23 results on '"Ayako Ishikita"'
Search Results
2. Successful Total Management of Multi-Causative Sleep-Disordered Breathing Complicated with Patient with Adult Congenital Heart Disease
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Tomoyasu, Suenaga, Ayako, Ishikita, Ichiro, Sakamoto, Mari, Nishizaka, Akiko, Nishizaki, Shintaro, Umemoto, Hazumu, Nagata, Kenichiro, Yamamura, Hiromichi, Sonoda, Hiroko, Yoshida, Shin-Ichi, Ando, Akira, Shiose, and Hiroyuki, Tsutsui
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Adult ,Heart Defects, Congenital ,Sleep Apnea Syndromes ,Humans ,Paralysis ,Cardiomegaly ,Female ,Hypoventilation ,Obesity ,General Medicine ,Cardiology and Cardiovascular Medicine - Abstract
Sleep-disordered breathing is one of the complications commonly seen in patients with adult congenital heart disease (ACHD) due to multiple causes including complex underlying cardiac defects, cardiomegaly, previous thoracotomies, obesity, scoliosis, and paralysis of the diaphragm. It is often hard to determine its main cause and predict the efficacy of each treatment in its management. We herein report a 30-year-old woman after biventricular repair of pulmonary atresia with intact ventricular septum diagnosed as sleep-related hypoventilation disorder. Simultaneous treatment targeting obesity, paralysis of the diaphragm, and cardiomegaly followed by respiratory muscle reinforcement through non-invasive ventilation resolved her sleep-related hypoventilation disorder. Such management for each factor responsible for the hypoventilation is expected to provide synergetic therapeutic efficacy and increase daily activity in a patient with ACHD.
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- 2022
3. High-echoic line tracing of transthoracic echocardiography accurately assesses right ventricular enlargement in adult patients with atrial septal defect
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Tasuku, Sato, Ichiro, Sakamoto, Ken-Ichi, Hiasa, Masateru, Kawakubo, Ayako, Ishikita, Shintaro, Umemoto, Min-Jeong, Kang, Hiroyuki, Sawatari, Akiko, Chishaki, Hiroshi, Shigeto, and Hiroyuki, Tsutsui
- Abstract
Purpose: Accurate measurement of right ventricular (RV) size using transthoracic echocardiography (TTE) is important for evaluating the severity of congenital heart diseases. The RV end-diastolic area index (RVEDAi) determined using TTE is used to assess RV dilatation; however, the tracing line of the RVEDAi has not been clearly defined by the guidelines. This study aimed to determine the exact tracing method for RVEDAi using TTE.Methods: We retrospectively studied 107 patients with atrial septal defects who underwent cardiac magnetic resonance imaging (CMR) and TTE. We measured the RVEDAi according to isoechoic and high-echoic lines, and compared it with the RVEDAi measured using CMR. The isoechoic line was defined as the isoechoic endocardial border of the RV free wall, whereas the high-echoic line was defined as the high-echoic endocardial border of the RV free wall more outside than the isoechoic line. Results: RVEDAi measured using high-echoic line (high-RVEDAi) was more accurately related to RVEDAi measured using CMR than that measured using isoechoic line (iso-RVEDAi). The difference in the high-RVEDAi was 0.3 cm2/m2, and the limit of agreement (LOA) was −3.7 to 4.3 cm2/m2. With regard to inter-observer variability, high-RVEDAi was superior to iso-RVEDAi. Conclusion: High-RVEDAi had greater agreement with CMR-RVEDAi than with iso-RVEDAi. High-RVEDAi can become the standard measurement of RV size using two-dimensional TTE.
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- 2022
4. Usefulness of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Diagnosis of Infective Endocarditis in Patients With Adult Congenital Heart Disease
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Shintaro Umemoto, Hazumu Nagata, Yoshiyuki Kitamura, Yuzo Yamasaki, Hiromichi Sonoda, Hiroyuki Tsutsui, Ayako Ishikita, Kenichiro Yamamura, Akira Shiose, Ichiro Sakamoto, and Hideki Tatewaki
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medicine.medical_specialty ,Heart disease ,medicine.diagnostic_test ,business.industry ,Clinical course ,Computed tomography ,General Medicine ,030204 cardiovascular system & hematology ,medicine.disease ,Duke criteria ,030218 nuclear medicine & medical imaging ,Fluorodeoxyglucose positron emission tomography ,03 medical and health sciences ,0302 clinical medicine ,Positron emission tomography ,Infective endocarditis ,Medicine ,In patient ,Radiology ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Infective endocarditis (IE) in patients with adult congenital heart disease (ACHD) remains a diagnostic challenge due to difficulties in detecting endocardial lesions by echocardiography. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has shown good diagnostic performance in prosthetic valve IE. This study aimed to assess its additional diagnostic value in ACHD-associated IE and to characterize its advantages.Methods and Results:Overall, 22 patients with ACHD and clinical suspicion of IE were retrospectively studied. 18F-FDG PET/CT was performed in addition to conventional assessment based on the modified Duke criteria. The final IE diagnosis was determined by an expert team during a 3-month clinical course, resulting in 18 patients diagnosed with IE. Seven patients (39%) were diagnosed with definite IE only by initial echocardiography. An 18F-FDG PET/CT assessment revealed endocardial involvement in the other 9 patients, resulting in the diagnosis of definite IE in 16 in total (88%). Right-sided endocardial lesions were more common (n=12, 67%) but rarely identified by echocardiography, whereas 18F-FDG PET/CT revealed right-sided lesions in 9 patients. A negative 18F-FDG PET/CT (n=7, 39%) assessment was associated with a native valve IE (71% vs. 0%). In 4 patients who were identified with not-IE, neither echocardiography nor 18F-FDG PET/CT detected any suspicious cardiac involvement. Conclusions In the diagnosis of ACHD-associated IE, characterized by right-sided IE, 18F-FDG PET/CT assessment should be useful.
