Faculty Profiles - AKAGI Satoshi

Papers - AKAGI Satoshi

Division display 61 - 80 of about 85 ／ All the affair displays >>

Enhanced EP4 Expression in a Pulmonary Artery Aneurysm With Dissection in a Patient With Pulmonary Arterial Hypertension. Reviewed International journal

Satoshi Akagi, Kazufumi Nakamura, Utako Yokoyama, Shingo Kasahara, Toshihiro Sarashina, Kentaro Ejiri, Hiroshi Ito

Circulation. Cardiovascular imaging 10 ( 2 ) 2017.2

Feasibility of Repairing Defects Followed by Treatment with Pulmonary Hypertension-specific Drugs (Repair and Treat) in Patients with Pulmonary Hypertension Associated with Atrial Septal Defect: Study Protocol for Interventional Trial. Reviewed

Satoshi Akagi, Kazufumi Nakamura, Teiji Akagi, Koji Nakagawa, Yoichi Takaya, Toshihiro Sarashina, Kentaro Ejiri, Hiroshi Ito

Acta medica Okayama 70 ( 5 ) 397 - 400 2016.10

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

A treatment strategy for patients with pulmonary hypertension (PH) and atrial septal defect (ASD) remains unclear. This study was designed to evaluate the effects of initial repair of ASD followed by treatment with PH-specific drugs in patients with PH and ASD. Eligible patients receive transcatheter ASD closure followed by treatment with bosentan and sildenafil. Right heart catheterization is performed at baseline and at 12, 24 and 48 weeks. The primary endpoint is change in pulmonary artery pressure and pulmonary vascular resistance from baseline to follow-up. This study should provide valuable information to establish a therapeutic strategy for PH and ASD.

Intratracheal Administration of Prostacyclin Analogue-incorporated Nanoparticles Ameliorates the Development of Monocrotaline and Sugen-Hypoxia-induced Pulmonary Arterial Hypertension. Reviewed International journal

Satoshi Akagi, Kazufumi Nakamura, Hiromi Matsubara, Megumi Kondo, Daiji Miura, Tetsuya Matoba, Kensuke Egashira, Hiroshi Ito

Journal of cardiovascular pharmacology 67 ( 4 ) 290 - 8 2016.4

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

Nanoparticles (NPs) have been used as novel drug delivery systems. Drug-incorporated NPs for local delivery might optimize the efficacy and minimize the side effects of drugs. Intravenous prostacyclin improves long-term survival in patients with pulmonary arterial hypertension (PAH), but it causes serious side effects such as catheter-related infections. We investigated the efficacy and safety of intratracheal administration of a prostacyclin analogue, beraprost (BPS), incorporated NPs in Sugen-hypoxia-normoxia and monocrotaline rat models of PAH and in human PAH pulmonary arterial smooth muscle cells (PASMCs). After a single administration, BPS NPs significantly decreased right ventricular pressure, right ventricular hypertrophy, and pulmonary artery muscularization in the 2 rat models. BPS NPs significantly improved the survival rate in the monocrotaline rat model. No infiltration of inflammatory cells, hemorrhage, or fibrosis was found in the liver, kidney, spleen, and heart after the administration of BPS NPs. No liver or kidney dysfunction was found in the blood examinations. BPS and BPS NPs significantly inhibited the proliferation of human PAH PASMCs after 24 hours of treatment. BPS NPs significantly continued to inhibit the proliferation of human PAH PASMCs at 24 hours after the removal of BPS NPs. BPS NPs significantly induced apoptosis in PAH PASMCs compared to that in non-PAH PASMCs. Intratracheal administration of BPS NPs ameliorates pulmonary hypertension in PAH rat models by a sustained antiproliferative effect and a proapoptotic effect on PAH PASMCs.

DOI： 10.1097/FJC.0000000000000352

Treat and Repair Strategy in Patients With Atrial Septal Defect and Significant Pulmonary Arterial Hypertension. Reviewed

Yasufumi Kijima, Teiji Akagi, Yoichi Takaya, Satoshi Akagi, Koji Nakagawa, Kengo Kusano, Shunji Sano, Hiroshi Ito

Circulation journal : official journal of the Japanese Circulation Society 80 ( 1 ) 227 - 34 2016

