Research Achievements - Original paper -
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Obstructed bi-leaflet prosthetic mitral valve imaging with real-time three-dimensional transesophageal echocardiography.
Mai Shimbo, Hiroyuki Watanabe, Shunsuke Kimura, Mai Terada, Takako Iino, Kenji Iino, Hiroshi Ito
Journal of clinical ultrasound : JCU 43 ( 1 ) 64 - 7 2015.01 [Refereed]
Research paper (journal)
Real-time three-dimensional transesophageal echocardiography (RT3D-TEE) can provide unique visualization and better understanding of the relationship among cardiac structures. Here, we report the case of an 85-year-old woman with an obstructed mitral prosthetic valve diagnosed promptly by RT3D-TEE, which clearly showed a leaflet stuck in the closed position. The opening and closing angles of the valve leaflets measured by RT3D-TEE were compatible with those measured by fluoroscopy. Moreover, RT3D-TEE revealed, in the ring of the prosthetic valve, thrombi that were not visible on fluoroscopy. RT3D-TEE might be a valuable diagnostic technique for prosthetic mitral valve thrombosis.
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Apnea during Cheyne-Stokes-like breathing detected by a piezoelectric sensor for screening of sleep disordered breathing
Takashi Koyama, Shinichi Sato, Takashi Kanbayashi, Hideaki Kondo, Hiroyuki Watanabe, Seiji Nishino, Tetsuo Shimizu, Hiroshi Ito, Kyoichi Ono
SLEEP AND BIOLOGICAL RHYTHMS 13 ( 1 ) 57 - 67 2015.01 [Refereed]
Research paper (journal)
A simplified diagnostic/monitoring instrument for use in primary screening for sleep-disordered breathing (SDB) has been desired. This study was designed to assess the validity of a newly developed piezoelectric sensor as a simple and noninvasive tool for primary screening for sleep-disordered breathing. Forty-three consecutive patients suspected of having sleep-disordered breathing and 10 healthy volunteers were enrolled. Breathing movement was detected with the piezoelectric sensor (180 × 30 × 1 mm), which was placed under a bed sheet under patients, and simultaneous polysomnographic recordings were obtained. We counted the number of apneas of >10 s, irrespective of central or obstructive, that appeared during Cheyne-Stokes-like breathing with a waxing and waning pattern with an amplitude ratio of >10 in the piezoelectric sensor signal. The correlation coefficient between the number of apneas and apnea–hypopnea index (AHI) was 0.74 (P < 0.0001). The sensitivity/specificity of the number of apneas for distinguishing non-SDB patients from mild SDB patients (AHI ≥ 5) were 92.1/60.0% and those for separating moderate to severe (AHI ≥ 15) and severe (AHI ≥ 30) SDB patients from the other patients were 96.9/100% and 93.8/86.5%, respectively. There were no complaints from patients about the use of the piezoelectric sensor. The results indicate that the number of apneas detected by this piezoelectric sensor during Cheyne-Stokes-like breathing is a potential new index for primary screening for SDB at least for cardiac patients. Thus, the piezoelectric-sensor system might be useful for simple, noninvasive and comfortable SDB screening at home, hospitals and health care facilities.
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Subclinical microalbuminuria as a predictor of heart failure prognosis.
Hiroyuki Watanabe, Kenji Iino, Hiroshi Ito
Circulation journal : official journal of the Japanese Circulation Society 78 ( 12 ) 2838 - 9 2014.12 [Refereed]
Research paper (journal)
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Morning pentraxin3 levels reflect obstructive sleep apnea-related acute inflammation.
