Researchers Database

kimura naoyuki

    ComprehensiveMedicine2 Professor
Last Updated :2021/12/07

Researcher Information


Research funding number

  • 20382898

J-Global ID

Research Areas

  • Life sciences / Respiratory surgery
  • Life sciences / Cardiovascular surgery

Academic & Professional Experience

  • 2012  Jichi Medical UniversitySchool of Medicine助教

Published Papers

  • Tetsu Ohnuma, Naoyuki Kimura, Yusuke Sasabuchi, Kayo Asaka, Junji Shiotsuka, Tetsuya Komuro, Hideyuki Mouri, Alan T. Lefor, Hideo Adachi, Masamitsu Sanui
    HEART AND VESSELS 30 (3) 355 - 361 0910-8327 2015/05 [Refereed][Not invited]
    Little evidence exists regarding the need for a reduction in postoperative heart rate after repair of type A acute aortic dissection. This single-center retrospective study was conducted to determine if lower heart rate during the early postoperative phase is associated with improved long-term outcomes after surgery for patients with type A acute aortic dissection. We reviewed 434 patients who underwent aortic repair between 1990 and 2011. Based on the average heart rate on postoperative days 1, 3, 5, and 7, 434 patients were divided into four groups, less than 70, 70-79, 80-89, and greater than 90 beats per minute. The mean age was 63.3 +/- 12.1 years. During a median follow-up of 52 months (range 16-102), 10-year survival in all groups was 67 %, and the 10-year aortic event-free rate was 79 %. The probability of survival and being aortic event-free using Kaplan-Meier estimates reveal that there is no significant difference when stratified by heart rate. Cox proportional regression analysis for 10-year mortality shows that significant predictors of mortality are age [Hazard Ratio (HR) 1.04; 95 % confidence interval (CI) 1.07-1.06; p = 0.001] and perioperative stroke (HR 2.30; 95 % CI 1.18-4.50; p = 0.024). Neither stratified heart rate around the time of surgery nor beta-blocker use at the time of discharge was significant. There is no association between stratified heart rate in the perioperative period with long-term outcomes after repair of type A acute aortic dissection. These findings need clarification with further clinical trials.
  • Naoyuki Kimura, Tetsu Ohnuma, Satoshi Itoh, Yusuke Sasabuchi, Kayo Asaka, Junji Shiotsuka, Koichi Adachi, Koich Yuri, Harunobu Matsumoto, Atsushi Yamaguchi, Masamitsu Sanui, Hideo Adachi
    AMERICAN JOURNAL OF CARDIOLOGY 113 (4) 724 - 730 0002-9149 2014/02 [Refereed][Not invited]
    The Penn classification, a risk assessment system for acute type A aortic dissection (AAAD), is based on preoperative ischemic conditions. We investigated whether Penn classes predict outcomes after surgery for AAAD. Three hundred fifty-one patients with DeBakey type I AAAD treated surgically, January 1997 to January 2011, were divided into 4 groups per Penn class: Aa (no ischemia, n = 187), Ab (localized ischemia with branch malperfusion, n = 67), Ac (generalized ischemia with circulatory collapse, n = 46), and Abc (localized and generalized ischemia, n = 51). Early and late outcomes were compared between groups. In-hospital mortality was 3% (6 of 187) for Penn Aa, 6% (4 of 67) for Penn Ab, 17% (8 of 46) for Penn Ac, and 22% (11 of 51) for Penn Abc. Multivariate logistic regression analysis showed Penn classes Ac and Abc, operation time >6 hours, and entry in the descending thoracic aorta to be risk factors for in-hospital mortality. Incidences of neurologic, respiratory, and hepatic complications differed between groups. Five-year cumulative survival was 85% in the Penn Aa group, 74% in the Penn Ab group (p = 0.027 vs Penn Aa), 78% in the Penn Ac group, and 67% in the Penn Abc group (p <0.001 vs Penn Aa). In conclusion, morbidity and mortality are high in patients with generalized ischemia. The Penn classification appears to be a useful risk assessment system for AAAD, predictive of outcomes. (C) 2014 Elsevier Inc. All rights reserved.
  • Hideki Morita, Naoyuki Kimura, Koichi Yuri, Koichi Adachi, Atsushi Yamaguchi, Hideo Adachi
    ANNALS OF THORACIC AND CARDIOVASCULAR SURGERY 20 702 - 704 1341-1098 2014 [Refereed][Not invited]
    Hereditary hemorrhagic telangiectasia (HHT; Osler-Weber-Rendu syndrome) is an uncommon disease characterized by abnormal telangiectasias and arteriovenous malformations that cause recurrent bleeding. Here, we present the case of a patient with HHT, who had a history of pulmonary and hepatic arteriovenous malformations and endocarditis of a prosthetic aortic valve that was caused by methicillin-resistant Staphylococcus aureus. The patient underwent the Bentall operation after coil embolization for pulmonary arteriovenous malformations. The postoperative course was uneventful.
  • Manabu Shiraishi, Atsushi Yamaguchi, Kenichi Muramatsu, Naoyuki Kimura, Koichi Yuri, Harunobu Matsumoto, Kouichi Adachi, Hideo Adachi
    General Thoracic and Cardiovascular Surgery 63 (1) 30 - 37 1863-6713 2014 [Refereed][Not invited]
    Objective: Waffle procedure, a small grid-like incision of epicardium, is a surgical technique for constrictive pericarditis with epicardial thickening. Yet evidences to endorse this approach for improved outcomes are lacking. The aim of this study is to elucidate better surgical treatment strategy for constrictive pericarditis with epicardial thickening. Methods: Twenty-five patients (mean 64.1 years) who underwent pericardiectomy for constrictive pericarditis between January 1992 and July 2012 were included in this study and were classified into two groups according to the procedure they received single total pericardiectomy (Group A, n = 17) and total pericardiectomy with the Waffle procedure (Group B, n = 8). Early and mid-term outcomes were analyzed for each group. Results: No major postoperative complications or all-cause deaths at 30 days were observed in each group. Upon discharge, postoperative echocardiography showed statistically significant increase of left ventricular end-diastolic volume (from 76.6 ± 30.3 to 91.0 ± 27.3 ml p <  0.02) and systolic volume (from 44.4 ± 19.1 to 54.5 ± 17.3 ml p <  0.05) in Group B than those in Group A. The 5-year cardiac event-free rate was similar between groups [83.6 ± 10.8 % for group A and 83.3 ± 15.2 % for group B (p = NS)] as well as the mean value of NYHA classification for each at the mid-term periods (1.5 for Group A and 1.3 for Group B). Conclusion: Waffle procedure improved echocardiographic elements of diastolic function of patients with epicardial thickening more than did total pericardiectomy without additional compromises.
