著者
Lin Gao Grant Bledsoe Hang Yin Bo Shen Lee Chao Julie Chao
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-12-1585, (Released:2013-05-21)
参考文献数
35
被引用文献数
5 13

Background: Genetically modified mesenchymal stem cells (MSCs) are a promising approach to the treatment of cardiac injury after myocardial infarction (MI). Methods and Results: Rat MSCs were transduced with adenovirus containing human tissue kallikrein (TK) gene (TK-MSCs), and they secreted human TK into culture medium. Cultured TK-MSCs were more resistant to hypoxia-induced apoptosis and exhibited reduced caspase-3 activity compared to control GFP-MSCs. The effect of TK-MSC injection on cardiac injury was evaluated in rats at 1 and 14 days after MI. At 1 day after MI, human TK expression in the myocardium was associated with improved cardiac function and decreased inflammatory cell accumulation, proinflammatory gene expression and apoptosis. The beneficial effect of TK-MSCs against apoptosis was verified in cultured cardiomyocytes, as TK-MSC-conditioned medium suppressed hypoxia-induced apoptosis and caspase-3 activity, and increased Akt phosphorylation. At 2 weeks after MI, TK-MSCs improved cardiac function, decreased infarct size, attenuated cardiac remodeling, and promoted neovascularization, as compared to GFP-MSCs. Furthermore, the TK-MSC-conditioned medium, containing elevated vascular endothelial growth factor levels, stimulated the proliferation, migration and tube formation of cultured human endothelial cells. Conclusions: Our results indicate that TK-modified MSCs provide enhanced protection against cardiac injury, apoptosis and inflammation, and promote neovascularization after MI, leading to cardiac function improvement.
著者
Hiroaki Ichimori Shigetoyo Kogaki Kunihiko Takahashi Hidekazu Ishida Jun Narita Nobutoshi Nawa Hiroki Baden Toshiki Uchikawa Yoko Okada Keiichi Ozono
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-12-0997, (Released:2013-05-18)
参考文献数
37
被引用文献数
5 8

Background: To investigate the possible role of sex hormones in the pathogenesis of pulmonary arterial hypertension (PAH), the effect of β-estradiol (E2) on bone morphogenetic protein (BMP) signaling, a key signaling pathway involved in PAH, was studied in human pulmonary arterial endothelial cells (HPAEC). Methods and Results: BMP signaling molecules, including BMP receptor, Smad1/5/8 and Id1, were studied in HPAEC under 1% O2 (hypoxia) and 21% O2 (normoxia) as well as the effect of hypoxia-inducible factor (HIF)-1α expression in the presence of E2 on BMP signaling. The effects of an estrogen receptor (ER) antagonist (ICI 182,780) and cycloheximide, and the interaction of ER with Smad or HIF-1α were also studied. In the presence of E2, BMP signaling was augmented under normoxia but suppressed under hypoxia. HIF-1α accumulation suppressed BMP signaling, whereas HIF-1α inhibition augmented signaling. These effects were cancelled by ICI 182,780. Moreover, binding between ER, HIF-1α and phosphorylated (p)-Smad1/5/8 proteins occurred only under hypoxia. On inhibition of de novo synthesis with cycloheximide, however, p-Smad1/5/8 expression was suppressed only under normoxia. Conclusions: The effects of E2 on BMP signaling in HPAEC altered depending on O2 concentration and different mechanisms may be involved. BMP and sex hormones may play an important role in PAH development.
著者
Takayuki Yoshinaga Satoshi Ikeda Masahiro Shikuwa Yoshiyuki Miyahara Shigeru Kohno
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.67, no.3, pp.229-232, 2003 (Released:2003-02-25)
参考文献数
25
被引用文献数
17 23