Yusuke Kobukai, Takashi Koyama, Hiroyuki Watanabe, Hiroshi Ito
Journal of applied physiology (Bethesda, Md. : 1985) 117 ( 10 ) 1141 - 8 2014.11 [Refereed]
Research paper (journal)
This study investigated morning levels of pentraxin3 (PTX3) as a sensitive biomarker for acute inflammation in patients with obstructive sleep apnea (OSA). A total of 61 consecutive patients with OSA were divided into two groups: non-to-mild (n = 20) and moderate-to-severe (n = 41) OSA based on their apnea-hypopnea index (AHI) score. Those patients with moderate-to-severe OSA were further divided into continuous positive airway pressure (CPAP) treated (n = 21) and non-CPAP-treated (n = 20) groups. Morning and evening serum PTX3 and high-sensitivity (hs) C-reactive protein (CRP) levels were measured before and after 3 mo of CPAP therapy. The baseline hs-CRP and PTX3 levels were higher in patients with moderate-to-severe OSA than in those with non-to-mild OSA. Moreover, the serum PTX3 levels, but not the hs-CRP levels, were significantly higher after than before sleep in the moderate-to-severe OSA group (morning PTX3, 1.96 ± 0.52; evening PTX3, 1.71 ± 0.44 ng/ml). OSA severity as judged using the AHI was significantly correlated with serum PTX3 levels but not hs-CRP levels. The highest level of correlation was found between the AHI and morning PTX3 levels (r = 0.563, P < 0.001). CPAP therapy reduced evening and morning serum hs-CRP and PTX3 levels in patients with moderate-to-severe OSA; however, the reduction in PTX3 levels in the morning was greater than that in the evening (morning -29.8 ± 16.7% vs. evening -12.6 ± 26.8%, P = 0.029). Improvement in the AHI score following CPAP therapy was strongly correlated with reduced morning PTX3 levels(r = 0.727, P < 0.001). Based on these results, morning PTX3 levels reflect OSA-related acute inflammation and are a useful marker for improvement in OSA following CPAP therapy.
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Successful treatment of a patient with purulent pericarditis by daily intrapericardial washouts.
Mai Terada, Hiroyuki Watanabe, Yusuke Kobukai, Takashi Koyama, Mamika Motokawa, Fumio Yamamoto, Hiroshi Ito
The Annals of thoracic surgery 98 ( 4 ) 1451 - 4 2014.10 [Refereed]
Research paper (journal)
Purulent pericarditis in adults is rare, but once it develops, it carries a high mortality rate. Adequate pericardial drainage and proper antibiotic treatment are essential in the successful management of purulent effusions, for which percutaneous catheter drainage is the most commonly performed technique. We herein report the case of a 75-year-old woman with purulent pericarditis attributable to methicillin-resistant Staphylococcus aureus. Although percutaneous pericardial drainage by catheter was used, the drainage was insufficient because of hyperviscous effusion. We performed surgical subxiphoid pericardial drainage, and a piece of a purulent stone was found in the pericardial cavity with purulent effusion. Additionally, daily intrapericardial washouts with physiologic saline alone were used as adjunct therapy. Five weeks later, the patient had a decreasing inflammatory reaction and symptom relief. She was discharged with no complications such as constrictive pericarditis.
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Contralateral pulmonary embolism caused by pulmonary artery stump thrombosis after pneumonectomy.
Wakana Sato, Hiroyuki Watanabe, Teruki Sato, Kenji Iino, Kazuhiro Sato, Hiroshi Ito
The Annals of thoracic surgery 97 ( 5 ) 1797 - 8 2014.05 [Refereed]
Research paper (journal)
A 73-year-old man with atrial fibrillation and previous left pneumonectomy was admitted with pleural effusion. Anticoagulant therapy was discontinued because of chest tube drainage. Six days later, the patient experienced chest discomfort. Echocardiography showed a pedunculated thrombus with swaying motion in the left pulmonary artery (PA) stump. Contrast-enhanced computed tomography of the chest revealed filling defects in not only the left PA stump but also the right PA, implying contralateral pulmonary embolism. Anticoagulants were resumed, and thrombolysis was successful 3 days later. Patients undergoing pneumonectomy in whom anticoagulant therapy is discontinued should be recognized as being at high risk for PA stump thrombosis and subsequent contralateral pulmonary embolism.
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Inhalation anesthesia is preferable for recording rat cardiac function using an electrocardiogram.
