Search

The pharmacological characterization of endothelin-1 (ET-1) in the pulmonary circulation in pulmonary hypertension (PH) is not known precisely. We investigated the effect of intravenous injection of ET-1 (1000 pmol/kg) on right ventricular systolic pressure (RVSP) (which is equal to systolic pulmonary arterial pressure) in rats with monocrotaline-induced PH. ET-1 decreased RVSP in PH rats; however, ET-1 did not alter RVSP in control rats, suggesting that ET-1 causes dilatation of the pulmonary artery in PH rats. Under pretreatment with the endothelin-A- (ET(A)) receptor antagonist BMS 193884, ET-1 decreased RVSP in PH rats more than in control rats, suggesting that pulmonary vasodilator action of ET-I mediated via the ET(B)-receptor pathway is augmented in PH rats. Under pretreatment with the ET(A/B)-receptor antagonist SB 209670, the effect of ET-1 in lowering pulmonary arterial pressure was abolished in both groups of rats. These results suggest that the hypotensive effect of ET-1 on pulmonary circulation mediated via the ET(B)-receptor pathway is enhanced in PH rats compared with control normal rats. It is considered that the blockade of only the ET(A)-receptor pathway is preferable to the blockade of both the ET(A)- and ET(B)-receptor pathways in the treatment of PH.

Non-c-axis oriented epitaxial films of bismuth layer-structured ferroelectrics, SrBi2Ta2O9 (SBT) and SrBi2Nb2O9 (SBN), were prepared on SrTiO3(110) by coating-pyrolysis process. These films were found to be (106)-oriented (pseudo-tetragonal indices). Interestingly, this orientation is ‘stealthy’ or unseen in the conventional XRD θ–2θ scans due to extinction rule so that its presence was revealed by XRD pole-figure measurement and reciprocal-space mapping. The crystallographic relationship of the films and substrates was SBT, SBN (106)∥SrTiO3 (110) and SBT, SBN [010]∥SrTiO3 [001]. This epitaxial relationship was also discussed from the standpoint of ion arrangement.

Pb(Zr,Ti)O3 thin films (Pb:Zr:Ti=1:0.52:0.48) were prepared on various single-crystal substrates via dipping-pyrolysis process by use of metal naphthenates as starting materials. The alignments of these films were examined by X-ray diffraction (XRD) θ–2θ scans and β scans (pole figures). The films grown on Nb-doped SrTiO3, MgO or LaAlO3 showed an epitaxial relationship with substrates after heat treatment at 750°C, while those grown on sapphire and Si wafers exhibited polycrystalline or amorphous characteristics. Epitaxial films on SrTiO3 and LaAlO3 were found to consist of a c-axis oriented tetragonal phase, to minimize the lattice misfit with the substrates. These epitaxial films exhibited very smooth surfaces by SEM and AFM observations. In addition, the fluctuation of in-plane alignment was significantly dependent on the lattice-misfit values.

Endothelin (ET)-1 has a positive inotropic effect and induces hypertrophy in cardiomyocytes. We previously reported that the peptide level of ET-1 is increased in the failing heart of rats with chronic heart failure (CHF) and that treatment with an ETA-receptor antagonist greatly improves survival in rats with CHF. However, precise analysis for alteration of the myocardial ET system in the failing heart is not known. In this study, we used rats with CHF due to chronic myocardial infarction. Sham-operated rats served as a control. The results showed that the level of preproendothelin (preproET)-1 mRNA and the peptide level of ET-1 were markedly increased in the heart of rats with CHF, whereas the expression of endothelin-converting enzyme (ECE)-1 mRNA in the heart did not differ between CHF and control rats. The intensity of ET-1 staining (ET-1-like immunoreactivity) in cardiomyocytes was markedly stronger in rats with CHF than in control rats, and the fibrotic tissues of the infarcted area were not stained. The mRNA and protein levels of both ETAand ETBreceptors in the heart were significantly higher in rats with CHF than in control rats. The present study suggests that the increase in ET-1 peptide level in the heart of the rats with CHF originated from upregulation of preproET-1 mRNA, which was not attendant with the alteration of ECE-1 mRNA expression, and that both the ETA- and ETB-receptor systems are greatly accelerated in the failing heart.

Epitaxial YBa 2 Cu 3 O 7 (YBCO) films with high-critical-current density ( J c ) properties were successfully prepared on cerium oxide-buffered sapphire ( r- cut α-Al 2 O 3 ) substrates by an excimer-laser-assisted metalorganic deposition (ELAMOD) using a new irradiation manner. The previously reported ELAMOD process in which the laser beam is irradiated from the surface of the substrate has brought about the advantages of shorter heating time as well as high- J c of the YBCO films [M. Sohma, T. Tsuchiya, K. Tsukada, I. Yamaguchi, T. Manabe, T. Kumagai, K. Koyanagi, T. Ebisawa, H. Ohtsu, IEEE Trans. Appl. Supercond. 15 (2007) 3612; M. Sohma, T. Tsuchiya, K. Tsukada, I. Yamaguchi, T. Manabe, T. Kumagai, K. Koyanagi, T. Ebisawa, H. Ohtsu, Physica C 463–465 (2007) 891]. The J c values over 6 MA/cm 2 has been reported by an inductive method at 77.3 K only for the laser-irradiated areas. An awaiting solution has remained since the appropriate fluence range of the laser beam is much limited to obtain high- J c ELAMOD–YBCO films with good reproducibility. In this paper we report a new irradiation manner to resolve the difficulty. The backside of the substrate was irradiated by homogenized KrF excimer laser beam (scanning mode) after application of a fluorine-free ingredient solution. The indispensable laser fluence increased to obtain the high- J c YBCO films because of absorption from the substrate and the CeO 2 buffer. High- J c values of around 6 MA/cm 2 at 77.3 K using an inductive method were obtained in the area irradiated at a wider fluence range, while a part of unirradiated area also showed relatively high- J c of 2–5 MA/cm 2 . Attenuation and scattering effects are considered to bring the extended option of the laser fluence.

