Faculty Profiles - MUTSUGA Masato

金型使用による自己心膜のglutaraldehyde処理を行った弓部パッチによるNorwood手術

櫻井一, 阿部知伸, 櫻井寛久, 杉浦純也, 寺田貴史, 種市哲吉, 六鹿雅登

日本心臓血管外科学会雑誌 Vol. 42 ( Suppl. ) page： 215 - 215 2013.2

[Recurrence of cardiac myxoma in the left atrial after 28 years; report of a case].

Takanohashi A, Usui A, Mutsuga M, Tokuda Y, Araki Y, Narita Y, Oshima H, Ueda Y

Kyobu geka. The Japanese journal of thoracic surgery Vol. 65 ( 12 ) page： 1089 - 92 2012.11

Fast-track extubation after modified Fontan procedure Reviewed

Masato Mutsuga, Luis G. Quinonez, Andrew S. Mackie, Colleen M. Norris, B. Elaine Marchak, Jennifer M. Rutledge, Ivan M. Rebeyka, David B. Ross

JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Vol. 144 ( 3 ) page： 547 - 52 2012.9

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

Objective: In 2007, we introduced a policy to plan to extubate all patients after a modified Fontan procedure in the operating room. Our objective was to review the feasibility, safety, and clinical outcomes of this approach.
Methods: Patients who underwent a modified Fontan operation between May 2004 and May 2010 were reviewed.
Results: Ninety-seven patients underwent a modified Fontan operation (mean age, 3.9 +/- 2.2 years; mean weight, 15.1 +/- 5.0 kg); 46 patients (47%) were extubated in the operating room (group A). Nineteen patients were extubated in the intensive care unit within 24 hours (group B), and 32 patients had delayed extubation (group C). The 3 groups were not significantly different with respect to preoperative characteristics. Twenty-four hours postoperatively, group A had a lower mean central venous pressure compared with patients in group B or C (13 vs 14 vs 17 mm Hg, respectively, P <. 001); a higher base excess (0.4 vs -1.3 vs -3.4, P <. 001); a lower fluid balance (234 vs 514 vs 730 mL, P <. 001); and a lower inotrope score (4.6 vs 6.7 vs 10.8, P <. 001). Group C had a longer median intensive care unit length of stay (2 vs 3 vs 6 nights, P = .01), kept their chest tubes longer (8 vs 9 vs 15 days, P = .001), and had a longer median hospital length of stay (9 vs 11 vs 21 days, P = .001).
Conclusions: Extubation in the operating room after a modified Fontan procedure seems feasible. This approach is associated with improved early postoperative hemodynamics, earlier time to chest tube removal, and shorter intensive care unit and hospital lengths of stay. (J Thorac Cardiovasc Surg 2012; 144:547-52)

DOI： 10.1016/j.jtcvs.2012.05.047

Biodegradable nanofibers in cardiovascular medicine: Drug delivery application

The Clinical Outcomes of Prolonged Donor Ischemic Time in Adult Patients Undergoing Heart Transplantation. A Single Center Experiences in Canada

Mutsuga M., Wang S., MacArthur R., Mullen J., Modry D., Ross D., Meyer S.

JOURNAL OF HEART AND LUNG TRANSPLANTATION Vol. 31 ( 4 ) page： S93 - S94 2012.4

Masato Mutsuga, Aika Yamawaki-Ogata, Makoto Satake, Hiroaki Kaneko, Yuichi Ueda, Yuji Narita

Nanomedicine and the Cardiovascular System page： 345 - 369 2011.1

Language：English Publishing type：Part of collection (book) Publisher：CRC Press

Nanotechnology will play a great role in the field of cardiovascular disease in the near future. It will be a very useful tool in drug delivery approaches to treat cardiovascular disease. Nanomedicine (medical treatment using nanotechnology) can be considered a refinement of molecular medicine and integrates advances in genomics and proteomics to facilitate the development of personalized medicine. Nanomedicine for cardiovascular disease has focused on materials at super-molecular levels to deliver increased therapeutic efficacy and diminish adverse effects, which have ultimately resulted in their clinical application. All the aforementioned developments have revolutionized the application of nanotechnologies and have led to improved understanding of the possibilities for drug delivery to diseased tissues and organs. In this chapter we introduce a novel drug delivery system (DDS) using biodegradable nano-scaled fiber for use in cardiovascular medicine. Occasionally, systemic administration of the drug for cardiovascular diseases not only fails to work sufficiently, but also causes adverse side effects due to the limited effective threshold of the drug. Therefore, these medicines may need to be released locally and gradually. Our newly developed DDS applied biodegradable polymer mixed with a drug used for surgical treatment of cardiovascular diseases, to achieve sustained release. The mechanisms of sustained release of a drug are quite simple
the drug is released with diffusion, hydrolysis of the biodegradable polymer and/or degradation of polymer by enzymatic or phagocytotic effects in vivo. An electrospinning procedure is used to fabricate the nanofiber configurations for these materials. In this chapter, we review the DDS scaffold using electrospinning nanofiber technology, and also highlight our recent results using our new DDS with biodegradable nano-scaled fiber for cardiovascular diseases to prevent anastomotic stricture and treat aortic aneurysm.