Manabu Murakami, Hidetoshi Niwa, Tetsuya Kushikata, Hiroyuki Watanabe, Kazuyoshi Hirota, Kyoichi Ono, Takayoshi Ohba
Biological & pharmaceutical bulletin 37 ( 5 ) 834 - 9 2014.05 [Refereed]
Research paper (journal)
The effects of inhalation anesthesia (2% isoflurane, sevoflurane, or enflurane) and intraperitoneal anesthesia with pentobarbital (65 mg/kg) were compared in rats using an electrocardiogram (ECG) and determination of blood oxygen saturation (SPO2) levels. Following inhalation anesthesia, heart rate (HR) and SPO2 were acceptable while pentobarbital anesthesia decreased HR and SPO2 significantly. This indicates that inhalation anesthesia is more preferable than pentobarbital anesthesia when evaluating cardiovascular factors. Additionally, pentobarbital significantly increased HR variability (HRV), suggesting a regulatory effect of pentobarbital on the autonomic nervous system, and resulted in a decreased response of the baro-reflex system. Propranolol or atropine had limited effects on ECG recording following pentobarbital anesthesia. Taken together, these data suggest that inhalation anesthesia is suitable for conducting hemodynamic analyses in the rat.
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Immunochemical fecal occult blood tests predict dual antiplatelet therapy discontinuation after coronary stenting.
Ken Ikeda, Takashi Koyama, Masaru Ishida, Megumi Okawa, Yasunori Oguma, Yutaka Terata, Kenji Iino, Toshimitsu Kosaka, Hiroyuki Watanabe, Hiroshi Ito
Internal medicine (Tokyo, Japan) 53 ( 5 ) 375 - 81 2014.03 [Refereed]
Research paper (journal)
OBJECTIVE: The discontinuation of dual antiplatelet therapy (DAPT) increases the risk of stent thrombosis after coronary stenting. Some patients must discontinue DAPT due to gastrointestinal (GI) tract disease; however, the type of examination that is most useful for detecting GI tract diseases has not been fully evaluated. The purpose of this study was to clarify whether the immunochemical fecal occult blood test (iFOBT) can be used to predict GI tract disease-related DAPT discontinuation following stent implantation in patients with coronary artery disease. METHODS: A total of 181 consecutive DAPT-naïve patients who underwent coronary stenting were divided into two groups according to the results of iFOBTs: a positive iFOBT group (n=32) and a negative iFOBT group (n=149). During the 12-month follow-up period, the DAPT discontinuation rate was lower in the negative iFOBT group than in the positive iFOBT group (3.4 vs. 18.8%, p=0.005). Kaplan-Meier event-free curves showed that the DAPT discontinuation rate in the negative iFOBT group was lower than that observed in the positive iFOBT group (log-rank test: p=0.001). Logistic and Cox regression analyses showed that a positive iFOBT result was the strongest predictor of the risk of DAPT discontinuation after coronary stenting. CONCLUSION: A positive iFOBT result is associated with DAPT discontinuation following coronary stenting.
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Apelin is a positive regulator of ACE2 in failing hearts.
Teruki Sato, Takashi Suzuki, Hiroyuki Watanabe, Ayumi Kadowaki, Akiyoshi Fukamizu, Peter P Liu, Akinori Kimura, Hiroshi Ito, Josef M Penninger, Yumiko Imai, Keiji Kuba
The Journal of clinical investigation 123 ( 12 ) 5203 - 11 2013.12 [Refereed]
Research paper (journal)
Angiotensin converting enzyme 2 (ACE2) is a negative regulator of the renin-angiotensin system (RAS), catalyzing the conversion of Angiotensin II to Angiotensin 1-7. Apelin is a second catalytic substrate for ACE2 and functions as an inotropic and cardioprotective peptide. While an antagonistic relationship between the RAS and apelin has been proposed, such functional interplay remains elusive. Here we found that ACE2 was downregulated in apelin-deficient mice. Pharmacological or genetic inhibition of angiotensin II type 1 receptor (AT1R) rescued the impaired contractility and hypertrophy of apelin mutant mice, which was accompanied by restored ACE2 levels. Importantly, treatment with angiotensin 1-7 rescued hypertrophy and heart dysfunctions of apelin-knockout mice. Moreover, apelin, via activation of its receptor, APJ, increased ACE2 promoter activity in vitro and upregulated ACE2 expression in failing hearts in vivo. Apelin treatment also increased cardiac contractility and ACE2 levels in AT1R-deficient mice. These data demonstrate that ACE2 couples the RAS to the apelin system, adding a conceptual framework for the apelin-ACE2-angiotensin 1-7 axis as a therapeutic target for cardiovascular diseases.