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: A therapeutic strategy in patients with atrial septal defect (ASD) and significant pulmonary arterial hypertension (PAH) remains controversial. This study aimed to assess the effect of PAH-specific medications and subsequent transcatheter shunt closure (ie, a treat and repair strategy) in these patients. METHODS AND RESULTS: Among 646 patients with ASD, 22 patients (mean age of 56±20 years) who had PAH [mean pulmonary artery pressure ≥25 mmHg and pulmonary vascular resistance (PVR) ≥3 Wood units] underwent successful transcatheter ASD closure. Prior to the procedure, 8 patients received PAH-specific medications (PHM group) and 14 patients did not (non-PHM group). Initially, the PHM group had higher PVR compared with non-PHM group (9.6±3.8 vs. 4.2±1.0 Wood units, P<0.01). After treatment with PAH-specific medications, PVR in this group decreased to 4.0±0.8 Wood units (P<0.01). No adverse events were observed in either the PHM or non-PHM group during or after the transcatheter procedure. In the PHM group, during a treatment period of 52±48 months, the World Health Organization Functional Classification significantly improved (3.0±0.5 to 2.0±0.0, P<0.01), as well as in the non-PHM group (2.1±0.6 to 1.5±0.5, P<0.01). CONCLUSIONS: Treat and repair strategy provided substantial improvement and no worsening of the WHO-FC, even in patients with ASD and significant PAH. Long-term hemodynamic follow-up is mandatory to evaluate the ultimate efficacy and safety of this new strategy.

DOI： 10.1253/circj.CJ-15-0599

Epoprostenol Therapy for Pulmonary Arterial Hypertension. Invited Reviewed

Satoshi Akagi, Kazufumi Nakamura, Hiromi Matsubara, Aiko Ogawa, Toshihiro Sarashina, Kentaro Ejiri, Hiroshi Ito

Acta medica Okayama 69 ( 3 ) 129 - 36 2015.8

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

Pulmonary arterial hypertension (PAH) is characterized by elevation of pulmonary artery pressure caused by pulmonary vasoconstriction and vascular remodeling, which leads to right heart failure and death. Epoprostenol (prostaglandin I2) has a potent short-acting vasodilator property, and intravenous continuous epoprostenol is therefore used for treatment of PAH. Here we review evidence for the usefulness of intravenous continuous epoprostenol therapy in patients with PAH. Epoprostenol therapy is effective in idiopathic PAH patients and in patients with PAH associated with connective tissue disease, portal hypertension or congenital heart diseases, but it is not effective in patients with pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis. High-dose epoprostenol therapy markedly improved hemodynamics in some patients with PAH, possibly due to reverse remodeling of pulmonary arteries. This therapy has several side effects and complications such as headache, hypotension and catheter-related infections. Intravenous continuous epoprostenol is an effective treatment, but there are still some problems to be resolved.

Epoprostenol sodium for treatment of pulmonary arterial hypertension. Invited Reviewed International journal

Yukihiro Saito, Kazufumi Nakamura, Satoshi Akagi, Toshihiro Sarashina, Kentaro Ejiri, Aya Miura, Aiko Ogawa, Hiromi Matsubara, Hiroshi Ito

Vascular health and risk management 11 265 - 70 2015.5

Language：English Publishing type：Research paper (scientific journal)

The release of endogenous prostacyclin (PGI2) is depressed in patients with pulmonary arterial hypertension (PAH). PGI2 replacement therapy by epoprostenol infusion is one of the best treatments available for PAH. Here, we provide an overview of the current clinical data for epoprostenol. Epoprostenol treatment improves symptoms, exercise capacity, and hemodynamics, and is the only treatment that has been shown to reduce mortality in patients with idiopathic PAH (IPAH) in randomized clinical trials. We have reported that high-dose epoprostenol therapy (>40 ng/kg/min) also results in marked hemodynamic improvement in some patients with IPAH. High-dose epoprostenol has a pro-apoptotic effect on PAH-PASMCs via the IP receptor and upregulation of Fas ligand (FasL) in vitro. However, long-term intravenous administration of epoprostenol is sometimes associated with catheter-related infections and leads to considerable inconvenience for the patient. In the future, the development of new routes of administration or the development of powerful PGI2 analogs, IP-receptor agonists, and gene and cell-based therapy enhancing PGI2 production with new routes of administration is required.