Pulmonary thromboembolism (PTE) is associated with various electrocardiogram (ECG) abnormalities, but the utility of evaluating the severity of PTE based on ECG abnormalities alone has not been investigated in Japanese patients previously. The purpose of this study was to examine the relationship between ECG abnormalities and the mean pulmonary artery pressure (MPAP) in patients with acute massive PTE (AMPTE). ECG examination of 21 patients, who were diagnosed with AMPTE by pulmonary arteriography, found that S1Q3T 3 was the most frequently observed abnormality (in 67% of the patients), followed by negative T (62%), clockwise rotation (57%), and ST elevation (48%). When these patients were divided into 2 groups based on the level of MPAP, 8 of the 11 ECG findings, which were associated with PTE in a previous report, were more frequently observed in Group H (MPAP ≥40 mmHg) than in Group L (MPAP <40 mmHg). MPAP correlated significantly with the total number of ECG abnormalities (r=0.82, p<0.001). In particular, at least 5 ECG abnormalities were noted in patients with MPAP ≥45 mmHg. These results suggested that the total number of ECG abnormalities in patients with AMPTE can be used to evaluate the severity of APTE, including PAP level. (Circ J 2003; 67: 229 - 232)
著者
Masami Kosuge Kazuo Kimura Toshiyuki Ishikawa Toshiaki Ebina Kiyoshi Hibi Kengo Tsukahara Masahiko Kanna Noriaki Iwahashi Jyun Okuda Naoki Nozawa Hiroyuki Ozaki Hideto Yano Tatuya Nakati Ikuyoshi Kusama Satoshi Umemura
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.70, no.6, pp.750-755, 2006 (Released:2006-05-25)
参考文献数
27
被引用文献数
31 35

Background The significance of inverted T waves remains unclear in patients with acute pulmonary embolism (PE). Methods and Results The relationship of the number of leads with inverted T waves to the severity of PE in 40 patients with acute PE was studied. Patients were classified into 3 groups according to the number of leads with inverted T waves on the admission electrocardiogram (ECG): 15 patients, ≤3 leads (group L); 12 patients, 4-6 leads (group M); and 13 patients, ≥7 leads (group H). In groups L, M and H, the rates of right ventricular dysfunction on echocardiography were 47%, 92% and 100% (p<0.01), respectively, and the rates of in-hospital complicated events (including death or the need for catecholamine support, cardiopulmonary resuscitation or mechanical cardiovascular support because of hemodynamic instability) were 0%, 8% and 46% (p=0.004), respectively. On multivariate analysis, arterial hypotension at presentation (odds ratio (OR) 8.96, p=0.049) and inverted T waves in ≥7 leads on the admission ECG (OR 16.8, p=0.037) were the only independent predictors of in-hospital complicated events. Conclusions The number of leads with inverted T waves may be a useful and simple marker of increased risk for early complications in patients with acute PE. (Circ J 2006; 70: 750 - 755)
著者
Ryozo Nagai Koichiro Kinugawa Hiroshi Inoue Hirotsugu Atarashi Yoshihiko Seino Takeshi Yamashita Wataru Shimizu Takeshi Aiba Masafumi Kitakaze Atsuhiro Sakamoto Takanori Ikeda Yasushi Imai Takashi Daimon Katsuhiro Fujino Tetsuji Nagano Tatsuaki Okamura Masatsugu Hori the J-Land Investigators
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.77, no.4, pp.908-916, 2013 (Released:2013-03-25)
参考文献数
24
被引用文献数
21 93

Background: A rapid heart rate (HR) during atrial fibrillation (AF) and atrial flutter (AFL) in left ventricular (LV) dysfunction often impairs cardiac performance. The J-Land study was conducted to compare the efficacy and safety of landiolol, an ultra-short-acting β-blocker, with those of digoxin for swift control of tachycardia in AF/AFL in patients with LV dysfunction. Methods and Results: The 200 patients with AF/AFL, HR ≥120beats/min, and LV ejection fraction 25–50% were randomized to receive either landiolol (n=93) or digoxin (n=107). Successful HR control was defined as ≥20% reduction in HR together with HR <110beats/min at 2h after starting intravenous administration of landiolol or digoxin. The dose of landiolol was adjusted in the range of 1–10μg·kg–1·min–1 according to the patient’s condition. The mean HR at baseline was 138.2±15.7 and 138.0±15.0beats/min in the landiolol and digoxin groups, respectively. Successful HR control was achieved in 48.0% of patients treated with landiolol and in 13.9% of patients treated with digoxin (P<0.0001). Serious adverse events were reported in 2 and 3 patients in each group, respectively. Conclusions: Landiolol was more effective for controlling rapid HR than digoxin in AF/AFL patients with LV dysfunction, and could be considered as a therapeutic option in this clinical setting.  (Circ J 2013; 77: 908–916)
著者
Ryozo Nagai Koichiro Kinugawa Hiroshi Inoue Hirotsugu Atarashi Yoshihiko Seino Takeshi Yamashita Wataru Shimizu Takeshi Aiba Masafumi Kitakaze Atsuhiro Sakamoto Takanori Ikeda Yasushi Imai Takashi Daimon Katsuhiro Fujino Tetsuji Nagano Tatsuaki Okamura Masatsugu Hori the J-Land Investigators
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-12-1618, (Released:2013-03-15)
参考文献数
24
被引用文献数
21 93