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- 2021
5. Preoperative Threshold for Normalizing Right Ventricular Volume After Transcatheter Closure of Adult Atrial Septal Defect
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Yuzo Yamasaki, Kohtaro Abe, Kenichi Hiasa, Ichiro Sakamoto, Shintaro Umemoto, Ayako Ishikita, Hiroyuki Tsutsui, and Tomomi Ide
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Adult ,Male ,Cardiac Catheterization ,medicine.medical_specialty ,Magnetic Resonance Imaging, Cine ,030204 cardiovascular system & hematology ,Independent predictor ,Heart Septal Defects, Atrial ,03 medical and health sciences ,0302 clinical medicine ,Cardiac magnetic resonance imaging ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Retrospective Studies ,Ventricular Remodeling ,medicine.diagnostic_test ,business.industry ,Age Factors ,General Medicine ,Middle Aged ,Treatment Outcome ,Ventricular Function, Right ,Cardiology ,Ventricular volume ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background The latest guidelines recommend early intervention in adult atrial septal defect (ASD) patients with signs of right ventricular (RV) enlargement. However, the criteria of RV enlargement for optimal intervention remain unclear. We investigated the preoperative determinants for normalizing the RV volume after transcatheter closure of ASD in adults.Methods and Results:We retrospectively analyzed 52 ASD patients who underwent transcatheter closure. Cardiac magnetic resonance imaging (CMR) measured RV volume before and 1 year after the closure. The patients were divided into normalized (postoperative RV end-systolic volume index [RVESVI] Conclusions Preoperative RVESVI is an independent predictor for normalization of RV volume at 1 year after transcatheter closure of ASD in adults. Early intervention before RVESVI reaches 75 mL/m2may confer optimal timing for normalizing RV volume.
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- 2020
6. Elaborate evaluation of serial changes in electrocardiograms of atrial septal defects after transcatheter closure for a better understanding of the recovery process
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Chizuko Kamiya, Min Jeong Kang, Hiroyuki Sawatari, Hiroaki Chishaki, Tasuku Sato, Mari Nishizaka, Koichiro Niwa, Hiroyuki Tsutsui, Ichiro Sakamoto, Kanae Fujita, Kenichi Hiasa, Shintaro Umemoto, Akiko Chishaki, Ryoji Shinbara, Keiko Yamasaki, and Ayako Ishikita
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Adult ,Male ,Cardiac Catheterization ,medicine.medical_specialty ,Time Factors ,Septal Occluder Device ,Action Potentials ,030204 cardiovascular system & hematology ,Risk Assessment ,Severity of Illness Index ,Heart Septal Defects, Atrial ,Atrial septal defects ,Electrocardiography ,03 medical and health sciences ,QRS complex ,0302 clinical medicine ,Heart Rate ,Predictive Value of Tests ,Risk Factors ,Left atrial ,Internal medicine ,Atrial Fibrillation ,medicine ,Humans ,cardiovascular diseases ,030212 general & internal medicine ,PR interval ,Aged ,Retrospective Studies ,Heart Failure ,business.industry ,Middle Aged ,Vascular surgery ,medicine.disease ,Cardiac surgery ,Treatment Outcome ,Heart failure ,Right heart ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Serial changes of electrocardiograms (ECG) could be used to assess their clinical features in atrial septal defects (ASD) after transcatheter closure together with other clinical parameters. We retrospectively studied 100 ASD patients who underwent transcatheter closure. Complications of persistent atrial fibrillation occurred in five ASD patients, and they were excluded. We divided the other 95 patients according to PQ intervals before closure (normal
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- 2020
7. Differential Presentation of Renal Disease in Adult Fontan Patients with or Without Liver Disease
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Mamoru Muraoka, Hazumu Nagata, Ichiro Sakamoto, Kenichiro Yamamura, Ayako Ishikita, Akiko Nishizaki, Yoshimi Eguchi, Shouji Fukuoka, Kiyoshi Uike, Yusaku Nagatomo, Yuichiro Hirata, Kei Nishiyama, Hiroyuki Tsutsui, and Shouichi Ohga
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- 2022
8. Right-Sided Endocarditis With Mitral Valve Aneurysm
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Takamori, Kakino, Ichiro, Sakamoto, Akiko, Nishizaki, Akihito, Ishikita, Ayako, Ishikita, Hiromichi, Sonoda, Akira, Shiose, and Hiroyuki, Tsutsui
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General Medicine ,Cardiology and Cardiovascular Medicine - Published
- 2023
9. Visibility of Pulmonary Valve and Pulmonary Regurgitation on Intracardiac Echocardiography in Adult Patients with Tetralogy of Fallot
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Ichiro Sakamoto, Kenichiro Yamamura, Ayako Ishikita, Kisho Ohtani, Shintaro Umemoto, Hidetaka Kaku, Yuzo Yamasaki, Kohtaro Abe, Tomomi Ide, and Hiroyuki Tsutsui
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Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,intracardiac echocardiography ,pulmonary valve ,pulmonary regurgitation ,tetralogy of Fallot - Abstract
