詳細

中嶋　康文 （ナカジマ　ヤスフミ）

  • 医学科　教授/主任
Last Updated :2024/04/25

コミュニケーション情報 byコメンテータガイド

  • コメント

    麻酔科学に関連する領域と連携し、強い倫理観を持ったバランスのとれた麻酔科医を育成していきたいと考えています。

研究者情報

学位

  • 医学博士（京都府立医科大学）

ホームページURL

J-Global ID

研究キーワード

  • 集中治療医学   麻酔学   Environmental Physiology   

現在の研究分野（キーワード）

    麻酔科学に関連する領域と連携し、強い倫理観を持ったバランスのとれた麻酔科医を育成していきたいと考えています。

研究分野

  • ライフサイエンス / 麻酔科学

経歴

  • 2022年03月 - 現在  近畿大学麻酔科学講座
  • 2015年01月 - 2022年03月  関西医科大学 大学院医学研究科 麻酔学
  • 1992年04月 - 2014年12月  京都府立医科大学麻酔科学教室

所属学協会

  • European Society of Anaesthesiology   日本心エコー図学会   日本心臓血管麻酔学会   日本臨床麻酔学会   日本集中治療学会   日本麻酔科学会   

研究活動情報

論文

  • Shota Tsukimoto; Atsuhiro Kitaura; Hidetaka Kuroda; Uno Imaizumi; Fumihiko Yoshino; Ayaka Yoshida; Shinchi Nakao; Noriyuki Ohta; Yasuhumi Nakajima; Takuro Sanuki
    Immunity, inflammation and disease 12 3 e1218  2024年03月 
    BACKGROUND: Anesthetic agents, particularly intravenous anesthetics, may affect immune function and tumorigenic factors. We herein investigated whether the anti-inflammatory effects of anesthetic agents are attributed to their antioxidant properties. The antioxidant and anti-inflammatory effects of remimazolam, a new anesthetic, remain unclear. We hypothesized that remimazolam exerts anti-inflammatory effects due to its antioxidant properties, which may affect the postoperative inflammatory response. This retrospective clinical study examined this hypothesis using laboratory and clinical approaches. METHODS: The antioxidant effects of remimazolam and dexmedetomidine were assessed by electron spin resonance (ESR) spectroscopy, and postoperative inflammatory responses were compared in 143 patients who underwent transcatheter aortic valve replacement at Kindai University Hospital between April 2021 and December 2022. The primary endpoint was the presence or absence of the antioxidant effects of the anesthetics themselves using ESR. RESULTS: Remimazolam at clinical concentrations exerted antioxidant effects, whereas dexmedetomidine did not. Increases in C-reactive protein (CRP) levels on POD3 from preoperative values were significantly smaller in the remimazolam group than in the dexmedetomidine group (1.33 ± 1.29 vs. 2.17 ± 1.84, p = .014). CONCLUSIONS: Remimazolam exerted stronger anti-inflammatory effects than dexmedetomidine, and these effects were enhanced by its antioxidant properties, which may have affected postoperative CRP production.
  • Hiroatsu Sakamoto; Atsuhiro Kitaura; Shota Tsukimoto; Yukari Yoshino; Takashi Mino; Haruyuki Yuasa; Yasufumi Nakajima
    JA clinical reports 10 1 13 - 13 2024年02月
  • Atsuhiro Kitaura; Hiroatsu Sakamoto; Shinichi Hamasaki; Shota Tsukimoto; Yasufumi Nakajima
    Medicina (Kaunas, Lithuania) 59 12 2023年12月 
    Background and Objectives: Remimazolam is a new ultrashort-acting benzodiazepine anesthetic. Remimazolam appears to be useful in patients with severe valvular disease because of its minimal cardiovascular impact. In this retrospective case series study, we assessed the efficacy and safety of remimazolam for maintaining hemodynamic stability during anesthetic induction and maintenance. Cases: MitraClip was performed on 18 cases with severe mitral regurgitation with low left ventricular function who presented with heart failure, and remimazolam was administered for general anesthesia with induction (12 mg/kg/h) and maintenance (1 mg/kg/h). The impact of remimazolam on the hemodynamics at anesthetic induction and during anesthetic maintenance was investigated retrospectively using electronic medical records. Blood pressure decreased significantly during anesthetic induction with remimazolam (78.5 [72, 81.25] and 66.1 [62.2, 74.2], median [IQR], p = 0.0001), but only mildly, by about 10 mmHg. There was no significant change in the cardiac index (2.0 [1.8, 2.4] vs. 1.9 [1.8, 2.3], p = 0.57642) or pulse rate (73.5 ± 8.85 vs. 74.7 ± 11.7, mean ± SD, p = 0.0876) during anesthetic induction with remimazolam. All patients underwent MitraClip without major hemodynamic concerns, with no or small increases in inotropes. Conclusions: Remimazolam may be used safely in patients with severe mitral regurgitation and low left ventricular function presenting with heart failure.
  • Atsuhiro Kitaura; Shota Tsukimoto; Hiroatsu Sakamoto; Shinichi Hamasaki; Shinichi Nakao; Yasufumi Nakajima
    Scientific Reports 13 1 17074 - 17074 2023年10月 [査読有り]
     
    Remimazolam, an ultrashort-acting benzodiazepine, allows for rapid and reliable arousal. Rapid awakening using remimazolam may be beneficial in transcatheter aortic valve replacement (TAVR), as it allows rapid detection of neurologic deficits. The purpose of this study was to compare arousal time and outcomes between monitored anesthesia care (MAC) with remimazolam and remifentanil and conventional MAC with dexmedetomidine, propofol, and remifentanil. This study was a single center retrospective study. All TAVR cases performed under MAC (MAC-TAVR) at our institution between 2019 and 2021 were included. Patients were classified by anesthesia method into remimazolam and dexmedetomidine groups. Among 258 MAC-TAVR patients, 253 were enrolled. After propensity score matching, 76 patients were assigned to each group. The time from end of drug-administration to arousal [20.0 (16.0, 24.0) min vs. 38.5 (30.0, 56.3) min, p < 0.0001] and the time from attempted-arousal to arousal [1.0 (1.0, 1.0) min vs. 12.5 (3.0, 26.8) min, p < 0.0001] were significantly shorter in the remimazolam group. There was no significant difference in the length of ICU stay [2.0 (2.0, 2.0) days vs. 2.0 (2.0, 2.0) days, p = 0.157] and postoperative hospital stay [6.0 (4.0, 9.0) days vs. 5.0 (4.0, 8.0) days, p = 0.262].Trial registration: Clinical trial number: R03-123, Registry URL: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000051635 Registration number: UMIN000045195, Principal investigator's name: Atsuhiro Kitaura, Date of registration: 20 August 2021.
  • 秋山 浩一; 坂本 悠篤; 北條 絵理; 小角 怜子; 鎌本 洋通; 中嶋 康文
    Cardiovascular Anesthesia 27 Suppl. 184 - 184 (一社)日本心臓血管麻酔学会 2023年09月
  • 坂本 悠篤; 秋山 浩一; 北條 絵理; 北浦 淳寛; 中嶋 康文
    Cardiovascular Anesthesia 27 Suppl. 239 - 239 (一社)日本心臓血管麻酔学会 2023年09月
  • 北條 絵理; 東方 謙介; 小角 怜子; 坂本 悠篤; 秋山 浩一; 中嶋 康文
    Cardiovascular Anesthesia 27 Suppl. 252 - 252 (一社)日本心臓血管麻酔学会 2023年09月
  • 東方 謙介; 秋山 浩一; 坂本 悠篤; 北條 絵理; 小角 怜子; 中嶋 康文
    Cardiovascular Anesthesia 27 Suppl. 270 - 270 (一社)日本心臓血管麻酔学会 2023年09月
  • Jun Takeshita; Yoshinobu Nakayama; Kazuya Tachibana; Yasufumi Nakajima; Hirofumi Hamaba; Nobuaki Shime
    British journal of anaesthesia 2023年08月 
    BACKGROUND: Arterial catheterisation in children can be challenging and time-consuming. We aimed to compare the success rates of ultrasound-guided arterial catheterisation utilising the short-axis out-of-plane approach with dynamic needle tip positioning in the radial, dorsalis pedis, and posterior tibial arteries in paediatric patients. We also examined the factors influencing the catheterisation success using dynamic needle tip positioning. METHODS: Paediatric patients (aged <3 yr) undergoing cardiac surgery were randomly assigned to three groups based on puncture sites: radial artery (Group R), dorsalis pedis artery (Group D), and posterior tibial artery (Group P). The first-attempt and overall success rates of arterial catheterisation were compared, followed by multiple logistic regression analysis (dependent variable: first-attempt success; independent variables: body weight, diameter and depth of the artery, targeted artery, and trisomy 21). RESULTS: The study included 270 subjects (n=90 per group). There was no significant difference in the first-attempt (Group R: 82%, Group D: 76%, and Group P: 81%) and overall success rates (Group R: 94%, Group D: 93%, and Group P: 91%) among the three groups. The diameter of the artery (per 0.1 mm) (odds ratio: 1.32, 95% confidence interval: 1.09-1.60) and trisomy 21 (odds ratio: 0.43, 95% confidence interval: 0.20-0.92) were independent predictors of first-attempt success or failure. CONCLUSION: The first-attempt and overall success rates of arterial catheterisation of the dorsalis pedis and posterior tibial arteries were not inferior to those in the radial artery when using dynamic needle tip positioning. These two lower extremity peripheral arteries present viable alternative catheterisation sites in paediatric patients. CLINICAL TRIAL REGISTRATION: UMIN000042847.
  • Atsuhiro Kitaura; Tatsushige Iwamoto; Shinichi Hamasaki; Shota Tsukimoto; Yasufumi Nakajima
    Cureus 15 8 e44003  2023年08月 
    Andexanet alfa is an analog of activated factor X and is used as an antagonist of anti-activated factor X agents. Andexanet alfa is useful for hemostasis in emergent bleeding during direct oral anticoagulant administration, which contributes to safety. In patients undergoing surgery with cardiopulmonary bypass because of heparin resistance, anesthesiologists are faced with a choice of anticoagulants. Herein, we experienced anesthesia for vascular prostheses with cardiopulmonary bypass for acute aortic dissection in a patient who had received andexanet alfa preoperatively. Heparin was initially used as the anticoagulant during cardiopulmonary bypass; however, despite the administration of large doses and antithrombin III preparations, anticoagulation was insufficient. Therefore, nafamostat mesilate was administered and sufficient anticoagulation was attained. The patient completed surgery under cardiopulmonary bypass, coagulation function was recovered shortly after withdrawal, and no obvious adverse effects were observed.
  • Atsuhiro Kitaura; Shinichi Hamasaki; Hiroatsu Sakamoto; Shota Tsukimoto; Yasufumi Nakajima
    Cureus 15 7 e42576  2023年07月 [査読有り]
     
