64 +/-23.48 microns 2, n = 10). The selective antagonist at CGRP1, receptors, CGRP8-37(200nM), significantly attenuated the effects of CGRP (100 pM and 1 nM). CGRP caused a marked up-regulation of the expression of mRNA encoding skeletal alpha-actin and ANP, respectively, maximally after 12 h and at a concentration of 100 pM, to values approximately 3.6- and 2.5-fold greater than in the absence of peptide. These effects of the peptide were completely abolished in the presence of CGRP8-37(100 nM). In conclusion, CGRP increases cell surface area and induces expression of ANP and skeletal alpha-actin mRNA in hypertrophying cardiomyocytes via the CGRP1, receptor subtype.

Actins↗
PubMed1997

Nitric oxide contributes to the progression of myocardial damage in experimental autoimmune myocarditis in rats.

BACKGROUND: Excess amounts of NO produced by an inducible NO synthase (iNOS) in response to cytokines may be cytotoxic and can be destructive to tissue. We investigated the role of NO in the development of myocardial damage and the effects of aminoguanidine (AG), an inhibitor of iNOS, on experimental autoimmune myocarditis in rats. METHODS AND RESULTS: Autoimmune myocarditis was induced in 20 Lewis rats by injection of porcine cardiac myosin. Ten of the 20 rats were administered AG. The severity of myocarditis was evaluated by measuring the size of myocarditic lesion and serum levels of CK-MB. Serum NO levels were determined using the Cd/Cu method. Tissue specimens were immunohistochemically examined for iNOS and nitrotyrosine. Histopathological study revealed extensive myocardial destruction and massive inflammatory cell infiltration in AG-untreated rats but only focal mononuclear cell infiltration in AG-treated rats. The mean percent areas of inflammatory lesions in the untreated and treated rats were 56 +/- 13% and 3 +/- 2%, respectively (P < .001). NO levels were 102 +/- 23 and 25 +/- 9 IU/L, respectively (P < .01). CK-MB levels were 68 +/- 13 and 16 +/- 13 nmol/L, respectively (P < .01). Superoxide production as measured with an ex vivo monitoring system was also significantly decreased in the treated rats. Nitrotyrosine relating to the generation of peroxynitrite was detected through immunostaining in the inflammatory lesions of untreated rats but not in those of treated rats. CONCLUSIONS: Excess amounts of NO produced by iNOS appear to contribute to the progression of myocardial damage in myocarditis. AG may prove to be useful in the treatment of myocarditis.

Animals↗
PubMed1997

Stimulation of collagen synthesis in rat cardiac fibroblasts by exposure to hypoxic culture conditions and suppression of the effect by natriuretic peptides.

Synthesis of type I and type III collagens by rat cardiac fibroblasts was stimulated when the cells were cultured under 95% N2/5% CO2 for one hour followed by incubation under normoxic conditions for 24 hours. The stimulative effect was attenuated by the presence of atrial natriuretic peptide (ANP, 10(-6) M) or brain natriuretic peptide (BNP, 10 6 M) in the culture medium. Northern blot analysis indicated that alpha1(I) and alpha1(III) collagen mRNA levels were also increased by hypoxia, and decreased with the addition of ANP or BNP in a dose-dependent manner. These results indicate interaction between intracellular signals of a physical stimulus (hypoxic stress) and those of a chemical one (ANP or BNP) and demonstrate that both signals regulate collagen synthesis by cardiac fibroblasts at the levels of the mRNAs. The results also suggest that natriuretic peptides produced by cardiomyocytes in vivo may function as paracrine factors that play a role in the prevention of cardiac fibrosis in ischaemic heart diseases.

Animals↗