  • Purvesh Khatri, Silke Roedder, Naoyuki Kimura, Katrien De Vusser, Alexander A. Morgan, Yongquan Gong, Michael P. Fischbein, Robert C. Robbins, Maarten Naesens, Atul J. Butte, Minnie M. Sarwal
    JOURNAL OF EXPERIMENTAL MEDICINE 210 (11) 2205 - 2221 0022-1007 2013/10 [Refereed][Not invited]
    Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for nontransplant indications, could regulate specific CRM genes and reduce the number of graft-infiltrating cells during AR. We treated mice with HLA-mismatched mouse cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft-infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatin on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients followed for up to 22 yr. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning, and rational drug design.
  • Atsushi Yamaguchi, Koichi Adachi, Koichi Yuri, Naoyuki Kimura, Chieri Kimura, Atsushi Tamura, Hideo Adachi
    CIRCULATION JOURNAL 77 (6) 1461 - 1465 1346-9843 2013/06 [Refereed][Not invited]
    Background: Ischemic mitral regurgitation (IMR) with ischemic cardiomyopathy (ICM) was treated with surgical procedures, and mitral leaflet tethering was assessed. Twenty-two patients with both ICM (left ventricular ejection fraction <0.35) and IMR (>2) underwent coronary artery bypass grafting (CABG), mitral annuloplasty (MAP) with or without surgical ventricular restoration (SVR) and procedures targeting the subvalvular apparatus. Methods and Results: Fourteen patients (group 1) underwent CABG and MAP, and the remaining 8 (group 2) underwent CABG, MAP, SVR, papillary muscle approximation (PMA), and papillary muscle suspension (PMS). PMA joined the entire papillary muscles with 3 mattress sutures. For PMS, 2 ePTFE sutures were placed between papillary muscle tips and fibrous annuli. Anterior and posterior mitral leaflet tethering angles (ALA and PLA) relative to the line connecting annuli, posterior and apical displacement of coaptation, and IMR grade were measured on echocardiography. Although preoperative ALA and PLA in group 2 were significantly larger than in group 1, there was no significant difference between groups at 1 month after surgery. At 1 year after surgery, however, the situation reversed: ALA and PLA in group 1 were significantly larger than in group 2. Conclusions: In addition to MAP, procedures targeting the subvalvular apparatus including PMA and PMS achieved persistent reduction of mitral valve leaflet tethering, which might lead to the improvement of long-term outcome.
  • Silke Roedder, Naoyuki Kimura, Homare Okamura, Szu-Chuan Hsieh, Yongquan Gong, Minnie M. Sarwal
    PLOS ONE 8 (2) e56657  1932-6203 2013/02 [Refereed][Not invited]
    Despite advanced immunosuppression, redundancy in the molecular diversity of acute rejection (AR) often results in incomplete resolution of the injury response. We present a bioinformatics based approach for identification of these redundant molecular pathways in AR and a drug repositioning approach to suppress these using FDA approved drugs currently available for non-transplant indications. Two independent microarray data-sets from human renal allograft biopsies (n = 101) from patients on majorly Th1/IFN-y immune response targeted immunosuppression, with and without AR, were profiled. Using gene-set analysis across 3305 biological pathways, significant enrichment was found for the IL17 pathway in AR in both data-sets. Recent evidence suggests IL17 pathway as an important escape mechanism when Th1/IFN-y mediated responses are suppressed. As current immunosuppressions do not specifically target the IL17 axis, 7200 molecular compounds were interrogated for FDA approved drugs with specific inhibition of this axis. A combined IL17/IFN-y suppressive role was predicted for the antilipidemic drug Fenofibrate. To assess the immunregulatory action of Fenofibrate, we conducted in-vitro treatment of anti-CD3/CD28 stimulated human peripheral blood cells (PBMC), and, as predicted, Fenofibrate reduced IL17 and IFN-gamma gene expression in stimulated PMBC. In-vivo Fenofibrate treatment of an experimental rodent model of cardiac AR reduced infiltration of total leukocytes, reduced expression of IL17/IFN-y and their pathway related genes in allografts and recipients' spleens, and extended graft survival by 21 days (p < 0.007). In conclusion, this study provides important proof of concept that meta-analyses of genomic data and drug databases can provide new insights into the redundancy of the rejection response and presents an economic methodology to reposition FDA approved drugs in organ transplantation.
  • Naoyuki Kimura, Susumu Nakae, Satoshi Itoh, Denis R. Merk, Xi Wang, Yongquan Gong, Homare Okamura, Paul A. Chang, Hideo Adachi, Robert C. Robbins, Michael P. Fischbein
    ANNALS OF THORACIC SURGERY 2 94 (2) 542 - 548 0003-4975 2012/08 [Refereed][Not invited]