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Remote ischemic pre-conditioning alleviates contrast-induced acute kidney injury in patients with moderate chronic kidney disease.
Gen Igarashi, Kenji Iino, Hiroyuki Watanabe, Hiroshi Ito
Circulation journal : official journal of the Japanese Circulation Society 77 ( 12 ) 3037 - 44 2013.12 [Refereed]
Research paper (journal)
BACKGROUND: Although remote ischemic preconditioning (RIPC) is shown to preserve kidney function in patients at high risk of contrast-induced acute kidney injury (CI-AKI), the effect in patients at low-moderate risk remains unknown. The preventive effects of RIPC in patients not at high risk of CI-AKI were examined, and biomarkers with anticipated roles in renal protection via RIPC investigated. METHODS AND RESULTS: Sixty patients who had moderate chronic kidney disease and who underwent angiography were randomly assigned to the control (n=30) or RIPC (intermittent arm ischemia, n=30) group. The baseline characteristics in the 2 groups did not differ significantly. CI-AKI was evaluated by measuring urinary liver-type fatty acid-binding protein (L-FABP). Biomarkers were measured before and 24 and 48 h after angiography. Twenty-four hours after angiography, the percent change in urinary L-FABP level in the RIPC group was significantly smaller than in the control group (41.3±15.6 vs. 159±34.1%, P=0.003). L-FABP-based CI-AKI developed in 8 control patients (26.9%) vs. only 2 patients in the RIPC group (7.7%), suggesting that RIPC prevents CI-AKI. Factors contributing to CI-AKI were analyzed. Neither high-sensitivity C-reactive protein nor pentraxine-3 level differed significantly between the 2 groups, while the percent change in asymmetrical dimethy larginine (ADMA) level and blood derivatives of reactive oxidative metabolite levels were significantly smaller in the RIPC group. CONCLUSIONS: RIPC alleviates CI-AKI in patients at low-moderate risk. This effect might be mediated partly by decreasing oxidative stress and plasma ADMA level.
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Impaired renal function is a major determinant of left ventricular diastolic dysfunction: assessment by stress myocardial perfusion imaging.
Wakana Sato, Toshimitsu Kosaka, Takashi Koyama, Masaru Ishida, Kenji Iino, Hiroyuki Watanabe, Hiroshi Ito
Annals of nuclear medicine 27 ( 8 ) 729 - 36 2013.10 [Refereed]
Research paper (journal)
OBJECTIVE: Relationships between myocardial scintigraphic parameters and renal function have not been fully determined. We investigated correlations between estimated glomerular filtration rate (eGFR) and left ventricular (LV) diastolic function using stress electrocardiographic (ECG)-gated myocardial single photon emission computed tomography (SPECT). METHODS: We enrolled 136 consecutive patients with suspected coronary artery disease (CAD) who were assessed using technetium-99m stress ECG-gated myocardial SPECT. We evaluated SPECT images using 17-segment defect scores graded on a 5-point scale, summed stress score, summed rest score and summed difference score (SDS). The parameters for assessing LV diastolic function were peak filling rate (PFR), 1/3 mean filling rate and time to peak filling. The CAD was defined as SDS ≥2. Chronic kidney disease (CKD) was defined as eGFR <60 mL/min/1.73 m(2). Patients were assigned to the following four groups (no CAD/no CKD: control group, n = 68; CAD/no CKD: CAD group, n = 24; no CAD/CKD: CKD group, n = 34; CAD/CKD: CAD + CKD group, n = 10). RESULTS: The PFR was significantly impaired after stress in the CKD and CAD + CKD groups compared with controls (p < 0.001 for both). Furthermore, PFR at rest positively correlated with eGFR (r = 0.29, p < 0.001) and inversely correlated with SDS (r = -0.18, p < 0.05). Multivariate stepwise regression analysis independently associated eGFR with PFR (β coefficient = 0.260, p = 0.002). CONCLUSIONS: Our data suggest that impaired renal function is a significant determinant of LV diastolic dysfunction in patients with suspected CAD.
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Rho-kinase in leukocytes. An emerging biomarker for heart failure.