Pulmonary regurgitation (PR) is a risk factor for sudden cardiac death in adult patients with repaired tetralogy of Fallot (TOF). However, transthoracic echocardiography (TTE) cannot fully visualize the pulmonary valve (PV) and PR. We investigated whether intracardiac echocardiography (ICE) could visualize the PV and PR better than TTE. Thirty adult patients with TOF (mean age 33 ± 15 years) scheduled for cardiac catheterization underwent ICE. The visualization of PV and the severity of PR were classified into three grades. ICE depicted the PV better than TTE (ICE vs. TTE: not visualized, partially visualized, and fully visualized: n = 1 [3%], n = 13 [43%], and n = 16 [53%] vs. n = 14 [47%], n = 13 [43%], and n = 3 [10%], p < 0.001). Especially in patients after pulmonary valve replacement (PVR), the PV was more fully visualized by ICE. The assessment of PR by TTE underestimated the severity of PR in comparison to cardiac magnetic resonance imaging (MRI) (severe PR: 8 [28%] vs. 22 [76%], p = 0.004), while there was no discrepancy between the results of ICE and MRI (21 [72%] vs. 22 [76%], p = 1.000). In comparison to TTE, ICE can safely provide better visualization of the PV and PR in adults with TOF, especially in patients who have undergone PVR.
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- 2023
10. Hemodynamic Characteristics After Fontan Procedure in Patients with Down's Syndrome
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Masakazu, Otsuka, Yoshihiko, Kodama, Ayako, Kuraoka, Yuichi, Ishikawa, Makoto, Nakamura, Toshihide, Nakano, Hideaki, Kado, Shintaro, Umemoto, Ayako, Ishikita, Ichiro, Sakamoto, Tomomi, Ide, Hiroyuki, Tsutsui, and Koichi, Sagawa
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Heart Defects, Congenital ,Central Venous Pressure ,Hemodynamics ,Humans ,Down Syndrome ,Child ,Fontan Procedure ,Retrospective Studies - Abstract
Patients with Down's syndrome (DS) are generally regarded as not being good candidates for the Fontan procedure. However, detailed hemodynamic changes over time are not fully clarified. A retrospective chart review of all patients with DS who underwent the Fontan procedure and 5 times that number of Fontan patients without DS performed in Fukuoka Children's Hospital and Kyushu University Hospital. Seven Fontan patients with DS were identified, and 35 Fontan patients without DS were recruited. During the mean observational periods of 14.7 years and 15.0 years (DS and non-DS, respectively) after the Fontan procedure, only one DS patient died. Central venous pressure (CVP) and transpulmonary pressure gradient significantly increased, and arterial oxygen saturation significantly decreased over time in DS patients after the Fontan procedure compared with those without DS. CVP in DS patients after the Fontan procedure increased over time compared with non-DS patients. Better management including the efficacy of Pulmonary arterial hypertension-specific therapy should be clarified in further studies.
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- 2021
11. Nanoparticle‐Mediated Simultaneous Targeting of Mitochondrial Injury and Inflammation Attenuates Myocardial Ischemia‐Reperfusion Injury
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Kaku Nakano, Jun Ichiro Koga, Tetsuya Matoba, Hiroyuki Tsutsui, Gentaro Ikeda, Kensuke Egashira, Ayako Ishikita, and Kazuhiro Nagaoka
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Male ,Time Factors ,ischemia‐reperfusion injury ,Translational Studies ,Interleukin-1beta ,Anti-Inflammatory Agents ,030204 cardiovascular system & hematology ,Pharmacology ,Mitochondria, Heart ,0302 clinical medicine ,Polylactic Acid-Polyglycolic Acid Copolymer ,Ischemia ,Coronary Heart Disease ,drug delivery system ,Myocytes, Cardiac ,Original Research ,Mice, Knockout ,Cardioprotection ,Drug Carriers ,0303 health sciences ,nanotechnology ,Drug Combinations ,cardioprotection ,Cyclosporine ,Quinolines ,Inflammation Mediators ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Cyclophilin D ,Myocardial ischemia ,Receptors, CCR2 ,Drug Compounding ,Myocardial Reperfusion Injury ,Inflammation ,03 medical and health sciences ,NLR Family, Pyrin Domain-Containing 3 Protein ,medicine ,Animals ,030304 developmental biology ,Mitochondrial Permeability Transition Pore ,business.industry ,Therapeutic effect ,medicine.disease ,Mice, Inbred C57BL ,Disease Models, Animal ,Mitochondrial permeability transition pore ,Nanoparticles ,business ,Reperfusion injury - Abstract
Background The opening of mitochondrial permeability transition pore and inflammation cooperatively progress myocardial ischemia‐reperfusion (IR) injury, which hampers therapeutic effects of primary reperfusion therapy for acute myocardial infarction. We examined the therapeutic effects of nanoparticle‐mediated medicine that simultaneously targets mitochondrial permeability transition pore and inflammation during IR injury. Methods and Results We used mice lacking cyclophilin D (CypD, a key molecule for mitochondrial permeability transition pore opening) and C‐C chemokine receptor 2 and found that CypD contributes to the progression of myocardial IR injury at early time point (30–45 minutes) after reperfusion, whereas C‐C chemokine receptor 2 contributes to IR injury at later time point (45–60 minutes) after reperfusion. Double deficiency of CypD and C‐C chemokine receptor 2 enhanced cardioprotection compared with single deficiency regardless of the durations of ischemia. Deletion of C‐C chemokine receptor 2, but not deletion of CypD, decreased the recruitment of Ly‐6C high monocytes after myocardial IR injury. In CypD‐knockout mice, administration of interleukin‐1β blocking antibody reduced the recruitment of these monocytes. Combined administration of polymeric nanoparticles composed of poly‐lactic/glycolic acid and encapsulating nanoparticles containing cyclosporine A or pitavastatin, which inhibit mitochondrial permeability transition pore opening and monocyte‐mediated inflammation, respectively, augmented the cardioprotection as compared with single administration of nanoparticles containing cyclosporine A or pitavastatin after myocardial IR injury. Conclusions Nanoparticle‐mediated simultaneous targeting of mitochondrial injury and inflammation could be a novel therapeutic strategy for the treatment of myocardial IR injury.