Epitaxially grown c -axis-oriented and `single phase' Yb(Ba 1− x Sr x ) 2 Cu 4 O 8 ( x =0–0.1) films were successfully fabricated on SrTiO 3 (001) substrates by a coating–pyrolysis process. The substitution limit of Sr decreased with increasing temperature in the range from 760 to 800°C. The films prepared at 780°C in flowing O 2 at ambient pressure were found to consist of an almost single phase of c -axis-oriented Yb(Ba 1− x Sr x ) 2 Cu 4 O 8 and a trace amount of c -axis YbBa 2 Cu 3 O 7− y . The reciprocal-map analysis of the films showed that the Yb(Ba 1− x Sr x ) 2 Cu 4 O 8 phase is pseudotetragonal. The superconducting transition temperatures increased by Sr-substitution and T c,zero (r)=81 K by dc-resistance and T c,onset (s)=81 K by ac-susceptibility measurements were obtained for the Yb(Ba 0.9 Sr 0.1 ) 2 Cu 4 O 8 film. The film with x =0.1, quenched from 600°C, also showed metallic behavior with T c,zero (r)=76 K.

A 72-year-old male patient with dilated cardiomyopathy was treated with oral flecainide (100 mg/day) for persistent atrial fibrillation (AF) that could not be converted to sinus rhythm by electrical cardioversion. Initiation of flecainide treatment provided sinus rhythm without prolongation of QRS and QTc, bradycardia and first-degree atrioventricular block at a serum flecainide level of 438 ng/mL. Then, he received cardiac resynchronization therapy (CRT). Dose reduction to 50 mg/day because of stabilization of heart rate after CRT produced AF at a serum flecainide level of 270 ng/mL. Electrical cardioversion did not restore the AF to a sinus or pacing rhythm. Dose escalation of flecainide (to 100 mg/day) restored the pacing rhythm at a serum flecainide level of 401 ng/mL. This case suggests that in the Japanese population, serum flecainide level should be maintained at >300 ng/mL to control AF even after effective CRT.

Epitaxially grown c -axis-oriented and nearly single phase YbBa 2 Cu 4 O 8 (Yb124) films were prepared on SrTiO 3 (001) substrates by coating-pyrolysis process. Based on X-ray diffraction θ –2 θ and β scanning, the film heat-treated at 780°C in flowing O 2 at 1 atm was found to consist of c -axis-oriented Yb124 and a trace amount of c -axis YbBa 2 Cu 3 O 7− y (Yb123). This film showed metallic behaviour in the normal state and sharp superconducting transition at T c, zero =76 K by dc-resistance measurement, and T c, onset =78 K by ac-susceptibility measurement. The Yb124 phase is considered to form through a novel solid-state epitaxy route from the Yb 2 O 3 –BaCO 3 –CuO precursor, accompanying the decomposition of BaCO 3 , at ambient pressure without melt formation.

Epitaxially grown La 0.7 Sr 0.3 MnO 3 (LSMO) films were prepared on SrTiO 3 (001), LaAlO 3 (001) and MgO(001) single-crystal substrates by dipping-pyrolysis process. The fluctuation of alignments (mosaicity) of the films was evaluated based on X-ray diffraction 2 θ / θ scans, β scans (pole figures) and asymmetric 2 θ / ω scans (reciprocal-space maps). Lattice types and epitaxy were examined in the films after heat treatment at 1473–1873 K; the lattice type of the films on SrTiO 3 was pseudocubic, whereas those on LaAlO 3 and MgO were pseudocubic or rhombohedral, depending on the heat-treatment temperature. A mosaic spread (Δ ω ) of the LSMO film varied with the lattice-mismatch value between film and substrate. The LSMO films on SrTiO 3 (lattice misfit ≈1%) showed high epitaxy with a low Δ ω (≈0.50°), whereas the films on MgO (misfit ≈8%) exhibited a larger Δ ω (≈2.8°). Also, surface morphology of the film was found to markedly depend on the kind of substrate materials and annealing temperature.

Exercise hypotension has been documented in patients with hypertrophic cardiomyopathy (HCM). Some investigators reported that this is due to an inadequate increase of systemic vascular resistance during or after exercise. The aim of this study was to investigate the pathogenesis of limb vascular response abnormalities in patients with idiopathic HCM. Thirteen patients with HCM and 9 healthy controls were administered an endothelium-dependent dilator (acetylcholine), a direct smooth muscle dilator (nitroglycerin), an alpha-adrenergic stimulator (phenylephrine), and a beta-adrenergic stimulator (isoproterenol) by intra-arterial infusion. Peripheral vascular resistance was assessed by forearm plethysmography at rest and during each infusion to obtain the percentage change in vascular resistance. Isoproterenol, acetylcholine and nitroglycerin produced dose-related vasodilatation with no significant differences between HCM patients and healthy controls. The percentage increase in vascular resistance was significantly less in HCM patients than in healthy controls after phenylephrine infusions of 0.5μg/min (155±38% vs 195±47%, mean ± SD, p

The objective of this study was to investigate the effects of inhaled nitric oxide (NO) on chronic pulmonary hypertension (PH). Thirty patients with valvular heart diseases (n=8, group A), chronic lung diseases (n=16, group B), primary PH or PH due to collagen disease (n=6, group C) were studied. NO was delivered for 20 min at concentration of 5, 10, and 20 ppm in spontaneous respiration. After inhalation, percentages of systolic pulmonary artery pressure (%SPAP) levels in group A were significantly decreased compared with those for pre-inhalation by 12%, 14%, and 14% at 5, 10 and 20 ppm, respectively (p

ホルター心電図装着中の心臓突然死の解析によるとそれに関与する不整脈の80%が心室頻拍・細動であり, 20%が徐脈性不整脈あるいは電気収縮解離である.前者の多くに器質的心疾患の診断を受けた既往歴がある.リエントリーの発生要因である伝導遅延,一方向性ブロックは器質的障害によっても発生するが,機能的な刺激伝導と心筋の不応期の不均質性も重要な成因になる.これらの直接的な要因の背景には自律神経の関与がある.

