Language：Japanese   Publisher：(NPO)小切開・鏡視外科学会  

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Language：Japanese   Publisher：日本心脈管作動物質学会  

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Language：Japanese   Publisher：(NPO)日本医工学治療学会  

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Language：Japanese   Publisher：(NPO)日本医工学治療学会  

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Language：Japanese   Publisher：(NPO)日本医工学治療学会  

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

Objectives: The molecular mechanisms underlying post-operative pericardial adhesions remain poorly understood. We aimed to unveil the temporal molecular and cellular mechanisms underlying tissue dynamics during adhesion formation, including inflammation, angiogenesis, and fibrosis. Methods and Results: We visualized cell-based tissue dynamics during pericardial adhesion using histological evaluations. To determine the molecular mechanism, RNA-seq was performed. Chemical inhibitors were administered to confirm the molecular mechanism underlying adhesion formation. A high degree of adhesion formation was observed during the stages in which collagen production was promoted. Histological analyses showed that arterioles excessively sprouted from pericardial tissues after the accumulation of neutrophils on the heart surface in mice as well as humans. The combination of RNA-seq and histological analyses revealed that hyperproliferative endothelial and smooth muscle cells with dedifferentiation appeared in cytokine-exposed sprouting vessels and adhesion tissue but not in quiescent vessels in the heart. SMAD2/3 and ERK activation was observed in sprouting vessels. The simultaneous abrogation of PI3K/ERK or TGF-β/MMP9 signaling significantly decreased angiogenic sprouting, followed by inhibition of adhesion formation. Depleting MMP9-positive neutrophils shortened mice survival and decreased angiogenic sprouting and fibrosis in the adhesion. Our data suggest that TGF-β/matrix metalloproteinase-dependent tissue remodeling and PI3K/ERK signaling activation might contribute to unique angiogenesis with dedifferentiation of vascular smooth muscle cells from the contractile to the synthetic phenotype for fibrosis in the pericardial cavity. Conclusions: Our findings provide new insights in developing prevention strategies for pericardial adhesions by targeting the recruitment of vascular cells from heart tissues.

DOI： 10.3389/fcvm.2021.761591

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Language：Japanese   Publisher：(NPO)日本心臓血管外科学会  

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Language：Japanese   Publisher：(一社)日本人工臓器学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Electrospinning is commonly used to generate polymeric scaffolds for tissue engineering. Using this approach, we developed a small-diameter tissue engineered vascular graft (TEVG) composed of poly-ε-caprolactone-co-L-lactic acid (PCLA) fibers and longitudinally assessed its performance within both the venous and arterial circulations of immunodeficient (SCID/bg) mice. Based on in vitro analysis demonstrating complete loss of graft strength by 12 weeks, we evaluated neovessel formation in vivo over 6-, 12- and 24-week periods. Mid-term observations indicated physiologic graft function, characterized by 100% patency and luminal matching with adjoining native vessel in both the venous and arterial circulations. An active and robust remodeling process was characterized by a confluent endothelial cell monolayer, macrophage infiltrate, and extracellular matrix deposition and remodeling. Long-term follow-up of venous TEVGs at 24 weeks revealed viable neovessel formation beyond graft degradation when implanted in this high flow, low-pressure environment. Arterial TEVGs experienced catastrophic graft failure due to aneurysmal dilatation and rupture after 14 weeks. Scaffold parameters such as porosity, fiber diameter, and degradation rate informed a previously described computational model of vascular growth and remodeling, and simulations predicted the gross differential performance of the venous and arterial TEVGs over the 24-week time course. Taken together, these results highlight the requirement for in vivo implantation studies to extend past the critical time period of polymer degradation, the importance of differential neotissue deposition relative to the mechanical (pressure) environment, and further support the utility of predictive modeling in the design, use, and evaluation of TEVGs in vivo. Statement of Significance: Herein, we apply a biodegradable electrospun vascular graft to the arterial and venous circulations of the mouse and follow recipients beyond the point of polymer degradation. While venous implants formed viable neovessels, arterial grafts experienced catastrophic rupture due to aneurysmal dilation. We then inform a previously developed computational model of tissue engineered vascular graft growth and remodeling with parameters specific to the electrospun scaffolds utilized in this study. Remarkably, model simulations predict the differential performance of the venous and arterial constructs over 24 weeks. We conclude that computational simulations should inform the rational selection of scaffold parameters to fabricate tissue engineered vascular grafts that must be followed in vivo over time courses extending beyond polymer degradation.

DOI： 10.1016/j.actbio.2019.05.063

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A 78-year-old man with no history of allergy, underwent endovascular aortic repair for abdominal aortic aneurysm rupture. Postoperatively, he had low-grade fever and persistently raised white blood cell counts, but tests showed no infection. A skin rash appeared on the trunk and upper arms; we suspected a drug allergy. Despite withdrawal and/or change of medications, the symptoms remained. Finally, a patch test for nickel showed a strongly positive result. Oral prednisone 5 mg·day was started, and the clinical findings resolved thereafter. No recurrence of allergy, infection, or exacerbation of the treated abdominal aortic aneurysm was noted at the 2-year follow-up. −1

DOI： 10.1177/0218492318784736

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD  

Objective: Hesperidin, an abundant flavonoid in citrus fruit, and its aglycone, hesperetin, have been reported to possess various physiological activities, including antioxidant, anti-inflammatory, hypolipidemic, and antihypertensive activities. In this study, we investigated whether α-glucosyl hesperidin and water-dispersible hesperetin have protective effects on atherosclerotic progression in apolipoprotein E knockout (Apo-E KO) mice. Methods: Ten-week-old male Apo-E KO mice were randomly assigned a regular high-fat diet, a high-fat diet with 0.5% α-glucosyl hesperidin, or a high-fat diet with 0.1% water-dispersible hesperetin for 12 weeks. Measurement of plasma total cholesterol levels, histological staining of aortic root, and immunohistochemistry for macrophages were performed to evaluate atherosclerotic plaque formation. Vascular reactivity of mouse aortic rings was also measured. Results: Both α-glucosyl hesperidin and water-dispersible hesperetin reduced plasma total cholesterol level. They also reduced plaque formation area, adipose deposition, and macrophage infiltration into atherosclerotic lesion. Vascular-endothelium-dependent relaxation in response to acetylcholine was improved in both experimental diet groups compared to the high-fat diet group. Conclusions: Our study suggests that both α-glucosyl hesperidin and water-dispersible hesperetin exert protective effects on atherosclerotic progression in Apo-E KO mice because they exhibit hypolipidemic activity, reduce inflammation through macrophages, and prevent endothelial dysfunction.

DOI： 10.1080/07315724.2018.1468831

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ANNALS VASCULAR DISEASES EDITORIAL OFFICE  

Objective: To evaluate the relationship between systemic inflammatory biomarkers and efficacy of surgical treatment of primary varicose veins of the lower extremities.Methods: Total 12 patients who underwent endovenous laser ablation or stripping of varicose veins and six healthy subjects were enrolled. Structural and molecular changes of varices were assessed by immunohistochemical staining with anti-monocyte chemotactic protein-1 (MCP-1). MCP-1 and interleukin-6 (IL-6) levels in systemic antecubital blood were measured before and at 12 weeks after treatment.Results: Immunohistochemical staining revealed prominent manifestation of MCP-1-positive endothelial cells in the walls of varices. Preoperative serum MCP-1 and IL-6 levels in the patients were significantly higher than those in the control (166 +/- 12 pg/mL vs 99 +/- 10 pg/mL, p=0.003; 5.1 +/- 0.95pg/mL vs 0.0 +/- 0.0 pg/mL, p=0.001, respectively). The values were significantly correlated with the severity of chronic venous insufficiency (CVI). Postoperative serum MCP-1 level significantly decreased compared with the preoperative level (152 +/- 10 pg/mL vs 166 +/- 12 pg/mL, p=0.048). The values after endovenous laser ablation did not significantly decrease compared with those after stripping.Conclusion: Varicose veins with CVI increase inflammatory biomarker levels in the local tissue and systemic blood. Appropriate treatment of symptomatic varicose veins de- creases inflammatory biomarker levels.

DOI： 10.3400/avd.oa.19-00011

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MARY ANN LIEBERT, INC  

Objectives: Tissue-engineered vascular grafts (TEVGs) have demonstrated potential for treating congenital heart disease (CHD); however, quantitative imaging for tracking functional and structural remodeling of TEVGs has not been applied. Therefore, we evaluated the potential of magnetic resonance (MR) imaging for assessing TEVG wall shear stress (WSS) and wall thickness in a large animal model. Methods: Cell-seeded (n = 3) or unseeded (n = 3) TEVGs were implanted as inferior vena cava interposition grafts in juvenile lambs. Six months following implantation, two-dimensional phase-contrast MR imaging was performed at 3 slice locations (proximal, middle, and distal) to assess normalized WSS (i.e., WSS-to-cross sectional area). T2-weighted MR imaging was performed to assess TEVG wall thickness. Histology was qualitatively assessed, whereas immunohistochemistry was semiquantitatively assessed for smooth muscle cells (αSMA), macrophage lineage cells (CD11b), and matrix metalloproteinase activity (MMP-2 and MMP-9). Picrosirius Red staining was performed to quantify collagen content. Results: TEVG wall thickness was significantly higher for proximal, middle, and distal slices in unseeded versus cell-seeded grafts. Significantly higher WSS values existed for proximal versus distal slice locations for cell-seeded TEVGs, whereas no differences in WSS existed between slices for unseeded TEVGs. Additionally, no differences in WSS existed between cell-seeded and unseeded groups. Both groups demonstrated elastin formation, without vascular calcification. Unseeded TEVGs possessed greater content of smooth muscle cells when compared with cell-seeded TEVGs. No differences in macrophage, MMP activity, or collagen content existed between groups. Conclusion: MR imaging allows for in vivo assessment of functional and anatomical characteristics of TEVGs and may provide a nonionizing approach that is clinically translatable to children undergoing treatment for CHD.

DOI： 10.1089/ten.tec.2018.0144

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MOSBY-ELSEVIER  

Objective: This study aimed to determine the perioperative predictors of contrast medium-induced nephropathy (CIN) after endovascular aortic repair (EVAR). Materials and Methods: The data of 203 consecutive patients who underwent elective EVAR for thoracic and abdominal aortic aneurysm between January 2014 and September 2014 were retrospectively analyzed. CIN was defined according to the diagnostic criteria of the European Society of Urogenital Radiology. Results: Fourteen patients (6.9%) developed CIN after EVAR. Contrast medium volume (CV), preoperative serum creatinine, estimated glomerular filtration rate (eGFR), and the CV/eGFR ratio were significantly related with CIN development after EVAR. The CV/eGFR ratio was significantly higher in patients with CIN than those without CIN. Receiver operator characteristic curve analysis showed that the area under the curve of the CV/eGFR ratio was 0.782, indicating that it was the most important predictor. The appropriate CV/eGFR ratio cutoff was 1.62. Sensitivity and specificity were 85.7% and 65.6%, respectively. Conclusions: The CV/eGFR ratio was a useful predictor of contrast medium-induced nephropathy after EVAR. It is possible that the score can be used in patients when managing the EVAR techniques and contrast medium volume.

DOI： 10.2152/jmi.65.116

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：HINDAWI LTD  

Introduction. Blunt thoracic aortic injury (BTAI) is a critical condition. Thoracic endovascular aortic repair (TEVAR) is considered a surgical treatment for BTAI. Reports reveal that some patients benefit from conservative and delayed operation rather than emergency operative therapy. Here, we present three BTAI cases that were treated with TEVAR using different timings. Case Presentation. Case 1 involved a 49-year-old man injured in a car accident and who went into shock. After stabilization with Advanced Trauma Life Support in the emergency room, TEVAR was performed immediately. Case 2 involved a 69-year-old man who was injured after falling. His hemodynamic status was stable and enhanced computed tomography revealed intraluminal hematoma. He underwent TEVAR 15 days after the injury occurred, following conservative therapy. Case 3 involved a 60-year-old man who was injured in a car accident and presented BTAI with subarachnoid hemorrhage and diaphragm tear. A pseudoaneurysm was observed in the distal aortic arch. After open abdominal exploration, diaphragm repair, and observation for subarachnoid hemorrhage, TEVAR was performed 8 hours after arrival. All three patients survived. Conclusions. We treated BTAI successfully. We suggest that TEVAR is useful for BTAI. The timing of the operation and therapeutic option, including conservative therapy, should be decided for each patient.

DOI： 10.1155/2018/7061509

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：FUTURE MEDICINE LTD  

Aim: Surgical management of pediatric extrahepatic portal vein obstruction requires meso-Rex bypass using autologous or synthetic grafts. Tissue-engineered vascular grafts (TEVGs) provide an alternative, but no validated animal models using portal TEVGs exist. Herein, we preclinically assess TEVGs as portal vein bypass grafts. Materials & methods: TEVGs were implanted as portal vein interposition conduits in SCID-beige mice, monitored by ultrasound and micro-computed tomography, and histologically assessed postmortem at 12 months. Results: TEVGs remained patent for 12 months. Histologic analysis demonstrated formation of neovessels that resembled native portal veins, with similar content of smooth muscle cells, collagen type III and elastin. Conclusion: TEVGs are feasible portal vein conduits in a murine model. Further preclinical evaluation of TEVGs may facilitate pediatric clinical translation.

DOI： 10.2217/rme-2017-0021

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Covering and embolizing the celiac artery has been reported to be a relatively safe procedure, owing to the rich collateral pathway between the celiac artery and superior mesenteric artery. A 69-year-old man presented with an aneurysm on the distal descending aorta. The proximity of the aneurysm to the celiac artery origin necessitated covering the artery with a stent graft. Additionally, the celiac trunk was short, increasing the risk for Type II endoleak. The origin of the celiac artery was covered after embolization of the branches of the celiac artery. Postoperatively, nausea and abdominal pain appeared, and the amylase level and white blood cell count were elevated. Contrast-enhanced computed tomography and abdominal ultrasonography revealed necrosis and cyst formation in the pancreatic tail, resulting in a diagnosis of acute pancreatitis caused by pancreatic ischemia. Conservative treatment was applied. After discharge, although walled-off necrosis remained, the patient was doing well, without any clinical symptoms.