    Background. Although alpha beta T cells are known to participate in the development of acute cardiac allograft rejection, the role of gamma delta T cells remains poorly understood. We hypothesized that gamma delta T cells contribute to acute allograft rejection thru interleukin (IL)-17 production. Methods. Donor hearts from FVB mice (H-2(q)) were heterotopically transplanted into C57BL/6-wild type (WT) and gamma delta T cell-deficient (TCR delta(-/-)) recipient mice (H-2(b)). Overall graft survival was monitored. Graft infiltrating cell profile, including gamma delta T cell subtype, cytokine expression, and myeloperoxidase activity were measured by flow cytometry, TaqMan (Applied Biosystems, Carlsbad, CA) polymerase chain reaction, and myeloperoxidase assay, respectively, on postoperative days 3 and 6. Results. Graft survival was prolonged in TCR delta(-/-) recipients compared with WT controls. Graft infiltrating cells, including CD45(+), CD4(+), CD8(+), and Gr1(+) cells were significantly decreased in TCR delta(-/-) recipients compared with WT. Donor hearts transplanted into TCR delta(-/-) recipients had reduced IL-17 and IL-6 messenger RNA expression. Corroborating the gene expression, intracellular cytokine staining showed decreased IL-17 producing cells in TCR delta(-/-) recipients. Finally, V gamma 1(+) and V gamma 4(+) T cells did not produce IL-17, although both represent 20% to 30% total graft infiltrating gamma delta T cells. Conclusions. The gamma delta T cells promote acute cardiac allograft rejection, presumably by producing IL-17. The gamma delta T cell depletion may prove beneficial in prolonging allograft survival by suppressing IL-17 production. (Ann Thorac Surg 2012;94:542-8) (c) 2012 by The Society of Thoracic Surgeons
  • Masashi Tanaka, Naoyuki Kimura, Atsushi Yamaguchi, Hideo Adachi
    ANNALS OF THORACIC AND CARDIOVASCULAR SURGERY 18 (1) 18 - 23 1341-1098 2012/02 [Refereed][Not invited]
    Background: Our surgical strategies for acute type A aortic dissection (AAAD) are prompt establishment of cardiopulmonary bypass and primary entry resection. We investigated our experience with surgery for AAAD. Methods: Between January 1997 and December 2006, 243 consecutive patients with AAAD underwent emergency surgery. Clinical and diagnostic data of these patients were analyzed retrospectively. Results: Surgical procedures included ascending aorta or hemiarch replacement (n = 212) and total or partial arch replacement (n = 31), and those for proximal reconstruction included modified Bentall procedure (n = 8), and aortic valve replacement (n = 3). Hospital mortality was 6.9%, and entry resection was performed in 74% of patients. Actuarial survival rate at 5 and 10 years was 86% +/- 14% and 77% +/- 23%, respectively. A total of 13 patients required re-operation: 5, an aortic root; 3, an aortic arch; and 5, a descending aorta. Actuarial freedom from re-operation at 5 and 10 years was 95% +/- 5%, and 81% +/- 18%, respectively. Conclusions: Our surgical strategy for AAAD seems to be pertinent with acceptable short- and long-term results. Since we lost 8 patients due to rupture of false lumen postoperatively, careful follow-up for a residual false lumen may improve the patients' prognosis.
  • Denis R. Merk, Jocelyn T. Chin, Benjamin A. Dake, Lars Maegdefessel, Miquell O. Miller, Naoyuki Kimura, Philip S. Tsao, Cristiana Iosef, Gerald J. Berry, Friedrich W. Mohr, Joshua M. Spin, Cristina M. Alvira, Robert C. Robbins, Michael P. Fischbein
    CIRCULATION RESEARCH 110 (2) 312 - + 0009-7330 2012/01 [Refereed][Not invited]
    Rationale: Marfan syndrome (MFS) is a systemic connective tissue disorder notable for the development of aortic root aneurysms and the subsequent life-threatening complications of aortic dissection and rupture. Underlying fibrillin-1 gene mutations cause increased transforming growth factor-beta (TGF-beta) signaling. Although TGF-beta blockade prevents aneurysms in MFS mouse models, the mechanisms through which excessive TGF-beta causes aneurysms remain ill-defined. Objective: We investigated the role of microRNA-29b (miR-29b) in aneurysm formation in MFS. Methods and Results: Using quantitative polymerase chain reaction, we discovered that miR-29b, a microRNA regulating apoptosis and extracellular matrix synthesis/deposition genes, is increased in the ascending aorta of Marfan (Fbn1(C1039G/+)) mice. Increased apoptosis, assessed by increased cleaved caspase-3 and caspase-9, enhanced caspase-3 activity, and decreased levels of the antiapoptotic proteins, Mcl-1 and Bcl-2, were found in the Fbn1(C1039G/+) aorta. Histological evidence of decreased and fragmented elastin was observed exclusively in the Fbn1(C1039G/+) ascending aorta in association with repressed elastin mRNA and increased matrix metalloproteinase-2 expression and activity, both targets of miR-29b. Evidence of decreased activation of nuclear factor kappa B, a repressor of miR-29b, and a factor suppressed by TGF-beta, was also observed in Fbn1(C1039G/+) aorta. Furthermore, administration of a nuclear factor kappa B inhibitor increased miR-29b levels, whereas TGF-beta blockade or losartan effectively decreased miR-29b levels in Fbn1(C1039G/+) mice. Finally, miR-29b blockade by locked nucleic acid antisense oligonucleotides prevented early aneurysm development, aortic wall apoptosis, and extracellular matrix deficiencies. Conclusions: We identify increased miR-29b expression as key to the pathogenesis of early aneurysm development in MFS by regulating aortic wall apoptosis and extracellular matrix abnormalities. (Circ Res. 2012;110:312-324.)
  • Naoyuki Kimura, Satoshi Itoh, Susumu Nakae, Robert C. Axtell, Jeffrey B. Velotta, Ernst Jan Bos, Denis R. Merk, Yongquan Gong, Homare Okamura, Claude M. Nagamine, Hideo Adachi, Hardy Kornfeld, Robert C. Robbins, Michael P. Fischbein
    JOURNAL OF HEART AND LUNG TRANSPLANTATION 30 (12) 1409 - 1417 1053-2498 2011/12 [Refereed][Not invited]