    We report the inadequate efficacy of remimazolam in two patients undergoing long-term benzodiazepine analog therapy. Remimazolam is a recently developed ultrashort-acting benzodiazepine. It is primarily used as an anesthetic in surgical procedures, as it has minimal effect on cardiac function and antagonists are available. It is expected to become more widely used in the future. On the other hand, similar to other benzodiazepines, benzodiazepine tolerance can also pose a challenge with remimazolam. Herein, we report two cases who were taking long-term oral benzodiazepine analogs. One patient did not fall asleep despite a sufficient dose of remimazolam and required a change to propofol. The other patient required a high dose of remimazolam to fall asleep; however, multiple signs of arousal were noted intraoperatively. Our findings suggest that remimazolam may not be an ideal anesthetic in long-term benzodiazepine analog users. Comprehensive assessment of preoperative medications and careful monitoring of intraoperative sedation levels are necessary. Furthermore, it may be advisable to consider the use of alternative agents such as propofol.
  • 閉塞性肥大型心筋症患者の左室流出路心筋切除前後における,心室内圧較差(IVPD)の変化
    坂本 悠篤; 岡本 健; 法里 慧; 石崎 智哉子; 冬田 昌樹; 岩元 辰篤; 太田 典之; 中嶋 康文; 秋山 浩一
    日本集中治療医学会雑誌 30 Suppl.1 S754 - S754 (一社)日本集中治療医学会 2023年06月
  • 胸骨圧迫により心破裂を起こした一症例
    別府 賢; 一杉 正仁; 元濱 啓介; 藤沢 聖哉; 岡田 奈月; 徳山 裕貴; 杉谷 勇季; 益満 茜; 笹橋 望; 中嶋 康文
    日本集中治療医学会雑誌 30 Suppl.1 S568 - S568 (一社)日本集中治療医学会 2023年06月
  • 重症急性膵炎後の被包化壊死に伴う敗血症に対して,4ヵ月間の集中治療によって治癒に至った一症例
    大田 典之; 岡本 健; 北浦 淳寛; 木村 誠志; 中嶋 康文
    日本集中治療医学会雑誌 30 Suppl.1 S414 - S414 (一社)日本集中治療医学会 2023年06月
  • 閉塞性肥大型心筋症患者の左室流出路心筋切除前後における,心室内圧較差(IVPD)の変化
    坂本 悠篤; 岡本 健; 法里 慧; 石崎 智哉子; 冬田 昌樹; 岩元 辰篤; 太田 典之; 中嶋 康文; 秋山 浩一
    日本集中治療医学会雑誌 30 Suppl.1 S754 - S754 (一社)日本集中治療医学会 2023年06月
  • Koichi Akiyama; Isaac Y Wu; Kei Hori; Hiroatsu Sakamoto; Reiko Kosumi; Hirokazu Koto; Satoshi Asada; Yasufumi Nakajima
    Journal of cardiothoracic and vascular anesthesia 37 9 1833 - 1834 2023年05月
  • Koichi Akiyama; Paolo C. Colombo; Eric J. Stöhr; Ruiping Ji; Isaac Y. Wu; Keiichi Itatani; Shohei Miyazaki; Teruyasu Nishino; Naotoshi Nakamura; Yasufumi Nakajima; Barry J McDonnell; Koji Takeda; Melana Yuzefpolskaya; Hiroo Takayama
    Frontier's in Cardiovascular Medicine 10 1093576 - 1093576 2023年05月 [査読有り]
     