DOI： 10.1093/jscr/rjx029

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：UNIV TOKUSHIMA SCH MEDICINE  

The strategy for an infant with congenital mitral stenosis should be determined by three important factors: left ventricular volume, the degree of the systemic outflow tract obstruction, and the type of mitral valve dysfunction. A successful staged biventricular repair in early infancy for a patient who had congenital mitral stenosis with short chordae, hypoplastic left ventricle and coarctation of the aorta, and the long-term results are described. There were the following important hemodynamic factors that led to the successful biventricular repair in the patient. Total systemic output was barely supplied through the hypoplastic left ventricle after closure of the ductus arteriosus on admission. The neonate underwent repair of coarctation of the aorta alone as the initial stage at 9 days after birth. Also, spontaneous closure of the foramen ovale following repair of coarctation of the aorta accelerated the progressive left ventricular growth. Open mitral commissurotomy with an interatrial fenestration using the modified Brawley’s approach was performed for a 40-day-old infant. Good left ventricular growth and good mitral valve function have been observed for 18 years after open mitral commissurotomy. Appropriate early augmentation of left ventricular inflow through the mitral valve might be effective for growth of a hypoplastic left ventricle.

DOI： 10.2152/jmi.64.187

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Thoracic endovascular aortic repair (TEVAR) has been reported to be an effective treatment option for aortic emergencies. However, there are few reports about TEVAR for aortic rupture due to radiation injury. A 54-year-old man presented with haemoptysis. He had a history of lung cancer, which had been treated with chemotherapy and radiation therapy (72 Gy/16 times) 3 years previously, and the cancer lesion did not progress. On chest radiography, pneumonia was suspected in the radiated lesion. However, after admission, he presented with back pain, progressive anaemia and hypotension. Enhanced computed tomography revealed extravasation of contrast medium in the distal aortic arch. He was diagnosed with aortic rupture due to radiation injury. TEVAR was performed. He was extubated one day after the operation, and the haemoptysis disappeared. He was discharged from the hospital without any complications. He is well 1 year after the surgery, without aortic disease progression or lung cancer recurrence.

DOI： 10.1093/jscr/rjx092

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：UNIV TOKUSHIMA SCH MEDICINE  

Objectives: To investigate the effects of human umbilical cord blood-derived mononuclear cell (hUCB-MNC) transplantation on pulmonary hypertension (PH) induced by monocrotaline (MCT) in immunodeficient mice and their distribution. Methods: MCT was administered to BALB/c Slc-nu/nu mice, and PH was induced in mice 4 weeks later. Fresh hUCB-MNCs harvested from a human donor after her delivery were injected intravenously into those PH mice. The medial thickness of pulmonary arterioles, ratio of right ventricular to septum plus left ventricular weight (RV/S+LV), and ratio of acceleration time to ejection time of pulmonary blood flow waveform (AT/ET) were determined 4 weeks after hUCB-MNC transplantation. To reveal the incorporation into the lung, CMTMR-labeled hUCB-MNCs were observed in the lung by fluorescent microscopy. DiR-labeled hUCB-MNCs were detected in the lung and other organs by bioluminescence images. Results: Medial thickness, RV/S+ LV and AT/ET were significantly improved 4 weeks after hUCB-MNC transplantation compared with those in mice without hUCB-MNC transplantation. CMTMR-positive hUCB-MNCs were observed in the lung 3 hours after transplantation. Bioluminescence signals were detected more strongly in the lung than in other organs for 24 hours after transplantation. Conclusions: The results indicate that hUCB-MNCs are incorporated into the lung early after hUCB-MNC transplantation and improve MCT-induced PH.

DOI： 10.2152/jmi.64.43

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：ELSEVIER SCIENCE INC  

Background Current commercialized small-diameter arterial grafts have not shown clinical effectiveness due to their poor patency rates. The present study evaluated the feasibility of an arterial bioresorbable vascular graft, which has a porous sponge-type scaffold, as a small-diameter arterial conduit. Methods The grafts were constructed by a 50:50 poly (1-lactic-co-ε-caprolactone) copolymer (PLCL) scaffold reinforced by a poly (1-lactic acid) (PLA) nanofiber. The pore size of the PLCL scaffold was adjusted to a small size (12.8 ± 1.85 μm) or a large size (28.5 ± 5.25 μm). We compared the difference in cellular infiltration, followed by tissue remodeling, between the groups. The grafts were implanted in 8- to 10-week-old female mice (n = 15 in each group) as infrarenal aortic interposition conduits. Animals were monitored for 8 weeks and euthanized to evaluate neotissue formation. Results No aneurysmal change or graft rupture was observed in either group. Histologic assessment demonstrated favorable cell infiltration into scaffolds, neointimal formation with endothelialization, smooth muscle cell proliferation, and elastin deposition in both groups. No significant difference was observed between the groups. Immunohistochemical characterization with anti-F4/80 antibody demonstrated that macrophage infiltration into the grafts occurred in both groups. Staining for M1 and M2, which are the two major macrophage phenotypes, showed no significant difference between groups. Conclusions Our novel bioresorbable vascular grafts showed well-organized neointimal formation in the high-pressure arterial circulation environment. The large-pore scaffold did not improve cellular infiltration and neotissue formation compared with the small-pore scaffold.

DOI： 10.1016/j.athoracsur.2016.01.110

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Oxidized cholesterols (oxycholesterols) in food have been recognized as strong atherogenic components, but their tissue distributions and roles in cardiovascular diseases remain unclear. To investigate whether accumulation of oxycholesterols is linked to cardiac morphology and function, and whether reduction of oxycholesterols can improve cardiac performance, domestic male swine were randomized to a control diet (C), high caloric diet (HCD) or HCD + Ezetimibe, an inhibitor of intestinal cholesterol absorption, group (HCD + E) and evaluated for: (1) distribution of oxycholesterol components in serum and tissues, (2) levels of oxycholesterol-related enzymes, (3) paracardial and epicardial coronary fat thickness, and (4) cardiac performance. Ezetimibe treatment for 8 weeks attenuated increases in oxycholesterols in the HCD group almost completely in liver, but reduced only levels of 4β-hydroxycholesterol in left ventricular (LV) myocardium. Ezetimibe treatment altered the expression of genes for cholesterol and fatty acid metabolism and decreased the expression of CYP3A46, which catabolizes cholesterol to 4β-hydroxycholesterol, strongly in liver. An increase in epicardial fat thickness and impaired cardiac performance in the HCD group were improved by ezetimibe treatment, and the improvement was closely related to the reduction in levels of 4β-hydroxycholesterol in LV myocardium. In conclusion, an increase in oxycholesterols in the HCD group was closely related to cardiac hypertrophy and dysfunction, as well as an increase in epicardial fat thickness. Ezetimibe may directly reduce oxycholesterol in liver and LV myocardium, and improve cardiac morphology and function.

DOI： 10.1016/j.jnutbio.2016.05.010

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Language：Japanese   Publisher：(一社)日本病態栄養学会  

ヘスペリジン(ビタミンP)はフラボノイドの一種であり、その生理作用は抗酸化作用・血流改善効果・毛細血管の強化・血中コレステロール値の改善効果・抗アレルギー作用など多数報告され、動脈硬化に対しても抑制作用が期待される。ヘスペリジンを酵素処理して配糖化し体内吸収性を高めた糖転移ヘスペリジンと、ヘスペリジンのアグリコンであるヘスペレチンに微粒子化処理を行い水への分散性を高めた分散ヘスペレチンを、動脈硬化モデルである高脂肪食負荷ApoEノックアウトマウスに12週間混餌投与した。大動脈起始部の硬化巣面積は、投与群で有意に減少しており、血中の総コレステロール値においても投与群で有意に低かった。免疫染色を用いて硬化巣におけるマクロファージを検出したところ、投与群で浸潤が減少していることが示唆された。これらの結果より、糖転移ヘスペリジン及び分散ヘスペレチンが動脈硬化進展に対して抑制効果をもつ可能性が示唆された。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

When endovascular treatment is performed, angulation of the access route for a device can make the operative procedure difficult. We encountered a case in which we successfully completed thoracic endovascular aortic repair (TEVAR) in a patient with severely angulated aorta by applying 'double-wire technique'. The patient was an 80-year-old woman. An aneurysm with a 71-mm diameter was observed in the descending aorta. We performed TEVAR. Device delivery could not be achieved by a conventional procedure using one guide wire since the peripheral aorta was severely angulated. Therefore, in addition to a guide wire for main body, a stiff wire and a stiff sheath were introduced to straighten the angulation. The device was successfully introduced and TEVAR was completed. We used the Relay Plus(A (R)) that facilitates tracking through the angulation. The device has a dual structure consisting of a hard sheath and a flexible sheath. We performed TEVAR successfully.

DOI： 10.1093/jscr/rjw125

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

Background: Factors associated with survival prognosis among patients who undergo endovascular aortic repair (EVAR) for ruptured abdominal aortic aneurysms (rAAA) have not been sufficiently investigated. In the present study, we examined correlations between perioperative coagulopathy and 24-h and 30-day postoperative survival. Relationships between coagulopathy and the content of blood transfusions, volumes of crystalloid infusion and survival. Methods: This was a retrospective study of the medical records of all patients who underwent EVAR for rAAA at Chiba-Nishi General Hospital during the period from October 2013 to December 2015. Major coagulopathy was defined using the international normalized ratio or activated partial thromboplastin time (APTT) ratio of at least 1.5, or platelet count less than 50 × 10/l. We quantified the amounts of blood transfusions and crystalloid infusions administered from arrival to the hospital to admission to ICU following operations. Results: Coagulopathy among patients with rAAA was found to progress even after they had presented at the hospital. No statistically significant correlation between preoperative coagulopathy and mortality was found, although a significantly greater degree of postoperative coagulopathy was seen among patients who died both within 24-h and 30 days postoperatively. Among patients with postoperative coagulopathy, lesser quantities of fresh frozen plasma (FFP) compared with red cell concentrate (RCC) were used during the period from hospital arrival to postoperative ICU entry. In both groups of patients who did not survive after 24-h and 30 days, FFP was used less than RCC. Large transfusions of crystalloids administered during the periods from hospital arrival to surgery and from hospital arrival to the end of surgery were associated with postoperative incidence of major coagulopathy, death within 24-h, and death within 30 days. Conclusion: Coagulopathy progressed during care in the emergency outpatient clinic and operations. Postoperative coagulopathy was associated with poorer outcomes. Smaller FFP/RCC ratios and larger volumes of crystalloid infusion were associated with development of coagulopathy and poorer prognosis of survival. Trial registration: This study is retrospectively registered in UMIN Clinical Trials Registry (Registration 19 April 2016, registered number is R000025334 UMIN000021978 ).

DOI： 10.1186/s13017-016-0087-0

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：HINDAWI LTD  

Endovascular stent graft placement has become a major treatment for thoracic and abdominal aneurysms. While endovascular therapy is less invasive than open surgery, it involves the use of a contrast medium. Contrast media can cause renal impairment, a condition termed as contrast-induced nephropathy (CIN). This study sought to evaluate the incidence and risk factors of CIN following endovascular stent graft placement for aortic aneurysm repair. The study included 167 consecutive patients who underwent endovascular stent graft placement in our hospital from October 2013 to June 2014. CIN was diagnosed using the European Society of Urogenital Radiology criteria. Patients with and without CIN were compared. Chi-squared tests, t -tests, and multivariate logistic regression analyses were performed. Thirteen patients (7.8%) developed CIN. Left ventricular dysfunction and intraoperative blood transfusion were significantly more frequent in the CIN group (P = 0.017 and P = 0.032, resp.). Multivariate analysis showed that left ventricular dysfunction had the strongest influence on CIN development (odds ratio 9.34, P = 0.018, and 95% CI - 1.46-59.7). Patients with CIN also experienced longer ICU and hospital stays. Measures to improve renal perfusion flow should be considered for patients with left ventricular dysfunction who are undergoing endovascular stent graft placement.

DOI： 10.1155/2016/5950986

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

Background and objective: Peroxisome proliferator-activated receptor (PPAR) -γ agonist, which is an anti-diabetes drug and reduces expression of tumor necrosis factor (TNF)-α, reported to have the effects for anti-inflammation in our body. In cardiovascular fields, this PPAR-γ agonist already reported to suppress progression of coronary atherosclerosis. Various cytokines, which is secreted from fat tissues around artery, promote atherosclerosis and/or aneurysmal changes in aorta/artery. Objective of our study is to clarify whether PPAR-γ agonist has anti-inflammatory effects in aorta of patients with aortic aneurysm (AA). Patients and methods: The medical ethics committee in Tokushima University Hospital approved protocol for this study. Sixteen patients with AA (more than 5 cm in diameter, scheduled open surgery) were divided into two groups; one is PPAR-γ agonist administrating group $$\langle$$⟨n = 6, group P$$\rangle$$⟩, and another is the without group $$\langle$$⟨n = 10, group C$$\rangle$$⟩. PPAR-γ agonist, whose dose was 15 mg/day, was administrated in the group P for more than 2 months before aneurysectomy and grafting (mean; 4.2 ± 3.4 months) (Supplemental Table 1). Biopsy specimens were obtained from abdominal subcutaneous fat, greater omentum, retroperitoneal periaortic fat and aneurysmal wall in surgical procedure. Blood examination also achieved before/after procedure. Harvested specimens were analyzed with histology (HE and EVG), immunohistochemistry (macrophage) and RT-PCR (adiponectin, MCP-1, TNF-α, CD68, matrix metalloprotease (MMP)-2, MMP-9). Results: Macrophage infiltration in aortic wall and retroperitoneal periaortic fat among group P was significantly decreased compared to that among group C. Adiponectin expressions in both subcutaneous fat and retroperitoneal periaortic fat among the group P (adiponectin/β-actin) were significantly increased compared to those among the group C [subcutaneous fat; 16.8 ± 13.9 vs. 5.82 ± 2.94 (P = 0.04), retroperitoneal periaortic fat; 21.3 ± 24.1 vs. 2.12 ± 1.69 (P = 0.04)]. On the other hand, expressions of TNF-α, and MMP-9 in both aortic aneurysmal wall and retroperitoneal periaortic fat among group P were significantly decreased. [(Aortic aneurysmal wall; TNF-α; 0.45 ± 0.15 vs. 5.18 ± 3.49 (P = 0.02), MMP-9; 39.6 ± 69.0 vs. 721 ± 741 (P = 0.04)], [retroperitoneal periaortic fat; TNF-α; 1.14 ± 0.36 vs. 26.4 ± 25.0 (P = 0.048), MMP-9; 0.18 ± 0.21 vs. 50.0 ± 41.8 (P = 0.047)]. Conclusion: These data may indicate that PPAR-γ agonist become the way for preventing or delaying aortic aneurysm progression in patients. More studies will be needed to clarify this drug effects in detail.