    BACKGROUND: IL-16 promotes the recruitment of various cells expressing CD4; a receptor for IL-16. The precise role of IL-16 in transplant rejection remains unknown; therefore, the present study investigated the contribution of IL-16 to the development of chronic rejection in heart transplants. METHODS: C-H-2(bm12)KhEg (H-2(bm12)) donor hearts were transplanted into (1) IL-16-deficient (IL-16(-/-)) C57BL/6J or (b) wild type (WT) control recipients (MHC class II mismatch). Grafts were harvested at 52 days, parenchymal rejection was assessed by the ISHLT grading system, and CAV was examined morphometrically. Graft infiltrating cells were detected 10 and 52 days after transplantation. Intragraft cytokine and chemokine profiles were assessed. To confirm the role of IL-16 in CAV development, C-H-2(bm12)KhEg (H-2(bm12)) donor hearts were transplanted into C57BL/6J WT recipients treated with (1) anti-IL-16-neutralization monoclonal antibody or (b) control immunoglobulin G. Grafts were harvested at 52 days, and CAV was quantified morphometrically. Graft-infiltrating cells were examined histologically. RESULTS: Parenchymal rejection and CAV was significantly attenuated in donor hearts transplanted into IL-16(-/-) recipient mice compared with WT controls. Donor hearts transplanted into IL-16(-/-) recipients had a significant reduction in coronary artery luminal occlusion, intima-to-media ratio, and percentage of diseased vessels. CAV was associated with decreased donor organ inflammation, as well as donor organ cytolcine (IL-1 beta and IL-6) and chemokine (MCP-1 and KC) protein expression. Intimal proliferation and inflammatory cell infiltration were significantly reduced in hearts transplanted into recipients treated with an IL-16-neutralization antibody. CONCLUSIONS: IL-16-deficiency reduced graft inflammatory cell recruitment, and allograft inflammatory cytokine and chemokine production. Therefore, IL-16 neutralization may provide a potential target for novel therapeutic treatment for cardiac allograft rejection. J Heart Lung Transplant 2011;30:1409-17 (C) 2011 International Society for Heart and Lung Transplantation. All rights reserved.
  • Chin JT, Troke JJ, Kimura N, Itoh S, Wang X, Palmer OP, Robbins RC, Fischbein MP
    The Yale journal of biology and medicine 4 84 423 - 432 0044-0086 2011/12 [Refereed][Not invited]
  • Naoyuki Kimura, Masashi Tanaka, Koji Kawahito, Satoshi Itoh, Homare Okamura, Atsushi Yamaguchi, Takashi Ino, Hideo Adachi
    CIRCULATION JOURNAL 75 (9) 2135 - 2143 1346-9843 2011/09 [Refereed][Not invited]
    Background: Acute type A aortic dissection (AAAD) is rare in young people. The early- and long-term outcomes after surgery for AAAD in patients aged <= 45 years was investigated. Methods and Results: Subjects were 355 patients who had undergone emergency surgery for AAAD. The patients were grouped as those aged <= 45 years (n=30; mean age, 38.3 years; younger group) and those aged >45 years (n=325; mean age, 65.3 years; older group). Clinical and prognostic variables were compared between the groups. Male sex, Marfan syndrome, and severe aortic regurgitation were more prevalent in the younger group. In-hospital mortality (16.7% vs. 8.6%, P=0.15) and postoperative patency of the distal aorta (90.8% vs. 59.1%, P<0.01) were more frequent in the younger group. The leading causes of late death were aortic rupture in the younger group (75.0%) and malignancy in the older group (27.5%). Although actuarial survival at 10 years was similar (64.5% vs. 62.5%), freedom from aortic reoperation at 10 years was decreased in the younger group (49.4% vs. 85.0%, P=0.012). A distal aorta >45 mm (P<0.001), Marfan syndrome (P<0.01), and age <= 45 years (P=0.045) were shown to be independent risk factors for reoperation. Conclusions: Early- and long-term surgical outcomes are not better for patients <= 45 years, and the risk for reoperation is high in this group. Careful follow up is important in young patients with AAAD. (Circ J 2011; 75: 2135-2143)
  • Satoshi Itoh, Naoyuki Kimura, Robert C. Axtell, Jeffrey B. Velotta, Yongquan Gong, Xi Wang, Naoki Kajiwara, Aya Nambu, Eri Shimura, Hideo Adachi, Yoichiro Iwakura, Hirohisa Saito, Ko Okumura, Katsuko Sudo, Lawrence Steinman, Robert C. Robbins, Susumu Nakae, Michael P. Fischbein
    CIRCULATION 124 (11) S187 - S196 0009-7322 2011/09 [Refereed][Not invited]
    Background-Interleukin-17 (IL-17), which is predominantly produced by T helper 17 cells distinct from T helper 1 or T helper 2 cells, participates in the pathogenesis of infectious, autoimmune, and allergic disorders. However, the precise role in allograft rejection remains uncertain. In the present study, we investigated the role of IL-17 in acute allograft rejection using IL-17-deficient mice. Methods and Results-Donor hearts from FVB mice were heterotopically transplanted into either C57BL/6J-IL-17-deficient (IL-17(-/-)) or -wild-type mice. Allograft survival was significantly prolonged in IL-17(-/-) recipient mice due to reduced local inflammation accompanied by decreased inflammatory cell recruitment and cytokine/chemokine expression. IL-17(-/-) recipient mice exhibited decreased IL-6 production and reciprocally enhanced regulatory T cell expansion, suggesting a contribution of regulatory T cells to prolonged allograft survival. Indeed, allografts transplanted into anti-CD25 mAb-treated IL-17(-/-) recipient mice (regulatory T cell-depleted) developed acute rejection similar to wild-type recipient mice. Surprisingly, we found that gamma delta T cells rather than CD4(+) and CD8(+) T cells were key IL-17 producers in the allografts. In support, equivalent allograft rejection was observed in Rag-2(-/-) recipient mice engrafted with either wild-type or IL-17(-/-) CD4(+) and CD8(+) T cells. Finally, hearts transplanted into gamma delta T cell-deficient mice resulted in decreased allograft rejection compared with wild-type controls. Conclusions-During heart transplantation, (1) IL-17 is crucial for acceleration of acute rejection; (2) IL-17-deficiency enhances regulatory T cell expansion; and (3) gamma delta T cells rather than CD4(+) and CD8(+) T cells are a potential source of IL-17. IL-17 neutralization may provide a potential target for novel therapeutic treatment for cardiac allograft rejection. (Circulation. 2011;124[suppl 1]:S187-S196.)