DOI： 10.2147/VHRM.S50368

Delivery of imatinib-incorporated nanoparticles into lungs suppresses the development of monocrotaline-induced pulmonary arterial hypertension. Reviewed

Satoshi Akagi, Kazufumi Nakamura, Daiji Miura, Yukihiro Saito, Hiromi Matsubara, Aiko Ogawa, Tetsuya Matoba, Kensuke Egashira, Hiroshi Ito

International heart journal 56 ( 3 ) 354 - 9 2015.5

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

Platelet-derived growth factor (PDGF) is implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Imatinib, a PDGF-receptor tyrosine kinase inhibitor, improved hemodynamics, but serious side effects and drug discontinuation are common when treating PAH. A drug delivery system using nanoparticles (NPs) enables the reduction of side effects while maintaining the effects of the drug. We examined the efficacy of imatinib-incorporated NPs (Ima-NPs) in a rat model and in human PAH-pulmonary arterial smooth muscle cells (PASMCs). Rats received a single intratracheal administration of PBS, FITC-NPs, or Ima-NPs immediately after monocrotaline injection. Three weeks after monocrotaline injection, intratracheal administration of Ima-NPs suppressed the development of pulmonary hypertension, small pulmonary artery remodeling, and right ventricular hypertrophy in the rat model of monocrotaline-induced PAH. We also examined the effects of imatinib and Ima-NPs on PDGF-induced proliferation of human PAH-PASMCs by (3)H-thymidine incorporation. Imatinib and Ima-NPs significantly inhibited proliferation after 24 hours of treatment. Ima-NPs significantly inhibited proliferation compared with imatinib at 24 hours after removal of these drugs. Delivery of Ima-NPs into lungs suppressed the development of MCT-induced PAH by sustained antiproliferative effects on PAS-MCs.

DOI： 10.1536/ihj.14-338

Catecholamine support at the initiation of epoprostenol therapy in pulmonary arterial hypertension. Reviewed International journal

Satoshi Akagi, Aiko Ogawa, Katsumasa Miyaji, Kengo Kusano, Hiroshi Ito, Hiromi Matsubara

Annals of the American Thoracic Society 11 ( 5 ) 719 - 27 2014.6

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

RATIONALE: Epoprostenol is a first-line therapy for patients with pulmonary arterial hypertension (PAH) in World Health Organization functional class IV who often have low cardiac output and hypotension. However, initiation of epoprostenol can cause hemodynamic collapse in these vulnerable patients. Inotropic agent support may prevent the hemodynamic instability caused by initiation of epoprostenol; however, a protocol for supportive therapy has not been established. OBJECTIVES: To assess the reliability and prognostic effects of dobutamine and dopamine support at the initiation of epoprostenol therapy in patients with PAH. METHODS: We initiated epoprostenol therapy in 71 patients with PAH. Hemodynamics at the initiation of epoprostenol were measured by right heart catheterization. We initiated dobutamine when a patient's mixed venous oxygen saturation was less than 60% or cardiac index was less than 2.0 L/min/m(2) or when right ventricular failure was clinically suspected. We initiated dopamine when a patient's systolic blood pressure was less than 90 mm Hg or urine volume was less than 20 ml/h. MEASUREMENTS AND MAIN RESULTS: At the initiation of epoprostenol, dobutamine and/or dopamine were required to support 46 patients according to protocol. Eight patients died during the hospitalization and one patient received a living-donor lobar lung transplant after the initiation of epoprostenol therapy. Neither inotropic agent was an independent risk factor for short-term mortality (dobutamine: hazard ratio, 1.63; 95% confidence interval, 0.33-8.11; dopamine: hazard ratio, 0.22; 95% confidence interval, 0.03-1.70). Sixty-two patients were discharged for home infusion of epoprostenol. Transplant-free survival rates at 5 years were 80.0% for patients who did not require inotropic support at the start of epoprostenol and 76.6% for patients with who did require dopamine and/or dobutamine support (P = 0.45). CONCLUSIONS: Temporary use of dobutamine and dopamine appears to be safe for hemodynamic support at the initiation of epoprostenol therapy for selected patients with PAH with low cardiac output and hypotension. The protocol presented here requires validation at other centers.