DOI： 10.1007/s11748-015-0576-1

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Language：English   Publisher：CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

DOI： 10.1016/j.cardfail.2015.08.233

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective - Despite successful translation of bioresorbable vascular grafts for the repair of congenital heart disease, stenosis remains the primary cause of graft failure. In this study, we investigated the efficacy of long-term treatment with the antiplatelet drugs, aspirin and cilostazol, in preventing stenosis and evaluated the effect of these drugs on the acute phase of inflammation and tissue remodeling. Approach and Results - C57BL/6 mice were fed a drug-mixed diet of aspirin, cilostazol, or normal chow during the course of follow-up. Bioresorbable vascular grafts, composed of poly(glycolic acid) mesh sealed with poly(l-lactide-co-ε-caprolactone), were implanted as inferior vena cava interposition conduits and followed up for 2 weeks (n=10 per group) or 24 weeks (n=15 per group). Both aspirin and cilostazol suppressed platelet activation and attachment onto the grafts. On explant at 24 weeks, well-organized neotissue had developed, and cilostazol treatment resulted in 100% graft patency followed by the aspirin (67%) and no-treatment (60%) groups (P<0.05). Wall thickness and smooth muscle cell proliferation in the neotissue of the cilostazol group were decreased when compared with that of the no-treatment group at 24 weeks. In addition, cilostazol was shown to have an anti-inflammatory effect on neotissue at 2 weeks by regulating the recruitment and activation of monocytes. Conclusions - Cilostazol prevents stenosis of bioresorbable vascular graft in a mouse inferior vena cava implantation model up to 24 weeks and is accompanied by reduction of smooth muscle cell proliferation and acute inflammation.

DOI： 10.1161/ATVBAHA.115.306027

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Objective Autologous grafts are used to repair atherosclerotic cardiovascular diseases; however, many patients lack suitable donor graft tissue. Recently, tissue engineering techniques have emerged to make biologically active blood vessels. We applied this technique to produce arterial grafts using established biodegradable materials without cell seeding. The grafts were evaluated in vivo for vessel remodeling during 12 months. Methods Poly(l-lactide-co-ε-caprolactone) scaffolds reinforced by poly(lactic acid) (PLA) fiber were prepared as arterial grafts. Twenty-eight cell-free grafts were implanted as infrarenal aortic interposition grafts in 8-week-old female SCID/Bg mice. Serial ultrasound and micro computed tomography angiography were used to monitor grafts after implantation. Five grafts were harvested for histologic assessments and reverse transcription-quantitative polymerase chain reaction analysis at time points ranging from 4 months to 1 year after implantation. Results Micro computed tomography indicated that most implanted mice displayed aneurysmal changes (three of five mice at 4 months, four of five mice at 8 months, and two of five mice at 12 months). Histologic assessments demonstrated extensive tissue remodeling leading to the development of well-circumscribed neovessels with an endothelial inner lining, a neointima containing smooth muscle cells and elastin, and a collagen-rich extracellular matrix. There were a few observed calcified deposits, located around residual PLA fibers at 12 months after implantation. Macrophage infiltration into the scaffold, as evaluated by F4/80 immunohistochemical staining, remained after 12 months and was focused mostly around residual PLA fibers. Reverse transcription-quantitative polymerase chain reaction analysis revealed that gene expression of Itgam, a marker for macrophages, and of matrix metalloproteinase 9 was higher than in native aorta during the course of 12 months, indicating prolonged inflammation (Itgam at 8 months: 11.75 ± 0.99 vs native aorta, P <.01; matrix metalloproteinase 9 at 4 months: 4.35 ± 3.05 vs native aorta, P <.05). Conclusions In this study, we demonstrated well-organized neotissue of cell-free biodegradable arterial grafts. Although most grafts experienced aneurysmal change, such findings provide insight into the process of tissue-engineered vascular graft remodeling and should allow informed rational design of the next generation of arterial grafts.

DOI： 10.1016/j.jvs.2014.03.011

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MARY ANN LIEBERT, INC  

Our approach for fabricating tissue-engineered vascular grafts (TEVG), applied in the surgical management of congenital heart disease, is accomplished by seeding isolated bone marrow-derived mononuclear cells (BM-MNCs) onto biodegradable scaffolds. The current method used for isolation of BM-MNCs is density centrifugation in Ficoll. This is a time-consuming, labor-intensive, and operator-dependent method. We previously demonstrated that a simpler, faster, and operator-independent method for isolating BM-MNCs using a filter elution technique was feasible. In this study, we compare the use of each technique to determine if the BM-MNCs isolated by the filtration elution method are biologically equivalent to BM-MNCs isolated using density centrifugation. Scaffolds were constructed from a nonwoven poly(glycolic acid) fiber mesh coated with 50:50 poly(l-lactide-co-ε-caprolactone) sealant. BM-MNCs were isolated from the bone marrow of syngeneic C57BL/6 mice by either density centrifugation with Ficoll or filtration (Ficoll vs. Filter), then statically seeded onto scaffolds, and incubated overnight. The TEVG were implanted in 10-week-old C57BL/6 mice (n=23 for each group) as inferior vena cava interposition grafts and explanted at 14 days for analysis. At 14 days after implantation, there were no significant differences in graft patency between groups (Ficoll: 87% vs. Filter: 78%, p=0.45). Morphometric analysis by hematoxylin and eosin staining showed no difference of graft luminal diameter or neointimal thickness between groups (luminal diameter, Ficoll: 620.3±82.9 μm vs. Filter: 633.3±131.0 μm, p=0.72; neointimal thickness, Ficoll: 37.9±7.8 μm vs. Filter: 37.9±11.2 μm, p=0.99). Histologic examination demonstrated similar degrees of cellular infiltration and extracellular matrix deposition, and endothelial cell coverage on the luminal surface, in either group. Macrophage infiltration showed no difference in the number of F4/80-positive cells or macrophage phenotypes between the two experimental groups (Ficoll: 2041±1048 cells/mm² vs. Filter: 1887±907.7 cells/mm², p=0.18). We confirmed the biological equivalence of BM-MNCs, isolated using either density centrifugation or filtration, for making TEVG.

DOI： 10.1089/ten.tec.2014.0442

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The surgical repair of heart and vascular disease often requires implanting synthetic grafts. While synthetic grafts have been successfully used for medium-to-large sized arteries, applications for small diameter arteries (<6 mm) is limited due to high rates of occlusion by thrombosis. Our objective was to develop a tissue engineered vascular graft (TEVG) for small diameter arteries. TEVGs composed of polylactic acid nanofibers with inner luminal diameter between 0.5 and 0.6 mm were surgically implanted as infra-renal aortic interposition conduits in 25 female C17SCID/bg mice. Twelve mice were given sham operations. Survival of mice with TEVG grafts was 91.6%at 12 months post-implantation (sham group: 83.3%). No instances of graft stenosis or aneurysmal dilatation were observed over 12 months post-implantation, assessed by Doppler ultrasound and microCT. Histologic analysis of explanted TEVG grafts showed presence of CD31-positive endothelial monolayer and F4/80-positive macrophages after 4, 8, and 12 months in vivo . Cells positive for innodataalpha-smooth muscle actin were observed within TEVG, demonstrating presence of smooth muscle cells (SMCs). Neo-extracellular matrix consisting mostly of collagen types I and III were observed at 12 months post-implantation. PCR analysis supports histological observations. TEVG group showed significant increases in expressions of SMC marker, collagen-I and III, matrix metalloproteinases-2 and 9, and itgam (a macrophage marker), when compared to sham group. Overall, patency rates were excellent at 12 months after implantation, as structural integrity of these TEVG. Tissue analysis also demonstrated vessel remodeling by autologous cell.

DOI： 10.1371/journal.pone.0120328

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Language：English   Publisher：ELSEVIER SCIENCE INC  

DOI： 10.1016/j.jacc.2014.08.057

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MARY ANN LIEBERT, INC  

We developed a prototype for a closed apparatus for assembling tissue-engineered vascular grafts (TEVGs) with the goal of creating a simple operator-independent method for making TEVGs to optimize safety and enable widespread application of this technology. The TEVG is made by seeding autologous bone marrow-derived mononuclear cells onto a biodegradable tubular scaffold and is the first man-made vascular graft to be successfully used in humans. A critical barrier, which has prevented the widespread clinical adoption of the TEVG, is that cell isolation, scaffold seeding, and incubation are performed using an open method. To reduce the risk of contamination, the TEVG is assembled in a clean room. Clean rooms are expensive to build, complex to operate, and are not available in most hospitals. In this investigation, we used an ovine model to compare the safety and efficacy of TEVGs created using either a standard density centrifugation-based open method or the new filter-based closed system. We demonstrated no graft-related complications and maintenance of growth capacity in TEVGs created using the closed apparatus. In addition, the use of the closed system reduced the amount of time needed to assemble the TEVG by ∼50%. Adaptation of similar methodologies may facilitate the safe translation and the widespread use of other tissue engineering technologies.

DOI： 10.1089/ten.tec.2014.0160

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：HINDAWI LTD  

Delirium is an acute form of nervous system dysfunction often observed in patients in the intensive care unit. Endovascular aortic repair (EVAR) is considered a minimally invasive surgical treatment for abdominal aortic aneurysm. Although the operation method is widely used, there are few investigations of the rate and risk factors of delirium development after the operation. In this study, we retrospectively examined the rate of delirium development in the intensive care unit (ICU) after EVAR, as well as the associated preoperative risk factors and effects on the lengths of ICU and hospital stays. We examined the 81 consecutive patients who underwent elective EVAR between November 2013 and August 2014. The Intensive Care Delirium Screening Checklist was used to diagnose delirium. Twenty patients (24.7%) were diagnosed with delirium in this study. The ICU and hospital length of stays of patients with delirium were 3.3 +/- 2.4 days and 14.5 +/- 11.9 days, respectively, the latter of which was significantly longer than that of patients without delirium (p = 0.019). Additionally, renal dysfunction, preoperative benzodiazepine use, and intraoperative transfusion were found to be risk factors for the development of delirium after elective EVAR.

DOI： 10.1155/2015/405817

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：HINDAWI PUBLISHING CORP  

Delirium is an acute form of nervous system dysfunction often observed in patients in the intensive care unit. Endovascular aortic repair (EVAR) is considered a minimally invasive surgical treatment for abdominal aortic aneurysm. Although the operation method is widely used, there are few investigations of the rate and risk factors of delirium development after the operation. In this study, we retrospectively examined the rate of delirium development in the intensive care unit (ICU) after EVAR, as well as the associated preoperative risk factors and effects on the lengths of ICU and hospital stays. We examined the 81 consecutive patients who underwent elective EVAR between November 2013 and August 2014. The Intensive Care Delirium Screening Checklist was used to diagnose delirium. Twenty patients (24.7%) were diagnosed with delirium in this study. The ICU and hospital length of stays of patients with delirium were 3.3 ± 2.4 days and 14.5 ± 11.9 days, respectively, the latter of which was significantly longer than that of patients without delirium (p= 0.019). Additionally, renal dysfunction, preoperative benzodiazepine use, and intraoperative transfusion were found to be risk factors for the development of delirium after elective EVAR.

DOI： 10.1155/2015/405817

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Infectious abdominal aortic aneurysms often present with abdominal and lower back pain, but prolonged fever may be the only symptom. Infectious abdominal aortic aneurysms initially presenting with meningitis are extremely rare; there are no reports of their successful treatment. Cases with Streptococcus pneumoniae as the causative bacteria are even rarer with a higher mortality rate than those caused by other bacteria. We present the case of a 65-year-old man with lower limb weakness and back pain. Examination revealed fever and neck stiffness. Cerebrospinal fluid showed leukocytosis and low glucose levels. The patient was diagnosed with meningitis and bacteremia caused by Streptococcus pneumoniae and treated with antibiotics. Fever, inflammatory response, and neurologic findings showed improvement. However, abdominal computed tomography revealed an aneurysm not present on admission. Antibiotics were continued, and a rifampicin soaked artificial vascular graft was implanted. Tissue cultures showed no bacteria, and histological findings indicated inflammation with high leukocyte levels. There were no postoperative complications or neurologic abnormalities. Physical examination, blood tests, and computed tomography confirmed there was no relapse over the following 13 months. This is the first reported case of survival of a patient with an infectious abdominal aortic aneurysm initially presenting with meningitis caused by Streptococcus pneumoniae.

DOI： 10.1155/2015/825069

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We report the case of aortic arch aneurysm rupture treated successfully with thoracic endovascular aneurysm repair ( TEVAR) accompanied by aortic arch debranching using the chimney graft technique. A 94-year-old man was transported to the hospital after complaining of chest pain for one day. Contrast-enhanced computed tomographic ( CT) images revealed an aortic arch aneurysm rupture. Considering the patient's age and postoperative activities of daily living, TEVAR was used. In order to place an indwelling stent graft from the ascending aorta to the periphery, the chimney graft technique was used to debranch the brachiocephalic artery. Hemodynamics was stabilized postsurgically. Plain CT performed 20 days postoperatively confirmed that the intrathoracic hematoma had decreased in size. Although respiratory failure was persistent, there were improvements and the patient was extubated 34 days postoperatively and discharged from the intensive care unit 37 days postoperatively. On postoperative day 75, he was discharged from the hospital toanelder care facility. Few reports have focused on stent grafting for treating aortic arch aneurysm rupture. TEVAR using the chimney graft technique could be an effective treatment option for patients with a decreased ability to tolerate surgery.

DOI： 10.1155/2015/780147

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OBJECTIVES: To determine the efficacy and the optimal timing of thoracic endovascular aortic repair (TEVAR) for closing the primary entry in uncomplicated patients with chronic type B aortic dissection and a patent false lumen (FL). METHODS: Thirteen patients underwent TEVAR for aortic dissection between 2008 and 2012. These patients had chronic dissection with a patent FL and expansion of the aorta. Early TEVAR was performed for five patients within 1-7 months from the index dissection (TEVAR-EC group) and delayed TEVAR was performed for eight patients within 1-16 years (TEVAR-DC group). Changes in the diameters and volumes of the true lumen (TL) and FL and the aortic remodeling were assessed by multidetector computed tomography for 3 years after TEVAR. RESULTS: The reduction rate of FL in the thoracic aorta was notably higher in the TEVAR-EC group than in the TEVAR-DC group regardless of the presence or absence of distal retrograde flow. There was a significant TL expansion despite different timings of TEVAR. CONCLUSIONS: Early TEVAR resulted in good prognosis and preferable aortic remodeling in uncomplicated patients with chronic type B aortic dissection and a patent FL, and we recommend early TEVAR within seven months after the index dissection.