    OBJECTIVES: Right ventricular (RV) failure remains a major concern in heart failure (HF) patients undergoing left ventricular assist device (LVAD) implantation. We aimed to measure the kinetic energy of blood in the RV outflow tract (KE-RVOT) - a new marker of RV global systolic function. We also aimed to assess the relationship of KE-RVOT to other echocardiographic parameters in all subjects and assess the relationship of KE-RVOT to hemodynamic parameters of RV performance in HF patients. METHODS: Fifty-one subjects were prospectively enrolled into 4 groups (healthy controls, NYHA Class II, NYHA Class IV, LVAD patients) as follows: 11 healthy controls, 32 HF patients (8 NYHA Class II and 24 Class IV), and 8 patients with preexisting LVADs. The 24 Class IV HF patients included 21 pre-LVAD and 3 pre-transplant patients. Echocardiographic parameters of RV function (TAPSE, St', Et', IVA, MPI) and RV outflow color-Doppler images were recorded in all patients. Invasive hemodynamic parameters of RV function were collected in all Class IV HF patients. KE-RVOT was derived from color-Doppler imaging using a vector flow mapping proprietary software. Kruskal-Wallis test was performed for comparison of KE-RVOT in each group. Correlation between KE-RVOT and echocardiographic/hemodynamic parameters was assessed by linear regression analysis. Receiver operating characteristic curves for the ability of KE-RVOT to predict early phase RV failure were generated. RESULTS: KE-RVOT (median ± IQR) was higher in healthy controls (55.10 [39.70 to 76.43] mW/m) than in the Class II HF group (22.23 [15.41 to 35.58] mW/m, p < 0.005). KE-RVOT was further reduced in the Class IV HF group (9.02 [5.33 to 11.94] mW/m, p < 0.05). KE-RVOT was lower in the LVAD group (25.03 [9.88 to 38.98] mW/m) than the healthy controls group (p < 0.005). KE-RVOT had significant correlation with all echocardiographic parameters and no correlation with invasive hemodynamic parameters. RV failure occurred in 12 patients who underwent LVAD implantation in the Class IV HF group (1 patient was not eligible due to death immediately after the LVAD implantation). KE-RVOT cut-off value for prediction of RV failure was 9.15 mW/m (sensitivity: 0.67, specificity: 0.75, AUC: 0.66). CONCLUSIONS: KE-RVOT, a novel noninvasive measure of RV function, strongly correlates with well-established echocardiographic markers of RV performance. KE-RVOT is the energy generated by RV wall contraction. Therefore, KE-RVOT may reflect global RV function. The utility of KE-RVOT in prediction of RV failure post LVAD implantation requires further study.
  • Jun Takeshita; Yoshinobu Nakayama; Kazuya Tachibana; Yasufumi Nakajima; Nobuaki Shime
    Journal of cardiothoracic and vascular anesthesia 2023年05月 
    OBJECTIVES: To compare the efficacy of the ultrasound-guided approach with and without dynamic needle-tip positioning and the palpation technique regarding success for peripheral venous catheterization in children. DESIGN: A systematic review with network meta-analysis. SETTING: Databases of MEDLINE (via PubMed) and Cochrane Central Register of Controlled Trials. PARTICIPANTS: Patients (<18 years) undergoing peripheral venous catheter insertion. INTERVENTIONS: Randomized clinical trials were included to compare the following techniques: the ultrasound-guided short-axis out-of-plane approach with dynamic needle-tip positioning, the approach without dynamic needle-tip positioning, and the palpation technique. MEASUREMENTS AND MAIN RESULTS: The outcomes were first-attempt and overall success rates. Eight studies were included in the qualitative analyses. According to the estimate of network comparison, dynamic needle-tip positioning was associated with higher first-attempt (risk ratio [RR] 1.67; 95% CI 1.33-2.09) and overall success rates (RR 1.25; 95% CI 1.08-1.44) than palpation. The approach without dynamic needle-tip positioning was not associated with higher first-attempt (RR 1.17; 95% CI 0.91-1.49) and overall success rates (RR 1.10; 95% CI 0.90-1.33) than palpation. Compared to the approach without dynamic needle-tip positioning, dynamic needle-tip positioning was associated with a higher first-attempt success rate (RR 1.43; 95% CI 1.07-1.92), but not a higher overall success rate (RR 1.14; 95% CI 0.92-1.41). CONCLUSIONS: Dynamic needle-tip positioning is efficacious for peripheral venous catheterization in children. It would be better to include dynamic needle-tip positioning for the ultrasound-guided short-axis out-of-plane approach.
  • Atsuhiro Kitaura; Rina Yamamoto; Shota Tsukimoto; Shinichi Hamasaki; Yasuhumi Nakajima
    Cureus 15 4 e37436  2023年04月 
    A small percentage of cases of dermatomyositis are positive for anti-mitochondrial antibodies (AMA), a known marker for primary biliary cirrhosis. AMA-positive myositis is a rare disease that has been reported to be accompanied by myocarditis, resulting in low left ventricular function, supraventricular arrhythmias, and abnormalities of the conduction system. We present a case of AMA-positive myocarditis resulting in sinus arrest during general anesthesia. A 66-year-old female with AMA-positive myocarditis underwent artificial femoral head replacement for osteonecrosis of the femoral head under general anesthesia. During general anesthesia, a nine-second sinus arrest occurred without any inducement. The sinus arrest was thought to be influenced by not only over-suppression caused by severe supraventricular tachycardia derived from sick sinus syndrome but sympathetic depression caused by general anesthesia. Because of the potential for life-threatening cardiovascular events during anesthesia in patients with AMA-positive myositis, it was considered essential to provide adequate preoperative management and intraoperative monitoring during anesthesia for patients with this disease. Herein, we report our case with a literature review.
  • Haruyuki Yuasa; Atsuhiro Kitaura; Yasuyo Miura; Shota Tsukimoto; Yasufumi Nakajima; Shinichi Nakao
    Acta Med Kindai Univ 48 1 21 - 26 2023年03月 [査読有り]
  • Jun Takeshita; Yoshinobu Nakayama; Kazuya Tachibana; Yasufumi Nakajima; Nobuaki Shime
    Anaesthesia, critical care & pain medicine 101206 - 101206 2023年02月 
    The efficacy of the short-axis out-of-plane (SA-OOP) approach with and without dynamic needle tip positioning (DNTP) remains unclear. This systematic review with network meta-analysis aimed to compare the success rate of arterial line insertion in children using the SA-OOP approach with and without DNTP and the palpation technique. We searched MEDLINE (via PubMed) and the Cochrane Central Register of Controlled Trials. We included randomized controlled trials that compared two of the following techniques for arterial line insertion in children: (1) the ultrasound-guided SA-OOP approach with DNTP; (2) the ultrasound-guided SA-OOP approach without DNTP; and (3) the palpation technique. A network meta-analysis was performed. The outcomes were first-attempt and overall success rates. Eight studies were finally included in this network meta-analysis. The ultrasound-guided SA-OOP approach with DNTP was associated with increased first-attempt (relative risk RR = 3.45 [95% confidence interval (CI) 2.51-4.74]) and overall success rates (RR = 1.81 [1.41-2.32]) when compared with palpation. The same approach performed without DNTP was also associated with increased first-attempt (RR = 1.96 [1.59-2.42]) and overall success rates (RR = 1.25 [1.05-1.49]) when compared with palpation. The ultrasound-guided SA-OOP approach with DNTP was associated with increased first-attempt (RR = 1.76 [1.26-2.44]) and overall success rates (RR = 1.45 [1.10-1.91]) when compared with the same approach performed without DNTP. DNTP should be performed during the ultrasound-guided SA-OOP approach for arterial line insertion in children, as this can help increase first attempt and overall success rates.
  • Atsuhiro Kitaura; Shinichi Nakao; Haruyuki Yuasa; Shota Tsukimoto; Yasuhumi Nakajima
    The American journal of case reports 23 e938609  2022年12月 
    BACKGROUND Prevention of lethal arrhythmias in congenital long QT syndrome type 1 (LQT1) requires avoidance of sympathoexcitation, drugs that prolong QT, and electrolyte abnormalities. However, it is often difficult to avoid all these risks in the perioperative period of open heart surgery. Herein, we report hypokalemia-induced cardiac arrest in a postoperative cardiac patient with LQT1 on catecholamine. CASE REPORT A 79-year-old woman underwent surgical aortic valve replacement for severe aortic stenosis. Although the initial plan was not to use catecholamine, catecholamine was used in the Postoperative Intensive Care Unit with attention to QT interval and electrolytes due to heart failure caused by postoperative bleeding. Serum potassium levels were controlled above 4.5 mEq/L, and no arrhythmic events occurred. On postoperative day 4, the patient was started on insulin owing to hyperglycemia. Cardiac arrest occurred after the first insulin dose; the implantable cardioverter defibrillator was activated, and the patient's own heartbeat resumed. Subsequent examination revealed that a marked decrease in serum potassium level had occurred after insulin administration. The electrocardiogram showed obvious QT prolongation and ventricular fibrillation following R on T. Thereafter, under strict potassium management, there was no recurrence of cardiac arrest events. CONCLUSIONS A patient with LQT1 who underwent open heart surgery developed ventricular fibrillation after Torsades de Pointes, probably due to hypokalemia after insulin administration in addition to catecholamine. It is important to check serum potassium levels to avoid the onset of Torsades de Pointes in patients with long QT syndrome. In addition, the impact of insulin administration was reaffirmed.
  • Matsumoto Tomoyuki; Shirai Toru; Nakajima Yasufumi; Nakao Shinichi
    Acta Medica Kinki University 47 2 53 - 57 2022年12月
  • Atsushi Kainuma; Keiichi Itatani; Koichi Akiyama; Yoshifumi Naito; Maki Ishii; Masaru Shimizu; Junya Ohara; Naotoshi Nakamura; Yasufumi Nakajima; Satoshi Numata; Hitoshi Yaku; Teiji Sawa
    Frontiers in Surgery 9 2022年02月 
    Background There is currently no subjective, definitive evaluation method for therapeutic indication other than symptoms in aortic regurgitation. Energy loss, a novel parameter of cardiac workload, can be visualized and quantified using echocardiography vector flow mapping. The purpose of the present study was to evaluate whether energy loss in patients with chronic aortic regurgitation can quantify their subjective symptoms more clearly than other conventional metrics. Methods We studied 15 patients undergoing elective aortic valve surgery for aortic regurgitation. We divided the patients into symptomatic and asymptomatic groups using their admission records. We analyzed the mean energy loss in one cardiac cycle using transesophageal echocardiography during the preoperative period. The relationships between symptoms, energy loss, and other conventional metrics were statistically analyzed. Results There were seven and eight patients in the symptomatic and asymptomatic groups, respectively. The mean energy loss of one cardiac cycle was higher in the symptomatic group (121 mW/m [96–184]) than in the asymptomatic group (87 mW/m [80–103]) (p = 0.040), whereas the diastolic diameter was higher in the asymptomatic group (65 mm [59–78]) than in the symptomatic group (57 mm [51–57]) (p = 0.040). There was no significant difference between the symptomatic and asymptomatic groups in terms of other conventional metrics. Conclusions An energy loss can quantify patients' subjective symptoms more clearly than other conventional metrics. The small sample size is the primary limitation of our study, further studies assessing larger cohort of patients are warranted to validate our findings.
  • Takeshi Umegaki; Susumu Kunisawa; Kota Nishimoto; Yasufumi Nakajima; Takahiko Kamibayashi; Yuichi Imanaka
    Journal of cardiothoracic and vascular anesthesia 2021年07月 
    OBJECTIVES: To comparatively examine the risk of postoperative paraplegia between open surgical descending aortic repair and thoracic endovascular aortic repair (TEVAR) among patients with thoracic aortic disease. DESIGN: Retrospective cohort study. SETTING: Acute-care hospitals in Japan. PARTICIPANTS: A total of 6,202 patients diagnosed with thoracic aortic disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome of this study was the incidence of postoperative paraplegia. Multiple logistic regression models, using inverse probability of treatment weighting and an instrumental variable (ratio of TEVAR use to open surgical repair and TEVAR uses), showed that the odds ratios of paraplegia for TEVAR (relative to open surgical descending aortic repair) were 0.81 (95% confidence interval: 0.42-1.59; p = 0.55) in the inverse probability of treatment-weighted model and 0.88 (0.42-1.86; p = 0.75) in the instrumental-variable model. CONCLUSIONS: There were no statistical differences in the risk of paraplegia between open surgical repair and TEVAR in patients with thoracic aortic disease. Improved perioperative management for open surgical repair may have contributed to the similarly low incidence of paraplegia in these two surgery types.
  • Koichi Akiyama; Keiichi Itatani; Isaac Y Wu; Yosuke Tachibana; Yurie Obata; Yasufumi Nakajima; Masaaki Yamagishi; Hiroo Takayama; Teiji Sawa
    Journal of cardiothoracic and vascular anesthesia 35 7 2242 - 2243 2021年07月
  • Jun Takeshita; Koichi Akiyama; Natsuki Anada; Yasufumi Nakajima
    Journal of cardiothoracic and vascular anesthesia 35 6 1830 - 1832 2021年06月 
    A stuck mechanical valve leaflet is a well-known cardiovascular complication; however, a stuck bioprosthetic valve is a rare but potentially fatal complication. Herein a case of stuck bioprosthetic mitral valve caused by a loop of suture, which was detected on intraoperative 3-dimensional (3D) transesophageal echocardiography immediately after cardiopulmonary bypass, is presented. Restricted motion of the 2 leaflets during diastole and incomplete coaptation during systole were observed clearly on 3D imaging. Thus, intraoperative 3D transesophageal echocardiography imaging is useful for detecting such complications immediately after cardiopulmonary bypass.
  • Jun Takeshita; Kazuya Tachibana; Yoshinobu Nakayama; Yasufumi Nakajima; Hirofumi Hamaba; Tomonori Yamashita; Nobuaki Shime
    British journal of anaesthesia 126 4 e140-e142  2021年04月
  • Jun Takeshita; Kazuya Tachibana; Yasufumi Nakajima; Nobuaki Shime
    The journal of vascular access 1129729820983158 - 1129729820983158 2020年12月 
    Herein, we report the case of a 2-year-old boy in whom a bent peripheral venous catheter was inserted using ultrasound-guided dynamic needle tip positioning via a short-axis out-of-plane approach. The peripheral venous catheter appeared to be successfully inserted into the cephalic vein in the forearm using dynamic needle tip positioning via a short-axis out-of-plane approach. However, after removing the inner needle, no blood return was confirmed. The removed catheter was noted to be bent at approximately one-third of the catheter length from the tip. A large change in the puncture angle during dynamic needle tip positioning for a deeply located vein might have caused this bend. Deeply located veins are not targeted when a blind puncture technique is used, as they are not visible and palpable. They can be visualized by ultrasonography and can be targeted using DNTP; however, the catheter may bend. Clinicians should be aware of this issue and, therefore, they are suggested to ensure that the puncture angle is not too steep and use a long length catheter; in addition, very deep veins should not be targeted.
  • Jun Takeshita; Kazuya Tachibana; Yasufumi Nakajima; Gaku Nagai; Ai Fujiwara; Hirofumi Hamaba; Hideki Matsuura; Tomonori Yamashita; Nobuaki Shime
    Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 21 11 e996-e1001  2020年11月 
    OBJECTIVES: The aim of this study was to compare the occurrence of posterior wall puncture between the long-axis in-plane and the short-axis out-of-plane approaches in a randomized controlled trial of pediatric patients who underwent cardiovascular surgery under general anesthesia. DESIGN: Prospective randomized controlled trial. SETTING: Operating room of Osaka Women's and Children's Hospital. PATIENTS: Pediatric patients less than 5 years old who underwent cardiovascular surgery. INTERVENTIONS: Ultrasound-guided central venous catheterization using the long-axis in-plane approach and short-axis out-of-plane approach. MEASUREMENTS AND MAIN RESULTS: The occurrence of posterior wall puncture was compared between the long-axis in-plane and short-axis out-of-plane approaches for ultrasound-guided central venous catheterization. Patients were randomly allocated to a long-axis group or a short-axis group and underwent ultrasound-guided central venous catheterization in the internal jugular vein using either the long-axis in-plane approach (long-axis group) or the short-axis out-of-plane approach (short-axis group). After exclusion, 97 patients were allocated to the long-axis (n = 49) or short-axis (n = 48) groups. Posterior wall puncture rates were 8.2% (4/49) and 39.6% (19/48) in the long-axis and short-axis groups, respectively (relative risk, 0.21; 95% CI, 0.076-0.56; p = 0.0003). First attempt success rates were 67.3% (33/49) and 64.6% (31/48) in the long-axis and short-axis groups, respectively (relative risk, 1.04; 95% CI, 0.78-1.39; p = 0.77). Overall success rates within 20 minutes were 93.9% (46/49) and 93.8% (45/48) in the long-axis and short-axis groups, respectively (relative risk, 0.99; 95% CI, 0.90-1.11; p = 0.98). CONCLUSIONS: The long-axis in-plane approach for ultrasound-guided central venous catheterization is a useful technique for avoiding posterior wall puncture in pediatric patients, compared with the short-axis out-of-plane approach.
  • Yoshinobu Nakayama; Jun Takeshita; Yasufumi Nakajima; Nobuaki Shime
    Critical care (London, England) 24 1 592 - 592 2020年09月 
    Peripheral vascular catheterization (PVC) in pediatric patients is technically challenging. Ultrasound guidance has gained the most interest in perioperative and intensive care fields because it visualizes the exact location of small target vessels and is less invasive than other techniques. There have been a growing number of studies related to ultrasound guidance for PVC with or without difficult access in pediatric patients, and most findings have demonstrated its superiority to other techniques. There are various ultrasound guidance approaches, and a comprehensive understanding of the basics, operator experience, and selection of appropriate techniques is required for the successful utilization of this technique. This narrative review summarizes the literature regarding ultrasound-guided PVC principles, approaches, and pitfalls to improve its clinical performance in pediatric settings.
  • Jun Takeshita; Yasufumi Nakajima; Atsushi Kawamura; Masashi Taniguchi; Yoshiyuki Shimizu; Muneyuki Takeuchi; Nobuaki Shime
    Critical care medicine 47 10 e836-e840  2019年10月 
    OBJECTIVES: In pediatric patients, indwelling peripheral venous catheters are sometimes displaced to extravascular positions, causing infiltration or extravasation. No reliable techniques are available to confirm accurate IV catheterization. However, ultrasonographic detection of micro-bubble turbulence in the right atrium after saline injection has been reported to be useful in confirming central venous catheter positions in both adults and children. This study evaluated whether this micro-bubble detection test can offer better confirmation of peripheral venous catheter positions compared with the smooth saline injection technique in pediatric patients. DESIGN: Randomized controlled study. SETTING: Single tertiary PICU. PATIENTS: Pediatric patients (weighing < 15 kg) who already had or required a peripheral venous catheter. INTERVENTIONS: Patients were randomly allocated to either of the two groups (150 patients per group): undergoing either the micro-bubble detection test (M group) or the smooth saline injection test (S group). MEASUREMENTS AND MAIN RESULTS: The peripheral venous catheters were confirmed to be IV located in the final position in 137 and 139 patients in the M and S groups, respectively. In properly located catheters, the tests were positive in 100% (n = 137/137; sensitivity, 100%; 95% CI, 97.8-100), and in 89% (n = 124/139; 95% CI, 82.8-93.8) of the M and S groups, respectively (p = 0.0001). Among the catheters located in extravascular positions, the tests were negative in 100% (n = 13/13; specificity, 100%; 95% CI, 79.4-100), and in 64% (n = 7/11; 95% CI, 30.8-89.1) of the M and S groups, respectively (p = 0.017). CONCLUSIONS: The micro-bubble detection test is a useful technique for detecting extravasation and confirming proper positioning of peripheral IV catheters in pediatric patients.
  • Jun Takeshita; Takayuki Yoshida; Yasufumi Nakajima; Yoshinobu Nakayama; Kei Nishiyama; Yukie Ito; Yoshiyuki Shimizu; Muneyuki Takeuchi; Nobuaki Shime
    Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 20 9 e410-e414  2019年09月 [査読有り]
     