  • William Stein, Sonja Schrepfer, Satoshi Itoh, Naoyuki Kimura, Jeffrey Velotta, Owen Palmer, Jason Bartos, Xi Wang, Robert C. Robbins, Michael. P. Fischbein
    JOURNAL OF HEART AND LUNG TRANSPLANTATION 30 (7) 761 - 769 1053-2498 2011/07 [Refereed][Not invited]
    BACKGROUND: In this study we systematically dissect the prenylation pathway to better define the mechanism behind statin inhibition in chronic allograft rejection in heart transplants, or transplant' coronary artery disease (TCAD). METHODS: Utilizing a murine heterotopic heart transplant model, animals received daily treatments of either statin or selective isoprenoid blockade inhibitors to block the four major downstream branches of the mevalonate pathway. TCAD was assessed by morphometric analysis at Day 52. Graft-infiltrating cells, cytokine production, smooth muscle cell proliferation and migration and endothelial cell MHC II expression were detected on Day 7. RESULTS: Atorvastatin and two prenylation inhibitors, NE-10790 and manumycin A, significantly reduced TCAD lesions compared with untreated animals. Perillyl alcohol treatment resulted in a trend toward decreased luminal narrowing. Finally, zaragozic acid (cholesterol blockade only) did not alter TCAD severity. Statins and prenylation inhibitors reduced inflammatory cell allograft recruitment, but did not always correlate with TCAD reduction. Cytokine production was decreased in recipient spleens in all treatment groups. Both in vitro and in vivo IFN-gamma-stimulated MHC II expression was decreased in a dose-dependent manner in the atorvastatin, perillyl alcohol and NE-10790 groups. In vitro smooth muscle cell proliferation was decreased in all treatment groups. Finally, in vitro smooth muscle cell migration was decreased in the atorvastatin, NE-10790 and manumycin A groups only. CONCLUSIONS: FPT and GGPT-2 (inhibition) are the key enzymes in the HGM-CoA reductase pathway and most influential in TCAD prevention. TCAD reduction is most closely related to smooth muscle cell migration, but not its anti-inflammatory properties. J Heart Lung Transplant 2011;30:761-9 (C) 2011 International Society for Heart and Lung Transplantation. All rights reserved.
  • Jeffrey B. Velotta, Naoyuki Kimura, Stephanie H. Chang, Jaehoon Chung, Satoshi Itoh, Jonathan Rothbard, Philip C. Yang, Lawrence Steinman, Robert C. Robbins, Michael P. Fischbein
    ANNALS OF THORACIC SURGERY 6 91 (6) 1907 - 1913 0003-4975 2011/06 [Refereed][Not invited]
    Background. This study investigates the protective effect of exogenous alpha B-crystallin (CryAB) on myocardial function after ischemia-reperfusion injury. Methods. Mice underwent temporary left anterior descending artery occlusion for 30 minutes. Either CryAB (50 mu g) or phosphate-buffered saline (100 mu L [n = 6, each group]) were injected in the intramyocardial medial and lateral perinfarct zone 15 minutes before reperfusion. Intraperitoneal injections were administered every other day. Left ventricular ejection fraction was evaluated on postoperative day 40 with magnetic resonance imaging. To investigate the effect of CryAB on apoptosis after hypoxia/reoxygenation in vitro, murine atrial cardiomyocytes (HL-1 cells) or human microvascular endothelial cells (HMEC-1) were incubated with either 50 mu g CryAB (500 mu g /10 mL) or phosphate-buffered saline in a hypoxia chamber for 6, 12, and 24 hours, followed by 30 minutes of reoxygenation at room air. Apoptosis was then assessed by western blot (Bcl-2, free bax, cleaved caspases-3, 9, PARP) and enzyme-linked immunosorbent assay analyses (cytoplasmic histone-associated DNA fragments and caspase-3 activity). Results. On postoperative day 40, CryAB-treated mice had a 1.8-fold increase in left ventricular ejection fraction versus control mice (27% +/- 6% versus 15% +/- 4% SD, p < 0.005). In vitro, (1) the HL-1 cells showed no significant difference in apoptotic protein expression, cytoplasmic histone-associated DNA fragments, or caspase-3 activity; (2) the HMEC-1 cells had increased but not significant apoptotic protein expression with, however, a significant decrease in cytoplasmic histone-associated DNA fragments (1.5-fold, p < 0.01) and caspase-3 activity (2.7-fold, p < 0.005). Conclusions. Exogenous CryAB administration significantly improves cardiac function after ischemia-reperfusion injury, in vivo. The protective anti-apoptotic affects of CryAB may target the endothelial cell.
  • Homare Okamura, Atsushi Yamaguchi, Naoyuki Kimura, Koichi Adachi, Hideo Adachi
    General Thoracic and Cardiovascular Surgery 59 (1) 38 - 41 1863-6705 2011/01 [Refereed][Not invited]
    Intravenous leiomyomatosis with cardiac extension is rare and may result in a fatal outcome. A 58-year-old woman with a surgical history of myoma uteri was admitted to our hospital for treatment of intravenous leiomyomatosis extending into the right atrium through the inferior vena cava. We partially resected the tumor inside the right atrium and the inferior vena cava via the right atrium using cardiopulmonary bypass. There is no progression of the residual tumor after 25 months of follow-up. © 2011 The Japanese Association for Thoracic Surgery.