DOI： 10.3400/avd.oa.15-00069

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A 71-year-old man visited our hospital with the chief complaint of back pain and was diagnosed with acute aortic dissection (Debakey type III, Stanford type B). He was found to have a variant branching pattern in which the right subclavian artery was the fourth branch of the aorta. We performed conservative management for uncomplicated Stanford type B aortic dissection, and the patient was discharged. An ulcer-like projection (ULP) was discovered during outpatient follow-up. Complicated type B aortic dissection was suspected, and we performed thoracic endovascular aortic repair (TEVAR). The aim of operative treatment was ULP closure; thus we placed two stent grafts in the descending aorta from the distal portion of the right subclavian artery. The patient was released without complications on postoperative day 5. Deliberate sizing and examination of placement location were necessary when placing the stent graft, but operative techniques allowed the procedure to be safely completed.

DOI： 10.1155/2015/746354

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Objective: Tissue engineering techniques have emerged that allow bioresorbable grafts to be implanted that restore function and transform into biologically active arteries. However, these implants are susceptible to calcification during the remodeling process. The objective of this study was to evaluate the role of pore size of bioabsorbable grafts in the development of calcification. Methods: Two types of grafts were prepared: a large-pore graft constructed of poly(l-lactic acid) (PLA) fibers coated with poly(l-lactide-co-ε-caprolactone) (PLCL) (PLA-PLCL), and a small-pore graft made of electrospun PLA nanofibers (PLA-nano). Twenty-eight PLA-PLCL grafts and twenty-five PLA-nano grafts were implanted as infra-renal aortic interposition conduits in 8-week-old female SCID/Bg mice, and followed for 12 months after implantation. Results: Large-pore PLA-PLCL grafts induced a well-organized neointima after 12 months, and Alizarin Red S staining showed neointimal calcification only in the thin neointima of small-pore PLA-nano grafts. At 12 months, macrophage infiltration, evaluated by F4/80 staining, was observed in the thin neointima of the PLA-nano graft, and there were few vascular smooth muscle cells (VSMCs) in this layer. On the other hand, the neointima of the PLA-PLCL graft was composed of abundant VSMCs, and a lower density of macrophages (F4/80 positive cells, PLA-PLCL; 68.1±41.4/mm vs PLA-nano; 188.3±41.9/mm , p=0.007). The VSMCs of PLA-PLCL graft expressed transcription factors of both osteoblasts and osteoclasts. Conclusion: These findings demonstrate that in mouse arterial circulation, large-pore PLA-PLCL grafts created a well-organized neointima and prevented calcific deposition compared to small-pore, electrospun PLA-nano grafts. 2 2

DOI： 10.1016/j.atherosclerosis.2014.09.030

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Results The seeded grafts demonstrated significant luminal and longitudinal growth from 2 to 6 months. In vivo imaging revealed subjectively greater matrix metalloproteinase activity in grafts versus native tissue. Ex vivo imaging confirmed a quantitative increase in matrix metalloproteinase activity and demonstrated greater activity in unseeded versus seeded grafts. The glycosaminoglycan content was increased in seeded grafts versus unseeded grafts, without significant differences in collagen content.

DOI： 10.1016/j.jtcvs.2014.05.037

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

Although the right-ventricle to pulmonary artery( RV-PA) shunt as a source of pulmonary blood supply of Norwood procedure has improved early outcomes, disadvantages including right ventricular dysfunction or arrhythmias have been reported. So it has been still remained controversial whether BT shunt or RV-PA conduit should be selected. We examined the influence of Blalock-Taussig( BT) shunt size on regulation of the pulmonary blood flow in experimental model of a univentricular heart to determine the specific guidelines regarding suitable shunt size in the Norwood procedure. The canine univentricular heart model with the ratio of shunt size to body weight (SS/BW) of 0.8 to 1.1 showed significant negative correlation between the pulmonary/systemic blood flow ratio( Qp/Qs)and arterial PCo2, but those with SS/BW of 1.1 to 1.4 did not. Similar phenomena were shown with the grouped data on relationship between the Qp/Qs and inspired oxygen fraction. These findings imply that when SS/BW is 0.8 to 1.1, the Qp/Qs is controllable by physiologic respiratory manipulations. In the context of our clinical experiences, SS/BW of 0.9 to 1.0 is considered a useful index for suitable BT shunt in the Norwood procedure.

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In surgical repair for heart disease, it is often necessary to implant conduits or correct tissue defects. Commonly used graft materials include artificial grafts, autologous tissues, allografts and xenografts. However, none of these offer growth potential, and all are associated with varying levels of thrombogenicity and susceptibility to infection. Lack of growth potential of these four options is particularly important in pediatric cardiac surgery, where patients will often outgrow their grafts and require additional operations. Vascular tissue engineering offers a solution that produces neovessels and neo-organs from autologous cells that can grow, remodel, rebuild and respond to injury. © 2014 Woodhead Publishing Limited All rights reserved.

DOI： 10.1533/9780857096715.3.389

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

Tissue engineering holds great promise to address complications and limitations encountered with the use of traditional prosthetic materials, such as thrombogenicity, infection, and future degeneration which represent the major morbidity and mortality after device implant surgery. The general concept of tissue engineering consists of three main components: a scaffold material, a cell type for seeding the scaffold, and biochemical, physio-chemical signaling and remodeling process. This remodeling process is guided by cell signals derived from both seeded cells and host inflammatory cells that infiltrate the scaffold and deposit extracellular matrix, forming the neotissue. Vascular tissue engineering is at the forefront in the translation of this technology to clinical practice, as tissue engineered vascular grafts (TEVGs) have now been successfully implanted in children with congenital heart disease. In this report, we review the history, advances, and state of the art in TEVGs. © 2013 Wiley Periodicals, Inc.

DOI： 10.1002/ar.22838

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It may be difficult to access a route to deliver a stent-graft for abdominal aortic aneurysm in high-risk patients with bilateral iliofemoral occlusive disease. These two patients underwent both endovascular aortic aneurysm repair by a modified iliac access conduit technique and sequential ipsilateral iliofemoral artery bypass using the conduit, which provided excellent results. The iliac access conduit facilitates endovascular aortic aneurysm repair and ipsilateral iliofemoral bypass of high-risk patients with abdominal aortic aneurysm and bilateral iliofemoral occlusive disease.

DOI： 10.2152/jmi.61.204

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Language：English   Publisher：JAPANESE CIRCULATION SOC  

The development of vascular bioengineering has led to a variety of novel treatment strategies for patients with cardiovascular isease. Notably, combining biodegradable scaffolds with autologous cell seeding to create tissue-engineered ascular grafts (TEVG) allows for in situ formation of organized neovascular tissue and we have demonstrated he clinical viability of this technique in patients with congenital heart defects. The role of the scaffold is to rovide a temporary 3-dimensional structure for cells, but applying TEVG strategy to the arterial system requires caffolds that can also endure arterial pressure. Both biodegradable synthetic polymers and extracellular matrixbased atural materials can be used to generate arterial scaffolds that satisfy these requirements. Furthermore, the ole of specific cell types in tissue remodeling is crucial and as a result many different cell sources, from matured omatic cells to stem cells, are now used in a variety of arterial TEVG techniques. However, despite great progress n the field over the past decade, clinical effectiveness of small-diameter arterial TEVG (<6 mm) has remained elusive. o achieve successful translation of this complex multidisciplinary technology to the clinic, active participation f biologists, engineers, and clinicians is required.

DOI： 10.1253/circj.CJ-13-1440

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Over the last decade, advancements in the field of vascular tissue engineering have generated a variety of novel treatment strategies for patients with cardiac defects and vascular disease. Notably, the technique of seeding cells onto biodegradable polymeric scaffolds to create tissue-engineered vascular grafts (TEVGs) allows for the formation of organized neovascular tissue and enables the implanted construct to grow with the patient. Studies in animal models have resulted in a greater understanding of the complex and dynamic processes behind neovessel development and enabled the creation of a TEVG seeded with bone marrow-derived mononuclear cells for use in a pilot clinical trial. Current research indicates that this tissue engineering approach is safe and effective, and the ongoing translation of this technology holds great promise. In this text, we review the scaffold materials, cell types, and seeding methods for TEVG creation, and we introduce our clinical application of TEVGs. © 2014 Elsevier Inc. All rights reserved.

DOI： 10.1016/B978-0-12-398523-1.00058-6

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Background: Although systemic hypertension is closely associated with aortic aneurysm (AA) formation, there are many patients with AA without hypertension. In these patients, an inflammation-mediated progression of aneurysmal disease is likely responsible for AA growth and eventual rupture. Unfortunately, there remains no reproducible and durable small animal model of aortic aneurysmal disease, the development of which would enable the investigation of the pathophysiology of this vexing condition. The first aim was to establish a useful wild-type mouse model of AA with low mortality. The second aim was to use this model to assess the protective effect of azelnidipine, a new calcium channel blocker, against the progression of the AA independent of its antihypertensive effect. Methods: Angiotensin II and β-aminopropionitrile (a lysyl oxidase inhibitor) were administrated subcutaneously in 7-week-old C57BL/6J mice using an osmotic minipump for 4 weeks to generate a wild-type mouse model of AA. Concurrently, azelnidipine (a calcium channel blocker) or a placebo was administrated orally for 4 weeks. Mice were humanely killed and assessed at the end of the 4 weeks of pharmacologic manipulation. Results: The combined infusion of angiotensin II and β-aminopropionitrile induced degenerative aneurysm of the thoracic and/or abdominal aorta (11/12; 92%). The majority of aneurysms were located in the distal aortic arch and suprarenal abdominal aorta. Although there was no difference in systolic blood pressure between the control and azelnidipine-treated groups, azelnidipine significantly reduced the incidence of AA (2/11; 18%). Azelnidipine treatment reduced the pathologic findings normally associated with aneurysm formation within the aortic wall. Azelnidipine also reduced the number of macrophage antigen-3 (MAC-3)-positive cells in the periaortic adipose tissue and reduced the gene expression levels of tumor necrosis factor-alpha and matrix metalloproteinase-2 and -9 within the aortic wall. Conclusions: This study demonstrates that combined treatment with angiotensin II and β-aminopropionitrile induces degenerative AAs in wild-type mice, and azelnidipine prevents aneurysm progression via its anti-inflammatory effect. Copyright © 2013 by The American Association for Thoracic Surgery.

DOI： 10.1016/j.jtcvs.2013.02.073

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Objective: Endogenous ligands such as high-mobility group box 1 (HMGB1) and nucleic acids are released by dying cells and bind to Toll-like receptors (TLRs). As TLR9 is involved in both microbial and sterile inflammation by detecting both bacterial and endogenous DNA, we investigated its role in inflammation and lesion formation in a mouse model of vascular injury. Methods and results: C57BL/6 (WT) and TLR9 KO mice were subjected to wire-mediated vascular injury. Anti-HMGB1 antibody and purified HMGB1 protein were chronically delivered around the injured arteries by gelatin hydrogel, and neointima formation at 4 weeks after injury was evaluated. In addition, the same vascular injury was performed in bone-marrow chimeric mice (WT bone marrow into TLR KO mice; TLR9 KO bone marrow into WT mice). We also evaluated the production of inflammatory cytokines by mouse macrophages in response to HMGB1 and CpG-ODN. In wild-type mice after vascular injury, anti-HMGB1 antibody significantly reduced neointima formation and HMGB1 protein accelerated neointima hyperplasia. HMGB1 failed to accelerate lesion formation in TLR9 KO mice. The bone marrow transplantation study revealed that TLR9 in bone marrow-derived cells played a fundamental role in neointima formation. Invitro, HMGB1 and CpG-ODN synergistically induced the production of inflammatory cytokines by macrophages. Conclusions: HMGB1 serves as an endogenous mediator of inflammation and lesion formation via the TLR9 pathway in response to vascular injury. Blockade of HMGB1 and/or TLR9 may represent a novel approach to treating atherosclerosis. © 2013 Elsevier Ireland Ltd.

DOI： 10.1016/j.atherosclerosis.2013.09.010

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Background: The optimal medical management to delay the progression of aortic aneurysms has not been fully clarified, and the only standard treatment at present is antihypertensive therapy. Previous studies have shown beneficial effects of selective mineralocorticoid receptor (MR) antagonists on cardiovascular remodeling. The aim of the present study was to investigate the effect of a selective MR antagonist on aortic aneurysm progression. Methods: Seven-week-old C57BL/6J male mice were administered with angiotensin II and β-aminopropionitrile for 4 weeks. The mice received either vehicle or eplerenone, a selective MR antagonist (100 mg/kg daily) every day by gavage, starting at 7 weeks of age. The production of inflammatory cytokines in cultures of high mobility group box-1-stimulated macrophages with or without a MR antagonist was also analyzed using an enzyme-linked immunosorbent assay. Results: Although no differences were found in the peak systolic blood pressure between the experimental groups, the mice in the eplerenone group showed a significant reduction in aneurysm development. On histologic analysis, coarse and stretched elastic fibers were markedly improved in the aortic wall in the eplerenone group. Real-time polymerase chain reaction of both aortic wall and perivascular adipose tissue demonstrated the expression of tumor necrosis factor-α, interleukin-6, and matrix metalloproteinase-2 was significantly decreased in eplerenone group, and that of monocyte chemoattractant protein-1 in the aortic wall was also significantly decreased. Macrophage infiltration in the aortic wall and perivascular adipose tissue in the eplerenone group was also significantly decreased. The production of tumor necrosis factor-α and interleukin-6 in macrophage culture, which was stimulated by high mobility group box-1 and CpG oligodeoxynucleotides, was also significantly decreased in the eplerenone group. Conclusions: Eprelenone suppressed aortic aneurysm progression through an anti-inflammatory effect. Thus, selective MR antagonists might be effective in preventing the progression of aortic aneurysms. © 2013 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.jss.2013.05.002

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Multiple murine models have proven useful in studying the natural history of neovessel development in the tissue engineering of vascular grafts. Nevertheless, to better understand longitudinal changes in the biomechanics of such neovessels, we must first quantify native tissue structure and properties. In this paper, we present the first biaxial mechanical data for, and nonlinear constitutive modeling of, &QJ;the inferior vena cava from two models used in tissue engineering: wild-type C57BL/6 and immunodeficient CB-17 SCID/bg mice. Results show that inferior vena cava from the latter are significantly stiffer in the circumferential direction, both materially (as assessed by a stored energy function) and structurally (as assessed by the compliance), despite a lower intramural content of fibrillar collagen and similar wall thickness. Quantifying the natural history of neovessel development in different hosts could lead to increased insight into the mechanisms by which cells fashion and maintain extracellular matrix in order to match best the host stiffness while ensuring sufficient vascular integrity. © 2013.