Spinal cord protection during a thoracoabdominal aortic repair for a chronic type B aortic dissection using the aortic tailoring strategy Reviewed

Masato Mutsuga, Yuji Narita, Yoshimori Araki, Atsuo Maekawa, Hideki Oshima, Akihiko Usui, Yuichi Ueda

INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY Vol. 11 ( 1 ) page： 15 - 18 2010.7

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

This study evaluated the clinical advantage of a novel technique to reconstruct a true lumen with aortic wall tailoring for aortic repair (aortic tailoring) or the reimplantation of intercostal arteries (vascular tube) in a chronic type B aortic dissection. Thirty-three consecutive extended thoracoabdominal aortic repairs have been performed for chronic type B dissection since 2000. The novel strategy was applied in 17 cases since 2004 including eight cases of aortic repair (group A) and nine cases of a vascular tube (group B). The other 16 cases were graft interposition in five and no reimplantation in 11 for group C. There were no surgical deaths in either group A or B, and only one late death in group C. No patients sustained transient or permanent paraplegia in group A and B, while three cases of paraplegia occurred in group C (18.8%). All of the intercostal arteries were well preserved in group A and an average of 9.8 intercostal arteries for nine patients were reimplantated in group B. The present technique can optimally preserve the intercostal arteries maximally and showed an excellent surgical mortality and morbidity, especially with regard to the protection of the spinal cord. (C) 2010 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.

DOI： 10.1510/icvts.2009.223099

Effects of Extracellular Matrix on Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells into Smooth Muscle Cell Lineage: Utility for Cardiovascular Tissue Engineering Reviewed

Shuichi Suzuki, Yuji Narita, Aika Yamawaki, Yosuke Murase, Makoto Satake, Masato Mutsuga, Hideki Okamoto, Hideaki Kagami, Minoru Ueda, Yuichi Ueda

CELLS TISSUES ORGANS Vol. 191 ( 4 ) page： 269 - 280 2010

Publishing type：Research paper (scientific journal) Publisher：KARGER

Background: Bone marrow-derived mesenchymal stem cells (MSCs) can differentiate into various types of cell, and the extracellular matrix (ECM) is acknowledged to be important for the regulation of cell functions. In this study, we demonstrated the effects of ECMs on the differentiation of human bone marrow-derived MSCs into a smooth muscle cell (SMC) lineage. Methods: Human MSCs (hMSCs) were cultured on dishes coated with 3 types of ECM including laminin (LM), collagen type IV (Col-IV) and fibronectin for 7 days, and simultaneously cultured on a noncoated dish as a control. Cell numbers of these cultured hMSCs were counted, and their expression of SMC-specific genes and proteins was evaluated. hMSCs were then seeded on LM-coated biodegradable sheets and implanted into rat subcutaneous space. After 2 weeks of implantation, these tissues were evaluated. Results: The number of hMSCs was significantly increased by culture on Col-IV-coated dishes. The expression of SMC-specific genes and proteins (alpha-smooth muscle actin, ASMA; h1-calponin, CALP) in hMSC was significantly upregulated from culture on LM-coated dishes. LM-coated sheets showed
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a significantly increased expression of ASMA and CALP protein in vivo. Moreover, a fully differentiated marker (SM2) was expressed in the in vivo implanted hMSCs in the course of 2 weeks on the LM-coated sheet. Conclusion: These results suggest that the signal transduction of the cell-matrix interaction for the differentiation of hMSCs into SMCs was activated when cultured with LM. LM-coated materials may thus be useful for cardiovascular tissue engineering. Copyright (C) 2009 S. Karger AG, Basel