We have previously reported that production of endothelin (ET)- I is markedly increased in failing hearts of rats with chronic heart failure (CHF). It was also reported that the production of angiotensin II (Ang II) is increased in the failing heart. In this study we investigated both converting enzymes of the ET-1 system and the angiotensin system. We used left coronary artery-ligated rats as a model of CHF. The peptide level of ET- I in the left ventricle (LV) was markedly higher in CHF rats than in control rats. In the LV, expression of preproET-1 mRNA was also markedly higher in CHF rats than in controls. The expression of endothelin-converting enzyme (ECE)-1 mRNA in the rats with CHF was similar to that in controls. Therefore. we believed that the increase in ET-1 production in the failing heart originated from an increase in preproET-I production rather than increase in ECE. The expression of angiotensin-converting enzyme (ACE) mRNA in failing hearts of CHF rats was significantly higher than that of the sham-operated rats. The expression of angiotensinogen mRNA in failing hearts of these CHF rats was slightly higher than that of the sham-operated rats. This study suggests that there is a difference in the role of peptide synthesis between the ECE system and the ACE system in rats with CHF.

BaTiO3 thin films were prepared by using metal organic acid salts on MgO(100) substrates, which have large lattice-misfit with BaTiO3. Amorphous films prefired at 470°C were crystallized to BaTiO3 phase by heat treatment at higher temperature. Crystallinity and in-plane alignment of the prepared films were found to depend on the heat-treatment conditions. BaTiO3 films with high crystallinity but poor (100)-orientation were obtained in air at higher than 1200°C. Whereas, (100)-oriented epitaxial BaTiO3 film was fabricated by annealing at 900°C under low oxygen partial pressure (p(O2)). Low carbon dioxide partial pressure (p(CO2)) is also found to be essential for preparation of epitaxial BaTiO3 films on MgO substrates by using metal organic acid salts.

京都市地下鉄における世界的にも例を見ない4本超近接シールドエ事に関し, 筆者らはその計画・設計段階から併設シールドの諸問題について研究し, 重点的な情報化施工による確認作業を重ねて工事を遂行してきた. 本研究は, 将来の併設シールドの影響評価に資することを目的に, 工事で得られた地盤とトンネル挙動を詳細に分析し, その中から一般化できる事項を抽出し評価を試みるものである.本文では, 設計・施工上の影響予測について言及し, その中の後続シールドの推進力が先行トンネルに与える影響荷重, 併設シールドにおける長期的影響の荷重変動からみた特性, および併設シールドにおける地盤挙動メカニズムの解析的表現手法について, その評価と応用に関する考察を述べる.

Epitaxially grown PZT films with crack- and void-free smooth surfaces were successfully prepared on MgO (100) by DP process using a constituent metal naphthenate solution. Epitaxial PZT was considered to crystallize directly from the amorphous precursor, not via pyrochlore, and the orientation relationship between PZT films and MgO substrates was: PZT (100)//MgO (100) and PZT [001]//MgO [010], [001].Epitaxy and surface morphology of the films were found to depend chiefly on their crystallinity. The crystallinity and epitaxy of the films increased with increasing final heat treatment temperature in the range 650-750°C. However, optimum surface morphology, i.e., a smooth and homogeneous texture, was obtained at lower crystallinity, for example, with a film pyrolyzed at 500°C and finally heat-treated at 650°C. On the other hand, low-temperature prefiring lowered the crystallinity of the product films if the final heat treatment temperature was the same. Namely, a film prefired at 200°C and finally heat-treated at 750°C showed similar crystallinity and morphology with the above 500°C-pyrolyzed and 650°C-annealed film.

Background and hypothesis: Patients with dilated cardiomyopathy (DCM) with left ventricular hypertrophy (LVH) have been found to have a better prognosis than patients without LVH. However, the pathophysiologic mechanism for that has not been investigated. We sought to clarify the pathophysiologic significance of LVH in DCM. Methods: We performed isoproterenol infusion echocar-diography (0.02 mg/kg/min) in 17 patients with DCM, and measured plasma epinephrine and norepinephrine levels at rest and at the end of ergometer exercise in 14 of the 17 patients. Patients were classified into groups according to the presence (9 patients) (LVH+) or absence (8 patients) (LVH-) of LVH. Left ventricular hypertrophy was defined as an inter-ventricular thickness or posterior wall thickness ≥13 mm. Results: Although there was no significant difference between groups in fractional shortening at rest during isoproterenol infusion, fractional shortening was significantly higher in the LVH (+) group than in the LVH (-) group (29 ± 9 vs. 17 ± 8%;p

Objectives.We sought to assess whether isoproterenol stress echocardiography could detect in advance in which patients hypertrophic cardiomyopathy would progress to a phase resembling dilated cardiomyopathy.Background.In a few patients, hypertrophic cardiomyopathy has been reported to progress to a phase characterized by systolic dysfunction and left ventricular dilation, resembling dilated cardiomyopathy.Methods.Echocardiograms were recorded before and immediately after intravenous infusion of isoproterenol (0.02 μg/kg body weight per min) for 5 min in 18 patients with typical hypertrophic cardiomyopathy (i.e., hypertrophied, hyperdynamic and nondilated) to determine the difference in fractional shortening. The patients were categorized into those with a good response (difference in fractional shortening >7%, 14 patients) and those with a poor response (difference ≤ 7%, 4 patients). Changes in left ventricular end-diastolic diameter and fractional shortening were evaluated by using serial echocardiography over an average follow-up period of 5.4 years.Results.In the good response group, neither end-diastolic diameter nor fractional shortening changed significantly during the follow-up period. In the poor response group, end-diastolic diameter significantly increased from a mean ± SD of 41 ± 5 to 53 ± 5 mm (p < 0.05), and fractional shortening significantly decreased from 40 ± 12% to 29 ± 10% (p < 0.05). All patients in the poor response group showed a substantial decrease (≥ 5%) in fractional shortening and an increase (≥5 mm) in end-diastolic diameter. One patient developed congestive heart failure due to systolic dysfunction during the observation period.Conclusions.The present study confirmed that impaired responses to isoproterenol infusion are related to future deterioration of left ventricular performance in patients with typical hypertrophic cardiomyopathy.