Background: A rapid heart rate (HR) during atrial fibrillation (AF) and atrial flutter (AFL) in left ventricular (LV) dysfunction often impairs cardiac performance. The J-Land study was conducted to compare the efficacy and safety of landiolol, an ultra-short-acting β-blocker, with those of digoxin for swift control of tachycardia in AF/AFL in patients with LV dysfunction. Methods and Results: The 200 patients with AF/AFL, HR ≥120beats/min, and LV ejection fraction 25–50% were randomized to receive either landiolol (n=93) or digoxin (n=107). Successful HR control was defined as ≥20% reduction in HR together with HR <110beats/min at 2h after starting intravenous administration of landiolol or digoxin. The dose of landiolol was adjusted in the range of 1–10μg·kg–1·min–1 according to the patient’s condition. The mean HR at baseline was 138.2±15.7 and 138.0±15.0beats/min in the landiolol and digoxin groups, respectively. Successful HR control was achieved in 48.0% of patients treated with landiolol and in 13.9% of patients treated with digoxin (P<0.0001). Serious adverse events were reported in 2 and 3 patients in each group, respectively. Conclusions: Landiolol was more effective for controlling rapid HR than digoxin in AF/AFL patients with LV dysfunction, and could be considered as a therapeutic option in this clinical setting.
著者
Clément Delmas Olivier Lairez Emmanuel Mulin Thomas Delmas Nicolas Boudou Nicolas Dumonteil Caroline Biendel-Picquet Jérôme Roncalli Meyer Elbaz Michel Galinier Didier Carrié
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.77, no.1, pp.175-180, 2013 (Released:2012-12-25)
参考文献数
40
被引用文献数
17 53 32

Background: Recent retrospective studies suggest that psychiatric disorders could be a predisposing risk factor for Tako-tsubo cardiomyopathy (TTC). The aim of the present study was to characterize the prevalence of anxiodepressive disorders (ADD) and chronic psychological stress (CPS) in patients with TTC or acute coronary syndrome (ACS). Methods and Results: Between January 2010 and December 2011, 45 consecutive patients with TTC were prospectively screened by systematic interview with the Mini International Neuropsychiatric Interview. CPS was systematically recorded. During the same period, 50 patients admitted for ACS with troponin elevation and matched for age and sex were prospectively included as a control group. An acute stressful event within 72h before presentation was identified in 35 patients (78%) with TTC vs. 9 (18%) with ACS (P<0.001). Thirty-five patients (78%) and 13 (26%) had ADD in the TTC and ACS groups, respectively (P<0.001). CPS was found in 20 patients (44%) and in 9 (18%) with TTC and ACS, respectively (P=0.005). CPS and/or ADD were found in 35 patients (78%) and in 18 (36%) with TTC and ACS, respectively (P<0.001). Conclusions: ADD and CPS are common in patients with TTC and more frequent than in patients with ACS. This finding suggests that systemic effects of ADD and CPS could participate in the pathophysiology of TTC.  (Circ J 2013; 77: 175–180)
著者
Taigo Kintaka Takao Tanaka Makoto Imai Itaru Adachi Isamu Narabayashi Yasushi Kitaura
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.66, no.9, pp.819-825, 2002 (Released:2002-08-25)
参考文献数
35
被引用文献数
6 18