DOI： 10.1159/000260061

Institutional report - Congenital development of novel drug-eluting biodegradable nano-fiber for prevention of postoperative pulmonary venous obstruction Reviewed

Masato Mutsuga, Yuji Narita, Aika Yamawaki, Makoto Satake, Hiroaki Kaneko, Akihiko Usui, Yuichi Ueda

Interactive Cardiovascular and Thoracic Surgery Vol. 8 ( 4 ) page： 402 - 6; discussion 406 2009.4

Publishing type：Research paper (international conference proceedings)

Pulmonary venous obstruction (PVO) after correction of total anomalous pulmonary venous connection (TAPVC) frequently occurs due to intimal-hyperplasia and the required re-operation. We have developed a novel sustained-release drug delivery system, using Tacrolimuseluting biodegradable nano-fiber (TEBN). It consists of nano-scale fiber composed of biodegradable polymer and Tacrolimus. This study evaluated the effects of TEBN for prevention of venous anastomotic stricture in a rat model to apply to PVO operation. Tacrolimus was incorporated into poly (L-lactide-co-glycolide). The venous stricture model was made by rat inferior vena cava anastomosis. The IVC anastomosis was covered with TEBN with 1.0 wt% Tacrolimus (n=12) or without TEBN as a control (n=12), and evaluated histologically at 1, 2, and 4 weeks after operation. The ratio of intimal area was significantly reduced in the TEBN group compared with the control group (ratio
1 week: 0.43 ± 0.26 vs. 0.07 ± 0.04, P=0.04, 2 weeks: 0.39 ± 0.19 vs. 0.05 ± 0.02, P=0.01, 4 weeks: 0.31±0.15 vs. 0.09 ± 0.04, P=0.03, control vs. TEBN, respectively). Histological findings showed endothelialization along the inner surface of the vein even in TEBN. The TEBN reduced intimal hyperplasia and preserved endothelialization even in a venous stricture. These results suggested that this strategy might be useful for prevention of recurrent PVO after TAPVC correction. © 2009 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.

DOI： 10.1510/icvts.2008.192831

A new strategy for prevention of anastomotic stricture using tacrolimus-eluting biodegradable nanofiber Reviewed

Masato Mutsuga, Yuji Narita, Aika Yamawaki, Makoto Satake, Hiroaki Kaneko, Yoshihiro Suematsu, Akihiko Usui, Yuichi Ueda

JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Vol. 137 ( 3 ) page： 703 - 709 2009.3

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

Objective: We developed a novel sustained drug-eluting device using tacrolimus-eluting biodegradable nanofiber to prevent anastomotic stricture and evaluated the effects in a rat abdominal aortic anastomosis model.
Methods: In vitro and in vivo tacrolimus release tests for tacrolimus-eluting biodegradable nanofiber were performed to confirm its sustained release. To verify the prevention of anastomotic stricture, tacrolimus-eluting biodegradable nanofiber was placed around the end-to-end anastomosis of abdominal aorta in rats. Five rats were allocated to the following 5 groups: ( 1) control without tacrolimus-eluting biodegradable nanofiber, ( 2) 5 mg of nanofiber only ( 0 wt% of tacrolimus), ( 3) 5 mg of tacrolimus-eluting biodegradable nanofiber containing 0.04 wt% of tacrolimus, ( 4) 5 mg of tacrolimus-eluting biodegradable nanofiber containing 0.1 wt% of tacrolimus, and ( 5) 5 mg of tacrolimus-eluting biodegradable nanofiber containing 1.0 wt% of tacrolimus. Morphometric and histologic analyses including immunohistochemistry were performed in each of the groups 2 weeks after the operation.
Results: The tacrolimus-eluting biodegradable nanofiber gradually released tacrolimus for at least 1 month in vitro and in vivo. The ratio of intimal area was significantly reduced in the 1.0 wt% tacrolimus-eluting biodegradable nanofiber group compared with the other groups (0.26, 0.24, 0.25, 0.21, and 0.08 in control, 0 wt%, 0.04 wt%, 0.1 wt%, and 1.0 wt%, respectively, P <. 05). The cells, which constitute intimal hyperplasia, were positive for smooth muscle actin and SMemb, and factor VIII revealed that endothelial cells covered the surface of the aortic lumen even in the 1.0 wt% tacrolimus-eluting biodegradable nanofiber group in immunohistochemistry.
Conclusion: Tacrolimus-eluting biodegradable nanofiber reduced neointimal hyperplasia and preserved endothelialization. This device may be useful in the prevention of anastomotic stricture.