To investigate the regulation of endothelin-l (ET-1) production, cardiac catheterization was performed in young patients with congenital heart disease (27 ± 5 months old, mean ± SEM), and plasma levels of ET-1 in the inferior vena cava were measured by a sandwich-enzyme immunoassay. Plasma ET-1 levels of age-matched healthy controls were 1.55 ± 0.07 pg/ml (n = 6). In patients with atrial septal defect [without pulmonary hypertension (PH)] who had volume but not pressure overload to the pulmonary circulation (PC), plasma ET-1 levels were significantly lower than in controls. In patients with PH due to ventricular septal defect (VSD) who had both volume and pressure overload to PC, the levels were significantly higher than in controls. In patients with PH and severe pulmonary congestion due to pulmonary venous stenosis (PVS), plasma ET-1 levels were significantly higher than in those with VSD, suggesting that ET-1 production is also augmented by pulmonary congestion. The present findings suggest that ET-1 production is increased by pressure overload to PC but decreased by volume overload to PC.

Sixteen patients with dilated cardiomyopathy were studied to define the abnormality of the beta-adrenergic pathway non-invasively, using echocardiographic left ventricular responses to isoproterenol (ISP; 0.02 microgram/kg/min) and dibutyryl cyclic AMP (DBcAMP; 0.1 mg/kg/min) infusion. The increase in fractional shortening induced by ISP (delta FS-ISP) was 9 +/- 6% and that by DBcAMP (delta FS-DBcAMP) was 7 +/- 3%. The patients could be divided into three groups according to their left ventricular response to each agent: Group A; normal response to ISP (delta FS-ISPor = 11%), Group B-1; poor response to ISP but better response to DBcAMP (delta FS-ISP11%, delta FS-DBcAMPor = 7%; damage to beta-receptors), and Group B-2; poor response to ISP and DBcAMP (delta FS-ISP11%, delta FS-DBcAMP7%; damage including post receptor levels). Seven patients were in Group A, four in Group B-1, and five in Group B-2. DCM patients had a diversity of left ventricular responses to ISP and DBcAMP, according to the site of damage in the beta-adrenergic pathway.

Symmetry and structural properties of single state of composite crystal (Ca 0.5 Y 0.5 ) 0.80 CuO 2 , “Ca 2 Y 2 Cu 5 O 10 ” with one-dimensional CuO 2 chain have been investigated by means of the X-ray diffraction method and (3+1)-dimensional superspace group approach. By considering the satellite reflections, centrosymmetric superspace groups of (Ca 0.5 Y 0.5 ) 0.80 CuO 2 have been determined. It has become apparent that “Ca 2+ x Y 2− x Cu 5 O 10 ” phase should be generally described as (Ca 0.5+ x Y 0.5− x ) γ CuO 2 , “Ca 5 γ (0.5+ x ) Y 5 γ (0.5− x ) Cu 5 O 10 ”.

The aim of this study was to evaluate the volume doubling time (VDT) of lung cancer detected in our annual chest radiograph screening program and to compare it with those previously reported for computed tomography (CT) screening. In total, 209 patients who had a measurable tumor shadow and a history of participating in our chest radiograph mass screening program between 2006 and 2009 were included in this study. Indirect roentgenograms for patients with lung cancer were converted into digital images, and the section showing the tumor was enlarged on the monitor to a size of 0.01 mm. The mean VDT for all the patients was 158 days. Only 3.8% of the patients had a VDT of more than 400 days. In 140 patients with adenocarcinoma, the mean VDT was 177 days, and 5.0% of these patients had a VDT of more than 400 days. In the 44 patients with squamous cell carcinoma, the mean VDT was 133 days, and only 2.3% of these patients had a VDT of more than 400 days. These results were different from those previously reported for CT screening. In several reports on CT screening, more than 20% of the lung cancers had VDTs of more than 400 days. Since it is common knowledge that there are ‘indolent’ lung cancers with a VDT of more than 400 days, screening by annual chest radiography with rare overdiagnosis may need to be reconsidered.

Wall stress has been used as one of the parameters of myocardial mechanics. The present review focuses on recently developed data on ventricular wall stress, especially in relation to other newly developed areas in cardiology. In hypertensive hearts, there is a broad continuous spectrum in the structural and functional changes: those with low wall stress (inappropriate hypertrophy), those with normal wall stress (appropriate hypertrophy) and those with high wall stress (inadequate hypertrophy). Among them, the responses to neurohumoral stimuli are various, and their clinical features and courses also varied. These differences in wall stress among the different categories of hypertensive hearts may be caused by the variable influences of non-mechanical factors, such as molecular, metabolic and neurohumoral ones. Wall stress is an essential determinant of myocardial oxygen consumption, and is also an important determinant of the myocardial contractile state and diastolic function. In contrast to excitation-contraction coupling, contraction-excitation feedback has been studied, suggesting the importance of wall stress regulating electrical phenomena. The interrelationship between mechanical factors (including wall stress) and non-mechanical factors (including molecular, metabolic, neurohumoral and genetic ones) has been investigated intensively. In conclusion, wall stress (or force on the myocardial cell) may be a keystone in cardiology, relating to each of the cardiac phenomena. If wall stress deviates from the normal range, even with compensatory mechanisms, severe cardiac events occur. The compensatory mechanisms for wall stress may act as a risk factor on the heart, especially when the wall stress remains outside the normal range.

Thrombosis is a rare complication in patients with aplastic anemia because of the presence of coincidental thrombocytopenia. We have recently treated two cases, a 61-year-old male and a 59-year-old female, with acute myocardial infarction associated with aplastic anemia. Although their platelet counts were lower than normal in spite of treatment with anabolic steroids for aplastic anemia, the coronary angiographic findings strongly suggested coronary thrombosis in both cases. Anabolic steroids, which have been commonly used for the treatment of aplastic anemia, are a possible risk factor for coronary thrombosis because they have an accelerating effect on thrombus formation. We report two very rare but clinically important cases.

Peripartum cardiomyopathy is a rare cardiac disorder characterized by the development of heart failure in the last month of pregnancy or up to 5 months postpartum in women without other determinable causes of cardiac failure. Intracardiac thrombi have been found at autopsy in some patients with this condition and have been demonstrated in the left or right ventricles on 2-dimensional echocardiography. A 23-year-old woman presented with peripartum cardiomyopathy and biventricular thrombi on echocardiography. The thrombi were spherical, pedunculate, shaggy and irregular in configuration, and freely mobile, suggesting that they were fresh. She was treated with conventional heart failure therapy and anticoagulants. Four days later, the apical thrombi within both ventricles had disappeared and there was no evidence of embolism on physical examination. The hypercoagulable state of the peripartum period and the severe biventricular dysfunction most likely led to the formation of biventricular thrombi.