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- 2021
12. Usefulness of
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Ayako, Ishikita, Ichiro, Sakamoto, Kenichiro, Yamamura, Shintaro, Umemoto, Hazumu, Nagata, Yoshiyuki, Kitamura, Yuzo, Yamasaki, Hiromichi, Sonoda, Hideki, Tatewaki, Akira, Shiose, and Hiroyuki, Tsutsui
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Adult ,Heart Defects, Congenital ,Endocarditis ,Fluorodeoxyglucose F18 ,Positron Emission Tomography Computed Tomography ,Humans ,Retrospective Studies - Abstract
Infective endocarditis (IE) in patients with adult congenital heart disease (ACHD) remains a diagnostic challenge due to difficulties in detecting endocardial lesions by echocardiography.In the diagnosis of ACHD-associated IE, characterized by right-sided IE
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- 2021
13. Cyclin dependent kinase 1 (CDK1) positively regulates cardiac hypertrophy and fibrosis via TGF-beta pathway
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Taishi Yamamoto, Yoshitomo Tsutsui, Nobuyuki Enzan, Ryo Miyake, Soichiro Ikeda, Shouji Matsushima, Ayako Ishikita, Kosuke Okabe, Hiroyuki Tsutsui, and Masashi Sada
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Cyclin-dependent kinase 1 ,Fibrosis ,business.industry ,Cardiac hypertrophy ,TGF beta signaling pathway ,Cancer research ,medicine ,Cardiology and Cardiovascular Medicine ,medicine.disease ,business - Abstract
Background Transforming growth factor beta (TGF-β) critically mediates cardiac fibrosis by transforming fibroblasts to myofibroblasts in pathological conditions. Cyclin dependent kinases (CDKs), cell cycle-regulating proteins, are known to be intimately involved in cardiac fibrosis. Among CDK isoforms, CDK1 is essential for cell cycle progression and cell division. It is reported some interphase CDKs such as CDK4 or CDK6 were involved in cardiac fibrosis, however, detailed mechanisms of cardiac fibrosis through CDK1 and its interactions with TGF-β in cardiac fibrotic process haven't been elucidated. We hypothesize that CDK1 is involved in cardiac fibrotic process via TGF-β pathway and its suppression decreases TGF-β expression and transformation to myofibroblasts from fibroblasts presenting antifibrotic effect. Methods and results Isolated neonatal rat cardiac fibroblasts were treated with angiotensin II (ANG II, 1 μM, 24 h) or phosphate-buffered saline (PBS). ANG II increased CDK1 and TGF-β in cardiac fibroblasts, by 97% and 292%, respectively (p Conclusions CDK1 positively controls cardiac fibrotic process by regulating transformation to cardiac myofibroblasts from fibroblasts via TGF-β pathway. It also presents an antihypertrophic effect on ANG II stimulation. CDK1 is a potential therapeutic target of cardiac fibrosis and hypertrophy. Funding Acknowledgement Type of funding source: Other. Main funding source(s): KAKENHI
- Published
- 2020
14. Portosystemic venous shunt in the patients with Fontan circulation
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Hazumu Nagata, Ayako Ishikita, Shouichi Ohga, Kiyoshi Uike, Yusaku Nagatomo, Shouji Fukuoka, Ichiro Sakamoto, Yuichiro Hirata, and Kenichiro Yamamura
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Adult ,Heart Defects, Congenital ,Male ,medicine.medical_specialty ,Adolescent ,Vascular Malformations ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,Fontan Procedure ,Vascular anomaly ,Veins ,Fontan procedure ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Internal medicine ,Medicine ,Humans ,Abnormalities, Multiple ,030212 general & internal medicine ,Cardiac catheterization ,Retrospective Studies ,business.industry ,Central venous pressure ,Vascular surgery ,Middle Aged ,medicine.disease ,Cardiac surgery ,medicine.anatomical_structure ,Echocardiography ,Heart failure ,cardiovascular system ,Vascular resistance ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Portosystemic venous shunt (PSVS) is a vascular anomaly between the portal and systemic veins, resulting in several critical complications. Although PSVS is often associated with congenital heart diseases, the clinical association between Fontan circulation and PSVS has not been elucidated. This study aimed to investigate the clinical features of Fontan patients with PSVS. Two hundred thirteen patients who underwent Fontan procedure are being followed up at Adult Congenital Heart Disease clinic in Kyushu University Hospital. Among them, 139 adult patients underwent cardiac catheterization between January 1, 2011 and September 30, 2019. Medical records were reviewed to investigate the laboratory, echocardiography, and cardiac catheterization findings, as well as clinical manifestations and outcomes. Eleven Fontan patients received the diagnosis of PSVS. The median age at cardiac catheterization was 25 (range 18–45) years. Fontan operation was performed using extracardiac conduit or lateral tunnel 22 (16–35) years previously. Ten patients presented with chronic heart failure [New York Heart Association class 2 (n = 5) and 3 (n = 5)]. The median level of peripheral oxygen saturation was 87 (70–95)%. Cardiac catheterization showed increased cardiac index [5.3 (2.72–14.3) L/min/m2] with or without high central venous pressure [18 (9–25) mmHg]. Although the pulmonary vascular resistance was within the normal range, the systemic vascular resistance was decreased [7.08 (1.74–18.6) Wood units]. Fontan patients complicated with PSVS had increased cardiac output. The presence of PSVS in Fontan circulation might be associated with unfavorable long-term outcome.