DOI： 10.1016/j.jtcvs.2008.11.017

補助循環・人工肺・体外循環

阿部裕輔, 奥村高広, 岩田英理子, 六鹿雅登, 磯山隆

人工臓器 Vol. 35 ( 2 ) page： S171 - S173 2006

Acute occlusion of left coronary ostium associated with congenital quadricuspid aortic valve Reviewed

M Mutsuga, S Tamaki, Y Yokoyama, N Kato, J Yokote, N Ohata

ANNALS OF THORACIC SURGERY Vol. 79 ( 5 ) page： 1760 - 1 2005.5

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

A 10-year-old girl suffered from chest discomfort during exercise. She experienced an acute myocardial infarction accompanied by an obstruction in an orifice to the left coronary artery. An emergency operation revealed that the aortic valve was quadricuspid, and a left-sided small cusp had adhered to the aortic wall resulting in an unusual sac with a tiny slit. Resection of the sac disclosed the ostium to left coronary artery. Blood toward the left coronary artery passed through the tiny slit. The mechanisms of obstruction in the coronary artery were uncertain. She recovered well after the aortic valve replacement with resection of the aortic cusps. (c) 2005 by The Society of Thoracic Surgeons.

DOI： 10.1016/j.athoracsur.2003.11.052

Pseudoaneurysm from the Mitral-Aortic Intervalvular Fibrosa Following Endocarditis Reviewed

Yukifusa Yokoyama, Shuji Tamaki, Noriyuki Kato, Jun Yokote, Masato Mutsuga

Japanese Journal of Thoracic and Cardiovascular Surgery Vol. 51 ( 8 ) page： 374 - 7 2003.8

Publishing type：Research paper (international conference proceedings) Publisher：Japanese Association for Thoracic Surgery

A rare case of a pseudoaneurysm from the mitral-aortic intervalvular fibrosa following bacterial endocarditis in a 17-year-old male is presented. Destructive infection secondarily involved the mitral-aortic intervalvular fibrosa. Perforation of this portion resulted in the formation of the pseudoaneurysm situated at the base of the left ventricle between the aorta and the left atrium. With echocardiography, computed topography, angiography, and magnetic resonance imaging (MRI), a pseudoaneurysm was diagnosed. MRI especially revealed detailed information and the extension of pseudoaneurysm. Our patient underwent resection of the pseudoaneurysm, reconstruction of left ventricular outflow with glutaraldehyde-preserved bovine pericardium, and replacement of the aortic valve. His postoperative course was uneventful. No recurrence of endocarditis was detected in the following year.

DOI： 10.1007/BF02719470

新生児・乳児の人工心肺に対する血液浄化法の工夫充填血液に対するSingle Pass HDF及び持続的HDFの効果

小山富生, 玉木修治, 横山幸房, 加藤紀之, 横手淳, 六鹿雅登

The Japanese Journal of THORACIC AND CARDIOVASCULAR SURGERY Vol. 50 ( Suppl. ) page： 283 - 283 2002.9

PCPS長期補助例における血液浄化の有用性

横山幸房, 玉木修治, 伊藤正夫, 加藤紀之, 横手淳, 六鹿雅登, 岡田正穂, 小山富生, 山田哲也, 片山浩司

ICUとCCU Vol. 25 ( 12 ) page： 974 - 975 2001.12

Right atrial myxoma associated with atrial septal defect: a case report and review of the literature Reviewed

H Murayama, S Tamaki, N Kato, N Yuji, J Yokote, M Mutsuga, M Okada

Ann Thorac Cardiovasc Surg Vol. 7 ( 3 ) page： 166 - 169 2001.6

Repair of intercostal arteries in thoracoabdominal aneurysm Reviewed

Y. Yokoyama, S. Tamaki, M. Ito, N. Kato, J. Yokote, M. Mutsuga, M. Okada

Asian Cardiovascular and Thoracic Annals Vol. 9 ( 3 ) page： 221 - 222 2001

Language：English Publishing type：Research paper (scientific journal) Publisher：Asia Publishing Exchange Pte Ltd

A parallel aortic graft composed of a 20-mm graft with two 10-mm accessory grafts was used in the repair of a large thoracoabdominal aneurysm in a 50-year-old man. The graft was attached to 6 intercostal arteries and used immediately for spinal cord perfusion before repairing the aneurysm. The patient recovered quickly without paraplegia.

DOI： 10.1177/021849230100900315