DOI： 10.1513/AnnalsATS.201308-268OC

Reverse remodeling of pulmonary arteries by high-dose prostaglandin I2 therapy: A case report. Reviewed

Satoshi Akagi, Kazufumi Nakamura, Hiromi Matsubara, Keiko Ohta-Ogo, Chikao Yutani, Katsumasa Miyaji, Aiko Ogawa, Kengo Kusano, Takahiro Oto, Hatsue Ishibashi-Ueda, Hiroshi Ito

Journal of cardiology cases 9 ( 5 ) 173 - 176 2014.5

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

Idiopathic pulmonary arterial hypertension (IPAH) is characterized by pulmonary vascular remodeling. We have reported that high-dose prostaglandin I2 (PGI2) therapy markedly improved hemodynamics in IPAH patients and that PGI2 induced apoptosis of pulmonary artery smooth muscle cells obtained from IPAH patients. PGI2 is thought to have reverse remodeling effects, although it has not been histologically confirmed. In a case series, we examined the reverse pulmonary vascular remodeling effects of PGI2 in lung tissues obtained from an IPAH patient treated with high-dose PGI2 and an IPAH patient not treated with PGI2. Apoptotic cells were detected in small pulmonary arteries of the IPAH patient treated with high-dose PGI2 but not in those from the IPAH patient not treated with PGI2. Media of peripheral pulmonary arteries were thick in the IPAH patient not treated with PGI2. On the other hand, media of peripheral pulmonary arteries were thin in the IPAH patient treated with high-dose PGI2. The single case report suggested that high-dose PGI2 therapy has the potential for reverse pulmonary vascular remodeling by induction of apoptosis and reduction of medial hypertrophy. Accumulation of cases is needed for the application to generalized effect of high-dose PGI2. <Learning objective: Reverse pulmonary vascular remodeling would provide further improvement in patients with IPAH. High-dose PGI2 therapy has the potential for reverse pulmonary vascular remodeling in patients with IPAH.>.

DOI： 10.1016/j.jccase.2013.12.011

Effect of vildagliptin, a dipeptidyl peptidase 4 inhibitor, on cardiac hypertrophy induced by chronic beta-adrenergic stimulation in rats. Reviewed International journal

Toru Miyoshi, Kazufumi Nakamura, Masashi Yoshida, Daiji Miura, Hiroki Oe, Satoshi Akagi, Hiroki Sugiyama, Kaoru Akazawa, Tomoko Yonezawa, Jun Wada, Hiroshi Ito

Cardiovascular diabetology 13 43 - 43 2014.2

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Heart failure with left ventricular (LV) hypertrophy is often associated with insulin resistance and inflammation. Recent studies have shown that dipeptidyl peptidase 4 (DPP4) inhibitors improve glucose metabolism and inflammatory status. We therefore evaluated whether vildagliptin, a DPP4 inhibitor, prevents LV hypertrophy and improves diastolic function in isoproterenol-treated rats. METHODS: Male Wistar rats received vehicle (n = 20), subcutaneous isoproterenol (2.4 mg/kg/day, n = 20) (ISO), subcutaneous isoproterenol (2.4 mg/kg/day + oral vildagliptin (30 mg/kg/day, n = 20) (ISO-VL), or vehicle + oral vildagliptin (30 mg/kg/day, n = 20) (vehicle-VL) for 7 days. RESULTS: Blood pressure was similar among the four groups, whereas LV hypertrophy was significantly decreased in the ISO-VL group compared with the ISO group (heart weight/body weight, vehicle: 3.2 ± 0.40, ISO: 4.43 ± 0.39, ISO-VL: 4.14 ± 0.29, vehicle-VL: 3.16 ± 0.16, p < 0.05). Cardiac catheterization revealed that vildagliptin lowered the elevated LV end-diastolic pressure observed in the ISO group, but other parameters regarding LV diastolic function such as the decreased minimum dp/dt were not ameliorated in the ISO-VL group. Histological analysis showed that vildagliptin attenuated the increased cardiomyocyte hypertrophy and perivascular fibrosis, but it did not affect angiogenesis in cardiac tissue. In the ISO-VL group, quantitative PCR showed attenuation of increased mRNA expression of tumor necrosis factor-α, interleukin-6, insulin-like growth factor-l, and restoration of decreased mRNA expression of glucose transporter type 4. CONCLUSIONS: Vildagliptin may prevent LV hypertrophy caused by continuous exposure to isoproterenol in rats.