Homozygous or compound heterozygous mutation of the CD36 gene (CD36-/-) in humans results in severe defects of the uptake of long-chain fatty acids (LCFAs) in the heart. Because the effect of a single mutation of this gene (CD36+/-) on the LCFA uptake is not known, it was evaluated in 29 subjects with the CD36 wild-type gene (WT) (6 healthy subjects, 10 patients with heart disease), CD36+/- (4 healthy subjects, 5 patients) and CD36-/- (4 patients). The CD36 genotype was identified in the coding region of genomic DNA, and the expression of CD36 protein was examined by flow cytometry after staining with monoclonal anti-CD36 antibody. The LCFA uptake in the heart was assessed as the radioactivity accumulation ratio of heart to mediastinum after intravenous administration of iodine-123 15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid (H/M ratio). The H/M ratios in WT, CD36+/- and CD36-/- were 2.28±0.10, 1.90±0.06 and 1.40±0.11, respectively (p<0.0001, among groups). The H/M ratio between healthy subjects and patients with heart disease for WT and CD36+/- did not differ significantly (ie, those of WT and CD36+/- in healthy subjects and patients were 2.29±0.08 vs 2.27±0.12 and 1.90±0.07 vs 1.89±0.05, respectively). Not only CD36-/- but also CD36+/- resulted in a significant reduction of the LCFA uptake in the heart independent of heart disease, suggesting genotype dependency and that CD36 might be a fundamental determinant of myocardial LCFA uptake. (Circ J 2002; 66: 819 - 825)
著者
Tsukasa Kamakura Takeru Makiyama Kenichi Sasaki Yoshinori Yoshida Yimin Wuriyanghai Jiarong Chen Tetsuhisa Hattori Seiko Ohno Toru Kita Minoru Horie Shinya Yamanaka Takeshi Kimura
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-12-0987, (Released:2013-02-09)
参考文献数
34
被引用文献数
28 221

Background: In the short- to mid-term, cardiomyocytes generated from human-induced pluripotent stem cells (hiPSC-CMs) have been reported to be less mature than those of adult hearts. However, the maturation process in a long-term culture remains unknown. Methods and Results: A hiPSC clone generated from a healthy control was differentiated into CMs through embryoid body (EB) formation. The ultrastructural characteristics and gene expressions of spontaneously contracting EBs were analyzed through 1-year of culture after cardiac differentiation was initiated. The 14-day-old EBs contained a low number of myofibrils, which lacked alignment, and immature high-density Z-bands lacking A-, H-, I-, and M-bands. Through the long-term culture up to 180 days, the myofibrils became more tightly packed and formed parallel arrays accompanied by the appearance of mature Z-, A-, H-, and I-bands, but not M-bands. Notably, M-bands were finally detected in 360-day-old EBs. The expression levels of the M-band-specific genes in hiPSC-CMs remained lower in comparison with those in the adult heart. Immunocytochemistry indicated increasing number of MLC2v-positive/MLC2a-negative cells with decreasing number of MLC2v/MLC2a double-positive cells, indicating maturing of ventricular-type CMs. Conclusions: The structural maturation process of hiPSC-CMs through 1-year of culture revealed ultrastructural sarcomeric changes accompanied by delayed formation of M-bands. Our study provides new insight into the maturation process of hiPSC-CMs.
著者
Francisco J. Pastor-Pérez Sergio Manzano-Fernández Rebeca Goya-Esteban Domingo A. Pascual-Figal Oscar Barquero-Pérez Jose Luis Rojo-Álvarez Estrella Everss Maria Dolores Martinez Martinez-Espejo Mariano Valdés Chavarri Arcadi García-Alberola
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.76, no.9, pp.2124-2129, 2012 (Released:2012-08-24)
参考文献数
30
被引用文献数
3

Background: Abnormalities in autonomic control are a feature of neuroendocrine activation in HF and are responsible for dysregulation of biological rhythms. The purpose was to investigate the presence and the prognostic significance of long-period heart rate (HR) rhythms in heart failure (HF) patients. Methods and Results: In the study, 92 HF patients were enrolled (age 53±14 years and left ventricular ejection fraction [LVEF] 37±10%). A rhythmometric analysis was used to assess the HR rhythms in 7-days (7D) Holter recordings. Rhythms properties were quantified by mesor and amplitude, in beats/min and by acrophase, in hours. Cardiac death or HF decompensation were registered. All patients had 24-h rhythm, 61 patients (77%) had 8-h rhythm, and 66 patients (83%) had 7D rhythm. Twelve patients (15%) experienced events. Among rhythm parameters only 7D median amplitude was different between patients with or without events: 1.1beats/min [0.5–1.5] vs. 2.0beats/min [0.0–3.9], P=0.049 respectively. After multivariate adjustment, LVEF (per 1%, hazard ratio 0.92, 95% confidence interval (CI) 0.87 to 0.98, P=0.01), N-terminal portion of pro-natriuretic hormone type B (per 100pg/ml, hazard ratio 1.036, 95% CI 1.005–1.069, P=0.022), and 7D amplitude of the HR ≤1.71beats/min (hazard ratio 5.4, 95% CI 1.2–34.4, P=0.047) were independent predictors of events. Conclusions: A 7D HR rhythm is present in most patients with HF, and has prognostic significance.  (Circ J 2012; 76: 2124–2129)
著者
Jae-Sik Jang Han-Young Jin Jeong-Sook Seo Tae-Hyun Yang Dae-Kyeong Kim Tae Hee Kim Sang-Hwa Urm Dong-Soo Kim Dong-Kie Kim Sang-Hoon Seol Doo-Il Kim Kyoung-Im Cho Bo-Hyun Kim Yong Hyun Park Hyung-Gon Je Jung-Min Ahn Won-Jang Kim Jong-Young Lee Seung-Whan Lee
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.76, no.9, pp.2255-2265, 2012 (Released:2012-08-24)
参考文献数
65
被引用文献数
39 74