Hiroyuki Watanabe, Kenji Iino, Hiroshi Ito
Circulation journal : official journal of the Japanese Circulation Society 77 ( 10 ) 2471 - 2 2013.10 [Refereed]
Research paper (journal)
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Increased circulating CD3+/CD31+ T cells in patients with acute coronary syndrome.
Manabu Kakizaki, Kiyoshi Nobori, Hiroyuki Watanabe, Kenji Iino, Masaru Ishida, Hiroshi Ito
Heart and vessels 28 ( 5 ) 566 - 9 2013.09 [Refereed]
Research paper (journal)
The number of circulating endothelial progenitor cells (EPCs) is considered to be a surrogate marker for coronary artery disease (CAD). Recent studies have identified a novel T-cell subset labeled with CD3(+)/CD31(+), which is necessary for EPC colony formation and constitutes the central cluster. However, the clinical relevance of the CD3(+)/CD31(+) T cells in CAD remains unclear. We sought to clarify whether circulating CD3(+)/CD31(+) T cells are increased in patients with acute coronary syndrome (ACS). Circulating CD3(+)/CD31(+) T cells were determined in 16 ACS patients undergoing emergency percutaneous coronary intervention (PCI) and in 16 control subjects with angiographically normal coronary arteries. Although no differences between the groups were found in baseline patient characteristics, the ratio of circulating CD3(+)/CD31(+) T cells before PCI was higher in ACS patients as compared with that in control subjects (51.8 % ± 7.8 % vs 31.8 % ± 9.6 %, respectively; P < 0.001). The increased ratio of CD3(+)/CD31(+) T cells in ACS patients was not altered 24 h after PCI, but became comparable with that in control subjects within 6 months after PCI. These results suggest that mobilization of CD3(+)/CD31(+) T cells occurs in ACS, but is no longer detectable at 6 months after PCI.
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Adaptive servo-ventilation therapy improves cardiac sympathetic nerve activity in patients with heart failure.
Takashi Koyama, Hiroyuki Watanabe, Yoshikazu Tamura, Yasunori Oguma, Toshimitsu Kosaka, Hiroshi Ito
European journal of heart failure 15 ( 8 ) 902 - 9 2013.08 [Refereed]
Research paper (journal)
AIMS: This study investigated whether abnormal cardiac sympathetic nerve activity (SNA) is associated with the severity of central sleep apnoea (CSA) and whether adaptive servo-ventilation (ASV) therapy can improve cardiac SNA in heart failure (HF) patients with predominant CSA. METHODS AND RESULTS: Overnight polysomnography was conducted to diagnose CSA. Cardiac SNA was analysed by [123I]metaiodobenzylguanidine scintigraphy in 26 consecutive HF patients with predominant CSA. Of the 26 patients, 10 agreed to ASV therapy. Cardiac SNA was analysed 6 months after initiating ASV based on a non-randomized protocol. The apnoea-hypopnoea index and central apnoea index were significantly correlated with the washout rate (WR) and a delayed heart to mediastinal (H/M) ratio, suggesting that SNA is associated with abnormal breathing patterns. The WR, H/M ratio, plasma BNP level, and LVEF were significantly improved (WR, 40.0 ± 11.6% vs. 34.6 ± 11.4%, P = 0.046; H/M ratio, 1.5 ± 0.1 vs.1.8 ± 0.3, P = 0.013; ln BNP, 5.4 ± 1.0 vs. 4.6 ± 1.2, P = 0.007; and LVEF, 43.8 ± 10.4% vs. 47.0 ± 10.6%, P < 0.001) in the ASV group patients, but not in the non-ASV group patients. Multiple linear regression analyses showed that a decreased WR was strongly associated with an increased LVEF (coefficient = -0.454, P = 0.013). CONCLUSIONS: Abnormal cardiac SNA could be significantly correlated with the severity of CSA in HF patients. ASV therapy might improve cardiac function in these patients by partially mediating cardiac SNA regulation.
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Sildenafil prevents the up-regulation of transient receptor potential canonical channels in the development of cardiomyocyte hypertrophy.