DOI： 10.1016/j.jbiomech.2013.06.013

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AimsExcessive vascular remodelling leads to progression of a wide range of vasculopathies, and the immune response to intimal injuries is crucial in this process. This vascular remodelling occurs in the hypoxic microenvironment and is closely related to the immune system. Macrophages play a key role in immunological-cell-mediated arterial remodelling. In this study, we clarified the role of macrophage-derived hypoxia-inducible factor (HIF-1α) in vascular remodelling.Methods and resultsWire-induced femoral arterial injury was inflicted in mice lacking the macrophage-specific HIF-1α gene and in their wild-type counterparts. The mutant mice showed both suppressed wire-induced neointimal thickening and decreased infiltration of inflammatory cells in the adventitia, compared with wild-type mice. Studies to clarify the mechanism of restrained vascular remodelling in the mutant mice revealed decreased production of pro-inflammatory cytokines by the activated macrophages and suppressed macrophage migration activity in the mutant mice. Gene expressions of the HIF-1α-deficient macrophages positively correlated with the phenotypic profile of M2 macrophages and negatively correlated with that of M1 macrophages.ConclusionOur results show that HIF-1α in macrophages plays a crucial role in promoting vascular inflammation and remodelling. As decreasing HIF-1α activity in macrophages may prevent the progression of vascular remodelling, HIF-1α may be a possible therapeutic target in vascular diseases. © 2013 The Author.

DOI： 10.1093/cvr/cvt146

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The management of patients with multiple muscular trabecular ventricular septal defects (VSDs) remains controversial. In the past two decades, innovative techniques including a right ventricular apical infundibulotomy and transcatheter, intraoperative and perventricular device closure have been exploited, and essential right atrial approach and limited apical left ventriculotomy have also been refined. However, specific management guidelines for this difficult disease have not been established. In this article, the benefits and drawbacks of each technique are reviewed and discussed. Primary repair for infants with multiple muscular trabecular VSDs was associated with good late outcomes. The right atrial approach was satisfactory for all muscular VSDs, excluding apical defects that were well seen through a limited apical ventriculotomy. Surgical closure of apical defects could be achieved safely and completely in early infancy through a limited apical left ventriculotomy or a right ventricular apical infundibulotomy. Further follow-up and prudent evaluations of ventriculotomy-associated morbidities are needed. Pulmonary artery banding should be limited to a small infant with complex associated defects. Percutaneous device closure, the most desirable option, is impractical due to limitations between the delivery system and access route. Intraoperative device closure appears less successful than device closure in the catheterization laboratory. Perventricular device closure has a significant advantage of being a non-bypass procedure approach. A less invasive strategy for "true" Swiss cheese septum is needed. All may have an important role, and results obtained by using these techniques are encouraging. These hybrid approaches will promise future success on management guidelines of multiple muscular trabecular VSDs. © 2013 The Japanese Association for Thoracic Surgery.

DOI： 10.1007/s11748-013-0267-8

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

OBJECTIVE - : The impact of epicardial adipose tissue (EAT) over abdominal or overall adiposity on coronary artery disease (CAD) is currently unknown. We compared the association among EAT volume (EATV), cytokine/adipocytokine profiles in EAT and subcutaneous fat, and atherogenic CAD. APPROACH AND RESULTS - : Paired samples were obtained from EAT and subcutaneous adipose tissue during elective cardiac surgery for CAD (n=50) or non-CAD (n=50). EATV was the sum of cross-sectional EAT areas, and visceral and subcutaneous fat areas were determined at the umbilicus level on computed tomography scans. CD68, CD11c, and CD206 cells were counted using immunohistochemical staining. Cytokine/adipocytokine expression was evaluated using quantitative real-time polymerase chain reaction. Multivariate analysis indicated that male sex, age, diabetes mellitus, high triglycerides, and low high-density lipoprotein cholesterol, and EATV index (EATV/body surface area, cm/m) were significant CAD predictors (corrected R=0.401; P<0.001); visceral fat area, hypertension, smoking, low-density lipoprotein cholesterol (140 mg/dL [3.63 mmol/L]) or statin use were not predictors. The EATV index positively correlated with the CD68 and CD11c cell numbers and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), interleukin-1β, and interleukin-1R expression; and negatively correlated with adiponectin expression in EAT. A multivariate analysis model, including CD68 cells and interleukin-1β, and adiponectin expression in EAT strongly predicted CAD (corrected R=0.756; P<0.001). CONCLUSIONS - : EATV and macrophage and cytokine/adipocytokine signals in EAT strongly correlated with CAD. Our findings suggest that EATV and adipocytokine imbalance are strongly linked to human coronary atherosclerosis. © 2013 American Heart Association, Inc.

DOI： 10.1161/ATVBAHA.112.300829

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：MOSBY-ELSEVIER  

Objective: Thymectomy is often performed to secure an operative field in surgery for congenital heart defects in early infancy. However, how neonatal thymectomy affects the subsequent development of the immune system in humans remains unclear. We monitored patients for 3 years from the time of thymectomy that was performed during cardiac surgery in early infancy. Methods: For up to 3 years, we monitored the number of circulating lymphocytes and the clinical course of the children who underwent complete (n = 17), partial, and no (n = 15) thymectomy during congenital heart defect surgery performed at less than 3 months of age. The titers of immunoglobulin-G produced in response to vaccinated viruses and phytohemagglutinin responses were also measured. Results: Six months after surgery, the number of T cells, including CD4 and CD8 subpopulations, decreased in patients with complete but not partial thymectomy. The reduction in T-cell number persisted for 3 years, whereas the number of B cells did not change. In patients with complete thymectomy, the titers of immunoglobulin-G produced in response to vaccinated measles and rubella viruses were reduced, whereas the phytohemagglutinin-induced proliferation of T cells was not impaired. In addition, hospitalization frequency associated with infectious diseases increased in patients with complete but not partial thymectomy. Conclusions: The results revealed that complete thymectomy in early infancy reduces the number of circulating T cells and T-cell-mediated immune responses for at least 3 years, suggesting that the thymus should be at least partially preserved during surgery in early infancy to maintain protective immunity. Copyright © 2013 by The American Association for Thoracic Surgery. + +

DOI： 10.1016/j.jtcvs.2012.12.015

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Injury to the heart can result in cardiomyocyte hypertrophy, fibrosis, and cell death. Myocarditis sometimes progresses to dilated cardiomyopathy. We previously reported that ONO-1301, a synthetic prostacyclin agonist with thromboxane-synthase inhibitory activity, promotes production of hepatocyte growth factor (HGF) from various cell types and ameliorates ischemia-induced left ventricle dysfunction in the mouse, rat and pig. Here, we investigated the therapeutic efficacy of ONO-1301 in a rat model of myosin-induced experimental autoimmune myocarditis, in which the heart transits from an acute inflammatory phase to a chronic dilated cardiomyopathy phase. Four weeks after myosin injection to Lewis rats, ONO-1301 (6 mg/kg/day) was orally administered for 4 weeks (ONO-1301 group). Hemodynamic parameters and plasma brain natriuretic peptide (BNP) level were significantly improved by ONO-1301. Histological analysis revealed that capillary density in the myocardium was significantly increased by ONO-1301. ONO-1301 increased circulating endothelial progenitor cells (EPC) as determined by FACS analysis. These beneficial effects of ONO-1301 were partially abrogated by a neutralizing anti-HGF antibody (8 mg/kg/dose). These findings indicate beneficial effects of ONO-1301 in a rat experimental autoimmune myocarditis model. © 2012 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.ejphar.2012.11.045

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Exendin-4 is a glucagon-like peptide-1 receptor agonist that has been used as a drug for treatment of type 2 diabetes. To investigate the effect of exendin-4 on the cardiovascular system, we investigated the impact of exendin-4 on neointimal hyperplasia of the femoral artery after vascular injury. We performed wire-mediated endovascular injury in C57BL/6 mice, followed by administration of exendin-4 24 nmol/kg/day via infusion pump. Four weeks after the injury, exendin-4 treatment significantly attenuated neointimal hyperplasia of the injured artery, although it did not affect glucose metabolism and lipid profile in wild-type mice. Immunofluorescence study revealed abundant expression of GLP-1 receptor on α-smooth muscle actin-positive cells in the injured vessel. Cell proliferation assay using rat aortic smooth muscle cells showed that exendin-4 reduced PDGF-BB induced smooth muscle cell proliferation through the cAMP/PKA pathway. Exendin-4 also inhibited TNFα production by peritoneal macrophages in response to inflammatory stimulus. Our findings indicate that a GLP-1 receptor agonist attenuated neointimal formation after vascular injury. GLP-1 receptor agonists or drugs that raise endogenous GLP-1 level might be effective in the treatment of vascular diseases. © 2012 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.ejphar.2012.11.057

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An extremely rare case with delayed-onset heparin-induced thrombocytopenia (HIT) is described. A 46-year-old man underwent arch replacement for aortic dissection under cardiopulmonary bypass and initial exposure of unfractionated heparin. In post operative 7 days, persistent atrial fibrillation was occurred, so a continuous infusion of heparin (10000 IU/day) and Vitamine K antagonist (Warfarin) taking was started for preventing thrombosis. By 32 days after the operation, his platelet count had fallen (3 103 /μL) and oral hematoma and ecchymoma of bilateral lower legs were occurred. The value of HIT antibodies and the IgG antibody was 2.485 and 1.586 on 32-postoperative day, respectively. Heparin was immediately discontinued, and argatroban administrated. Platelet exceeded above 100 103/μL on 12 days of the therapy. To our knowledge, few cases of delayed-onset severe HIT associated with CPB surgery have been reported in Japan.

DOI： 10.2152/jmi.60.154

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Background: Telmisartan is a well-established angiotensin II type 1 receptor blocker that improves insulin sensitivity in animal models of obesity and insulin resistance, as well as in humans. Telmisartan has been reported to function as a partial agonist of the peroxisome proliferator-activated receptor (PPAR) γ, which is also targeted by the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase (SIRT1). Here, we investigated the pathways through which telmisartan acts on skeletal muscle, in vitro as well as in vivo.Methods: Nine-week-old male db/db mice were fed a 60% high-fat diet, with orally administrated either vehicle (carboxymethyl-cellulose, CMC), 5 mg/kg telmisartan, or 5 mg/kg telmisartan and 1 mg/kg GW9662, a selective irreversible antagonist of PPARγ, for 5 weeks. Effects of telmisartan on Sirt1 mRNA, AMPK phosphorylation, and NAD+/NADH ratio were determined in C2C12 cultured myocytes.Results and discussion: Telmisartan treatment improved insulin sensitivity in obese db/db mice fed a high-fat diet and led to reduction in the size of hypertrophic pancreatic islets in these mice. Moreover, in vitro treatment with telmisartan led to increased expression of Sirt1 mRNA in C2C12 skeletal muscle cells; the increase in Sirt1 mRNA in telmisartan-treated C2C12 myoblasts occurred concomitantly with an increase in AMPK phosphorylation, an increase in NAD+/NADH ratio, and increases in the mRNA levels of PGC1α, FATP1, ACO, and GLUT4.Conclusions: Our results indicate that telmisartan acts through a PPARγ-independent pathway, but at least partially exerts its effects by acting directly on skeletal muscle AMPK/SIRT1 pathways. © 2012 Shiota et al.; licensee BioMed Central Ltd.

DOI： 10.1186/1475-2840-11-139

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Telmisartan exerts anti-metabolic effects beyond its angiotensin receptor blockade activities, but the mechanisms have hitherto remained elusive. We sought to elucidate the peroxisome proliferator-activated receptor-γ (PPAR-γ)-dependent and PPAR-γ-independent mechanisms underlying the anti-metabolic effects of telmisartan in white adipose tissue. Nine-week-old male C57BL/6 mice were fed with a 60% high-fat diet for 6 weeks, with 1 mg/kg telmisartan or vehicle administrated orally during the last 3 weeks. 3T3-L1 adipocytes were cultured with telmisartan either with 2-chloro-5-nitro-N- phenylbenzamide (GW9662), a selective irreversible antagonist of PPAR-γ, or compound C, an ATP-competitive inhibitor of AMPK. Western blotting and semiquantitative RT-PCR analysis were used to assess adiponectin, Sirt1, and AMPK levels. Lipid accumulation was assessed by Oil red O staining. The activation of transcription factor PPAR-γ2 was evaluated by using a luciferase reporter assay for mPPAR-γ2 expression plasmid vector. Treatment with telmisartan increased serum adiponectin levels in high-fat diet-fed mice concomitantly with an upregulation of adiponectin mRNA in visceral adipose tissue. In vitro telmisartan treatment dose-dependently increased adiponectin mRNA in 3T3-L1 cells; the increase was inhibited by compound C, but not by GW9662. Telmisartan increased expression of Sirt1 mRNA and Sirt1 protein as well as the phosphorylation of AMPK in 3T3-L1 cells. Telmisartan can increase adiponectin production in white adipose tissue partly via a PPAR-γ2-independent mechanism. Precise understanding of this molecular mechanism will require further investigation. © 2012 Elsevier B.V.

DOI： 10.1016/j.ejphar.2012.07.026

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Background: Growing evidence suggests that epicardial adipose tissue (EAT) may contribute to the development of coronary artery disease (CAD). In this study, we explored gender disparities in EAT volume (EATV) and its impact on coronary atherosclerosis.Methods: The study population consisted of 90 consecutive subjects (age: 63 ± 12 years; men: 47, women: 43) who underwent 256-slice multi-detector computed tomography (MDCT) coronary angiography. EATV was measured as the sum of cross-sectional epicardial fat area on CT images, from the lower surface of the left pulmonary artery origin to the apex. Subjects were segregated into the CAD group (coronary luminal narrowing > 50%) and non-CAD group.Results: EATV/body surface area (BSA) was higher among men in the CAD group than in the non-CAD group (62 ± 13 vs. 33 ± 10 cm /m , p < 0.0001), but did not differ significantly among women in the 2 groups (49 ± 18 vs. 42 ± 9 cm /m , not significant). Multivariate logistic analysis showed that EATV/BSA was the single predictor for >50% coronary luminal narrowing in men (p < 0.0001). Predictors excluded were age, body mass index, hypertension, diabetes mellitus, and hyperlipidemia.Conclusions: Increased EATV is strongly associated with coronary atherosclerosis in men. © 2012 Dagvasumberel et al.; licensee BioMed Central Ltd. 3 2 3 2

DOI： 10.1186/1475-2840-11-106

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Background: Local skin flaps often present with flap necrosis caused by critical disruption of the blood supply. Although animal studies demonstrate enhanced angiogenesis in ischemic tissue, no strategy for clinical application of this phenomenon has yet been defined. Hypoxia-inducible factor 1 (HIF-1) plays a pivotal role in ischemic vascular responses, and its expression is induced by the prolyl hydroxylase inhibitor dimethyloxalylglycine (DMOG). We assessed whether preoperative stabilization of HIF-1 by systemic introduction of DMOG improves skin flap survival. Methods and Results: Mice with ischemic skin flaps on the dorsum were treated intraperitoneally with DMOG 48 hr prior to surgery. The surviving area with neovascularization of the ischemic flaps was significantly greater in the DMOG-treated mice. Significantly fewer apoptotic cells were present in the ischemic flaps of DMOG-treated mice. Interestingly, marked increases in circulating endothelial progenitor cells (EPCs) and bone marrow proliferative progenitor cells were observed within 48 hr after DMOG treatment. Furthermore, heterozygous HIF-1α-deficient mice exhibited smaller surviving flap areas, fewer circulating EPCs, and larger numbers of apoptotic cells than did wild-type mice, while DMOG pretreatment of the mutant mice completely restored these parameters. Finally, reconstitution of wild-type mice with the heterozygous deficient bone marrow cells significantly decreased skin flap survival. Conclusion: We demonstrated that transient activation of the HIF signaling pathway by a single systemic DMOG treatment upregulates not only anti-apoptotic pathways but also enhances neovascularization with concomitant increase in the numbers of bone marrow-derived progenitor cells. © 2012 Takaku et al.