  • Satoshi Itoh, Susumu Nakae, Robert C. Axtell, Jeffrey B. Velotta, Naoyuki Kimura, Naoki Kajiwara, Yoichiro Iwakura, Hirohisa Saito, Hideo Adachi, Lawrence Steinman, Robert C. Robbins, Michael P. Fischbein
    JOURNAL OF CLINICAL IMMUNOLOGY 30 (2) 235 - 240 0271-9142 2010/03 [Refereed][Not invited]
    Although interleukin-17 (IL-17) has been reported to participate in the pathogenesis of infectious, autoimmune and allergic disorders, the precise role in allograft rejection remains uncertain. This study illustrates that IL-17 contributes to the pathogenesis of chronic allograft rejection. Utilizing a murine heterotopic heart transplant model system, IL-17-deficient recipient mice had decreased allograft inflammatory cell recruitment, decreased IL-6, MCP-1, and KC production, and reduced graft coronary artery disease (GCAD). Intragraft gamma delta (gamma delta) T cells appear to be the predominant source of IL-17 production. Therefore, IL-17 neutralization may provide a potential target for novel therapeutic treatment for cardiac allograft rejection.
  • Naoyuki Kimura, Masashi Tanaka, Koji Kawahito, Atsushi Yamaguchi, Takashi Lno, Hideo Adachi
    Interactive Cardiovascular and Thoracic Surgery 8 (4) 431 - 434 1569-9293 2009/04 [Refereed][Not invited]
    We report our experience with patients who died of early aortic rupture following surgical treatment for acute type A aortic dissection in a consecutive series of 324 patients who underwent surgery for this condition between 1991 and 2007. In-hospital mortality rate was 9.9% (32/324), and seven patients (two men, mean age, 67 years) died of postoperative aortic rupture. Rupture sites were the proximal aorta in two and distal aorta in five patients. Surgical procedures included ascending aorta replacement in six and ascending aorta plus aortic arch replacement in one. The common characteristics of the two patients with proximal aortic rupture were preoperative aortic insufficiency, intraoperative bleeding from the proximal stump, and high blood pressure before the rupture. In contrast, the distal aortic ruptures occurred in patients with uncomplicated postoperative courses, with three distal aortic ruptures occurring on the inpatient ward. The only common characteristic of the distal aortic ruptures was residual patent false lumen (80%, 4/5 patients), the other patient had a large pre-existing aneurysm in the descending thoracic aorta. Careful postoperative management, including strict blood pressure control, is especially important in patients with residual patent false lumen following surgery for acute type A aortic dissection. © 2009 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.
  • Homare Okamura, Atsushi Yamaguchi, Masashi Tanaka, Kazuhiro Naito, Naoyuki Kimura, Chieri Kimura, Toshiyuki Kobinata, Takashi Ino, Hideo Adachi
    ANNALS OF THORACIC SURGERY 87 (1) 90 - 94 0003-4975 2009/01 [Refereed][Not invited]
    Background. When aortic valve replacement is performed in patients with a small aortic annulus, prosthesis-patient mismatch is of concern. Such prosthesis-patient mismatch may affect postoperative clinical status and survival. We investigated the outcomes of isolated aortic valve replacement performed with a 17-mm mechanical prosthesis in patients with aortic stenosis. Methods. Twenty-three patients with aortic stenosis (mean age, 74.6 +/- 6.3 years) underwent isolated aortic valve replacement with a 17-mm St. Jude Medical Regent prosthesis. Mean body surface area was 1.41 +/- 0.13 m(2). Preoperative echocardiography yielded a mean aortic valve area of 0.36 +/- 0.10 cm(2)/ m(2), a mean left ventricular-aortic pressure gradient of 68.4 +/- 25.3 mm Hg, and a mean left ventricular mass index of 200 +/- 69 g/m(2). Results. There was no operative mortality, and there were no valve-related events. Echocardiography at 14.0 +/- 10.0 months after aortic valve replacement showed a significant increase in the mean effective orifice area index (0.95 +/- 0.24 cm(2)/m(2)), decrease in the mean left ventricular-aortic pressure gradient (17.4 +/- 8.2 mm Hg), and decrease in the mean left ventricular mass index (124 +/- 37 cm(2)/m(2)). Prosthesis-patient mismatch (effective orifice area index < 0.85 cm(2)/m(2)) was present in 8 patients at discharge. In these patients as well as in those without prosthesis-patient mismatch, the left ventricular mass index decreased remarkably during follow-up. Conclusions. Aortic valve replacement with a 17-mm Regent prosthesis appears to provide satisfactory clinical and hemodynamic results in patients with a small aortic annulus. Remarkable left ventricular mass regression during follow-up was achieved irrespective of the effective orifice area index at discharge.
  • Naoyuki Kimura, Masashi Tanaka, Koji Kawahito, Masamitsu Sanui, Atsushi Yamaguchi, Takashi Ino, Hideo Adachi
    CIRCULATION JOURNAL 72 (11) 1751 - 1757 1346-9843 2008/11 [Refereed][Not invited]
    Background The aim of this study was to identify predictors of prolonged mechanical ventilation (PMV) following surgery for acute type A aortic dissection (AAAD) and to assess the influence of this complication on clinical outcomes. Methods and Results A total of 243 patients underwent emergency surgery for AAAD in the period of 1997-2006. Ten patients died within 48 h after surgery. The remaining 233 patients were divided into 2 groups according to the duration of mechanical ventilation; less than 48 h (group A: n=149) or 48 h or longer (group 13; n=84). Multivariate analysis was used to identify predictors of PMV. Short and late outcomes were compared between groups. Multivariate analysis showed that shock (systolic BP < 90 mmHg; p=0.007), postoperative renal dysfunction (creatinine > 2.0 mg/dl; p=0.016), coronary artery bypass grafting (CABG) (p=0.017), and limb ischemia (p=0.044) were independent predictors of PMV. There was no significant difference in in-hospital mortality (group A, 2.7% vs group B, 3.6%) or 5-year survival (group A, 85.9% vs group 13, 76.8%). Conclusions Shock, limb ischemia, CABG, and postoperative renal dysfunction increase the risk for PMV. Knowing the predictors of PMV should help optimize postoperative management of these patients. (Circ J 2008; 72: 1751-1757)