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- 2020
15. P1606Glutamine-fructose-6-phosphate amidotransferase 2 mediates isoproterenol-induced cardiac hypertrophy by increasing Akt O-GlcNAcylation through hexosamine biosynthesis pathway
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Hiroyuki Tsutsui, Tomomi Ide, Nobuyuki Enzan, Masashi Sada, Tomonori Tadokoro, Taishi Yamamoto, Ayako Ishikita, Shouji Matsushima, Soichiro Ikeda, Kosuke Okabe, Masataka Ikeda, and Hiroko Deguchi
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O glcnacylation ,chemistry.chemical_compound ,Biochemistry ,Biosynthesis ,chemistry ,business.industry ,Cardiac hypertrophy ,Medicine ,Fructose 6-phosphate ,Cardiology and Cardiovascular Medicine ,business ,Protein kinase B ,Glutamine amidotransferase - Abstract
Background Cardiac hypertrophy is an independent risk factor for heart failure and cardiac death. Hexosamine biosynthesis pathway (HBP), an accessory pathways of glycolysis, is known to be involved in the attachment of O-linked N-acetylglucosamine motif (O-GlcNAcylation) to proteins, a post-translational modification. However, the role of HBP has not been determined in pathological cardiac hypertrophy. Purpose The purpose of this study to examine whether glutamine-fructose-6-phosphate amidotransferase 2 (GFAT2), a critical enzyme of HBP, mediates cardiac hypertrophy by protein O-GlcNAcylation and activating hypertrophic signaling in cardiomyocytes. Methods and results C57BL/6J mice were treated with isoproterenol (ISO: 15 mg/kg/day, 1 week) with or without 6-Diazo-5-oxo-L-norleucine (DON, an inhibitor of GFAT: 500 μg/kg/day, 1week). ISO-treated mice (ISO+vehicle) showed cardiac hypertrophy, which were attenuated in ISO and DON-treated mice (ISO+DON) (heart weight to tibial length ratio: 7.70±0.09 vs. 7.11±0.15 mg/mm, n=12, p Conclusions GFAT2, a limiting enzyme of HBP, mediates pathological cardiac hypertrophy by Akt activation probably due to its O-GlcNAcylation. GFAT2-O-GlcNAcylation-Akt pathway might be a potential novel therapeutic target for cardiac hypertrophy.
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- 2019
16. P6305Activation of invariant natural killer T cells ameliorates doxorubicin-induced cardiomyopathy
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Kosuke Okabe, Hiroyuki Tsutsui, Tomomi Ide, Nobuyuki Enzan, Tomonori Tadokoro, Shouji Matsushima, Masataka Ikeda, Masashi Sada, Ayako Ishikita, Taishi Yamamoto, Y Deguchi, and Soichiro Ikeda
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business.industry ,Cancer research ,Medicine ,Cardiology and Cardiovascular Medicine ,Doxorubicin induced cardiomyopathy ,business ,Invariant natural killer T-cell - Abstract
Background Invariant natural killer T (iNKT) cells orchestrate tissue inflammation via regulating various cytokine productions, especially strongly upregulating interferon (IFN)-γ. Activation of iNKT cells have been previously reported to exert protective effects against post-infarcted cardiac remodeling and cardiac ischemia/reperfusion injury. However, the role of iNKT cells has not been determined in doxorubicin (DOX)-induced cardiomyopathy. Purpose The purpose of this study was to examine whether the activation of iNKT cells by α-galactosylceramide (αGC), which specifically activates iNKT cells, could affect DOX-induced cardiomyopathy, and if so, to elucidate its downstream target. Methods C57BL/6J mice were received the intraperitoneal injection of either αGC (0.1μg/g, n=11) or vehicle (n=13). After 1 week, these mice were treated with a low dose of DOX (18mg/kg via intravenous 3 injections over 1 week), and were followed during 14 days. Results DOX mice (DOX+vehicle) showed left ventricular (LV) dysfunction and dilatation, which were significantly ameliorated in DOX mice receiving αGC (DOX+αGC) (LV fractional shortening: 27.4±4.31 vs. 31.5±4.62%, p Conclusions Activation of iNKT cells by αGC play a protective role against DOX-induced cardiac dysfunction, which was associated with enhancing expression of IFN-γ and activating Akt. Therapies designed to activate iNKT cells might be beneficial to protect the heart from DOX injury.