A 59-year-old woman with partial atrial standstill was studied using magnetocardiograms (MCGs), which revealed through QRS-T subtraction and time-frequency analysis that there was a high-frequency (6 Hz) magnetic source at the low atrial septum. MCGs are useful for noninvasively evaluating the clinical course of patients with atrial fibrillation. (Circ J 2002; 66: 1178 - 1180)

Endothelin-1 (ET-1) is known to have potent contractile and proliferative effects on vascular smooth muscle cells and is known to induce myocardial cell hypertrophy. We studied the pathophysiological role of endogenous ET-1 in rats with monocrotaline-induced pulmonary hypertension. Four-week-old rats were given a single subcutaneous injection of 60 mg/kg monocrotaline (MCT rats) or saline (control rats) and were killed after 6, 10, 14, 18, and 25 days. In the MCT rats, right ventricular systolic pressure progressively increased and right ventricular hypertrophy developed in a parallel fashion. The venous plasma ET-1 concentration also progressively increased, and this increase preceded the development of pulmonary hypertension. The isolated pulmonary artery exhibited a significantly weaker response to ET-1 in the MCT rats on day 25 but not on days 6 and 14. In the MCT rats, the expression of prepro ET-1 mRNA as measured by Northern blot analysis significantly increased in the heart on days 18 and 25, whereas it gradually decreased in the lungs. The peptide level of ET-1 in the lungs also significantly decreased in the pulmonary hypertensive stage. The expression of prepro ET-1 mRNA had increased by day 6 only in the kidneys. Continuous infusion of BQ-123, a selective ETA receptor antagonist, by an osmotic minipump (14.3 mg per day per rat for 18 days) significantly inhibited the progression of both pulmonary hypertension (right ventricular systolic pressure, 77.8 +/- 4.2 [mean +/- SEM] mm Hg [n = 10] versus 52.3 +/- 2.4 mm Hg [n = 7]; P < .01) and right ventricular hypertrophy (right ventricle/[left ventricle +/- septum], 0.56 +/- 0.03 [n = 10] versus 0.41 +/- 0.02 [n = 7]; P < .01). Histological examination revealed that BQ-123 also effectively prevented pulmonary arterial medial thickening. The inhibition of right ventricular hypertrophy by BQ-123 may be partly ascribed to the blockade of excessive stimulation of the heart by ET-1, in addition to the prevention of pulmonary hypertension. The present findings suggest that endogenous ET-1 contributes to the progression of cardiopulmonary alterations in rats with MCT-induced pulmonary hypertension.

A 50-year-old woman with Wolff-Parkinson-White (WPW) syndrome presented with unusual electrocardiographic (ECG) findings following the termination of paroxysmal supraventricular tachycardia. The ECG showed three different QRS complexes and irregular R-R intervals. These QRS complexes consisted of: (1) narrow QRS; (2) wide QRS with delta wave; and (3) wide QRS with left bundle branch block (LBBB). The mechanisms of these findings, revealed by electrophysiological study, were: (1) intermittent anterograde left-sided accessory pathway conduction; (2) rate-dependent ipsilateral LBBB; and (3) intermittent retrogradely conducted atrial echoes that occurred due to intraventricular conduction delay resulting from LBBB. Cases of WPW syndrome with these unusual ECG findings, which were clearly interpreted by electrophysiological study, are rare.

To assess the relationship between aging and autonomic regulation of sinus node function, 56 subjects of various ages (range 14-75 years, mean 43 +/- 19 years) without sinus node disease were studied. Heart rate, corrected sinus node recovery time and sinoatrial conduction time were measured before (basic) and after (intrinsic) pharmacologic autonomic blockade (propranolol + atropine i.v.). Percent chronotropies of the above parameters were calculated by a modified Jordan's method. Basic heart rate and basic corrected sinus node recovery time did not vary with age (r = -0.15, r = 0.08, respectively), while basic sinoatrial conduction time tended to increase with age (r = 0.32, p0.05). Intrinsic heart rate decreased (r = -0.76, p0.001), and intrinsic corrected sinus node recovery time and intrinsic sinoatrial conduction time both increased with age (r = 0.55, p0.001; r = 0.56, p0.001, respectively). The younger the subject, the more negative the percent chronotropies of the above parameters were, and the percent chronotropies correlated positively with age (r = 0.68, p0.001; r = 0.52, p0.001 and r = 0.34, p0.05, respectively). In conclusion, intrinsic sinus node functions deteriorated with age. Furthermore, parasympathetic tone on the sinus node functions decreased with age, which may compensate for age-related deterioration of intrinsic sinus node function.

Double-sided epitaxial YbBa 2 Cu 4 O 8 (Yb124) films were grown on 20 × 20 mm 2 LaAlO 3 (0 0 1) substrates by coating-pyrolysis process. The Yb124 film, prepared through an annealing path with a heating rate of 10–20°C/min up to 780°C, exhibited very strong XRD intensities corresponding to the c -axis orientation. Inductive superconducting transitions were recognized at 77.4 and 77.6 K for both sides.

徐脈発作の臨床には洞不全症候群と房室ブロックがあり,その発生機序は前者が刺激生成能の低下であり後者が刺激伝導能の低下である.いずれも自律神経など外因性要因に修飾され臨床像は多様であり,体表面心電図による診断は比較的容易であっても発生機序には多くの要因が複雑に関与しあっている.その背景は各種検査法によって浮び上がる.適確な病態の把握と診断により適切な治療法,ペースメーカー療法の適応が明らかになる.