    OBJECTIVES: This study evaluated whether the dynamic needle tip positioning technique increased the success rate of ultrasound-guided peripheral venous catheterization in pediatric patients with a small-diameter vein compared with the static ultrasound-guided technique. DESIGN: Randomized controlled study. SETTING: Single institution, Osaka Women's and Children's Hospital. PATIENTS: The study population included 60 pediatric patients less than 2 years old who required peripheral venous catheterization in the PICU. INTERVENTIONS: Patients were randomly divided into the dynamic needle tip positioning (n = 30) or static group (n = 30). Each group received ultrasound-guided peripheral venous catheterization with or without dynamic needle tip positioning, respectively. The Fisher exact test, Kaplan-Meier curve plots, log-rank tests, and Mann-Whitney U test were used in the statistical analysis. MEASUREMENTS AND MAIN RESULTS: The first-attempt success rate was higher in the dynamic needle tip positioning group than in the static group (86.7% vs 60%; p = 0.039; relative risk = 1.44; 95% CI, 1.05-2.0). The overall success rate within 10 minutes was higher in the dynamic needle tip positioning group than in the static group (90% vs 63.3%; p = 0.03; relative risk = 1.42; 95% CI, 1.06-1.91). Significantly fewer attempts were made in the dynamic needle tip positioning group than in the static group (median [interquartile range, range] = 1 [1-1, 1-2] vs 1 [1-2, 1-3]; p = 0.013]). The median (interquartile range) catheterization times were 51.5 seconds (43-63 s) and 71.5 seconds (45-600 s) in the dynamic needle tip positioning and static groups, respectively (p = 0.01). CONCLUSIONS: Dynamic needle tip positioning increased the first-attempt and overall success rates of ultrasound-guided peripheral venous catheterization in pediatric patients less than 2 years old.
  • Takeshita S; Ogawa S; Nakayama Y; Mukai N; Nakajima Y; Mizobe T; Sawa T; Tanaka KA
    Anesthesia and analgesia 129 2 339 - 345 2019年08月 [査読有り]
  • Jun Takeshita; Takayuki Yoshida; Yasufumi Nakajima; Yoshinobu Nakayama; Kei Nishiyama; Yukie Ito; Yoshiyuki Shimizu; Muneyuki Takeuchi; Nobuaki Shime
    Journal of cardiothoracic and vascular anesthesia 33 7 1919 - 1925 2019年07月 [査読有り]
     
    OBJECTIVE: Arterial catheterization for infants and small children is technically challenging. This study evaluated whether the dynamic needle tip positioning (DNTP) technique improved the success rate of ultrasound-guided radial artery catheterization in patients with a radial artery depth ≥4 mm compared with the conventional ultrasound-guided technique. DESIGN: Randomized controlled study. SETTING: Single institution, Osaka Women's and Children's Hospital. PARTICIPANTS: Patients (n = 40; age <3 years) with artery depth ≥4 mm. INTERVENTIONS: Patients were divided randomly into 2 groups. The DNTP group received ultrasound-guided radial artery catheterization with DNTP; the conventional group received catheterization without DNTP. MEASUREMENTS AND MAIN RESULTS: First-attempt success rates were 85% and 50% in the DNTP and conventional groups, respectively (p = 0.018; relative risk = 1.7; 95% CI: 1.06-2.73). Overall success rates within 10 minutes were 95% and 60% in the DNTP and conventional groups, respectively (p = 0.008; relative risk = 1.58; 95% CI: 1.09-2.3). Posterior wall puncture rates were 5% and 50% in the DNTP and conventional groups, respectively (p = 0.0014; relative risk = 0.1; 95% CI: 0.014-0.71). Significantly fewer attempts were made in the DNTP group (median = 1 v 1.5; p = 0.01). The median catheterization times were 38 seconds (34-55.5) and 149 seconds (49.5-600) in the DNTP and conventional groups, respectively (p = 0.0003). CONCLUSION: Dynamic needle tip positioning improved first-attempt and overall success rates of ultrasound-guided radial artery catheterization in pediatric patients with a radial artery depth ≥4 mm.
  • Yoshida Takayuki; Anada Natsuki; Nakajima Yasufumi
    JA CLINICAL REPORTS 5 2019年03月 [査読有り]
  • Dynamic needle tip positioningを用いた小児患者の超音波ガイド下末梢静脈穿刺 ランダム化比較試験
    竹下 淳; 伊東 幸恵; 稲田 雄; 中嶋 康文; 中山 力恒; 西山 慶; 籏智 武志; 清水 義之; 竹内 宗之; 志馬 伸朗
    日本集中治療医学会雑誌 26 Suppl. [O52 - 1] (一社)日本集中治療医学会 2019年02月
  • Mukai N; Nakayama Y; Ishi S; Murakami T; Ogawa S; Kageyama K; Murakami S; Sasada Y; Yoshioka J; Nakajima Y
    PloS one 14 7 e0218797  2019年 [査読有り]
  • 竹下 淳; 吉田 敬之; 中嶋 康文; 中山 力恒; 竹内 宗之; 志馬 伸朗
    日本小児麻酔学会誌 24 Suppl. 96 - 96 (一社)日本小児麻酔学会 2018年10月
  • 竹下 淳; 吉田 敬之; 中山 力恒; 中嶋 康文
    Cardiovascular Anesthesia 22 Suppl. 155 - 155 (一社)日本心臓血管麻酔学会 2018年09月
  • 向井 信弘; 中山 力恒; 前田 祥子; 石井 祥代; 小川 覚; 穴田 夏樹; 溝部 俊樹; 中嶋 康文
    Cardiovascular Anesthesia 22 Suppl. 263 - 263 (一社)日本心臓血管麻酔学会 2018年09月
  • Shihoko Okabayashi; Satoru Ogawa; Kenichi A Tanaka; Takashi Nishiyama; Shusuke Takeshita; Yoshinobu Nakayama; Yasufumi Nakajima; Teiji Sawa; Toshiki Mizobe
    Journal of cardiothoracic and vascular anesthesia 32 4 1609 - 1614 2018年08月 
    OBJECTIVE: Point-of-care (POC) devices allow for prothrombin time/international normalized ratio (PT/INR) testing in whole blood (WB) and timely administration of plasma or prothrombin complex concentrate during cardiopulmonary bypass surgery. This study evaluated the sensitivities of a new POC PT test, a dry-hematology method with heparin neutralization technology (DRIHEMATO PT-S [DRI PT-S]; A&T Corporation, Kanagawa, Japan), and compared it with other POC tests currently available. DESIGN: Prospective, observational study. SETTING: University hospital, single center. PARTICIPANTS: Healthy volunteers and warfarin-treated and cardiac surgical patients. MEASUREMENT AND MAIN RESULTS: In WB samples obtained from 6 healthy volunteers, PT-INR results of DRI PT-S were not affected by an in vitro addition of heparin <6.0 U/mL. In warfarin-treated samples (n = 88, PT/INR 0.98-3.87), PT-INR with DRI PT-S showed acceptable correlation with the laboratory method (r2 = 0.85, p < 0.001). In blood samples obtained from cardiac surgical patients (n = 72), heparin prolonged the PT/INR with the laboratory assay, dry-hematology method with non heparin neutralization technology (DRI PT), Coaguchek XS (Roche Diagnostics, Basel, Switzerland), and Hemochron Jr. (Accriva Diagnostics, Edison, NJ), but DRI PT-S was not affected by heparin anticoagulation. In nonheparinized samples, different methods between DRI PT-S and the laboratory method yielded acceptable correlations (r2 = 0.76, p < 0.0001). There was a moderate correlation between factor levels and the PT-INR with DRI PT-S (factor [F]II: r2 = 0.63, FVII: r2 = 0.47, FX: r2 = 0.67; p < 0.0001). CONCLUSIONS: This study demonstrated that PT/INR can be accurately assessed using the dry-hematology method in WB under therapeutic heparin levels. Currently available other POC PT/INR tests are affected by heparin, and thus they are not recommended for coagulation monitoring during cardiopulmonary bypass.
  • Okabayashi S; Ogawa S; Tanaka KA; Nishiyama T; Takeshita S; Nakayama Y; Nakajima Y; Sawa T; Mizobe T
    Journal of cardiothoracic and vascular anesthesia 32 4 1609 - 1614 2018年08月 [査読有り]
  • Mukai N; Nakayama Y; Ishi S; Ogawa S; Maeda S; Anada N; Murakami S; Mizobe T; Sawa T; Nakajima Y
    Critical care medicine 46 8 e761 - e767 2018年08月 [査読有り]
  • Takeshi Umegaki; Susumu Kunisawa; Yasufumi Nakajima; Takahiko Kamibayashi; Kiyohide Fushimi; Yuichi Imanaka
    Journal of Cardiothoracic and Vascular Anesthesia 32 3 1281 - 1288 2018年06月 [査読有り]
     