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- 2019
17. P5694L-type calcium channel blocker attenuates doxorubicine-induced cardiomyopathy by inhibiting CaMKII-NF-kB axis
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Tomonori Tadokoro, Soichiro Ikeda, Shouji Matsushima, Masataka Ikeda, Ayako Ishikita, Hiroyuki Tsutsui, and Tomomi Ide
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medicine.drug_class ,business.industry ,Ca2+/calmodulin-dependent protein kinase ,Cardiomyopathy ,medicine ,Calcium channel blocker ,Pharmacology ,Cardiology and Cardiovascular Medicine ,medicine.disease ,business - Published
- 2018
18. P2826Teneligliptin attenuated AngII-induced cardiac hypertrophy by inhibiting Nox4-HDAC4 axis
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Hiroyuki Tsutsui, Tomomi Ide, Ayako Ishikita, Kosuke Okabe, Shouji Matsushima, Masataka Ikeda, Tomonori Tadokoro, and Soichiro Ikeda
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medicine.medical_specialty ,Endocrinology ,business.industry ,Internal medicine ,Cardiac hypertrophy ,medicine ,NOX4 ,Cardiology and Cardiovascular Medicine ,business ,HDAC4 - Published
- 2018
19. Nanoparticle-Mediated Delivery of Mitochondrial Division Inhibitor 1 to the Myocardium Protects the Heart From Ischemia-Reperfusion Injury Through Inhibition of Mitochondria Outer Membrane Permeabilization: A New Therapeutic Modality for Acute Myocardial Infarction
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Junichi Sadoshima, Tetsuya Matoba, Kaku Nakano, Gentaro Ikeda, Yajing Mao, Osamu Takeuchi, Kensuke Egashira, Jun Ichiro Koga, and Ayako Ishikita
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0301 basic medicine ,Pathology ,ischemia‐reperfusion injury ,Myocardial Infarction ,Biocompatible Materials ,030204 cardiovascular system & hematology ,Mitochondrion ,Pharmacology ,medicine.disease_cause ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Drug Delivery Systems ,Polylactic Acid-Polyglycolic Acid Copolymer ,Coronary Heart Disease ,drug delivery system ,Myocytes, Cardiac ,bcl-2-Associated X Protein ,Original Research ,Drug Carriers ,MPTP ,nanoparticle ,Cytochromes c ,Heart ,Oxidants ,mitochondria ,Protein Transport ,Mitochondrial Membranes ,Cardiology and Cardiovascular Medicine ,Dynamins ,Programmed cell death ,medicine.medical_specialty ,Cell Survival ,Ischemia ,Myocardial Reperfusion Injury ,Permeability ,03 medical and health sciences ,medicine ,Animals ,Lactic Acid ,Quinazolinones ,business.industry ,Isolated Heart Preparation ,Hydrogen Peroxide ,medicine.disease ,Rats ,Cytosol ,030104 developmental biology ,Mitochondrial permeability transition pore ,chemistry ,Nanoparticles ,business ,Reperfusion injury ,Oxidative stress ,Polyglycolic Acid ,Basic Science Research - Abstract
Background Mitochondria‐mediated cell death plays a critical role in myocardial ischemia‐reperfusion ( IR ) injury. We hypothesized that nanoparticle‐mediated drug delivery of mitochondrial division inhibitor 1 (Mdivi1) protects hearts from IR injury through inhibition of mitochondria outer membrane permeabilization ( MOMP ), which causes mitochondrial‐mediated cell death. Methods and Results We formulated poly (lactic‐co‐glycolic acid) nanoparticles containing Mdivi1 (Mdivi1‐ NP ). We recently demonstrated that these nanoparticles could be successfully delivered to the cytosol and mitochondria of cardiomyocytes under H 2 O 2 ‐induced oxidative stress that mimicked IR injury. Pretreatment with Mdivi1‐ NP ameliorated H 2 O 2 ‐induced cell death in rat neonatal cardiomyocytes more potently than Mdivi1 alone, as indicated by a lower estimated half‐maximal effective concentration and greater maximal effect on cell survival. Mdivi1‐ NP treatment of Langendorff‐perfused mouse hearts through the coronary arteries at the time of reperfusion reduced infarct size after IR injury more effectively than Mdivi1 alone. Mdivi1‐ NP treatment also inhibited Drp1‐mediated Bax translocation to the mitochondria and subsequent cytochrome c leakage into the cytosol, namely, MOMP , in mouse IR hearts. MOMP inhibition was also observed in cyclophilin D knockout (CypD‐ KO ) mice, which lack the mitochondrial permeability transition pore ( MPTP ) opening. Intravenous Mdivi1‐ NP treatment in vivo at the time of reperfusion reduced IR injury in wild‐type and CypD‐ KO mice, but not Bax‐ KO mice. Conclusions Mdivi1‐ NP treatment reduced IR injury through inhibition of MOMP , even in the absence of a CypD/ MPTP opening. Thus, nanoparticle‐mediated drug delivery of Mdivi1 may be a novel treatment strategy for IR injury.