DOI： 10.1371/journal.pone.0042964

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PURPOSE: Efficient and secure collection of CD34+ cells are crucial for the angiogenic therapies. We have developed autologous peripheral blood-mononuclear cell (MNC) transplantation induced by erythropoietin (rhEPO) for critical ischemic limbs. METHODS: Seven patients, including five with arteriosclerosis obliterans, one with Buerger's disease and one with progressive systemic sclerosis, underwent ten cell therapies. The first administration of rhEPO was performed two weeks before apheresis, and the second administration and blood donation were performed one week before apheresis to activate bone marrow. MNCs including CD34+ cells, isolated from peripheral blood by apheresis, were immediately injected intramuscularly into ischemic limbs. RESULTS: The number of peripheral blood-CD34 + cells had significantly increased from 1.32 ± 0.83/microL, before the rhEPO induction, to 1.86 ± 0.94/microL, before the apheresis. The number of transplanted MNCs ranged between 0.5 × 10(9) and 16.5 × 10(9), and that of CD34+ cells, between 0.1 × 10(6) and 12.7 × 10(6), accounting for 0.02%-0.1% of MNCs. There were no serious complications. Finger ulcers with Buerger's disease were significantly improved one month after the transplantations, but the same or other ulcer(s) appeared 2-6 months later. Three patients had an improvement in rest pain, and one patient extended maximum pain-free walking distance. CONCLUSIONS: Erythropoietin-induced autologous peripheral blood-MNC transplantation is a useful and safe alternative for ischemic limbs.

DOI： 10.3400/avd.oa.11.00070

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In surgical repair for heart or vascular disease, it is often necessary to implant conduits or correct tissue defects. The most commonly used graft materials to date are (a) artificial grafts; (b) autologous tissues, such as pericardium and saphenous vein; (c) allografts; and (d) xenografts. However, none of these four options offer growth potential, and all are associated with varying levels of thrombogenicity and susceptibility to infection. The lack of growth potential of these four options is particularly important in pediatric cardiac surgery, where patients will often outgrow their vascular grafts and require additional operations. Thus, developing a material with sufficient durability and growth potential that will function as the child grows older will eliminate the need for reoperation and significantly reduce morbidity and mortality of some types of congenital heart defects. Vascular tissue engineering is a relatively new field that has undergone enormous growth over the last decade. The goal of vascular tissue engineering is to produce neovessels and neo-organ tissue from autologous cells using a biodegradable polymer as a scaffold. The most important advantage of tissue-engineered implants is that these tissues can grow, remodel, rebuild, and respond to injury. Once the seeded autologous cells have deposited an extracellular matrix and the original scaffold is biodegraded, the tissue resembles and behaves as native tissue. When tissue-engineered vascular grafts are eventually put to use in the clinical arena, the quality of life in patients after surgery will be drastically improved. © AlphaMed Press.

DOI： 10.5966/sctm.2012-0044

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Aim: Ezetimibe, an inhibitor of cholesterol intestinal absorption, is a lipid lowering agent. However, anti-atherogenic effects of ezetimibe have not been fully elucidated. Therefore, the objective in this study was to clarify the vascular protective effects of ezetimibe in patients with hypercholesterolemia. Methods: Ezetimibe was administered to 20 patients with hypercholesterolemia (group E), and 20 age- and sex-matched patients with hypercholesterolemia were followed as controls (group C). Difference in metabolic profiles and cardiovascular surrogate markers before ezetimibe treatment and after 12 weeks of ezetimibe treatment were statistically evaluated. Results: Ezetimibe treatment significantly reduced serum levels of low-density lipoprotein cholesterol (LDL-C) and malondialdehyde-modified low-density lipoprotein (MDA-LDL). In addition, the values of body mass index, body weight, waist circumference, plasma HbA1c and urinary albumin were significantly decreased in group E compared to those in group C. On the other hand, high-density lipoprotein cholesterol (HDL-C) and adiponectin levels were significantly increased in group E compared to those in group C. The values of brachial-ankle pulse wave velocity (ba-PWV), mean arterial blood pressure (m-ABP), and % of flow-mediated dilation (FMD) were significantly improved in group E. Furthermore, ultrasonic studies demonstrated amelioration of the vascular stiffness of common carotid arteries in group E but not in group C. These vascular protective effects of ezetimibe were statistically correlated with the decreased values of MDA-LDL and MDA-LDL-to-LDL-C ratio but not with those of LDL-C. Conclusion: Ezetimibe has a lipid lowering-independent vascular protective effect in patients with hypercholesterolemia through decreasing oxidative stress.

DOI： 10.5551/jat.9548

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Objectives: The purpose of this report was to assess the link between macrophage polarization in epicardial adipose tissue and atherosclerosis in patients with coronary artery disease (CAD). Background: Macrophage accumulation enhances chronic inflammation in adipose tissue, but macrophage phenotypic change in human epicardial adipose tissue and its role in atherogenesis are unknown. Methods: Samples were obtained from epicardial and subcutaneous adipose tissue during elective cardiac surgery (CAD, n = 38; non-CAD, n = 40). Infiltration of M1/M2 macrophages was investigated by immunohistochemical staining with antibodies against CD11c and CD206, respectively. Expression of pro- and anti-inflammatory adipocytokines in adipose tissue was evaluated by real-time quantitative polymerase chain reaction. Results: Infiltration of macrophages and expression of pro- and anti-inflammatory cytokines were enhanced in epicardial fat of patients with CAD compared with that in non-CAD patients (p < 0.05). The ratio of M1/M2 macrophages was positively correlated with the severity of CAD (r = 0.312, p = 0.039). Furthermore, the expression of pro-inflammatory cytokines was positively correlated, and the expression of anti-inflammatory cytokines was negatively correlated with the ratio of M1/M2 macrophages in epicardial adipose tissue of CAD patients. By contrast, there was no significant difference in macrophage infiltration and cytokine expression in subcutaneous adipose tissue between the CAD and non-CAD groups. Conclusions: The ratio of M1/M2 macrophages in epicardial adipose tissue of CAD patients is changed compared with that in non-CAD patients. Human coronary atherosclerosis is associated with macrophage polarization in epicardial adipose tissue. © 2011 American College of Cardiology Foundation.

DOI： 10.1016/j.jacc.2011.01.048

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Purpose: Although several approaches have been tried to improve the durability of cryopreserved valves, cellular restoration after thawing remains to be investigated. The aim of our study was to assess the functional restoration of endothelial cells of cryopreserved heart valves by in vitro culture for an alternative step to improving longevity. Methods: Cryopreserved human umbilical vein endothelial cells (HUVECs) and porcine aortic cusps were cultivated for 14 days after thawing. Then the cellular activity of the enzymes cytosolic esterase and mitochondrial dehydrogenase was measured. The cellular viability of cryopreserved cusps was also assessed using confocal laser scanning microscopy. Results: The number of viable HUVECs decreased markedly after cryopreservation and thawing but recovered to pre-cryopreservation level after 14 days of culture. In contrast, the enzyme activity of the cryopreserved porcine aortic cusps showed recovery at 7 days of in vitro tissue culture after thawing. Confocal laser scanning microscopy findings showed that the cellular cytosolic esterase activity of cryopreserved cusps deteriorated after thawing but displayed considerable recovery by day 14 of culture. Conclusion: The functional recovery of endothelial cells in cryopreserved heart valves seems to require tissue culture of at least 14 days. Ex vivo endothelial restoration of cryopreserved heart valves may add to heart valve durability. © 2011 The Japanese Association for Thoracic Surgery.

DOI： 10.1007/s11748-010-0711-y

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Two adult patients with previous transient cerebral ischemic attacks (TIAs) or chest oppression were referred for further investigation. A swaying pedicled tumor was detected in the left atrium of the former patient and in the left coronary cusp of the latter by echocardiography. The TIA, or angina-like attack, was anticipated to be caused by thromboembolism of the tumor. Both patients underwent tumor extirpation. The histological findings demonstrated that both tumors were benign papillary fibroelastoma limited to the endocardium/ endothelium layer. In conclusion, early surgical resection of a cardiac papillary fibroelastoma should be performed. © 2011 The Japanese Association for Thoracic Surgery.

DOI： 10.1007/s11748-010-0654-3

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It has been hypothesized that epicardial fat, a local visceral fat depot with close proximity to coronary arteries, may serve as a source of inflammatory cytokines and cells in coronary atherosclerotic lesions. Here, we characterized infiltration of inflammatory cells and expression of adipocytokines in epicardial adipose tissue in patients with and without coronary artery disease (CAD). Pare samples were obtained from epicardial and subcutaneous adipose tissue during elective cardiac surgery (CAD, n = 8; non-CAD, n = 9). Inflammatory cell infiltration was investigated by immunohistochemical staining using antibodies against CD3, CD4, CD8 and CD68. Expression of adipocytokines was evaluated by real-time quantitative reverse transcription-polymerase chain reaction. Infiltration of macrophages and CD8-positive T cells in the epicardial adipose tissue in the CAD group was greater than that in the non-CAD group. In contrast, there was no significant difference between the two groups in the number of inflammatory cells in subcutaneous adipose tissue. No statistical difference could be found between the CAD group and the non-CAD group in the expression levels of adiponectin and inflammatory cytokines in epicardial adipose tissue. Our findings suggest that inflammatory cell infiltration is enhanced in epicardial adipose tissue, but not in subcutaneous fat, in patients with coronary artery disease. Chronic inflammation in epicardial fat may influence the pathogenesis of coronary atherosclerosis.

DOI： 10.1536/ihj.52.139

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Preferable surgical approaches to aortic diseases occurring between the aortic root and the arch in patients with functioning tracheotomy or permanent tracheostomy are described for securing adequate exposure and avoiding postoperative mediastinitis. Case 1: A 41-year-old man with Marfan syndrome presented with chronic type A thrombosed aortic dissection and severe aortic valve regurgitation. He had had a functional tracheostomy for managing respiratory function due to traumatic spinal cord damage. The heart and the ascending aorta were shifted to the right side of the chest and showed a significant counterclockwise rotation. Therefore, the reverse L-figure approach of a right-sided 3rd intercostal anterior thoracostomy and lower midline sternotomy was performed for Bentall operation. Case 2: A 76-year-old woman presented with thoracic aortic aneurysm of 11 cm in diameter. She had had a permanent tracheostomy with total laryngectomy. Therefore, cram shell approach was performed for total arch replacement. The 2 cases had no postoperative mediastinitis. These approaches are recommended for aortic diseases occurring in the ascending aorta or the aortic arch in patients with functioning tracheotomy.

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Objective: The thymus has been implicated as a possible site of origin that triggers autoimmunity in myasthenia gravis (MG). Although several groups have suggested that the decrease in the number of regulatory T (Treg) cells contributes to the onset of MG, the exact role of Treg cells in MG remains unclear. To address this point, we examined the number and distribution of Treg cells in a large number of patients with MG. Methods: Immunohistofluorescence analysis of Foxp3 along with CD4 and CD8 was performed in thymic sections of MG (+) (n = 24) and MG (-) patients (n = 27). Circulating CD4CD25 cells in the peripheral blood of patients with MG (n = 15) and age-matched healthy subjects (n = 15) were also analyzed. RESULTS: Foxp CD CD cells were predominantly found in the thymic medulla and their number declined with age. There was no significant difference in the number or the distribution of Foxp CD CD cells in the thymus between MG (+) and MG (-) patients. The number of circulating CD CD25 cells in the peripheral blood of patients with MG was not significantly altered compared to that in healthy subjects. Conclusion: The cellularity of Treg cells in the thymus and circulation is not diminished in patients with myasthenia gravis. Copyright © 2010 by AAN Enterprises, Inc. 3+ 4+ 8- 3+ 4+ 8- 4+ +

DOI： 10.1212/WNL.0b013e3181d31e47

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BACKGROUND AND PURPOSE-: Recent studies have shown that the cellular immune response in the development of vascular remodeling modulates the resulting pathological alterations. We show that hypoxia-inducible factor 1 (Hif-1) (specifically expressed in T cells) is involved in the immune response to vascular remodeling that accompanies arteriosclerosis. METHODS AND RESULTS-: To study the role of T cells in the development of vascular remodeling, femoral arterial injury induced by an external vascular polyethylene cuff was examined in mice lacking Hif-1 (specifically in T cells). We found that cuff placement caused prominent neointimal hyperplasia of the femoral artery in Hif-1-(T-cell)-deficient mice compared with that in control mice and that infiltration of inflammatory cells at the adventitia was markedly increased in the mutant mice. Studies to clarify the mechanism of augmented vascular remodeling in the mutant mice showed enhanced production of cytokines by activated T cells and augmented antibody production in response to a T-dependent antigen in the mutant mice. CONCLUSIONS-: The results of this study revealed that Hif-1α in T cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of T cell-mediated immune response. Potential new therapeutic strategies that target Hif-1α are described. © 2010 American Heart Association, Inc.

DOI： 10.1161/ATVBAHA.109.192666

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Lippincott Williams and Wilkins  

Objective: The thymus has been implicated as a possible site of origin that triggers autoimmunity in myasthenia gravis (MG). Although several groups have suggested that the decrease in the number of regulatory T (Treg) cells contributes to the onset of MG, the exact role of Treg cells in MG remains unclear. To address this point, we examined the number and distribution of Treg cells in a large number of patients with MG. Methods: Immunohistofluorescence analysis of Foxp3 along with CD4 and CD8 was performed in thymic sections of MG (+) (n = 24) and MG (-) patients (n = 27). Circulating CD4CD25 cells in the peripheral blood of patients with MG (n = 15) and age-matched healthy subjects (n = 15) were also analyzed. RESULTS: Foxp3+CD4+CD 8- cells were predominantly found in the thymic medulla and their number declined with age. There was no significant difference in the number or the distribution of Foxp3+CD4+CD8- cells in the thymus between MG (+) and MG (-) patients. The number of circulating CD 4+CD25+ cells in the peripheral blood of patients with MG was not significantly altered compared to that in healthy subjects. Conclusion: The cellularity of Treg cells in the thymus and circulation is not diminished in patients with myasthenia gravis. Copyright © 2010 by AAN Enterprises, Inc.