    Objective: The number of surgeries for valvular heart disease performed in Japan has greatly increased over the past decade, and surgical aortic valve replacements (SAVR) constitute the vast majority of aortic valve replacement procedures. Although transcatheter aortic valve implantation (TAVI) was recently introduced, studies have yet to compare the clinical outcomes between TAVI and SAVR in the Japanese healthcare setting. This study aimed to compare in-hospital outcomes between TAVI and SAVR using a multicenter administrative database. Design: Retrospective cohort study. Setting: Acute care hospitals in Japan. Participants: A total of 16,775 patients diagnosed with aortic valve stenosis. Interventions: None. Measurements and Main Results: The main study outcome measure was in-hospital mortality. Based on multiple logistic regression analysis using inverse probability of treatment weighting, the odds ratio of in-hospital mortality for TAVI (relative to SAVR) was calculated to be 0.36 (95% confidence intervals: 0.13–0.98 p = 0.04). In patients aged 80 years or older, the odds ratio was even lower at 0.34 (95% confidence intervals: 0.15-0.73 p < 0.01). In addition, the incidences of reoperations, hemorrhagic complications, cardiac tamponade, and postoperative infections were significantly higher in the SAVR patients. Conclusions: This large-scale multicenter comparative analysis of TAVI and SAVR in Japan indicated that TAVI produced better clinical outcomes in patients with aortic valve stenosis. The improved outcomes were particularly notable in patients aged 80 years or older.
  • Nobuhiro Mukai; Yoshinobu Nakayama; Satoshi Murakami; Toshihito Tanahashi; Daniel I Sessler; Sachiyo Ishii; Satoru Ogawa; Natsuko Tokuhira; Toshiki Mizobe; Teiji Sawa; Yasufumi Nakajima
    Pediatric Research 83 4 866 - 873 2018年04月 [査読有り]
     
    BackgroundChildren with cyanotic heart disease develop secondary erythrocytosis and thrombocytopenia via unknown mechanisms. Mature erythrocyte microRNAs may reflect clinical pathologies and cell differentiation processes pre-enucleation. This study evaluated erythrocyte microRNAs in children with cyanotic heart disease.MethodsErythrocyte microRNAs from children with cyanotic and acyanotic heart disease and without cardiac disease were quantified with Ion PGM System (n=10 per group). Differential expression was confirmed by quantitative PCR (qPCR n=20 per group).ResultsMir-486-3p, mir-486-5p, and mir-155-5p increased in patients with cyanotic heart disease compared with those without heart disease: fold differences (95% confidence interval): mir-486-3p: 1.92 (1.14-3.23), P=0.011 mir-486-5p: 2.27 (1.41-3.65), P< 0.001 and mir-155-5p: 1.44 (1.03-2.03), P=0.028. Mir-486-5p was increased, and let-7e-5p and mir-1260a were decreased in patients with acyanotic heart disease compared with those without heart disease: mir-486-5p: 1.66 (1.03-2.66), P=0.035 let-7e-5p: 0.66 (0.44-0.99), P=0.049 and mir-1260a: 0.53 (0.29-0.99), P=0.045.ConclusionSeveral microRNA levels changed in children with cyanotic and acyanotic heart disease. Mir-486-3p and -5p are associated with hematopoietic differentiation. Mir-486-3p regulates the erythroid vs. megakaryocyte lineage fate decision. Mir-155 is a hypoxia-inducible microRNA, whose overexpression inhibits megakaryocyte differentiation. Erythrocyte microRNA expression changes may contribute to erythrocytosis and thrombocytopenia in children with cyanotic heart disease.
  • Akiyama Koichi; Wu Isaac; Kainuma Atsushi; Nakajima Yasufumi; Sawa Teiji; Itatani Keiichi; Takayama Hiroo
    ANESTHESIA AND ANALGESIA 126 4 135  2018年04月 [査読有り]
  • 当院救命救急センターICUで死亡し、病理解剖を行なった6年間の症例の検討
    別府 賢; 中嶋 康文; 上田 忠弘; 濱中 訓生; 田中 博之; 笹橋 望; 西山 慶
    日本集中治療医学会雑誌 25 Suppl. [O50 - 1] (一社)日本集中治療医学会 2018年02月
  • Koichi Akiyama; Yoshifumi Naito; Mao Kinoshita; Maki Ishii; Yasufumi Nakajima; Keiichi Itatani; Takako Miyazaki; Masaaki Yamagishi; Hitoshi Yaku; Teiji Sawa
    Journal of cardiothoracic and vascular anesthesia 31 6 2118 - 2122 2017年12月
  • M. Murase; Y. Nakayama; D. I. Sessler; N. Mukai; S. Ogawa; Y. Nakajima
    BRITISH JOURNAL OF ANAESTHESIA 119 6 1118 - 1126 2017年12月 [査読有り]
     
    Background. Anucleate platelets can undergo apoptosis in response to various stimuli, as do nucleated cells. Cardiopulmonary bypass (CPB) causes platelet dysfunction and can also activate platelet apoptotic pathways. We therefore evaluated time-dependent changes in blood platelet Bax (a pro-apoptotic molecule) levels and platelet dysfunction after cardiac surgery. Methods. We assessed blood samples obtained from subjects having on-pump or off-pump coronary artery bypass graft surgery (n=20 each). We also evaluated the in vitro effects of platelet Bax increase in eight healthy volunteers. Results. Thrombin-induced platelet calcium mobilisation and platelet-surface glycoprotein Ib (GPIb) expression were lowest at weaning from CPB and did not recover on postoperative day one. On-pump surgery increased platelet expression of Bax, especially the oligomerised form, along with translocation of Bax from the cytosol to mitochondria and platelet-surface tumour necrosis factor-alpha (TNF-alpha)-converting enzyme (TACE) expression. In contrast, mitochondrial cytochrome c expression was reduced. While similar in direction, the magnitude of the observed changes was smaller in patients having off-pump surgery. In vitro, a cell-permeable Bax peptide increased platelet Bax expression to the same extent seen during bypass and produced similar platelet changes. These apoptotic-like changes were largely reversed by Bcl-xL pre-administration, and were completely reversed by combined application of inhibitors that stabilise outer mitochondrial membrane permeability and TACE. Conclusions. CPB increases platelet Bax expression, which contributes to reduced platelet-surface GPIb expression and thrombin-induced platelet calcium changes. These changes in platelet apoptotic signalling might contribute to platelet dysfunction after CPB. Clinical trial registration. UMIN Clinical Trials Registry (number UMIN000006033).
  • Koichi Akiyama; Yoshifumi Naito; Mao Kinoshita; Maki Ishii; Yasufumi Nakajima; Keiichi Itatani; Takako Miyazaki; Masaaki Yamagishi; Hitoshi Yaku; Teiji Sawa
    JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA 31 6 2118 - 2122 2017年12月 [査読有り]
  • Koichi Akiyama; Sachiko Maeda; Tasuku Matsuyama; Atsushi Kainuma; Maki Ishii; Yoshifumi Naito; Mao Kinoshita; Saeko Hamaoka; Hideya Kato; Yasufumi Nakajima; Naotoshi Nakamura; Keiichi Itatani; Teiji Sawa
    BMC cardiovascular disorders 17 1 172 - 172 2017年06月
  • Koichi Akiyama; Naotoshi Nakamura; Keiichi Itatani; Yoshifumi Naito; Mao Kinoshita; Masaru Shimizu; Saeko Hamaoka; Hideya Kato; Hiroaki Yasumoto; Yasufumi Nakajima; Toshiki Mizobe; Satoshi Numata; Hitoshi Yaku; Teiji Sawa
    INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY 24 6 869 - 875 2017年06月 [査読有り]
     