Background The Jervell and Lange-Nielsen (JLN) syndrome is a variant of long QT syndromes (LQTS) and is associated with congenital deafness. The syndrome is caused by homozygous or compound heterozygous mutations in genes KCNQ1 and KCNE1, which are responsible for encoding the delayed rectifier repolarizing current, IKs. Methods and Results A novel and homozygous KCNQ1 mutation in a 23-year-old deaf woman with a prolonged QT interval and recurrent syncope in a Japanese family was identified. Genetic analyses revealed that the proband harbored a KCNQ1 missense mutation (W248F) located in the intracellular S4-S5 linker on both alleles. The same mutation was identified in both maternal and paternal families in a heterozygous manner. However, the family members of both sides had no clinical evidence of LQTS or hearing defects. Functional assays using a heterologous expression system revealed that W248F KCNQ1 plus KCNE1 channels reconstitute hardly measurable IKs currents. In contrast, heterozygous wild-type/W248F KCNQ1 plus KCNE1 channels displayed biophysical properties similar to those of the wild-type KCNQ1 plus KCNE1 channels with a weak dominant-negative effect. Conclusion In this study, we present a family with JLN syndrome. The electrophysiological properties of the mutant IKs channels explain the pathophysiology underlying JLNS. (Circ J 2008; 72: 687 - 693)

Aims This study examined the impact of cardiac resynchronization therapy (CRT) by triangle ventricular pacing (Tri-V) on left ventricular (LV) function and dyssynchrony. Methods and results Twenty-one patients with NYHA class III or IV heart failure were studied. For Tri-V, two right ventricular (RV) leads were connected to the CRT device via a Y-connector with one lead anchored at the RV apex and the other at the RV outflow tract. The LV lead was positioned in the posterolateral or lateral cardiac vein. CRT with standard bi-ventricular pacing (Bi-V) was performed with the RV apical and LV leads. LV function was assessed by the measurement of LV positive d p /d t (d P /d t max) and cardiac output (CO). LV dyssynchrony was assessed using the standard deviation of the time to peak myocardial velocity during the systolic phase in 12 LV segments (Ts-SD) derived from tissue Doppler images. In comparison to Bi-V, Tri-V increased d P /d t max (baseline, 746 ± 165; Bi-V, 909 ± 186; Tri-V, 959 ± 195 mmHg/s, P = 0.04) and CO (baseline, 3.1 ± 1.0; Bi-V, 3.4 ± 1.1; Tri-V, 3.8 ± 1.2 L/min, P < 0.001), decreased Ts-SD (baseline, 54.0 ± 35.0; Bi-V, 33.6 ± 15.3; Tri-V, 22.4 ± 8.1 ms, P = 0.02). Conclusion The acute beneficial effects of Tri-V on LV function and dyssynchrony were greater than those of Bi-V.

Background. Pacemaker or implantable cardiovascular-defibrillator (ICD) leads may be a primary cause of symptomatic tricuspid regurgitation (TR). The aim of this study was to evaluate the utility of 3-dimensional echocardiography (3-DE) in identifying intracardiac routes of pacemaker or ICD leads in relation to TR. Methods. 3-DE examinations were performed to evaluate intracardiac lead routes from right atrium to ventricle and positions at the tricuspid valve in 73 patients: 53 patients with pacemaker and 20 patients with ICD. TR severity was assessed by 2-dimensional echocardiography and classified as mild, moderate, or severe based on the ratio of TR area to right atrium area. Results 3-DE identified the lead route and position at the tricuspid valve in 68 patients (93.1%). In the remaining 5 patients, an appropriate image could not be obtained due to artifacts caused by the lead. TR severity was classified as mild in 47 patients, moderate in 18 patients, and severe in 8 patients. In 7 of the 8 patients with severe TR, obstruction to tricuspid valve closing caused by the lead was identified (Figure ): obstruction of septal leaflet in 3 patients, posterior leaflet in 3 patients, and anterior leaflet in 1 patient. However, in all patients with mild to moderate TR, the lead was positioned at the annulus side between leaflets, and no closing obstruction was identified. Conclusion. 3DE can identify pacemaker or ICD lead route and position at the tricuspid valve and the obstruction to closing caused by the lead in patients with severe TR. Therefore, 3DE may be useful to evaluate the cause of severe TR in patients receiving a pacemaker or ICD.

We examined the effect of gender-associated differences in pharmacokinetics on the anti-arrhythmic effects of flecainide in Japanese patients with supraventricular tachyarrhythmia and in healthy subjects.The study population comprised 72 outpatients (52 males and 20 females) treated with oral flecainide for supraventricular tachyarrhythmias. Serum flecainide concentrations were determined by use of high-performance liquid chromatography. The anti-arrhythmic efficacy of flecainide was assessed for at least 2 months through evaluation of symptomatology, electrocardiograms, and Holter monitoring. Pharmacokinetics of flecainide after a single 50-mg dose was examined in 14 healthy subjects (7 males and 7 females).The daily dose of flecainide did not differ between males and females (2.87 +/- 0.68 versus 2.92 +/- 0.90 mg/kg). The serum flecainide concentration was significantly lower in males than in females (315 +/- 151 versus 408 +/- 184 ng/mL, P0.05). Clinically relevant efficacy of flecainide was achieved significantly (P0.05) less often in male patients (31 of 52; 60%) than in female patients (19 of 20; 95%). We confirmed that nonrenal clearance of flecainide among healthy subjects was significantly higher in males than in females (0.77 +/- 0.16 versus 0.57 +/- 0.06 L h(-1) kg(-1), P0.05).Our results suggest that the anti-arrhythmic efficacy of flecainide differed between males and females because of gender-associated differences in pharmacokinetics.

Background Regeneration of the lung microvasculature and replacing pulmonary artery lesions with functional endothelial cells could be a novel and effective therapeutic strategy for treating advanced pulmonary arterial hypertension (PAH). In the present study it was postulated that granulocyte colony-stimulating factor (G-CFS), which induces the proliferation of endothelial cells, would stimulate endothelial regeneration in situ at sites of impaired lung vasculature and prevent the development of PAH. Methods and Results Daily administration of G-CSF for 48 days did not affect the hemodynamism of normal Fischer 344 rats. PAH was induced with monocrotaline (60 mg/kg) and G-CSF was administered daily (100 μg/kg per day). Echocardiographic findings and an invasive catheter study indicated a significant decrease in the progression of PAH in rats given G-CSF. Furthermore, G-CSF increased Ki-67 positivity in the pulmonary arteries of PAH rats but did not accelerate c-kit positive cell recruitment into peripheral blood. Daily doses of G-CSF at both 2 and 100 μg/kg improved the survival and body weight gain of PAH rats. Conclusions G-CSF improved the progression of PAH in a rat model, possibly by stimulating pulmonary endothelial cells to proliferate at sites of impaired lung vasculature. These findings show that cytokine therapy for PAH is valid based on the concept of vascular regeneration. (Circ J 2007; 71: 138 - 143)