Background: Sodium bicarbonate has been postulated to prevent contrast-induced acute kidney injury (CI-AKI) by various mechanisms, although the reports are conflicting. Methods and Results: We searched MEDLINE, EMBASE, and the Cochrane databases for randomized controlled trials that compared a sodium chloride with a sodium bicarbonate hydration regimen with regard to CI-AKI. Data across 19 clinical trials consisting of 3,609 patients were combined. Preprocedural hydration with sodium bicarbonate was associated with a significant decrease in the rate of CI-AKI (odds ratio [OR] 0.56; 95% confidence interval [CI] 0.36–0.86; P=0.008). Stratified analyses by the type of contrast medium suggested lower odds of CI-AKI with sodium bicarbonate in studies using low-osmolar contrast media (OR 0.40; 95% CI 0.23–0.71, P=0.002) compared with those using the iso-osmolar agents (OR 0.76; 95% CI 0.41–1.43; P=0.40). No significant difference in the rates of postprocedural death (OR 0.49; 95% CI 0.23–1.04; P=0.06) and the requirement for renal replacement therapy (OR 0.94; 95% CI 0.46–1.91; P=0.86) was observed. However, we found significant changes in serum bicarbonate and potassium levels after sodium bicarbonate infusion. Conclusions: This updated meta-analysis demonstrates that sodium bicarbonate-based hydration is superior to sodium chloride in preventing CI-AKI of patients undergoing exposure to iodinated contrast media.  (Circ J 2012; 76: 2255–2265)
著者
Daisuke Hazeki Masao Yoshinaga Hideto Takahashi Yuji Tanaka Yasue Haraguchi Mayumi Abe Masami Koga Toshiro Fukushige Masami Nagashima
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.74, no.8, pp.1663-1669, 2010 (Released:2010-07-23)
参考文献数
12
被引用文献数
13 33 8

Background: The corrected QT interval (QTc) according to Bazett's formula (QTc = QT/RR1/2) has been used in clinical practice. Bazett's formula, however, overcorrects the QT interval at fast heart rates and undercorrects it at low heart rates. Guidelines and some investigators have recommended using Fridericia's formula (QTc = QT/RR1/3) in these cases, especially in tachycardic subjects. The aim of the present study was to determine cut-offs for QTc suitable for screening pediatric subjects with prolonged QT intervals, based on manually measured values corrected by Fridericia's formula in a large number of subjects. Methods and Results: Three consecutive QT and RR intervals were measured in 4,655, 4,655, and 5,273 1st, 7th, and 10th graders, aged 6, 12, and 15 years, respectively. Each QT interval was corrected by Fridericia's formula, and mean values were calculated. Determination of the cut-offs for screening was based on the prevalence of abnormal electrocardiographic phenotypes of 1:1,164 and on the upper 0.025 percentile in the QTc distribution derived from previous studies. The tentative cut-offs suitable for screening subjects with prolonged QT intervals were 430 ms for 1st graders, 445 ms for 7th graders, and 440 and 455 ms for 10th grade boys and girls, respectively. Conclusions: These tentative cut-offs can be used to screen subjects with prolonged QT intervals in the clinical setting. Further studies are needed to confirm their validity.  (Circ J 2010; 74: 1663 - 1669)
著者
Keita Noda Bo Zhang Atsushi Iwata Hiroaki Nishikawa Masahiro Ogawa Takashi Nomiyama Shin-ichiro Miura Hideto Sako Kunihiro Matsuo Eiji Yahiro Toshihiko Yanase Keijiro Saku on behalf of the STYLIST Study Investigators
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.76, no.6, pp.1335-1344, 2012 (Released:2012-05-25)
参考文献数
30
被引用文献数
10 15 4