DOI： 10.1186/1475-2840-13-43

Different sizes of centrilobular ground-glass opacities in chest high-resolution computed tomography of patients with pulmonary veno-occlusive disease and patients with pulmonary capillary hemangiomatosis. Reviewed International journal

Aya Miura, Satoshi Akagi, Kazufumi Nakamura, Keiko Ohta-Ogo, Katsushi Hashimoto, Satoshi Nagase, Kunihisa Kohno, Kengo Kusano, Aiko Ogawa, Hiromi Matsubara, Shinichi Toyooka, Takahiro Oto, Aiji Ohtsuka, Tohru Ohe, Hiroshi Ito

Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 22 ( 4 ) 287 - 93 2013

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Centrilobular ground-glass opacity (GGO) is one of the characteristic findings in chest high-resolution computed tomography (HRCT) of patients with pulmonary veno-occlusive disease (PVOD) and patients with pulmonary capillary hemangiomatosis (PCH). However, clinical differential diagnosis of these two diseases is difficult and has not been established. In order to clarify their differences, we compared the sizes of GGOs in chest HRCT and the sizes of capillary assemblies in pulmonary vascular casts between patients diagnosed pathologically with PVOD and PCH. METHODS: We evaluated chest HRCT images for four patients with idiopathic pulmonary arterial hypertension (IPAH), three patients with PVOD and three patients with PCH, and we evaluated pulmonary vascular casts of lung tissues obtained from those patients at lung transplantation or autopsy. RESULTS: Centrilobular GGOs in chest HRCT were observed in patients with PVOD and patients with PCH but not in patients with IPAH. We measured the longest diameter of the GGOs. The size of centrilobular GGOs was significantly larger in patients with PCH than in patients with PVOD (5.60±1.43 mm versus 2.51±0.79 mm, P<.01). We succeeded in visualization of the 3-dimensional structures of pulmonary capillary vessels obtained from the same patients with PVOD and PCH undergoing lung transplantation or autopsy and measured the diameters of capillary assemblies. The longest diameter of capillary assemblies was also significantly larger in patients with PCH than in patients with PVOD (5.44±1.71 mm versus 3.07±1.07 mm, P<.01). CONCLUSION: Measurement of the sizes of centrilobular GGOs in HRCT is a simple and useful method for clinical differential diagnosis of PVOD and PCH.

DOI： 10.1016/j.carpath.2012.12.002

Acute vasoreactivity testing with nicardipine in patients with pulmonary arterial hypertension. Reviewed

Yukihiro Saito, Kazufumi Nakamura, Katsumasa Miyaji, Satoshi Akagi, Hiroki Mizoguchi, Aiko Ogawa, Soichiro Fuke, Hideki Fujio, Takahiko Kiyooka, Satoshi Nagase, Kunihisa Kohno, Hiroshi Morita, Kengo F Kusano, Hiromi Matsubara, Tohru Ohe, Hiroshi Ito

Journal of pharmacological sciences 120 ( 3 ) 206 - 12 2012.10

Language：English Publishing type：Research paper (scientific journal)

Acute vasoreactivity testing for patients with pulmonary arterial hypertension (PAH) has been reported to be useful to identify patients with sustained beneficial response to oral calcium-channel blockers (CCBs), but there is a risk of exacerbation during the testing with oral CCBs. Therefore, we developed a testing method utilizing intravenous nicardipine, a short-acting CCB, and examined the safety and usefulness of acute vasoreactivity testing with nicardipine in PAH patients. Acute vasoreactivity testing with nicardipine was performed in 65 PAH patients. Nicardipine was administered by short-time continuous infusion (1 μg·kg⁻¹·min⁻¹ for 5 min and 2 μg·kg⁻¹·min⁻¹ for 5 min) followed by bolus injection (5 μg/kg). Hemodynamic responses were continuously measured using a right heart catheter. Acute responders were defined as patients who showed a decrease in mean pulmonary artery pressure of at least 10 mmHg to an absolute level below 40 mmHg with preserved or increased cardiac output. Two acute responders and sixty-three non-acute responders were identified. There was no hemodynamic instability requiring additional inotropic agents or death during the testing. Acute responders had good responses to long-term oral CCBs. The acute vasoreactivity testing with nicardipine might be safe and useful for identifying CCB responders in PAH patients.

Takotsubo cardiomyopathy associated with pulmonary resections after induction chemoradiotherapy for non-small cell lung cancer. Reviewed

Shinichi Toyooka, Satoshi Akagi, Masashi Furukawa, Kazufumi Nakamura, Junichi Soh, Masaomi Yamane, Takahiro Oto, Shinichiro Miyoshi

General thoracic and cardiovascular surgery 60 ( 9 ) 599 - 602 2012.9

Language：English Publishing type：Research paper (scientific journal)

Takotsubo cardiomyopathy (TTC), also known as transient left ventricular (LV) apical ballooning syndrome, is characterized by transient LV dysfunction. We present the case of a 72-year-old man who was diagnosed as having TTC after surgery for two lung tumors. The patient was treated with induction chemoradiotherapy (CRT) followed by pulmonary resections for double primary non-small cell lung cancers (NSCLC): cT4N1M0 disease in the right lung and cT2N0M0 in the left lung. Induction CRT was performed. A right upper lobectomy was initially performed, and a left upper divisionectomy was subsequently performed. At 3 days after the second surgery, he developed dyspnea and general fatigue accompanied by a T-wave inversion on electrocardiography (ECG). An echocardiogram revealed akinesis at the apex with a 30 % ejection fraction. He was diagnosed as having TTC and recovered with supportive care. This case is the first report of TTC occurring after tri-modality therapy for NSCLC.