Background: Much attention has been focused on the primary prevention of ischemic heart disease (IHD), but the prevalence and prognostic indicators of IHD remain unclear in healthy Japanese subjects. Hypothesis: The purpose of this study was to determine the predictors for the transition of IHD in healthy adult subjects using data from annual medical examinations. Methods: We analyzed clinical data on 2,710 healthy subjects (1,836 men and 874 women aged 26–76 years in 2000) who underwent medical examinations in both 2000 and 2002. Ischemic changes in the electrocardiogram (ECG) suggestive of IHD were defined as the existence of abnormal Q-wave and/or ST-T abnormalities without left ventricular high voltage. We assigned the subjects to two groups: the ischemic heart group (Group I), including subjects with normal ECG findings in 2000, followed by suspicious ischemic changes in the ECGs in 2002; and the normal group (Group N), including subjects with normal ECGs in both 2000 and 2002. Results: Fifty-nine subjects (2%, 20 women) were assigned to Group I and 2,538 subjects (96%, 810 women) were assigned to Group N. There were significant differences between the two groups in baseline age (Group I vs. Group N: 53 vs. 47 years, p < 0.001), body mass index (24 vs. 23 kg/m2, p = 0.036), systolic blood pressure (132 vs. 122 mmHg, p

Magnetocardiography (MCG) is a non-invasive and non-contact mapping technique to analyze cardiac electromagnetic activities. The SQUID (superconducting quantum interference device) system has made it possible to detect very weak cardiac magnetic signals noninvasively. In electrocardiography (ECG), the conductivity of electric current varies according to body composition, while in MCG, conductivity of magnetic field is constant regardless of body composition. Moreover, as the magnetic field detected in MCG originates not from the cardiac 'volume current' as in ECG, but from the cardiac 'primary current', the cardiac electromagnetic information of the MCG is minimally distorted. Furthermore, ECG is a record of a potential difference, so it gives only a relative value, while magnetic field strength is an absolute value. Therefore, MCG is expected to be more sensitive to minute electromagnetic abnormalities of heart disease than ECG. In this article, we discuss the usefulness of MCG in diagnosing ischemic heart diseases and arrhythmias.

Septic shock is characterized by hypotension and a hyporeactive response to vasopressor agents. The pathogenesis is due to vascular leaks and an increased synthesis of cytokines and nitric oxide (NO). The present study examined the time-dependent alterations of endothelin-1 (ET-1) and the expression of NO synthase (NOS) in lung tissue in a septic rat model. Normal Sprague-Dawley (SD) rats aged 10 weeks received 15 mg/kg lipopolysaccharide (LPS) and then were sacrificed at different time points (1, 3, 6, and 10 hrs). Rats that did not receive LPS were considered to be controls. Both systolic and diastolic pressure decreased in SD rats after LPS administration. Time-dependent onset of features of acute lung injury, such as the infiltration of inflammatory cells and thickening of alveolar septa, were seen in rats that received LPS. A 2.8-fold increase in the expression of preproET-1 level was observed in lung tissue 6 hrs after LPS administration. The expression of endothelial NOS (eNOS) was also altered in lung tissue in a time-dependent fashion. After the administration of LPS, there was a 16-fold increase in the expression of eNOS mRNA. The peak expression of inducible NOS (iNOS) in lung tissue specimens obtained from rats that received LPS was 45-fold higher than that in control rats. ET-1 is a potent vasoconstrictor and thereby may play an important role in the pathogenesis of acute lung injury in a septic rat model. The increased expression of NOS may result in excess NO production and may also play a role in the pulmonary complications of endotoxemia.

Human heart failure is preceded by a process called cardiac remodeling, in which heart chambers progressively enlarge and contractile function deteriorates. Programmed cell death (apoptosis) of cardiac muscle cells has been identified as an essential process in the progression to heart failure. The execution of the apoptotic program entails complex interactions between and execution of multiple molecular subprograms. Endothelin (ET)-1, a potent vasoconstrictor peptide, is synthesized and secreted by cardiomyocytes and induces hypertrophy of cardiomyocytes. The cardiovascular benefit of fish oil containing eicosapentaenoic acid (EPA) in humans and experimental animals was reported. Recently, we found that ET-1-induced cardiomyocytic remodeling could be prevented by pretreatment with EPA. The aim of the present study is to investigate whether there would be any alteration in the expression of important apoptosis-related molecules in ET-1-administered hypertrophied cardiomyocytes. We also sought to determine, if there are alterations in apoptotic molecules, what type of role for EPA would then exist. Ventricular cardiomyocytes were isolated from 2-day-old Sprague-Dawley rats and were cultured for 3 days. At Day 4 of culture, the cardiomyocytes were divided into three groups: control, the ET-1 (0.1 nM)-treated group, and the ET-1 group pretreated with EPA (10 microM). Twenty-four hours after the treatment, the gene expressions of three important molecules related to apoptosis (caspase-3, Bax, and Bcl-2) in three experimental groups were evaluated by real-time polymerase chain reaction. The present study could not demonstrate any significant or representative alteration in any of the above three apoptosis-related important markers in either ET-1-induced hypertrophied cardiomyocytes with or without EPA pretreatment. The present study would at least be able to exclude the involvement of some representative molecules related to apoptosis in ET-1-induced hypertrophied cardiomyocytes. In addition, the present study demonstrates that the antihypertrophic effect of EPA to ET-1-administered cardiomyocytes appears not to modulate the apoptosis signaling cascade.