Hironori Kiso, Takayoshi Ohba, Kenji Iino, Kazuhiro Sato, Yutaka Terata, Manabu Murakami, Kyoichi Ono, Hiroyuki Watanabe, Hiroshi Ito
Biochemical and biophysical research communications 436 ( 3 ) 514 - 8 2013.07 [Refereed]
Research paper (journal)
BACKGROUND: Transient receptor potential canonical (TRPCs) channels are up-regulated in the development of cardiac hypertrophy. Sildenafil inhibits TRPC6 activation and expression, leading to the prevention of cardiac hypertrophy. However, the effects of sildenafil on the expression of other TRPCs remain unknown. We hypothesized that in addition to its effects of TRPC6, sildenafil blocks the up-regulation of other TRPC channels to suppress cardiomyocyte hypertrophy. METHODS AND RESULTS: In cultured neonatal rat cardiomyocytes, a 48 h treatment with 10nM endothelin (ET)-1 induced hypertrophic responses characterized by nuclear factor of activated T cells activation and enhancement of brain natriuretic peptide expression and cell surface area. Co-treatment with sildenafil (1 μM, 48 h) inhibited these ET-1-induced hypertrophic responses. Although ET-1 enhanced the gene expression of TRPCs, sildenafil inhibited the enhanced gene expression of TRPC1, C3 and C6. Moreover, co-treatment with sildenafil abolished the augmentation of SOCE in the hypertrophied cardiomyocytes. CONCLUSIONS: These results suggest that sildenafil inhibits cardiomyocyte hypertrophy by suppressing the up-regulation of TRPC expression.
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Involvement of the orexin system in adrenal sympathetic regulation.
Takayuki Nemoto, Fumiyo Toyoshima-Aoyama, Yuto Ueda, Takayoshi Ohba, Toshihiko Yanagita, Hiroyuki Watanabe, Tetsuro Shirasaka, Isao Tsuneyoshi, Yasushi Ishida, Kazuyoshi Hirota, Akira Sawaguchi, Manabu Murakami
Pharmacology 91 ( 5-6 ) 250 - 8 2013.04 [Refereed]
Research paper (journal)
Orexin (hypocretin) is a neuropeptide secreted from hypothalamic neurons that is known to be activated during motivated behaviors and active waking. Presently, our knowledge of orexin is mainly limited to the central nervous system, and the involvement of the orexin system in peripheral tissues has received little attention. In the present study, we analyzed the existence of the orexin system in the adrenal medulla, which is part of the sympathetic nervous system. Orexin and its receptors are expressed in the bovine adrenal medulla. Orexins stimulated intracellular calcium changes and epinephrine release from cultured bovine adrenal medullary cells. Applied orexin decreased expression of prepro-orexin, orexin receptor-1 and orexin receptor-2, suggesting negative feedback regulation in the adrenal gland. Our results indicate involvement of the orexin system in the sympathetic regulation of the adrenal medulla.
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Possible involvement of TRP channels in cardiac hypertrophy and arrhythmia.
Hiroyuki Watanabe, Kenji Iino, Takayoshi Ohba, Hiroshi Ito
Current topics in medicinal chemistry 13 ( 3 ) 283 - 94 2013.03 [Refereed]
Research paper (journal)
Over the past 20 years, studies of transient receptor potential (TRP) channels have significantly extended our knowledge regarding the molecular basis of Ca2+ signals in cardiac myocytes. The functional significance of cardiac TRP channels is likely connected to the alteration of membrane potential or Ca2+ entry into a noncontractile compartment, where gene expression responsible for various cardiac diseases is induced. This review highlights some aspects of TRP channels with anticipated roles in cardiac disease. Evidence suggests that (a) increased activities of TRPC1, TRPC3, or TRPC6 are involved in the development of cardiac hypertrophy, where these TRPC channels act as unique sensors for a wide range of hypertrophic stimuli, and (b) mutations in TRPM4 are now recognized as causes of human cardiac conduction disorders. Ultimately, TRP channels may become novel pharmacological targets in the treatment of human cardiac disease.
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Questionnaire survey on the continuity of home oxygen therapy after a disaster with power outages.