  • Naoyuki Kimura, Masashi Tanaka, Koji Kawahito, Atsushi Yamaguchi, Takashi Ino, Hideo Adachi
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 136 (5) 1160 - U28 0022-5223 2008/11 [Refereed][Not invited]
    Objective: The fate of the dissected distal aorta after surgery for acute type A aortic dissection has not been fully understood. We assessed the influence of a residual patent false lumen on long-term outcomes. Methods: Two hundred eighteen patients underwent emergency surgery for DeBakey type I or IIIb retrograde acute type A aortic dissection (1997-2006). Aortic arch replacement was performed in selected patients whose entry site was in or extended into the aortic arch. In-hospital mortality was 7.3% (16/218), and 193 survivors (mean age 62 years) underwent enhanced computed tomography within 1 month after the operation. These patients were divided into two groups according to the status of the false lumen, whether patent (n = 124) or thrombosed (n 69). In each group, segment-specific aortic growth rate, distal reoperation, and late survival were examined. Results: Growth rate was determined in 139 (72.0%) patients who underwent serial computed tomography. Average growth rate in the patent group was greater than that in the thrombosed group (aortic arch [1.1 vs -0.41 mm per year; P.005], proximal descending aorta [1.9 vs-0.71 mm per year; P<. 001], and distal descending aorta [1.3 vs-0.70 mm per year; P = .002]). However, growth was slow (< 1 mmper year) in about 50% of patients in the patent group. There was no significant difference in distal reoperation or late survival between the two groups. Conclusions: The patent false lumen influences postoperative aortic enlargement. However, with careful followup, a favorable prognosis is expected even for patients with a residual patent false lumen.
  • Naoyuki Kimura, Hideo Adachi, Koichi Adachi, Munetaka Hashimoto, Atsushi Yamaguchi, Takashi Ino
    General Thoracic and Cardiovascular Surgery 56 (8) 417 - 420 1863-6705 2008/08 [Refereed][Not invited]
    A previously healthy 77-year-old woman with a 4-week history of back pain and fever was admitted to our hospital for chronic type A aortic dissection. The aortic arch was enlarged to 7.5 cm in diameter, and the large dissecting aortic aneurysm involved all three branches of the aortic arch and compressed the trachea. Laboratory tests showed an increased C-reactive protein level (10.5 mg/dl). Blood cultures performed upon admission were negative. Progression of the symptoms suggested the possibility of impending aneurysm rupture. The patient underwent urgent total arch replacement, and cultures of samples obtained from the aortic wall during surgery were positive for Listeria monocytogenes. Two months after surgery, advanced rectal cancer was diagnosed. It is believed that the rectal cancer predisposed the patient to development of an arterial infection associated with L. monocytogenes. © 2008 The Japanese Association for Thoracic Surgery.
  • Naoyuki Kimura, Koji Kawahito, Satoshi Ito
    SURGERY TODAY 38 (3) 249 - 252 0941-1291 2008/03 [Refereed][Not invited]
    An 80-year-old woman was admitted to our hospital complaining of severe abdominal and back pain. Computed tomography (CT) showed an 8.5 x 7.0-cm infrarenal abdominal aortic aneurysm (AAA) with a large contained retroperitoneal hematoma. Known situs inversus totalis was reconfirmed by CT. Just after the CT examination, the patient collapsed and was immediately taken to the operating room. Her hemodynamics stabilized after clamping of the descending aorta via a right anterolateral thoracotomy. A resection of the abdominal aneurysm and prosthetic graft replacement were successfully performed. To our knowledge, there has been no other report of a ruptured AAA in a patient with situs inversus totalis.
  • Naoyuki Kimura, Atsushi Yamaguchi, Masashi Tanaka, Homare Okamura, Hideo Adachi, Takashi Ino
    Asian Cardiovascular and Thoracic Annals 16 (5) 407 - 409 0218-4923 2008 [Refereed][Not invited]
    A 46-year-old man underwent emergency surgery for heart rupture after acute infarction of the posterior wall. Echocardiography revealed limited myocardial thinning, so rather than sutureless repair, a covering patch was used in view of the risk of recurrent rupture. Postoperative echocardiography showed the myocardial thinning had progressed to a wide defect, and computed tomography demonstrated that the covering patch had prevented a repeat rupture.
  • Naoyuki Kimura, Atsushi Yamaguchi, Kenichiro Noguchi, Koichi Adachi, Hideo Adachi, Takashi Ino
    General Thoracic and Cardiovascular Surgery 55 (5) 212 - 216 1863-6705 2007/05 [Refereed][Not invited]
    A 59-year-old man with a long history of hypertension and diabetes was admitted to our hospital with acute type B aortic dissection 14 days after the sudden onset of back pain. The dissecting descending thoracic aorta was enlarged to 5.2cm in diameter, and laboratory tests showed an elevated white blood cell count (15530/mm3) and an increased C-reactive protein level (19.2mg/dl). Computed tomography performed 2 days after admission revealed rapid growth of the aortic dissection. Blood cultures obtained upon admission were positive for Salmonella. Impending rupture of the aortic dissection complicated by Salmonella infection was strongly suspected, and the patient underwent emergency surgery consisting of debridement and prosthetic graft placement covered by an omental flap. In this case, it is believed that insidious Salmonella aortitis caused acute type B aortic dissection. © 2007 The Japanese Association for Thoracic Surgery.