Erectile dysfunction (ED) affects approximately 50% of male patients with diabetes mellitus (DM) and is possibly due to the vascular and neuropathic complications of DM. Recently, apoptosis has been regarded as a downstream event in ED. More recently, the importance of alterations in apoptosis-related molecules in the mechanism of DM-induced ED has begun to be appreciated. Endothelin-1 (ET-1) plays a role via ET(A) and ET(B) receptors in the regulation of cavernosal smooth-muscle tone in penile tissues. We found that the ET-1 level in the penis of rats with DM was higher than that in the penis of control animals. The present study investigated a rat model in which DM was induced by a 3-week regimen of streptozotocin (STZ) to assess the expression of several apoptosis-related molecules in penile tissue and, concomitantly, the effects of ET antagonism on these changes. Male Sprague-Dawley rats (weight [+/-SD], 450 +/- 26 g) received a citrate saline vehicle or STZ (65 mg/kg ip). DM was confirmed by the presence of hyperglycemia. Diabetic animals were further separated into two treatment groups 1 week after onset of disease: one group received ET(A/B) dual receptor antagonist (SB209670) by means of osmotic minipump at a dosage of 1 mg/day, and the other group received saline. Rats in both groups were treated for 2 weeks and then sacrificed. Plasma glucose levels (+/-SD) in rats with DM were significantly higher than those in rats without DM (506 +/- 70 vs. 111 +/- 11 mg/dl). In the penile tissue of rats with DM, a 35% decrease in the expression of Bcl-2 protein (an important antiapoptotic marker detectable by immunoblotting) was seen, and ET(A/B) dual antagonist was observed to significantly counteract this decrease. Real-time polymerase chain reaction revealed that the expression of Bcl-2 mRNA was consistent with Bcl-2 protein expression. Levels of Bax and caspase-3, two important proapoptotic markers, were not significantly altered in the present study. Thus, we conclude that, in the penis of rats with early stage DM, the protection against apoptosis has decreased but can be improved by ET antagonism.

During severe sepsis, several immunological defense mechanisms initiate a cascade of inflammatory events leading to multiorgan failure, including septic encephalopathy and ultimately death. Endothelin-1 (ET-1) has recently been investigated in different cerebral pathologies. Some reports suggest the involvement of ET-1 in sepsis. However, no study to date has reported the alterations in expression of the genes encoding preproET-1 and ET receptors in the frontal cortex of the septic brain. Male Sprague-Dawley (SD) rats 8 weeks of age were administered either saline or 15 mg/kg lipopolysaccharide (LPS) at different time points (1, 3, 6, and 10 hrs). Rats that did not receive LPS were considered to be controls. The rats were sacrificed with ether, and the brain tissues were harvested. Systolic and diastolic blood pressure decreased 1 hr after LPS administration and then gradually returned to normal, without any change in the heart rate. We confirmed the induction of endotoxemia in the brains of SD rats by measuring the expression of nitric oxide synthase (NOS) mRNA induced in the cerebrum. The expression of inducible NOS (iNOS) mRNA in the brains of SD rat after LPS administration was 30-fold higher than that in the brains of control rats. mRNA expression of preproET-1 in the frontal cortex of SD rats after LPS administration was 2-fold higher than that in control rats. A time-dependent increase in the expression of the gene encoding the ET(A) receptor (vasoconstrictive property) after LPS administration was observed in SD rat brain, whereas expression of the gene encoding the ET(B) receptor (vasodilatatory property) showed an initial upregulation and then gradually decreased as sepsis progressed. In conclusion, we report for the first time that expressions of the genes encoding ET-1 and ET receptors are altered in the endotoxemic brain and that these alterations are time-dependent in SD rats. The alterations in the ET system in brain tissue observed in the present study may contribute to the understanding of the pathophysiological changes in the endotoxemic brain.

Vascular tone is regulated through the actions of locally produced agents. Among the vasoconstrictors, the most potent agent is endothelin (ET), which exerts its vasoconstrictor actions principally through ET type A (ET(A)) receptors. Of the vasodilators, nitric oxide (NO) seems to be the most important contributor to the acute regulation of vascular tone. Vasculopathy is an important feature of diabetes mellitus (DM). Endogenous ET-mediated vasoconstrictor tone is augmented in diabetic states, and conflicting results persist concerning the NO system in diabetes. The present study investigated the expressions of inducible NO synthases (iNOS) and endothelial NOS (eNOS) in the heart of diabetic animals and the effects of a selective ET(A) receptor antagonist on these alterations. Type I diabetes was induced by intraperitoneal injection of streptozotocin (65 mg/kg) in Sprague-Dawley rats, while control (Con) rats received only citrate buffer. After 1 week, the streptozotocin-administered rats were randomly divided into two groups: the selective ET(A) receptor antagonist-administered group (DM+TA-0201, 1 mg/kg/day, by osmotic minipump for 2 weeks) and the DM+vehicle group (comprising the diabetic rats that received saline). The random blood glucose level was 405 +/- 103 mg/dl in DM animals, and this level was unchanged by ET antagonism. Body weight was more greatly decreased in DM rats than in Con rats, but the left ventricle to body weight ratio was increased in the DM group and was unaffected by ET antagonism. Protein expressions of eNOS and iNOS were assessed in the left ventricular tissues. eNOS expression was significantly increased in DM heart and was greatly inhibited by the treatment with ET antagonist. The expression of iNOS was also increased in early DM heart but was reversed by the ET antagonist. Thus, endothelin antagonism might be beneficial for DM heart by reversing the upregulated eNOS and iNOS expressions.

Cardiovascular complications are an important feature of diabetes mellitus (DM). Abnormal and decreased coronary collateral development has been implicated in the pathogenesis of cardiac complications in DM. More recently, decreased expression of vascular endothelial growth factor (VEGF) and its receptors has been found in diabetic heart. To our knowledge, no study has focused on the therapeutic improvement associated with VEGF in diabetic heart. DM was induced by intraperitoneal injection of streptozotocin (65 mg/kg) in Sprague-Dawley rats, while control rats received only citrate buffer. After 1 week, the streptozotocin-treated rats were randomly divided into two groups: one group received the selective endothelin (ET) type A receptor antagonist TA-0201 at a dose of 1 mg/kg/day for 2 weeks by osmotic mini-pump, and the vehicle group received saline only. The plasma glucose level was 504 +/- 75 mg/dl in the diabetic rats and was unchanged by treatment with ET antagonist. The body weight was decreased in the diabetic rats compared with the control rats, but the left ventricular (LV)-body weight ratio was increased in the diabetic group and was unaffected by treatment with ET antagonist. mRNA expression of VEGF and its receptors (Flt-1 and Flk-1) in the LV tissues was assessed using real-time polymerase chain reaction. VEGF expression was significantly decreased in diabetic heart and was greatly improved by treatment with ET antagonist. The expression of VEGF receptors was down-regulated in early diabetic heart but was not recovered by treatment with ET antagonist. ET and its receptor A might have differential regulation on the gene expressions of VEGF and its receptors in early diabetic heart.