Kazuhiro Sato, Ryo Morita, Kazuhito Tsukamoto, Narumi Sato, Yumiko Sasaki, Mariko Asano, Yuji Okuda, Hajime Miura, Masaaki Sano, Toshimitsu Kosaka, Hiroyuki Watanabe, Takanobu Shioya, Hiroshi Ito
Respiratory investigation 51 ( 1 ) 9 - 16 2013.03 [Refereed]
Research paper (journal)
BACKGROUND: After the Great East Japan Earthquake, oxygen-dependent patients in areas experiencing power outages could not continue home oxygen therapy (HOT) without oxygen cylinders. The purpose of this study was to examine use of oxygen cylinders in areas experiencing power outages and the effects of HOT interruption on patients' health. METHODS: Questionnaires were mailed to 1106 oxygen-dependent patients and HOT-prescribing physicians in Akita, near the disaster-stricken area. We investigated patients' actions when unable to use an oxygen concentrator and classified the patients based on oxygen cylinder use. Patients who experienced an interruption of or reduction in oxygen flow rate by their own judgment were assigned to the "interruption" and "reduction" groups, respectively; those who maintained their usual flow rate were assigned to the "continuation" group. Differences were tested using analysis of variance and the χ2 tests. RESULTS: In total, 599 patients responded to the questionnaire. Oxygen cylinders were supplied to 574 patients (95.8%) before their oxygen cylinders were depleted. Comparison of the continuation (n=356), reduction (n=64), and interruption (n=154) groups showed significant differences in family structure (p=0.004), underlying disease (p=0.014), oxygen flow rate (p<0.001), situation regarding use (p<0.001), knowledge of HOT (p<0.001), and anxiety about oxygen supply (p<0.001). There were no differences in changes in physical condition. CONCLUSIONS: Most patients could receive oxygen cylinders after the disaster. Some patients discontinued their usual oxygen therapy, but their overall health status was not affected.
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Comparison of anti-inflammatory effects and high-density lipoprotein cholesterol levels between therapy with quadruple-dose rosuvastatin and rosuvastatin combined with ezetimibe.
Daisuke Yamazaki, Masaru Ishida, Hiroyuki Watanabe, Kiyoshi Nobori, Yasunori Oguma, Yutaka Terata, Takashi Koyama, Kenji Iino, Toshimitsu Kosaka, Hiroshi Ito
Lipids in health and disease 12 9 - 9 2013.02 [Refereed]
Research paper (journal)
BACKGROUND: Statins are frequently administered to reduce low-density lipoprotein cholesterol (LDL-C) and vascular inflammation, because LDL-C and high sensitive C-reactive protein (hs-CRP) are associated with high risk for cardiovascular events. When statins do not reduce LDL-C to desired levels in high-risk patients with coronary artery disease (CAD), ezetimibe can be added or the statin dose can be increased. However, which strategy is more effective for treating patients with CAD has not been established. The present study compares anti-inflammatory effects and lipid profiles in patients with CAD and similar LDL-C levels who were treated by increasing the statin dose or by adding ezetimibe to the original rosuvastatin dose to determine the optimal treatment for such patients. METHODS: 46 patients with high-risk CAD and LDL-C and hs-CRP levels of >70 mg/dL and >1.0 mg/L, respectively, that were not improved by 4 weeks of rosuvastatin (2.5 mg/day) were randomly assigned to receive 10 mg (R10, n = 24) of rosuvastatin or 2.5 mg/day of rosuvastatin combined with 10 mg/day of ezetimibe (R2.5/E10, n = 22) for 12 weeks. The primary endpoint was a change in hs-CRP. RESULTS: Baseline characteristics did not significantly differ between the groups. At 12 weeks, LDL-C and inflammatory markers (hs-CRP, interleukin-6, tumour necrosis factor-alpha and pentraxin 3) also did not significantly differ between the two groups (LDL-C: R10 vs. R2.5/E10: -19.4 ± 14.2 vs. -22.4 ± 14.3 mg/dL). However, high-density lipoprotein cholesterol (HDL-C) was significantly improved in the R10, compared with R2.5/E10 group (4.6 ± 5.9 vs. 0.0 ± 6.7 mg/dL; p < 0.05). CONCLUSION: Both enhanced therapies exerted similar anti-inflammatory effects under an equal LDL-C reduction in patients with high-risk CAD despite 2.5 mg/day of rosuvastatin. However, R10 elevated HDL-C more effectively than R2.5/E10. TRIAL REGISTRATION: UMIN000003746.