    OBJECTIVES: We assessed vortex patterns and energy loss in left ventricular flow in patients who underwent mitral valve repair or replacement with bioprosthetic valves. METHODS: Vector flow mapping was performed before and after the procedure in 15 and 17 patients who underwent repair and replacement, respectively. The preprocedure mitral-septal angle was measured in all patients. Relationships between vortex patterns or energy loss change (ELC) and annuloplasty ring or bioprosthetic valve sizes or the effect of mitral leaflet resection in the repair group were statistically analysed. RESULTS: Normal vortex patterns were observed in 13 and 1 patients who underwent repair and replacement, respectively. Abnormal vortex patterns were observed in 2 and 16 patients who underwent repair and replacement, respectively. ELC was significantly higher in the replacement group (196.6 +/- 180.8) than in the repair group (71.9 +/- 43.9). In the repair group, preoperative mitral-septal angles in patients with normal vortex patterns (79.2 degrees +/- 3.4 degrees) were significantly larger than those in patients with abnormal vortex patterns (67.5 degrees +/- 3.5 degrees). No significant differences were observed in the effects of annuloplasty ring and bioprosthetic valve sizes on vortex patterns and ELC, and in the effect of mitral valve resection (80.4 +/- 56.3) and respect (without leaflet resection) (53.8 +/- 28.4) on ELC in the repair group. CONCLUSIONS: Mitral valve replacement alters the intraventricular vortex pattern and increases flow energy loss. A small mitral-septal angle is a risk factor for abnormal vortex patterns after mitral valve repair surgery.
  • Koichi Akiyama; Sachiko Maeda; Tasuku Matsuyama; Atsushi Kainuma; Maki Ishii; Yoshifumi Naito; Mao Kinoshita; Saeko Hamaoka; Hideya Kato; Yasufumi Nakajima; Naotoshi Nakamura; Keiichi Itatani; Teiji Sawa
    BMC CARDIOVASCULAR DISORDERS 17 1 172  2017年06月 [査読有り]
  • Koichi Akiyama; Maki Ishii; Keiichi Itatani; Mao Kinoshita; Atsushi Kainuma; Yasufumi Nakajima; Teiji Sawa
    ANESTHESIA AND ANALGESIA 124 145 - 146 2017年05月 [査読有り]
  • 強直間代性痙攣による非外傷性椎体破裂骨折の一例
    濱中 訓生; 藤野 光洋; 岡田 信長; 田中 博之; 竹下 淳; 別府 賢; 中嶋 康文; 笹橋 望; 西山 慶
    日本集中治療医学会雑誌 24 Suppl. DP157 - 2 (一社)日本集中治療医学会 2017年02月
  • Koichi Akiyama; Keiichi Itatani; Yoshifumi Naito; Mao Kinoshita; Masaru Shimizu; Saeko Hamaoka; Hiroaki Yasumoto; Hideya Kato; Yasufumi Nakajima; Satoshi Numata; Hitoshi Yaku; Teiji Sawa
    JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA 31 1 211 - 214 2017年02月 [査読有り]
  • Koichi Akiyama; Sachiko Maeda; Tasuku Matsuyama; Atsushi Kainuma; Maki Ishii; Yoshifumi Naito; Mao Kinoshita; Saeko Hamaoka; Hideya Kato; Yasufumi Nakajima; Naotoshi Nakamura; Keiichi Itatani; Teiji Sawa
    BMC CARDIOVASCULAR DISORDERS 17 1 21  2017年01月 [査読有り]
     
    Background: Vector flow mapping, a novel flow visualization echocardiographic technology, is increasing in popularity. Energy loss reference values for children have been established using vector flow mapping, but those for adults have not yet been provided. We aimed to establish reference values in healthy adults for energy loss, kinetic energy in the left ventricular outflow tract, and the energetic performance index (defined as the ratio of kinetic energy to energy loss over one cardiac cycle). Methods: Transthoracic echocardiography was performed in fifty healthy volunteers, and the stored images were analyzed to calculate energy loss, kinetic energy, and energetic performance index and obtain ranges of reference values for these. Results: Mean energy loss over one cardiac cycle ranged from 10.1 to 59.1 mW/m (mean +/- SD, 27.53 similar to 13.46 mW/m), with a reference range of 10.32 similar to 58.63 mW/m. Mean systolic energy loss ranged from 8.5 to 80.1 (23.52 +/- 14.53) mW/m, with a reference range of 8.86 similar to 77.30 mW/m. Mean diastolic energy loss ranged from 7.9 to 86 (30.41 +/- 16.93) mW/ m, with a reference range of 8.31 similar to 80.36 mW/m. Mean kinetic energy in the left ventricular outflow tract over one cardiac cycle ranged from 200 to 851.6 (449.74 +/- 177.51) mW/m with a reference range of 203.16 similar to 833.15 mW/m. The energetic performance index ranged from 5.3 to 37.6 (18.48 +/- 7.74), with a reference range of 5.80 similar to 36.67. Conclusions: Energy loss, kinetic energy, and energetic performance index reference values were defined using vector flow mapping. These reference values enable the assessment of various cardiac conditions in any clinical situation.
  • Yasufumi Nakajima
    JOURNAL OF ANESTHESIA 30 5 873 - 883 2016年10月 [査読有り]
     
    Although body temperature is a classic primary vital sign, its value has received little attention compared with the others (blood pressure, heart rate, and respiratory rate). This may result from the fact that unlike the other primary vital signs, aging and diseases rarely affect the thermoregulatory system. Despite this, when humans are exposed to various anesthetics and analgesics and acute etiologies of non-infectious and infectious diseases in perioperative and intensive care settings, abnormalities may occur that shift body temperature up and down. A recent upsurge in clinical evidence in the perioperative and critical care field resulted in many clinical trials in temperature management. The results of these clinical trials suggest that aggressive body temperature modifications in comatose survivors after resuscitation from shockable rhythm, and permissive fever in critically ill patients, are carried out in critical care settings to improve patient outcomes; however, its efficacy remains to be elucidated. A recent, large multicenter randomized controlled trial demonstrated contradictory results, which may disrupt the trends in clinical practice. Thus, updated information concerning thermoregulatory interventions is essential for anesthesiologists and intensivists. Here, recent controversies in therapeutic hypothermia and fever management are summarized, and their relevance to the physiology of human thermoregulation is discussed.
  • Yoshinobu Nakayama; Yuko Inagaki; Yasufumi Nakajima; Daniel I. Sessler; Nobuhiro Mukai; Satoru Ogawa; Toshiki Mizobe; Teiji Sawa
    ANESTHESIOLOGY 125 4 716 - 723 2016年10月 [査読有り]
     
    Background: The main cause of unsuccessful peripheral radial artery catheterization using traditional palpation is imprecisely locating the arterial center. The authors evaluated factors causing disparities between the arterial centers determined by palpation versus ultrasound. The authors applied them to create and test a novel catheterization training program. Methods: The arterial central axis was determined by ultrasound and palpation in 350 adults. Potential independent predictors of disparity included sex, body mass index, pulse pressure, transverse arterial diameter, subcutaneous arterial depth, chronic hypertension, and experience as an anesthesiologist (less than 3 vs. greater than or equal to 3 yr). Using the results, the authors developed a radial artery catheterization training program. It was tested by enrolling 20 first-year interns, randomized to a training or control group. The time to successful insertion was the primary outcome measure. The success rate and time required for catheterization by palpation were evaluated in 100 adult patients per group. Results: Independent predictors of central axis disparity were pulse pressure, subcutaneous radial artery depth, years of experience, and chronic hypertension. Training improved the catheterization time (training group 56 +/- 2 s vs. control group 109 +/- 2 s; difference -53 +/- 3 s; 95% CI, -70 to -36 s; P < 0.0001) and total success rate (training group 83 of 100 attempts, 83%; 95% CI, 75 to 90 vs. control group 57 of 100, 57%; 95% CI, 47 to 66; odds ratio, 3.7; 95% CI, 2.7 to 5.1). Conclusions: Misjudging the central axis position of the radial artery is common with a weak pulse and/or deep artery. The authors' program, which focused on both these issues, shortened the time for palpation-guided catheterization and improved success.
  • 竹下 淳; 中山 力恒; 中嶋 康文; 小川 覚; 佐和 貞治; 溝部 俊樹
    日本小児麻酔学会誌 22 1 118 - 118 (一社)日本小児麻酔学会 2016年09月
  • Nakamura E; Kageyama K; Okabayashi M; Kasai S; Nakajima Y; Sawa T; Nakamura K
    Masui. The Japanese journal of anesthesiology 65 8 820 - 823 2016年09月 [査読有り]
  • Koichi Akiyama; Keiichi Itatani; Mao Kinoshita; Masaru Shimizu; Saeko Hamaoka; Hideya Kato; Yoshifumi Naito; Yasufumi Nakajima; Satoshi Numata; Toshiki Mizobe; Hitoshi Yaku; Teiji Sawa
    JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 67 13 1701 - 1701 2016年04月 [査読有り]
  • Soeda R; Taniguchi F; Sawada M; Hamaoka S; Shibasaki M; Nakajima Y; Hashimoto S; Sawa T; Nakayama Y
    Case reports in anesthesiology 2016 6871565  2016年 [査読有り]
  • Jun Takeshita; Yoshinobu Nakayama; Yasufumi Nakajima; Daniel I. Sessler; Satoru Ogawa; Teiji Sawa; Toshiki Mizobe
    Critical Care 19 1 15  2015年01月 [査読有り]
     