DOI： 10.1007/s11748-012-0058-7

Pro-apoptotic effects of imatinib on PDGF-stimulated pulmonary artery smooth muscle cells from patients with idiopathic pulmonary arterial hypertension. Reviewed International journal

Kazufumi Nakamura, Satoshi Akagi, Aiko Ogawa, Kengo F Kusano, Hiromi Matsubara, Daiji Miura, Soichiro Fuke, Nobuhiro Nishii, Satoshi Nagase, Kunihisa Kohno, Hiroshi Morita, Takahiro Oto, Ryutaro Yamanaka, Fumio Otsuka, Aya Miura, Chikao Yutani, Tohru Ohe, Hiroshi Ito

International journal of cardiology 159 ( 2 ) 100 - 6 2012.8

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Remodeling of the pulmonary artery by an inappropriate increase of pulmonary artery smooth muscle cells (PASMCs) is problematic in the treatment of idiopathic pulmonary arterial hypertension (IPAH). Effective treatment that achieves reverse remodeling is required. The aim of this study was to assess the pro-apoptotic effects of imatinib, a platelet-derived growth factor (PDGF)-receptor tyrosine kinase inhibitor, on PASMCs obtained from patients with IPAH. METHODS: PASMCs were obtained from 8 patients with IPAH undergoing lung transplantation. Cellular proliferation was assessed by (3)H-thymidine incorporation. Pro-apoptotic effects of imatinib were examined using TUNEL and caspase-3,7 assays and using transmission electron microscopy. RESULTS: Treatment with imatinib (0.1 to 10 μg/mL) significantly inhibited PDGF-BB (10 ng/mL)-induced proliferation of PASMCs from IPAH patients. Imatinib (1 μg/mL) did not induce apoptosis in quiescent IPAH-PASMCs, but it had a pro-apoptotic effect on IPAH-PASMCs stimulated with PDGF-BB. Imatinib did not induce apoptosis in normal control PASMCs with or without PDGF-BB stimulation. PDGF-BB induced phosphorylation of Akt at 15 min, and Akt phosphorylation was inhibited by imatinib in IPAH-PASMCs. Akt-I-1/2 (1 μmol/L), an Akt inhibitor, in the presence of PDGF-BB significantly increased apoptotic cells compared with the control condition. Thus, Akt-I-1/2 could mimic the effects of imatinib on PASMCs. CONCLUSION: Imatinib has anti-proliferative and pro-apoptotic effects on IPAH-PASMCs stimulated with PDGF. The inhibitory effect of imatinib on Akt phosphorylation induced by PDGF plays an important role in the pro-apoptotic effect.

DOI： 10.1016/j.ijcard.2011.02.024

Intermittent arm ischemia induces vasodilatation of the contralateral upper limb. Reviewed

Kenki Enko, Kazufumi Nakamura, Kei Yunoki, Toru Miyoshi, Satoshi Akagi, Masashi Yoshida, Norihisa Toh, Mutsuko Sangawa, Nobuhiro Nishii, Satoshi Nagase, Kunihisa Kohno, Hiroshi Morita, Kengo F Kusano, Hiroshi Ito

The journal of physiological sciences : JPS 61 ( 6 ) 507 - 13 2011.11

Language：English Publishing type：Research paper (scientific journal)

Intermittent arm ischemia before percutaneous coronary intervention induces remote ischemic preconditioning (RIPC) and attenuates myocardial injury in patients with myocardial infarction. Several studies have shown that intermittent arm ischemia increases coronary flow and is related to autonomic nerve system. The aim of this study was to determine whether intermittent arm ischemia induces vasodilatation of other arteries and to assess changes in the autonomic nerve system during intermittent arm ischemia in humans. We measured change in the right brachial artery diameter during intermittent left arm ischemia through three cycles of 5-min inflation (200 mmHg) and 5-min deflation of a blood-pressure cuff using a 10-MHz linear array transducer probe in 20 healthy volunteers. We simultaneously performed power spectral analysis of heart rate. Ischemia-reperfusion of the left arm significantly dilated the right brachial artery time-dependently, resulting in a 3.2 ± 0.4% increase after the 3rd cycle. In the power spectral analysis of heart rate, the high-frequency domain (HF), which is a marker of parasympathetic activity, was significantly higher after the 3rd cycle of ischemia-reperfusion than baseline HF (P = 0.02). Intermittent arm ischemia was accompanied by vasodilatation of another artery and enhancement of parasympathetic activity. Those effects may play an important role in the mechanism of RIPC.