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- 2016
20. Nanoparticle-Mediated Delivery of Irbesartan Induces Cardioprotection from Myocardial Ischemia-Reperfusion Injury by Antagonizing Monocyte-Mediated Inflammation
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Masaki Tokutome, Shunsuke Katsuki, Jun Ichiro Koga, Yasuhiro Nakano, Ayako Ishikita, Kaku Nakano, Kensuke Egashira, Kazuhiro Nagaoka, Kenji Sunagawa, Tetsuya Matoba, Gentaro Ikeda, and Daiki Funamoto
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0301 basic medicine ,Myocarditis ,Cardiotonic Agents ,Myocardial Ischemia ,Tetrazoles ,Inflammation ,030204 cardiovascular system & hematology ,Pharmacology ,urologic and male genital diseases ,Monocytes ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Irbesartan ,Polylactic Acid-Polyglycolic Acid Copolymer ,medicine ,Animals ,Lactic Acid ,Cardioprotection ,Drug Carriers ,Multidisciplinary ,urogenital system ,business.industry ,Monocyte ,Biphenyl Compounds ,medicine.disease ,female genital diseases and pregnancy complications ,Biphenyl compound ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Treatment Outcome ,Reperfusion Injury ,Immunology ,Drug delivery ,Nanoparticles ,Administration, Intravenous ,medicine.symptom ,business ,Reperfusion injury ,Polyglycolic Acid ,medicine.drug - Abstract
Myocardial ischemia-reperfusion (IR) injury limits the therapeutic effect of early reperfusion therapy for acute myocardial infarction (AMI), in which the recruitment of inflammatory monocytes plays a causative role. Here we develop bioabsorbable poly-lactic/glycolic acid (PLGA) nanoparticles incorporating irbesartan, an angiotensin II type 1 receptor blocker with a peroxisome proliferator-activated receptor (PPAR)γ agonistic effect (irbesartan-NP). In a mouse model of IR injury, intravenous PLGA nanoparticles distribute to the IR myocardium and monocytes in the blood and in the IR heart. Single intravenous treatment at the time of reperfusion with irbesartan-NP (3.0 mg kg−1 irbesartan), but not with control nanoparticles or irbesartan solution (3.0 mg kg−1), inhibits the recruitment of inflammatory monocytes to the IR heart and reduces the infarct size via PPARγ-dependent anti-inflammatory mechanisms and ameliorates left ventricular remodeling 21 days after IR. Irbesartan-NP is a novel approach to treat myocardial IR injury in patients with AMI.
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- 2016
21. Nanoparticle-Mediated Targeting of Cyclosporine A Enhances Cardioprotection Against Ischemia-Reperfusion Injury Through Inhibition of Mitochondrial Permeability Transition Pore Opening
- Author
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Yasuhiro Nakano, Kenji Sunagawa, Tetsuya Matoba, Gentaro Ikeda, Kaku Nakano, Ayako Ishikita, Daiki Funamoto, Kazuhiro Nagaoka, and Kensuke Egashira
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Male ,0301 basic medicine ,Cardiotonic Agents ,Myocardial Reperfusion Injury ,030204 cardiovascular system & hematology ,Pharmacology ,Mitochondrial Membrane Transport Proteins ,Mitochondria, Heart ,Article ,Rats, Sprague-Dawley ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Reperfusion therapy ,Polylactic Acid-Polyglycolic Acid Copolymer ,Animals ,Medicine ,Myocytes, Cardiac ,Lactic Acid ,Ventricular remodeling ,Cells, Cultured ,Heart metabolism ,bcl-2-Associated X Protein ,Cardioprotection ,Drug Carriers ,Multidisciplinary ,Ventricular Remodeling ,Mitochondrial Permeability Transition Pore ,business.industry ,MPTP ,Cytochromes c ,Hydrogen Peroxide ,medicine.disease ,Rats ,Mice, Inbred C57BL ,Disease Models, Animal ,Oxidative Stress ,PLGA ,030104 developmental biology ,Mitochondrial permeability transition pore ,chemistry ,Cyclosporine ,Nanoparticles ,business ,Reperfusion injury ,Polyglycolic Acid - Abstract
Myocardial ischemia-reperfusion (IR) injury limits the therapeutic effects of early reperfusion therapy for acute myocardial infarction (MI), in which mitochondrial permeability transition pore (mPTP) opening plays a critical role. Our aim was to determine whether poly-lactic/glycolic acid (PLGA) nanoparticle-mediated mitochondrial targeting of a molecule that inhibits mPTP opening, cyclosporine A (CsA), enhances CsA-induced cardioprotection. In an in vivo murine IR model, intravenously injected PLGA nanoparticles were located at the IR myocardium mitochondria. Treatment with nanoparticles incorporated with CsA (CsA-NP) at the onset of reperfusion enhanced cardioprotection against IR injury by CsA alone (as indicated by the reduced MI size at a lower CsA concentration) through the inhibition of mPTP opening. Left ventricular remodeling was ameliorated 28 days after IR, but the treatment did not affect inflammatory monocyte recruitment to the IR heart. In cultured rat cardiomyocytes in vitro, mitochondrial PLGA nanoparticle-targeting was observed after the addition of hydrogen peroxide, which represents oxidative stress during IR and was prevented by CsA. CsA-NP can be developed as an effective mPTP opening inhibitor and may protect organs from IR injury.