DOI： 10.1212/WNL.0b013e3181d31e47

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Background: We investigated the effects and possible mechanism of syngeneic bone marrow mononuclear cell (BM-MNC) transplantation on pulmonary arterial hypertension induced by monocrotaline. Methods: Monocrotaline (80 mg/kg body weight) was administrated to C57BL/6 mice, and pulmonary arterial hypertension was induced 4 weeks later. Bone marrow mononuclear cells harvested from syngeneic donor mice were injected intravenously into those mice 4 weeks after monocrotaline administration. The ratio of right ventricular to septum plus left ventricular weight, the number of small pulmonary arteries, and medial thickness of pulmonary arteries were measured. Western immunoblotting of the lung tissue was performed to observe vascular endothelial growth factor and its receptor expression 1 week after BM-MNC transplantation. Vascular endothelial growth factor receptor-2 inhibitor was administered to pulmonary arterial hypertension mice simultaneously with BM-MNC transplantation. Results: The ratio of right ventricular to septum plus left ventricular weight increased, the number of pulmonary arteries decreased, and medial thickness increased significantly 4 weeks after monocrotaline injection compared with those of vehicle-injected mice. These indices of monocrotaline-injected mice improved significantly 4 weeks after BM-MNC transplantation compared with those of mice at 8 weeks after monocrotaline injection (0.22 ± 0.02 versus 0.31 ± 0.02; 17.1 ± 2.6 versus 8.2 ± 1.7; 7.7% ± 2.2% versus 20% ± 2.1%, respectively; p < 0.01). However, BM-MNCs were not incorporated into the lung at 1 week after transplantation, and significant vascular endothelial growth factor upregulation and without receptor expression was observed in lung tissue 1 week after transplantation. Improvement of pulmonary arterial hypertension was inhibited by simultaneous administration of vascular endothelial growth factor receptor-2 inhibitor with BM-MNC transplantation. Conclusions: These results indicate that syngeneic BM-MNC transplantation improves monocrotaline-induced pulmonary arterial hypertension by favorable pulmonary artery remodeling through vascular endothelial growth factor upregulation. © 2009 The Society of Thoracic Surgeons.

DOI： 10.1016/j.athoracsur.2009.04.105

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Language：English   Publisher：KARGER  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN ATHEROSCLEROSIS SOC  

Aim: Heparin cofactor (HC) specifically inactivates thrombin action at the injured vascular wall. We have reported that HC is a protective factor against coronary in-stent restenosis and carotid atherosclerosis; however, it is unclear whether there is any correlation between plasma HC levels and the development of peripheral arterial disease (PAD). Methods: Plasma HC activity and the ankle brachial pressure index (ABI) were determined in 494 elderly subjects with cardiovascular risk factors. PAD was diagnosed by ABI below 0.9, and 62 subjects were diagnosed with PAD. The relationship between factors that affect cardiovascular events and the prevalence of PAD was statistically evaluated. Results: Mean HC activity in PAD subjects was significantly lower than in non-PAD subjects (87.5 ± 19.7% v.s. 94.6 ± 17.8%, p 0.009). Multivariate logistic regression analysis showed that age (odds ratio [OR]: 1.062, p 0.0016), current smoking (OR 3.028, p 0.002) and diabetes mellitus (OR 2.656, p 0.008) were independent and progressive determinants of PAD. In contrast, HC was an independent inhibitory factor of PAD (OR: 0.982, p 0.048). Conclusions: Plasma HC activity is inversely related to the prevalence of PAD. HC may function as the sole protective factor against PAD in elderly people with cardiovascular risk factors.

DOI： 10.5551/jat.E695

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The University of Tokushima  

A successful transatrial repair in redo surgery of postinfarction posterior ventricular septal rupture (VSR) was performed after an infarct exclusion technique through left ventriculotomy incision of the infarcted area. For the infarct lesion, this approach provides excellent results with sufficient closure of the VSR and prevention of the ventricular remodeling for five years. A right atrial approach for postinfarction posterior VSR is very useful for avoiding any further ventriculotomy in an already impaired ventricle, securing a stable suture, and preserving the left ventricular geometry and function.

DOI： 10.2152/jmi.54.184

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Circulation Society  

Background: In vivo redundancy of pro-inflammatory cytokines results in a vicious cycle of systemic inflammatory response syndrome and low cardiac output syndrome (LOS). The purpose of this study was to elucidate the influence of peritoneal fluid (PF) drainage on cytokine dynamics in vivo and the significance of early induction for infants with LOS. Methods and Results: Seven infants, who underwent early PF drainage to manage LOS after repair of complex heart defects under cardiopulmonary bypass, were enrolled. The serum and PF levels of the pro- and antiinflammatory cytokines, interleukin (IL)-6, -8, -10 and tumor necrosis factor (TNF)-• ,•were measured during the perioperative period. Clinical outcomes were observed simultaneously. There were no cases of early or late death, or infectious complications. Drainage volume of PF peaked just after operation, and decreased completely. The amount of proinflammatory cytokines in the PF increased for 3 days after operation. Of the proinflammatory cytokines in the PF IL-6 increased the earliest and cleared the fastest. The amount of cleared IL-8 and TNF-• •peaked on the 3rd postoperative day and resembled the course of C-reactive protein (CRP). Serum levels of CRP and proinflammatory cytokines in patients with PF drainage decreased significantly more than those without PF drainage. Conclusions: Early initiation of PF drainage is useful in the postoperative critical care of infants with LOS by improving cytokine dynamics in vivo, although there are differences between the severity of patients undergoing PF drainage and those who do not.

DOI： 10.1253/circj.71.941

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CELL PRESS  

Immature CD4 CD8 thymocytes, which are generated in the thymic cortex, are induced upon positive selection to differentiate into mature T lymphocytes and relocate to the thymic medulla. It was recently shown that a chemokine signal via CCR7 is essential for the cortex-to-medulla migration of positively selected thymocytes in the thymus. However, the role of the cortex-to-medulla migration in T cell development and selection has remained unclear. The present study shows that the developmental kinetics and the thymic export of mature thymocytes were undisturbed in adult mice lacking CCR7 or its ligands (CCR7L). The inhibition of sphingosine-1-phosphate-mediated lymphocyte egress from the thymus led to the accumulation of mature thymocytes in the cortex of CCR7- or CCR7L-deficient mice, unlike the accumulation in the medulla of normal mice, thereby suggesting that mature thymocytes may be exported directly from the cortex in the absence of CCR7 signals. However, the thymocytes that were generated in the absence of CCR7 or CCR7L were potent in causing autoimmune dacryoadenitis and sialadenitis in mice and were thus incapable of establishing central tolerance to organ-specific antigens. These results indicate that CCR7-mediated cortex-to-medulla migration of thymocytes is essential for establishing central tolerance rather than for supporting the maturation or export of thymocytes. ©2006 Elsevier Inc. + +

DOI： 10.1016/j.immuni.2005.12.011

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Fatty acid cyclooxygenase-2 (COX-2) is induced by various hormones, cytokines, and prostaglandins (PGs) in a mouse osteoblastic cell line MC3T3-E1. The induction of the enzyme is suppressed by glucocorticoid. Recently we found a rapid and transient increase of COX activity by tumor necrosis factor a (TNFa) which was attributed to the induction of COX-2 rather than COX-1 on the basis of COX-2 specific inhibitor and Western and Northern blottings. Transcription factors presumably involved in the COX-2 induction were investigated. The 5'-flanking region of mouse COX-2 gene was cloned, and shown by luciferase analyses to include two positive regions with NFKB and NF-IL6 elements. Point mutations of these elements and gel shift assays suggested a potential role of both NFKB and NF-IL6 in the TNFa-dependent induction of COX-2 in MC3T3-E1 cells. When the cells were treated with dexamethasone (DEX), the TNFa-dependent COX activity was decreased in a dose-dependent manner. Induction of COX-2 protein and mRNA was suppressed by DEX. We are now investigating if other transcription factors in addition to NFKB and NF-IL6 are also involved in the COX-2 induction and how these transcription factors are related to the function of DEX.

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Language：Japanese   Publisher：血管外科症例検討会  

骨軟骨腫は頻度の高い良性骨腫瘍であるが時に悪性転化することもある。その骨腫頭による動脈破裂や形成された動脈瘤からの塞栓症、圧迫による深部静脈血栓症、神経障害を来す可能性があり、発見次第早期の手術が必要である。経験した症例は38歳男性。2ヵ月前からの左膝窩部から下腿後面の疼痛を主訴に来院した。CTにて骨軟骨腫および同部位の左膝窩動脈瘤と診断した。手術は、体位を腹臥位とし、後方アプローチを行った。まず軟骨腫を切除した後に膝窩動脈瘤を切除し、8mmリング付きePTFEグラフト(PROPATEN)を用い人工血管置換術を施行した。採取した動脈瘤は病理所見で真性動脈瘤であり骨軟骨腫の圧迫により形成されたと思われた。今回骨・血管同時手術を施行し、良好な結果が得られたので文献的考察を加えて報告する。(著者抄録)

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Language：Japanese   Publisher：(一社)日本人工臓器学会  

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Language：Japanese   Publisher：(NPO)日本心臓血管外科学会  

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Language：Japanese   Publisher：日本バイオマテリアル学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本集中治療医学会  

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Other Link： http://search.jamas.or.jp/link/ui/2018245847

Language：Japanese   Publisher：(NPO)日本心臓血管外科学会  

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Language：Japanese   Publisher：(一社)日本脈管学会  

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Language：Japanese   Publisher：(一社)日本脈管学会  

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Language：Japanese   Publisher：(一社)日本救急医学会  

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Language：Japanese   Publisher：(公社)日本医学放射線学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：MOSBY-ELSEVIER  

DOI： 10.1016/j.jvs.2017.03.072

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Language：Japanese   Publisher：(NPO)日本血管外科学会  

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：徳島医学会  

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Language：Japanese   Publisher：The Medical Association of Nippon Medical School  

<p>Over 190,000 patients die each year in japan due to ischemic heart disease. For these patients, percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) are done to improve the blood flow of coronary artery with stenosis. It would be better to prevent or mitigate the progress of atherosclerosis in these patients before requiring surgery. Recently, it has been reported that epicardial adipose tissue plays an important role in the progression of atherosclerosis and ischemic heart disease.</p><p>This review shows the recent trends about ischemic heart disease from the clinical perspective, including its' treatment, pathology and preventive measure. </p>

DOI： 10.1272/manms.13.210

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Other Link： http://search.jamas.or.jp/link/ui/2018120102

Language：Japanese   Publisher：Japanese Society of Phlebology  

<p>Therapeutic management of huge arteriovenous malformation (AVM) of the neck and trunk was described according to our experiences. Four patients with AVM were evaluated in this study. Case 1 was of a 24-year-old woman with a huge AVM of the neck who had cardiac failure and syncope. She underwent total resection of the AVM along with the right internal jugular vein, right subclavian artery and vein, right clavicle, right first rib and right hemi-manubrium of the sternum after embolization of the arteries. No recurrence was observed during 7 years after surgery. Case 2 was of a 32-year-old woman with a huge AVM of the neck and back with local pain, bleeding and heat sensation. She underwent sclerotherapy with ethanol. The AVM grew gradually in spite of temporary relief of the symptoms. The remaining two patients were 61 and 55-year-old men with pelvic AVM. They were observed without any treatments for AVM because no symptoms were found except for temporary hematuria. Our results suggested that a complete resection was preferable for symptomatic AVM after appropriate embolization to avoid the progressive deterioration of quality of life. The strategy to manage AVM should be planned by considering pathologies, especially those involving the structures of AVMs, symptoms and patient characteristics.</p>

DOI： 10.7134/phlebol.17-06

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Language：Japanese   Publisher：福田記念医療技術振興財団  

東大病院で2007〜2014年にCAVI検査が行われた18歳未満の患者130例を対象とし、心構造が正常な群、左右短絡疾患群、左心系閉塞性疾患群、右心系閉塞性疾患群、大血管転換群、単心室循環群に分け、CAVI値を群間比較した。結果、心構造が正常な群に比べて右心系閉塞性疾患群は有意な低値を示し、大血管転換群と単心室循環群は低値の傾向を示した。心構造が正常な群のみを対象とし、年齢とCAVI値との関連性について検討した結果、正相関が認められた。

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Other Link： http://search.jamas.or.jp/link/ui/2018145512

Language：Japanese   Publisher：(一社)日本救急医学会  

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Language：Japanese   Publisher：日本心脈管作動物質学会  

組織工学(TE)を用いた生体分解性人工血管(TEVG)の利点には、再生後に血管としての生理学的特性が期待できる、小児患児では身体的な成長に伴い生物学的成長が期待できる、傷害時の自己修復機転が期待できるなどがある。心臓・血管外科領域における生体分解性素材を用いた血管再生医療の現況について、以下の項目に分けて述べた。1)TEを用いた血管再生医療の構成、2)TEVGの臨床応用、3)再生血管における組織形成のメカニズム、4)小口径動脈でのTEVG、とした。

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Language：Japanese   Publisher：日本胸部外科学会-関東甲信越地方会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER IRELAND LTD  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J00349&link_issn=&doc_id=20140324040005&doc_link_id=40020027061&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F40020027061&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Language：Japanese   Publisher：(公社)日本栄養・食糧学会  

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Language：Japanese   Publisher：Japan Heart Foundation  

経静脈ペースメーカリードの前尖穿通により, 遠隔期に三尖弁の動きが障害され, 重症三尖弁逆流 (tricuspid regurgitation ; TR) をきたして手術した1例を経験したので報告する. 症例は, 83歳, 女性. 10年前に洞不全症候群にて経静脈的ペースメーカ植え込み術が施行された. 1年前より顔面浮腫と労作時呼吸困難が出現した. 経食道3D心エコー検査で, 三尖弁前尖を穿通する経静脈リードが弁尖の可動性を著明に制限しているために重症TRを生じていると診断した. 手術所見では, リードが前尖中央の弁腹を貫通し, 前乳頭筋と一体となって棍棒状に肥厚した線維束となり, 前尖中央に直接癒着し著明に弁機能を障害していた. 穿通したリードと傷んだ弁尖組織を可及的に切除し, 前尖を自己心膜で補填, 拡大し, DeVega法による弁輪縫縮術を施行し, ペースメーカを心筋リードに切り替えた. 術後しばらくは自覚症状の改善を認めたが, 1年後に再度TRの増悪をきたし三尖弁の生体弁置換術を施行した. 本例のように前尖を穿通する症例は極めて稀だが, ペースメーカ植え込み術時あるいは留置後早期に3D心エコーで経静脈リードの走行と三尖弁の形態と機能についてルーチンに精査しておくことが望ましい.