DOI： 10.1007/s12576-011-0172-9

Usefulness of acute pulmonary vasoreactivity test of sildenafil in treatment of portopulmonary hypertension. A case report. Reviewed

Satoshi Akagi, Kazufumi Nakamura, Soichiro Fuke, Kengo Fukushima Kusano, Hiroshi Ito

Journal of cardiology cases 4 ( 1 ) e31-e33 2011.8

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

A 50-year-old man diagnosed with liver cirrhosis type C was referred to our hospital because of right heart failure with pulmonary hypertension. Echocardiography revealed enlargement of the right atrium and ventricle with severe tricuspid regurgitation. The peak flow velocity of tricuspid regurgitation by continuous wave Doppler echocardiography was 452 cm/s. Right heart catheterization demonstrated severe pulmonary hypertension [pulmonary arterial pressure (PAP) systolic/diastolic/mean = 73/20/41 mmHg and pulmonary vascular resistance (PVR) = 509 dyn s cm-5] with portal hypertension. We diagnosed the patient as having portopulmonary hypertension (PoPH). Although we treated the patient with a prostacyclin analog, tricuspid regurgitation velocity was increased to 480 cm/s four years after the start of the therapy. To select drugs for the treatment of PoPH, we performed an acute vasoreactivity test of sildenafil during right heart catheterization. Since single administration of sildenafil (20 mg) decreased PAP (93/30/55-77/27/44 mmHg) and PVR (908-833 dyn s cm-5), we added sildenafil (20 mg, t.i.d.) to the prostacyclin analog. Tricuspid regurgitation velocity decreased to 403 cm/s one year after the addition of sildenafil. An acute vasoreactivity test of sildenafil during right heart catheterization was useful for the decision of the drug to be used in the treatment of PoPH.

DOI： 10.1016/j.jccase.2011.04.001

Circulating KCNH2 current-activating factor in patients with heart failure and ventricular tachyarrhythmia. Reviewed International journal

Hiroki Sugiyama, Kazufumi Nakamura, Hiroshi Morita, Satoshi Akagi, Yoshinori Tani, Yusuke Katayama, Nobuhiro Nishii, Toru Miyoshi, Satoshi Nagase, Kunihisa Kohno, Kengo Fukushima Kusano, Tohru Ohe, Junko Kurokawa, Tetsushi Furukawa, Hiroshi Ito

PloS one 6 ( 5 ) e19897 2011.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: It is estimated that approximately half of the deaths in patients with HF are sudden and that the most likely causes of sudden death are lethal ventricular tachyarrhythmias such as ventricular tachycardia (VT) or fibrillation (VF). However, the precise mechanism of ventricular tachyarrhythmias remains unknown. The KCNH2 channel conducting the delayed rectifier K(+) current (I(Kr)) is recognized as the most susceptible channel in acquired long QT syndrome. Recent findings have revealed that not only suppression but also enhancement of I(Kr) increase vulnerability to major arrhythmic events, as seen in short QT syndrome. Therefore, we investigated the existence of a circulating KCNH2 current-modifying factor in patients with HF. METHODOLOGY/PRINCIPAL FINDINGS: We examined the effects of serum of HF patients on recombinant I(Kr) recorded from HEK 293 cells stably expressing KCNH2 by using the whole-cell patch-clamp technique. Study subjects were 14 patients with non-ischemic HF and 6 normal controls. Seven patients had a history of documented ventricular tachyarrhythmias (VT: 7 and VF: 1). Overnight treatment with 2% serum obtained from HF patients with ventricular arrhythmia resulted in a significant enhancement in the peaks of I(Kr) tail currents compared to the serum from normal controls and HF patients without ventricular arrhythmia. CONCLUSIONS/SIGNIFICANCE: Here we provide the first evidence for the presence of a circulating KCNH2 channel activator in patients with HF and ventricular tachyarrhythmias. This factor may be responsible for arhythmogenesis in patients with HF.