Background: Dietary habits are associated with obesity, and both are important contributing factors to lifestyle-related diseases. The STYLIST study examined the effects of dietary counseling by registered dietitians and the delivery of proper calorie-controlled meals (UMIN Registration No: 000006582). Methods and Results: Two-hundred adult patients with hypertension and/or diabetes mellitus were randomly divided into 2 groups with/without dietary counseling and consumed an ordinary diet for 4 weeks. Each group was then subdivided into 2 groups with/without dietary counseling and received calorie-controlled lunch and dinner boxes for the next 4 weeks. The calories in the delivered meals were based on the subject's ideal body weight (BW) and physical activity level. BW, waist circumference, blood pressure, and laboratory data, including glycoalbumin, were measured at 0, 4, and 8 weeks. BW and the other parameters were significantly reduced during the study period in patients who received diet counseling in the ordinary diet period and/or delivered meal period but not in patients without dietary counseling, as assessed by linear mixed models for longitudinal data. Conclusions: The combination of dietary counseling by dietitians and delivery of calorie-controlled meals was effective in reducing BW, as well as blood pressure and glycoalbumin, in patients with hypertension and/or diabetes mellitus. (Circ J 2012; 76: 1335-1344)
著者
Hiroshi Fujii Yu Ikeuchi Yasutaka Kurata Nobuhito Ikeda Udin Bahrudin Peili Li Yuji Nakayama Ryo Endo Akira Hasegawa Kumi Morikawa Junichiro Miake Akio Yoshida Kyoko Hidaka Takayuki Morisaki Haruaki Ninomiya Yasuaki Shirayoshi Kazuhiro Yamamoto Ichiro Hisatome
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-12-0126, (Released:2012-09-04)
参考文献数
27
被引用文献数
3 2

Background: The prion protein (PrP) has been reported to serve as a surface maker for isolation of cardiomyogenic progenitors from murine embryonic stem (ES) cells. Although PrP-positive cells exhibited automaticity, their electrophysiological characteristics remain unresolved. The aim of the present study was therefore to investigate the electrophysiological properties of PrP-positive cells in comparison with those of HCN4p-or Nkx2.5-positive cells. Methods and Results: Differentiation of AB1, HCN5p-EGFP and hcgp7 ES cells into cardiac progenitors was induced by embryoid body (EB) formation. EBs were dissociated and cells expressing PrP, HCN4-EGFP and/or Nkx2.5-GFP were collected via flow cytometry. Sorted cells were subjected to reverse transcriptase-polymerase chain reaction, immunostaining and patch-clamp experiments. PrP-positive cells expressed mRNA of undifferentiation markers, first and second heart field markers, and cardiac-specific genes and ion channels, indicating their commitment to cardiomyogenic progenitors. PrP-positive cells with automaticity showed positive and negative chronotropic responses to isoproterenol and carbamylcholine, respectively. Hyperpolarization-activated cation current (If) was barely detectable, whereas Na+ and L-type Ca2+ channel currents were frequently observed. Their spontaneous activity was slowed by inhibition of sarcoplasmic reticulum Ca2+ uptake and release but not by blocking If. The maximum diastolic potential of their spontaneous firings was more depolarized than that of Nkx2.5-GFP-positive cells. Conclusions: PrP-positive cells contained cardiac progenitors that separated from the lineage of sinoatrial node cells. PrP can be used as a marker to enrich nascent cardiac progenitors.
著者
Francisco J. Pastor-Pérez Sergio Manzano-Fernández Rebeca Goya-Esteban Domingo A. Pascual-Figal Oscar Barquero-Pérez Jose Luis Rojo-Álvarez Estrella Everss Maria Dolores Martinez Martinez-Espejo Mariano Valdés Chavarri Arcadi García-Alberola
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-12-0192, (Released:2012-06-06)
参考文献数
30
被引用文献数
3