  • Naoyuki Kimura, Koji Kawahito, Satoshi Ito, Seiichiro Murata, Atsushi Yamaguchi, Hideo Adachi, Takashi Ino
    Interactive Cardiovascular and Thoracic Surgery 4 (5) 469 - 472 1569-9293 2005/10 [Refereed][Not invited]
    We have applied omental transfer in cases of deep sternal wound infection (DSWI) that occurred after the right gastroepiploic artery was used as a coronary artery bypass graft. Study subjects were 7 patients (mean age was 66 years) who underwent coronary artery bypass grafting with the right gastroepiploic artery during the period January 1990-March 2004, then suffered DSWI and underwent single-stage treatment consisting of debridement and omental transfer 33 days on average (range 12-93 days) after the primary surgery. Patients were followed-up, and the following data were collected in retrospect: clinical presentation and in-hospital and long-term results. Three of the 7 patients underwent omental transfer based on the left gastroepiploic artery alone, 3 underwent omental transfer based on blood supply from a branch of the right gastroepiploic artery, and 1 underwent omental transfer based on blood supply from both branches. The hospital mortality rate was 14% (1 of 7 patients) death was caused by recurrent mediastinitis. Postoperative hospitalization was 47 days (range 21-83 days). Two patients died of cardiac failure, and 1 patient suffered abdominal wall hernia during the follow-up period. Even after harvesting of the right gastroepiploic artery, omental transfer was effective for the treatment of DSWI.
  • Naoyuki Kimura, Koji Kawahito, Satoshi Ito, Seiichiro Murata, Atushi Yamaguchi, Hideo Adachi, Takashi Ino
    Journal of Artificial Organs 8 (3) 206 - 209 1434-7229 2005/09 [Refereed][Not invited]
    Percutaneous cardiopulmonary support (PCPS) is a powerful resuscitation tool for patients in cardiogenic shock. The femoral artery is generally used for arterial access however, vascular complications, particularly in atherosclerotic arteries, can occur. Although such complications occur infrequently, they can be fatal. We describe the case of a 75-year-old woman who required extended PCPS for cardiogenic shock secondary to coronary spasm after on-pump beating coronary artery bypass grafting. Limb ischemia occurred because of an occlusive cannula, and distal perfusion with a 20G elastic intravenous catheter inserted into the dorsalis pedis artery resolved the ischemia. The catheter was connected to the side port of an oxygenator and provided distal limb perfusion during PCPS. This technique appears to be useful in treating limb ischemia and may have application in patients with arterial occlusive disease who are dependent on mechanical support. © The Japanese Society for Artificial Organs 2005.
  • Naoyuki Kimura, Koji Kawahito, Seiichiro Murata, Atsushi Yamaguchi, Hideo Adachi, Takashi Ino
    Japanese Journal of Thoracic and Cardiovascular Surgery 53 (7) 382 - 385 1344-4964 2005 [Refereed][Not invited]
    A 55-year-old man was admitted for acute myocardial infarction. Cardiac catheterization revealed total occlusion of the left circumflex artery. During catheterization, he suffered cardiogenic shock. Percutaneous cardiopulmonary support was established, and the patient was transferred to the operating room. A blow-out left ventricular free wall rupture (LVFWR) with an epicardial tear, 1 mm in diameter, was found, and sutureless repair with a collagen hemostat (TachoComb™) was performed. However, on postoperative day 7, echocardiography revealed an echo-free space resembling a pseudoaneurysm. A second operation was performed immediately for impending re-rupture. An epicardial tear, 2×10 mm in diameter, was found at the previous bleeding point where hemostasis had been achieved with only one sheet of TachoComb™. The defect was closed with mattress sutures buttressed with Teflon® felt. We conclude that even if the risk of re-rupture is low, sutureless repair with a collagen hemostat alone should be avoided in treating blow-out LVFWR.
  • Naoyuki Kimura, Koji Kawahito, Seiichiro Murata, Atsushi Yamaguchi, Hideo Adachi, Takashi Ino
    Japanese Journal of Thoracic and Cardiovascular Surgery 53 (11) 619 - 623 1344-4964 2005 [Refereed][Not invited]
    A 58-year-old man was admitted for an aortoesophageal fistula (AEF) resulting from a thoracic aortic aneurysm. He underwent immediate in-situ prosthetic graft replacement, primary esophageal repair and wrapping of the aneurysm. Postoperative upper gastrointestinal endoscopy and computerized tomography (CT) findings were unremarkable. He was discharged on postoperative day (POD) 25. Three months after surgery, he was readmitted with complaints of worsening cough and hemoptysis. CT showed a thrombosed aneurysm adjacent to the left bronchus. Aortobronchial fistula due to mycotic pseudoaneurysm was suspected. The patient underwent immediate resection of the infected graft and prosthetic graft replacement positioned to avoid the infected area. The graft was wrapped with omentum. On POD 7, pleural empyema developed, and esophagography revealed a residual leak. Staged reconstruction of the esophagus was performed successfully. We conclude that even if the fistulous opening is small, simultaneous esophageal resection should be performed during the initial treatment of AEF.


Awards & Honors

  • 2010 スタンフォード大学 医学部長奨励研究賞
    受賞者: 木村直行
  • 2010 Stanford University Dean's postdoctoral fellowship
  • 2009 上原記念財団 海外留学助成リサーチフェローシップ
    受賞者: 木村直行

Research Grants & Projects

Copyright © MEDIA FUSION Co.,Ltd. All rights reserved.