DOI： 10.1371/journal.pone.0019897

Three-dimensional structure of pulmonary capillary vessels in patients with pulmonary hypertension. Reviewed International journal

Aya Miura, Kazufumi Nakamura, Kengo F Kusano, Hiromi Matsubara, Aiko Ogawa, Satoshi Akagi, Takahiro Oto, Takuro Murakami, Aiji Ohtsuka, Chikao Yutani, Tohru Ohe, Hiroshi Ito

Circulation 121 ( 19 ) 2151 - 3 2010.5

Inhibitory effects of simvastatin on platelet-derived growth factor signaling in pulmonary artery smooth muscle cells from patients with idiopathic pulmonary arterial hypertension. Reviewed International journal

Tetsuya Ikeda, Kazufumi Nakamura, Satoshi Akagi, Kengo Fukushima Kusano, Hiromi Matsubara, Hideki Fujio, Aiko Ogawa, Aya Miura, Daiji Miura, Takahiro Oto, Ryutaro Yamanaka, Fumio Otsuka, Hiroshi Date, Tohru Ohe, Hiroshi Ito

Journal of cardiovascular pharmacology 55 ( 1 ) 39 - 48 2010.1

Language：English Publishing type：Research paper (scientific journal)

Idiopathic pulmonary arterial hypertension (IPAH) is a progressive disease characterized by inappropriate increase of pulmonary artery smooth muscle cells (PASMCs) leading to occlusion of pulmonary arterioles. Inhibition of platelet-derived growth factor (PDGF) signaling is starting to garner attention as a targeted therapy for IPAH. We assessed the inhibitory effects of simvastatin, a 3-hydroxy-3-methylglutanyl coenzyme A reductase inhibitor, on PDGF-induced proliferation and migration of PASMCs obtained from 6 patients with IPAH who underwent lung transplantation. PDGF stimulation caused a significantly higher growth rate of PASMCs from patients with IPAH than that of normal control PASMCs as assessed by (3)H-thymidine incorporation. Simvastatin (0.1 micromol/L) significantly inhibited PDGF-induced cell proliferation of PASMCs from patients with IPAH but did not inhibit proliferation of normal control cells at the same concentration. Western blot analysis revealed that simvastatin significantly increased the expression of cell cycle inhibitor p27. PDGF significantly increased the migration distance of IPAH-PASMCs compared with that of normal PASMCs, and simvastatin (1 micromol/L) significantly inhibited PDGF-induced migration. Immunofluorescence staining revealed that simvastatin (1 micromol/L) inhibited translocation of Rho A from the cytoplasm to membrane and disorganized actin fibers in PASMCs from patients with IPAH. In conclusion, simvastatin had inhibitory effects on inappropriate PDGF signaling in PASMCs from patients with IPAH.

DOI： 10.1097/FJC.0b013e3181c0419c

Intravenous administration of nicorandil immediately before percutaneous coronary intervention can prevent slow coronary flow phenomenon. Reviewed International journal

Yusuke Kawai, Kenichi Hisamatsu, Hiromi Matsubara, Kazuhiro Dan, Satoshi Akagi, Katsumasa Miyaji, Mitsuru Munemasa, Yoshihisa Fujimoto, Kengo F Kusano, Tohru Ohe

European heart journal 30 ( 7 ) 765 - 72 2009.4

Language：English Publishing type：Research paper (scientific journal)

AIMS: To determine the effect of intravenous administration of nicorandil on slow coronary flow (SCF) phenomenon in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: In a preliminary study, 6 mg of nicorandil showed optimal efficacy for vasodilatation without causing significant haemodynamic instability. In the main study, a total of 408 patients were randomly assigned to receive intravenous administration of 6 mg of nicorandil immediately before PCI. The number of patients in the nicorandil group was 206 [acute coronary syndrome (ACS): 47, non-ACS: 159] and that in the control group was 202 (ACS: 61, non-ACS: 141). Nicorandil significantly decreased the incidence of post-procedural SCF phenomenon in both the ACS and non-ACS groups. The rate of target vessel revascularization (TVR) was significantly lower in the nicorandil group than in the control group in ACS patients. CONCLUSION: Our simple procedure prevented SCF phenomenon not only in patients with ACS but also in patients with non-ACS without any adverse effect. Additionally our procedure reduced the rate of TVR in patients with ACS.

DOI： 10.1093/eurheartj/ehp077

　 PREV - NEXT 　

1
2
3
4
5