DOI： 10.11281/shinzo.46.378

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：JAPANESE PHARMACOLOGICAL SOC  

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Language：Japanese   Publisher：血管外科症例検討会  

症例は69歳、男性。遠位弓部大動脈瘤に対する弓部全置換術を施行し順調に経過していたが、5年後に近傍の肺炎を契機に縦隔炎を発症した。縦隔洗浄とdebridementを施行後、約2ヵ月にわたり人工呼吸管理下に胸骨解放下の持続洗浄と頻回の縦隔洗浄、debridementをベッドサイドにて施行した。炎症反応の改善後に人工血管露出部の被覆目的に陰圧閉鎖療法を行い、周囲肉芽増生後の第68病日に縦隔debridementと大胸筋充填を施行し軽快した。(著者抄録)

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

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Language：Japanese   Publisher：(株)医学出版  

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Language：Japanese   Publisher：(NPO)日本小児循環器学会  

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Language：Japanese   Publisher：(NPO)日本小児循環器学会  

J-GLOBAL

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Language：Japanese   Publisher：(NPO)日本血管外科学会  

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Language：Japanese   Publisher：(NPO)日本血管外科学会  

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Language：Japanese   Publisher：(NPO)日本心臓血管外科学会  

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Language：Japanese   Publisher：(NPO)日本心臓血管外科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese  

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本肥満学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

Web of Science

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Language：Japanese  

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

Web of Science

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Language：Japanese  

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Language：Japanese   Publisher：(NPO)日本血管外科学会  

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Language：Japanese   Publisher：(NPO)日本血管外科学会  

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Language：Japanese   Publisher：日本静脈学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Books

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Language：Japanese   Publisher：(NPO)日本心臓血管外科学会  

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Language：Japanese   Publisher：(NPO)日本心臓血管外科学会  

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Language：Japanese   Publisher：(NPO)日本心臓血管外科学会  

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Language：Japanese   Publisher：(NPO)日本心臓血管外科学会  

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Language：Japanese   Publisher：The Japanese Society for Cardiovascular Surgery  

A 69-year-old woman had syncope and aphasia. Magnetic resonance imaging showed multiple cerebral infarctions in both hemispheres. Cardiogenic embolisms were suspected, but no arrhythmic causes were shown. Transesophageal echocardiography revealed a highly calcified mitral annulus (MAC) with a rough intraluminal surface and mild mitral regurgitation, but no thrombus or tumor in the left heart system. However, recurrent multiple cerebral embolisms occurred in spite of strict anticoagulation therapy. We speculated that spontaneous rupture of the MAC was the cause of the scattered cerebral embolisms, and we therefore planned to remove the MAC as safely as possible and to endothelialize the deficit of MAC with autologous pericardium. Operative findings revealed that the MAC in P2-P3 had ruptured longitudinally and the ostium of the left atrium was connected to the ostium of the left ventricle as an inter-atrioventricular tunnel beneath the posterior mitral annulus with a fragile calcified wall. The finding suggested that calcified particles that had peeled away from the MAC by normal heart beating resulted in the cerebral infarctions. Therefore, she underwent resection of the MAC and mitral valve replacement with reinforcement of the decalcified posterior mitral annulus between the posterior left ventricular wall and the left atrial wall using autologous pericardium, which enabled both appropriate insertion of a mechanical prosthetic valve and endothelial continuity covering the surface of the residual MAC. No systemic embolism has occurred for two and a half years after surgery. This is the first case report of cerebral embolism caused by a spontaneously ruptured MAC.

DOI： 10.4326/jjcvs.41.299

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Language：Japanese   Publisher：(株)ライフ・サイエンス  

徳島県内の医療機関20施設から外来通院中の高血圧患者117例を多施設共同研究であるUNICORN研究(UNisia Improving conCORdance and Normotension study)に登録した。117例中92例(78.6%)はカンデサルタンまたは他のアンジオテンシンII受容体拮抗薬(ARB)をベースにした降圧療法が施行され、94例(80.3%)にカルシウム拮抗薬が併用されていた。服用中の降圧薬の数は平均1.70±0.61剤であった。これら117例を対象とし、従来療法からカンデサルタン8mgとアムロジピン2.5mg/5mgを含有する配合錠ユニシアLD/HDに切り替えた際の実地診療下における降圧効果を最大12週間にわたり検討した。収縮期血圧、拡張期血圧の推移は、それぞれ145.1mmHgから134.8mmHgへ、79.1mmHgから74.1mmHgへと有意な低下を認めた。降圧目標達成率は、若年者・中年者(<130/85mmHg)で24.2%から48.5%へ、高齢者(<140/90mmHg)で33.1%から55.6%へ、それぞれ有意な改善を認めた。さらに、カンデサルタン8mgとアムロジピン5mgの併用例を対象とし、同一用量が配合されているユニシアHDに切り替えたところ、収縮期血圧は136.7mmHgから131.3mmHgへと有意な低下を示した。2剤が1剤になり、服薬コンコーダンスが改善した結果と推察された。配合錠へ切り替えることによって、降圧薬を2剤以上服用する患者の割合は65.0%から10.3%へ、服用薬剤数は1.70±0.61剤から1.12±0.40剤へ、それぞれ有意な減少を認めた。また、配合錠に関して患者に実施したアンケート調査によると、75%の患者が飲み忘れが減ったと回答し、58%の患者が負担額が減りメリットを感じたと回答した。以上より、降圧薬2剤を配合錠1剤に変更するだけで、血圧コントロールのみならず、費用面に関してもより大きなメリットを生じることが示唆された。(著者抄録)

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Language：Japanese   Publisher：(一社)日本体外循環技術医学会編集委員会  

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Language：Japanese   Publisher：(株)メディカルレビュー社  

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Language：Japanese   Publisher：(NPO)日本血管外科学会  

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Language：Japanese   Publisher：(NPO)日本血管外科学会  

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Language：Japanese   Publisher：(一社)日本肥満学会  

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Language：Japanese   Publisher：(一社)日本脈管学会  

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Language：Japanese   Publisher：(一社)日本肥満学会  

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Language：Japanese   Publisher：(一社)日本脈管学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER IRELAND LTD  

Web of Science

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(NPO)日本血管外科学会  

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Language：Japanese   Publisher：(NPO)日本血管外科学会  

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Language：Japanese   Publisher：(NPO)日本血管外科学会  

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Language：Japanese   Publisher：(NPO)日本血管外科学会  

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Language：Japanese   Publisher：(NPO)日本血管外科学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：徳島医学会  

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Language：Japanese   Publisher：(NPO)日本血管外科学会  

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Language：English  

DOI： 10.1007/s11748-010-0711-y

PubMed

CiNii Books

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Language：English  

DOI： 10.1007/s11748-010-0654-3

CiNii Books

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Language：Japanese   Publisher：(NPO)日本心臓血管外科学会  

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Language：Japanese   Publisher：(NPO)日本心臓血管外科学会  

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Language：Japanese   Publisher：日本心脈管作動物質学会  

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Language：Japanese   Publisher：日本心脈管作動物質学会  

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Language：Japanese   Publisher：The Japanese Society for Cardiovascular Surgery  

A 24-year-old woman underwent successful repair of a traumatic pseudoaneurysm of the aortic isthmus concomitant with right diaphragmatic hernia which developed after a traffic accident, and the steering wheel of the crashed car was considered responsible for both lesions. Due to the right diaphragmatic hernia, she could breathe mainly with the left lung only. The aortic isthmus aneurysm was considered to be a pseudoaneurysm, and because of the potential risk of rupture, we performed urgent aortic surgery. Prior to a left thoracotomy, we anastomosed an 8-mm prosthetic graft to the right axillary artery. When the left lung was collapsed in order to perform a femoro-femoral bypass, the SpO₂ level of her right index finger and her cerebral rSO₂ markedly decreased. Therefore, we administered additional perfusion via the right axillary artery, which provided sufficient oxygen to the upper body and brain. The patient underwent Marlex mesh reinforcement of the right diaphragmatic hernia 30 days after grafting, and is doing well 1 year postoperatively.

DOI： 10.4326/jjcvs.40.94

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J01122&link_issn=&doc_id=20110601170004&doc_link_id=20110601170005&url=http%3A%2F%2Fsearch.jamas.or.jp%2Flink%2Fbc%2F20110601170005&type=jamaslink&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F99999_1.gif

Language：Japanese  

J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：(株)南江堂  

開放気管切開孔または永久気管切開孔を有する症例での大動脈基部〜弓部の大動脈治療2例を報告し、その問題点とアプローチの工夫について考察した。症例1は41歳男で、慢性Stanford A型大動脈解離を伴う重症大動脈弁閉鎖不全症と診断され、術前画像で心臓の右方偏位と反時計方向回転を確認できたため、逆L字型アプローチによるBentall手術を行った。症例2は76歳女で、急速に拡大する胸部大動脈瘤に対し、検査結果および永久気管切開孔と手術創の位置関係を検討してcram shellアプローチによる上行弓部置換術を行った。いずれも術後縦隔炎などの合併症なく良好に経過した。個々の症例で術前の画像診断から解剖学的位置関係を正確に把握して適切なアプローチ法を考慮すべきであり、特にcram shellアプローチは大動脈基部〜弓部大動脈手術では推奨できるアプローチ法である。

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2010&ichushi_jid=J00349&link_issn=&doc_id=20101125080003&doc_link_id=40017389643&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F40017389643&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Language：Japanese   Publisher：徳島医学会  

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Language：Japanese   Publisher：(NPO)日本血管外科学会  

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Language：Japanese   Publisher：(一社)日本脈管学会  

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Language：Japanese   Publisher：徳島医学会  

Accumulating evidence suggests that inflammatory cytokines secreted from visceral fat tissues potentially promote atherosclerosis progression. Recent reports suggested that pioglitazone, which is an anti-diabetes drug, reduces expression of tumor necrosis factor（TNF）‐α and ameliorates insulin-resistance in diabetic mice. Pioglitazone was also reported to suppress progression of coronary atherosclerosis. The objective of this study is to assess the effect of pioglitazone on inflammatory changes in abdominal aortic aneurysms（AAAs）. This study protocol was approved by the medical ethics committee in Tokushima University Hospital. Patients with AAA were randomized into two groups. One was with pioglitazone（Group P）. The other was without pioglitazone（Group C）. Biopsy specimens were obtained from the abdominal subcutaneous fat, the greater omentum, the retroperitoneal periaortic fat and the aneurysmal wall. Immunohistochemistry of CD ６８in those specimens was performed. The number of macrophages in Group P was lower than that in Group C. Expressions of inflammatory cytokines in those specimens were evaluated by real-time quantitative reverse transcription-polymerase chain reaction analysis. Expression of inflammatory cytokines in Group P were reduced, when compaird with those in Group C. Our data may suggest that pioglitazone reduce inflammatory changes in human aortic aneurysm.

CiNii Books

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Language：Japanese   Publisher：徳島医学会  

Virchow triad（（１）blood stasis（, ２）changes in the vessel wall, and（３）hypercoagulability）are the major factors responsible for the development of venous thrombosis. This venous thrombosis leads to the pathogenesis of acute pulmonary thrombo-embolism which is known as"Economy Class Syndrome". A series of pathogenesis is widely recognized as"Venous thrombo-embolism syndrome". This syndrome occurs suddenly, and occasionally leads to fatal event. So the basic principle of treatment for this syndrome is to prevent deep vein thrombosis（DVT）. The prevention consists of three crucial treatments. Firstly, to recognize high-risk patients of DVT is initial step. Secondary, anticoagulation, elastic stocking and foot pump are well established treatments. Thirdly, venous filter is applicable for the most highest-risk patients. In this review, we would like to introduce the latest knowledge for"Venous thrombo-embolism syndrome".

CiNii Books

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Other Link： http://repo.lib.tokushima-u.ac.jp/110319

Language：Japanese  

The treatment of Aortic aneurythm is shifting stent graft treatment from open Surgery. Stent graft treatment is useful for the treatment of thoracic aortic aneurythm if the form is adaptable for the stent graft treatment. Open surgery is useful for the treatment of abdominal aortic aneurythm if the patient have no complication and high operative lisk but if the patint have complication and high operative lisk, Stent graft treatment is very useful because of the quality of life is kept

CiNii Books

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Other Link： http://repo.lib.tokushima-u.ac.jp/110318

Language：English   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(一社)日本医学教育学会  

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Language：Japanese   Publisher：(NPO)日本小児循環器学会  

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Language：English   Publisher：(NPO)日本小児循環器学会  

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Language：Japanese   Publisher：(NPO)日本小児循環器学会  

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Language：Japanese   Publisher：日本静脈学会  

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Language：Japanese   Publisher：日本静脈学会  

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Language：Japanese   Publisher：徳島医学会  

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Language：Japanese   Publisher：徳島医学会  

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Language：Japanese   Publisher：徳島医学会  

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Language：Japanese   Publisher：(NPO)日本血管外科学会  

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Language：Japanese   Publisher：(NPO)日本血管外科学会  

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Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Books

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Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Books

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Language：Japanese   Publisher：(NPO)日本心臓血管外科学会  

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Language：Japanese   Publisher：The Japanese Society for Cardiovascular Surgery  

A 48-year-old man with Buerger disease and intractable finger ulcers underwent successful transplantation of autologous peripheral blood-derived mononuclear cells pretreated with erythropoietin and blood donation to activate bone marrow function. Clinical symptoms on his finger ulcers improved significantly within 1 month after mononuclear cell transplantation, however, one of the intractable ulcers reappeared 2 months later. In total three transplantations were performed. Every cell transplantation revealed similar effectiveness 1 month later, and the interval of the subsequent disappearance of finger ulcers ranged from 3&ndash;6 months. There were no adverse effects based on this new therapy. These findings suggest that autologous peripheral mononuclear cell transplantation pretreated with erythropoietin and blood donation might be a non-invasive and safe alternatives for patients with Buerger disease and intractable finger ulcers.

DOI： 10.4326/jjcvs.39.29

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Language：Japanese   Publisher：徳島医学会  

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Language：Japanese   Publisher：(NPO)日本血管外科学会  

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Language：Japanese   Publisher：(NPO)日本血管外科学会  

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Language：Japanese  

J-GLOBAL

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