Background: Abnormalities in autonomic control are a feature of neuroendocrine activation in HF and are responsible for dysregulation of biological rhythms. The purpose was to investigate the presence and the prognostic significance of long-period heart rate (HR) rhythms in heart failure (HF) patients. Methods and Results: In the study, 92 HF patients were enrolled (age 53±14 years and left ventricular ejection fraction [LVEF] 37±10%). A rhythmometric analysis was used to assess the HR rhythms in 7-days (7D) Holter recordings. Rhythms properties were quantified by mesor and amplitude, in beats/min and by acrophase, in hours. Cardiac death or HF decompensation were registered. All patients had 24-h rhythm, 61 patients (77%) had 8-h rhythm, and 66 patients (83%) had 7D rhythm. Twelve patients (15%) experienced events. Among rhythm parameters only 7D median amplitude was different between patients with or without events: 1.1beats/min [0.5–1.5] vs. 2.0beats/min [0.0–3.9], P=0.049 respectively. After multivariate adjustment, LVEF (per 1%, hazard ratio 0.92, 95% confidence interval (CI) 0.87 to 0.98, P=0.01), N-terminal portion of pro-natriuretic hormone type B (per 100pg/ml, hazard ratio 1.036, 95% CI 1.005–1.069, P=0.022), and 7D amplitude of the HR ≤1.71beats/min (hazard ratio 5.4, 95% CI 1.2–34.4, P=0.047) were independent predictors of events. Conclusions: A 7D HR rhythm is present in most patients with HF, and has prognostic significance.
著者
Yoshitake Yamada Shigeo Okuda Masaharu Kataoka Akihiro Tanimoto Yuichi Tamura Takayuki Abe Tomonori Okamura Keiichi Fukuda Toru Satoh Sachio Kuribayashi
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.1204091687, (Released:2012-04-12)
参考文献数
24
被引用文献数
26 33

Background: Because few have reported the prognostic significance of cardiac magnetic resonance imaging (CMR) for idiopathic pulmonary arterial hypertension (IPAH), in this study we evaluated the value of CMR measurements as a prognostic predictor of IPAH before starting intravenous prostacyclin therapy. Methods and Results: A total of 121 consecutive CMR studies for evaluating right ventricular (RV) function were reviewed. Forty-one patients were diagnosed with IPAH and served as the study group. Factors, such as age, sex, New York Heart Association functional class (NYHAFC), 6-min walk test, plasma brain natriuretic peptide level, serum uric acid level and CMR measurements were analyzed as predictors of first hospitalization and death. The mean follow-up period was 1,350±769 days. Nine patients were hospitalized because of heart failure, and 4 patients died from cardiopulmonary causes. The univariate analyses suggested that the left ventricular (LV) mass index, the left and right ventricular end-diastolic volume indices (LVEDVI, RVEDVI), the LV and RV end-systolic volume indices (LVESVI, RVESVI) and NYHAFC predicted the risk for hospitalization and that RVEDVI, RVESVI and NYHAFC predicted mortality. The multivariate analyses suggested that RVEDVI and NYHAFC are independent predictors of both hospitalization and mortality. The effects of RVEDVI and NYHAFC on hospitalization were not substantially affected by the concomitant medication. Conclusions: In IPAH patients, the RVEDVI predicts both hospitalization for right heart failure and mortality before initiating intravenous prostacyclin therapy.
著者
Hiroki Taguchi Masaharu Kataoka Ryoji Yanagisawa Takashi Kawakami Yuichi Tamura Keiichi Fukuda Hideaki Yoshino Toru Satoh
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.1203131639, (Released:2012-03-16)
参考文献数
30
被引用文献数
15 21

Background: The recent development of various effective drugs, such as epoprostenol, sildenafil, and bosentan, has improved the prognosis for patients with idiopathic pulmonary arterial hypertension (IPAH). This study sought to determine survival rates and to identify predictive prognostic factors in patients with IPAH in the current era of combination therapy with new and more effective vasodilators. Methods and Results: In 65 consecutive IPAH patients treated from 2004 to 2009, hemodynamic parameters were significantly improved and brain natriuretic peptide was significantly decreased by combination therapy (observation period: 35±18 months). The Kaplan-Meier survival curves were determined, and 22 prognostic variables, including 9 hemodynamic variables and 6 biomarkers, were evaluated to obtain the best variables. The 1-year and 3-year survival rates were 98% and 86%, respectively. Only the platelet level was correlated with death (P<0.05), and the platelet level was significantly correlated with mean pulmonary arterial pressure (P<0.01). Patients with a lower platelet level (<20×104/μl (median value)) before treatment had a higher mortality rate compared to the other patients (78% vs. 95% for 3-year survival, P<0.01). Conclusions: Combination therapy contributed to an improvement in the prognosis of IPAH patients. Platelet level is a significant prognostic predictor in this new treatment era.