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- 2016
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22. Abstract 260: Nanoparticle-mediated Simultaneous Targeting to Mitochondria and Inflammatory Monocytes Confers Additive Cardioprotection Against Myocardial Ischemia-reperfusion Injury
- Author
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Gentaro Ikeda, Tetsuya Matoba, Ayako Ishikita, and Kensuke Egashira
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Physiology ,Cardiology and Cardiovascular Medicine - Abstract
Background: Targeting one mediator of myocardial ischemia-reperfusion (IR) injury failed to reduce infarct size in clinical trials, suggesting the necessity of the innovative strategy to target more than 2 mediators simultaneously. Previously, we have engineered poly(lactic acid/glycolic acid) nanoparticle containing cyclosporine A (CsA-NP) and pitavastatin (Pitava-NP), and reported that the former inhibits the opening of mitochondrial permeability transition pore (mPTP) and the latter reduces monocyte-mediated inflammation in IR hearts. Here we tested the hypothesis that nanoparticle-mediated simultaneous targeting to mPTP and monocytes confers additive cardioprotection against IR injury. Methods and Results: We produced mice deficient with both cyclophilin D (CypD, a key molecule for mPTP opening) and CCR2 (a receptor for monocyte chemoattractant protein-1), and found that the double-KO mice displayed dramatic reduction in myocardial IR injury model (Fig. A). Flow cytometric analysis and fluorescence molecular tomography showed that inflammation was markedly inhibited in CCR2-KO and CypD/CCR2-KO mice while residual inflammation was noted in CypD-KO mice. In CypD mice, Pitava-NP reduced recruitment of Ly6Chigh inflammatory monocytes and showed therapeutic effects (Fig. B). In contrast, CsA-NP reduced IR injury in CCR2-KO mice. Simultaneous treatment with CsA-NP and Pitava-NP at the time of reperfusion showed additive reduction in IR injury in wild-type mice (Fig. C). Conclusions: Nanoparticle-mediated simultaneous targeting to mitochondria and inflammatory monocytes can be developed as a novel therapeutic strategy in IR injury.
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- 2015
23. Abstract 258: Nanoparticle-mediated Targeting of a Chemical Inhibitor of Drp1 to the Mitochondria Induces Cardioprotection From Myocardial Ischemia-reperfusion Injury
- Author
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Kensuke Egashira, Gentaro Ikeda, Tetusya Matoba, and Ayako Ishikita
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Cardioprotection ,chemistry.chemical_compound ,Myocardial ischemia ,chemistry ,Physiology ,MPTP ,medicine ,Mitochondrion ,Pharmacology ,Cardiology and Cardiovascular Medicine ,medicine.disease ,Reperfusion injury - Abstract
Background: Mitochondria (MITO) injury including MITO permeability transition pore (mPTP) opening plays a major role in the mechanism of ischemia-reperfusion (IR) injury. Intravenous administration of an inhibitor of mPTP opening, cyclosporine A, can reduce IR injury in animals and patients with acute myocardial infarction (MI), however; the power of cardioprotection by cyclosporine A is insufficient. We tested the hypothesis that nanoparticle-mediated targeting of Mdivi1, a chemical inhibitor of Drp1, to MITO enhances cardioprotection from IR injury. Methods and Results: We formulated poly(lactic acid/glycolic acid) (PLGA) nanoparticles containing Mdivi1 (Mdivi1-NP) or FITC (FITC-NP). In neonatal rat cardiomyocytes, PLGA nanoparticles accumulated in MITO after the addition of hydrogen peroxide (H2O2) that represents oxidative stress during IR (Fig.A). Treatment with Mdivi1-NP reduced H2O2-induced MITO division and cardiomyocyte death (Fig.B). This Mdivi1-NP cardioprotective effect was not seen over adenovirus harboring Drp1 shRNA transduced cardiomyocyte. In an in vivo and ex vivo murine model, treatment with Mdivi1-NP at the time of reperfusion reduced infarct size more effectively than Mdivi1 alone (Fig.C). Interestingly, Mdivi1-NP inhibited the leakage of cytochrome c to cytosol and MITO swelling, and reduced IR injury in both wildtype and cyclophilin D (a key regulatory molecule for mPTP opening)-KO mice (Fig.D). Conclusions: Mdivi1-NP enhanced cardioprotection against IR injury through mechanisms independent of mPTP opening. Mdivi1-NP can be a novel cardioprotective strategy in acute MI.
- Published
- 2015
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