    Introduction: Venous catheterisation in paediatric patients can be technically challenging. We examined factors affecting catheterisation of invisible and impalpable peripheral veins in children and evaluated the best site for ultrasound-guided catheterisation. Methods: Systolic pressure, age, sex, and American Society of Anaesthesiologists (ASA) physical status were determined in 96 children weighing less than 20 kg. Vein diameter and subcutaneous depth were measured with ultrasound. Logistic regression was used to evaluate the contribution of these factors to cannulation success with (n=65) or without (n=31) ultrasound guidance. Thereafter, we randomly assigned 196 patients for venous catheter insertion in the dorsal veins of the hand, the cephalic vein in the forearm, or the great saphenous vein. Success rates and vein diameters were evaluated by using Dunn tests insertion time was evaluated by using Kaplan-Meier cumulative incidence analysis. Results: Independent predictors of catheterisation were ultrasound guidance (odds ratio (OR)=7.3, 95% confidence interval (CI) 2.0 to 26.0, P=0.002), vein diameter (OR=1.5 per 0.1 mm increase in diameter, 95% CI 1.1 to 2.0, P=0.007), and ASA physical status (OR=0.4 per status 1 increase, 95% CI 0.2 to 0.9, P=0.03). Cephalic veins were significantly larger (cephalic diameter 1.8 mm, P=0.001 versus saphenous 1.5 mm, P < 0.001 versus dorsal 1.5 mm). Catheterisation success rates were significantly better at the cephalic vein than either the dorsal hand or saphenous vein (cephalic 95%, 95% CI 89% to 100%, P < 0.001 versus dorsal 69%, 95% CI 56% to 82%, P=0.03 versus saphenous 75%, 95% CI 64% to 86%). Conclusions: The cephalic vein in the proximal forearm appears to be the most appropriate initial site for ultrasound-guided catheterisation in invisible and impalpable veins of paediatric patients. Trial registry number: UMIN Clinical Trials Registry as UMIN000010961. Registered on 14 June 2013.
  • Mao Kinoshita; Masayuki Shibasaki; Nobuaki Shime; Yasufumi Nakajima; Satoshi Yokono; Fumimasa Amaya; Teiji Sawa
    Masui. The Japanese journal of anesthesiology 64 1 98 - 102 2015年01月 
    BACKGROUND: The goal of this multicenter survey was to examine the variety of pediatric endotracheal tube (PETT) management methods utilized by anesthesiologists. METHODS: A postal survey for PETT management methods was performed among anesthesiologists at Kyoto Prefectural University of Medicine and its affiliated hospitals. RESULTS: Age was the primary criteria for PETT size selection, followed by height and weight, while the surgical procedure was the primary criteria for PETT type selection, followed by age and then weight. Cuffed PETTs were routinely used for more than 70% of their patients by 57.1% of respondents; however, 55.7% of respondents had no criteria clearly defining when and how to inflate the cuff. Strategies for airway complications, including post-extubation stridor, vary amongst anesthesiologists. CONCLUSIONS: The present study revealed that practice of PETT management depends on anesthesiologists. PETT management should be sophisticated with wide use of cuffed PETTs.
  • Satoru Ogawa; Kenichi A. Tanaka; Yasufumi Nakajima; Yoshinobu Nakayama; Jun Takeshita; Masatoshi Arai; Toshiki Mizobe
    ANESTHESIA AND ANALGESIA 120 1 18 - 25 2015年01月 [査読有り]
     
    BACKGROUND: An accurate and rapid determination of fibrinogen level is important during hemorrhage to establish a timely hemostatic intervention. The accuracy of fibrinogen measurements may be affected by the specific methodology for its determination, fluid therapies, and anticoagulant agents. The dry-hematology method (DRIHEMATO (R)) is a novel approach to determine fibrinogen levels in plasma and whole blood based on thrombin-activated coagulation time. We hypothesized that plasma or whole blood fibrinogen level using the dry-hematology method would be similar to those measured with conventional plasma fibrinogen assays. METHODS: Acquired hypofibrinogenemia was modeled by serial dilutions of blood samples obtained from 12 healthy volunteers. Citrated whole blood samples were diluted with either normal saline, 5% human albumin, or 6% hydroxyethyl starch to achieve 25%, 50%, and 75% volume replacement. The dry-hematology method, the Clauss method, the prothrombin time (PT)-derived method, determination of antigen levels, and thromboelastometric fibrin formation were compared in plasma or whole blood samples. The effect of heparin on each assay was examined (0 to 6 IU/mL). Comparisons of dry-hematology and other methods were also conducted using ex vivo samples obtained from cardiac surgical patients (n = 60). RESULTS: In plasma samples, there were no significant differences between dry-hematology and the Clauss method, while dry-hematology showed lower fibrinogen levels compared with PT-derived and antigen level methods. The dry-hematology method yielded acceptable concordance correlation coefficients (Pc) with the Clauss method, the PT-derived method, and fibrinogen antigen levels (Pc = 0.91-0.99). The type of diluents and heparin affected the results of the PT-derived method and thromboelastometric assay, but not the dry-hematology method. In cardiac surgical patients, the overall correlation in fibrinogen levels between dry-hematology and the other methods was comparable to the results from in vitro dilution experiments. The dry-hematology reported higher fibrinogen values in whole blood compared with those measured in plasma samples, but hematocrit adjustment decreased the bias between whole blood and plasma samples from 73 mg/dL (95% prediction interval: 40, 106) to -13 mg/dL (95% prediction interval: -35, 8.5). CONCLUSIONS: This study demonstrated that fibrinogen levels can be accurately assessed by the dry-hematology method in plasma and the results are not affected by heparin or colloids. For whole blood fibrinogen measurements by dry-hematology, hematocrit adjustment is necessary to compensate for dynamic changes in hematocrit in perioperative bleeding settings.
  • Mao Kinoshita; Masayuki Shibasaki; Nobuaki Shime; Yasufumi Nakajima; Satoshi Yokono; Fumimasa Amaya; Teiji Sawa
    Japanese Journal of Anesthesiology 64 1 98 - 102 2015年01月 [査読有り]
     
    Background: The goal of this multicenter survey was to examine the variety of pediatric endotracheal tube (PETT) management methods utilized by anesthesiologists. Methods: A postal survey for PETT management methods was performed among anesthesiologists at Kyoto Prefectural University of Medicine and its affiliated hospitals. Results: Age was the primary criteria for PETT size selection, followed by height and weight, while the surgical procedure was the primary criteria for PETT type selection, followed by age and then weight. Cuffed PETTs were routinely used for more than 70% of their patients by 57.1% of respondents:however. 55.7% of respondents had no criteria clearly defining when and how to inflate the cuff. Strategies for airway complications, including post-extubation stridor, vary amongst anesthesiologists. Conclusions: The present study revealed that practice of PETT management depends on anesthesiologists. PETT management should be sophisticated with wide use of cuffed PETTs.
  • Y. Nakayama; Y. Nakajima; K. A. Tanaka; D. I. Sessler; S. Maeda; J. Iida; S. Ogawa; T. Mizobe
    BRITISH JOURNAL OF ANAESTHESIA 114 1 91 - 102 2015年01月 [査読有り]
     
    Thromboelastometric evaluation of coagulation might be useful for prediction and management of bleeding after paediatric cardiac surgery. We tested the hypothesis that the use of a thromboelastometry-guided algorithm for blood product management reduces blood loss and transfusion requirements. We studied 78 patients undergoing paediatric cardiac surgery with cardiopulmonary bypass (CPB) for the initial 12 h after operation. Stepwise multiple linear regression was used to develop an algorithm to guide blood product transfusions. Thereafter, we randomly assigned 100 patients to conventional or algorithm-guided blood product management, and assessed bleeding and red cell transfusion requirements. CPB time, post-bypass rotational thromboelastometry (ROTEMA (R)) EXTEM amplitude at 10 min (A10), and FIBTEM-A10 were independently associated with chest tube drainage volume during the initial 12 h after operation. Discriminative analysis determined cut-off values of 30 mm for EXTEM-A10 and 5 mm for FIBTEM-A10, and estimated optimal intraoperative fresh-frozen plasma and platelet concentrate transfusion volumes. Thromboelastometry-guided post-bypass blood product management significantly reduced postoperative bleeding (9 vs 16 ml kg(-1), P < 0.001) and packed red cell transfusion requirement (11 vs 23 ml kg(-1), P=0.005) at 12 h after surgery, and duration of critical care stay (60 vs 71 h, P=0.014). Rotational thromboelastometry-guided early haemostatic intervention by rapid intraoperative correction of EXTEM-A10 and FIBTEM-A10 reduced blood loss and red cell transfusion requirements after CPB, and reduced critical care duration in paediatric cardiac surgical patients. UMIN Clinical Trials Registry UMIN000006832 (December 4, 2011).
  • 溝部 俊樹; 中山 力恒; 中嶋 康文
    LiSA 21 10 947 - 949 (株)メディカル・サイエンス・インターナショナル 2014年10月 
    食物のエネルギーは,食物中に含まれる炭水化物,脂質,タンパク質の熱量によって決まる。これを整数化したものが,Atwaterの係数(1895年)として有名な生理的燃焼価である。炭水化物とタンパク質は4kcal/g,脂質は9kcal/gとされるが,実際の燃焼価は物質ごとに異なり,炭水化物では,グルコースで3.74kcal/g,マルトースで3.95kcal/g,デンプンで4.18kcal/gである(ちなみに,アルコールは7.1kcal/gである)。(著者抄録)
  • 竹村 瞳; 中山 力恒; 橋本 壮志; 中嶋 康文; 佐和 貞治
    日本臨床麻酔学会誌 34 6 S267 - S267 日本臨床麻酔学会 2014年10月
  • 前田 祥子; 竹下 淳; 中山 力恒; 中嶋 康文; 溝部 俊樹
    Cardiovascular Anesthesia 18 Suppl. 289 - 289 (一社)日本心臓血管麻酔学会 2014年09月
  • 黒光 弘幸; 中山 力恒; 小川 覚; 中嶋 康文; 溝部 俊樹
    Cardiovascular Anesthesia 18 Suppl. 308 - 308 (一社)日本心臓血管麻酔学会 2014年09月
  • 竹下 淳; 中山 力恒; 前田 祥子; 小川 覚; 中嶋 康文; 溝部 俊樹
    Cardiovascular Anesthesia 18 Suppl. 318 - 318 (一社)日本心臓血管麻酔学会 2014年09月
  • 中山 力恒; 中嶋 康文; 溝部 俊樹
    LiSA 21 8 748 - 750 (株)メディカル・サイエンス・インターナショナル 2014年08月 
    周術期に腎臓を保護するとは,どういうことか。一体,"なに"から守ろうというのだろう。手術侵襲や麻酔が患者の腎臓を危険に曝すのだとすれば,何をすれば患者の腎臓を守ることになるのだろうか。"周術期"の"腎保護"を議論する場合,それは急性腎傷害acute kidney injury(AKI)から守ろうというのだろう。AKIの臨床症状は,尿量減少や体液電解質異常など,急性腎不全に準ずるが,術後に敗血症や呼吸器感染症を合併しやすく,いったん発症すると死亡率が高くなることが問題である。さらに,その発症率は非心臓手術で1.0%前後,心臓手術では最大20%と,遭遇する頻度も高い。したがって,本稿のテーマを,「周術期AKIを予防あるいは改善させる薬物とは」と言い換えても過言ではないだろう。周術期AKIを予防あるいは改善させる薬物については,古くから検討されている。しかし,いまだ確固たる地位を築いた薬物はない。その理由として,周術期AKIの誘因が多岐にわたり複雑であること,また,最近までAKIは一定の診断基準さえ確立されておらず,発展途上の分野であることが挙げられる。腎保護に有用とされる薬物のおのおのに関するエビデンスは多く見つかるが,全体像の把握が難しく釈然としないのは,そのためであると考えている。(著者抄録)
  • Yoshinobu Nakayama; Yasufumi Nakajima; Daniel I. Sessler; Sachiyo Ishii; Masayuki Shibasaki; Satoru Ogawa; Jun Takeshita; Nobuaki Shime; Toshiki Mizobe
    ANESTHESIA AND ANALGESIA 118 5 1019 - 1026 2014年05月 [査読有り]
     
    BACKGROUND: Radial arterial catheterization in pediatric patients is occasionally difficult despite ultrasound guidance. We therefore assessed the factors affecting catheterization and tested an intervention designed to improve its success. METHODS: For initial assessment, we performed multiple logistic regression analyses using 102 pediatric patients. Dependent variables included first-attempt and overall success or failure; independent variables were systolic blood pressure, weight, ASA physical status, trisomy 21, arterial diameter, and subcutaneous depth of the radial artery (<2, 2-4, 4 mm). The effect of subcutaneous arterial depth on cannulation success was assessed using Kaplan-Meier curves with log-rank and Dunn tests. We then assessed catheterization success in 60 patients who were randomized to no treatment or subcutaneous saline injection, as necessary, to increase the subcutaneous arterial depth from <2 to 2 to 4 mm. RESULTS: Subcutaneous arterial depth of 2 to 4 mm was derived as a significant independent predictor of initial and overall success from the multiple logistic regression analyses. The 2 to 4 mm group had a significantly shorter catheterization time compared with the other 2 groups in the log-rank test (2-4 vs <2 mm group; P = 0.01, 2-4 vs 4 mm group; P < 0.001), and higher success rate in the first attempt (<2 [43.8%] vs 2-4 mm [76.9%], P = 0.02; 2-4 [76.9%] vs 4.0 mm [19.4%], P < 0.001), and the overall attempt (<2 [62.5%] vs 2-4 mm [89.7%], P = 0.04; 2-4 [89.7%] vs 4.0 mm [51.6%], P = 0.002). Injecting subcutaneous saline to bring arterial depth from <2 mm to 2 to 4 mm significantly shortened catheterization time (P = 0.002), and improved the success rate in the first-attempt (saline injection [85.0%] vs <2 mm [30.0%], P < 0.001), and the overall attempt (saline injection [90.0%] vs <2 mm [55.0%], P = 0.02). CONCLUSIONS: Ultrasound-guided radial artery catheterization in pediatric patients was fastest and most reliable when the artery was 2 to 4 mm below the skin surface. For arteries located <2 mm below the skin surface, increasing the depth to 2 to 4 mm by subcutaneous saline injection reduced catheterization time and improved the success rate.
  • 超音波ガイド下胸部傍脊椎神経ブロックで巨大な胸壁血腫を起こした1例
    板東 瑞樹; 影山 京子; 木下 真央; 中嶋 康文; 佐和 貞治
    臨床麻酔 38 2 227 - 228 真興交易(株)医書出版部 2014年02月 [査読有り]
     
    77歳男。40歳時に胃潰瘍で胃亜全摘術、61歳時に慢性硬膜下血腫で血腫除去術の既往があった。今回、CTで右肺S6に結節影が認められ呼吸機能の混合性障害ほか、超音波で総頸動脈の狭窄率62%、内頸動脈起始部の狭窄を確認、胸腔鏡補助下にて右肺S6部分切除術が施行された。術後は左側臥位でUSG-TPVBが施行され、18GのTouhy針を用いてT7〜8に穿刺、T8〜9にもTPVBを行い、ロピバカインを注入した。更に翌日には左総頸動脈および内頸動脈の狭窄にヘパリンカルシウム皮下注とアスピリン内服を開始した。だが、術後16時間経過の胸部X線では右上肺部にextrapreural sign(+)、125×70mmの腫瘤陰影に加え経胸壁超音波では肋間筋と壁側胸膜間に液体貯留が認められた。以上より、本症例はTPVBブロック手技による胸壁血腫と診断され、抗凝固療法の中止と止血薬の投与、またバストバンド装置で保存療法が行われたが、術後2日目のX線では血腫の増大、CTでは巨大腫瘤陰影と胸水貯留、SpO2の低下を認めたためBiPAPが導入された。その結果、血腫増大なくなり、術後6日目にはBiPAPを離脱、血腫は縮小傾向となり、術後50日目のX線では完全消失が認められた。
  • Kyoko Kageyama; Shiori Kimura; Jun Takeshita; Yasufumi Nakajima; Takae Ibuki; Teiji Sawa
    Masui. The Japanese journal of anesthesiology 63 2 208 - 14 2014年02月 
    Anesthesia requires informed consent because it is an invasive procedure with high risks. We carried out a questionnaire study in 1,050 patients who were seen at the preoperative evaluation clinic (PAC). Patients who heard about PAC for the first time accounted for 77.9% in spite of having experienced anesthesia. Many patients were provided with the information about anesthesia the day before surgery and medication control and additional checking were difficult to carry out. Some patients (34.2%) were told about anesthesia with no attendant. In particular, about complications of anesthesia, many patients did not remember what the specific explanation had been offered in the past. We thought that it is necessary to explain the complications of anesthesia even if it is the second anesthesia for patients.
  • 小児患者に対する超音波ガイド下観血的動脈圧カテーテル留置および末梢静脈カテーテル留置に影響する因子
    中山 力恒; 中嶋 康文; 竹下 淳; 小川 覚; 前田 祥子; 溝部 俊樹
    日本集中治療医学会雑誌 21 Suppl. [DP - 1] (一社)日本集中治療医学会 2014年01月
  • ドライ法を用いた、全血フィブリノゲン値の検討(CG02N)
    小川 覚; 中山 力恒; 中嶋 康文; 溝部 俊樹
    日本集中治療医学会雑誌 21 Suppl. [DP - 5] (一社)日本集中治療医学会 2014年01月
  • Kyoko Kageyama; Shiori Kimura; Jun Takeshita; Yasufumi Nakajima; Takae Ibuki; Teiji Sawa
    Japanese Journal of Anesthesiology 63 2 208 - 214 2014年 [査読有り]
     
    Anesthesia requires informed consent because it is an invasive procedure with high risks. We carried out a questionnaire study in 1,050 patients who were seen at the preoperative evaluation clinic (PAC). Patients who heard about PAC for the first time accounted for 77.9% in spite of having experienced anesthesia Many patients were provided with the information about anesthesia the day before surgery and medication control and additional checking were difficult to carry out. Some patients (34.2%) were told about anesthesia with no attendant In particular, about complications of anesthesia many patients did not remember what the specific explanation had been offered in the past. We thought that it is necessary to explain the complications of anesthesia even if it is the second anesthesia for patients.
  • Yoshinobu Nakayama; Masayuki Shibasaki; Nobuaki Shime; Yasufumi Nakajima; Toshiki Mizobe; Teiji Sawa
    JOURNAL OF ANESTHESIA 27 6 850 - 854 2013年12月 [査読有り]
     
    Purpose The Risk Adjustment for Congenital Heart Surgery (RACHS-1) classification was originally designed to facilitate the prediction of in-hospital mortality for pediatric cardiac surgery patients. However, there have been few reports on clinical outcomes predicted by the RACHS-1 category, especially in an Asian population. The aim of this study was to determine whether RACHS-1 classification can predict patient outcomes. Methods A total of 580 pediatric cardiac surgery procedures performed from January 2005 to December 2009 were retrospectively classified into the six RACHS-1 categories. The association between RACHS-1 category and clinical outcomes, including length of catecholamine requirement, mechanical ventilation time, intensive care unit stay, and in-hospital mortality, were examined. Results The frequencies of RACHS-1 categories in the study population were: category 1, 10.7 %; category 2, 36.7 %; category 3, 42.8 %; category 4, 6.6 %; category 5, 0.0 %; category 6, 3.3 %. There was a significant linear correlation between RACHS-1 category and in-hospital mortality (r = 0.96, p < 0.001). Kaplan-Meier analysis demonstrated that length of catecholamine infusion, mechanical ventilation time, and ICU stay were significantly different (p < 0.05) in the different RACHS-1 categories, except for those between category 4 and 6 (p = 0.09). Conclusions Based on the results of our analysis, we conclude that the RACHS-1 stratification system can predict in-hospital mortality and patient outcomes in patients undergoing pediatric cardiac surgery.
  • 中山 力恒; 中嶋 康文; 小川 覚; 飯田 淳; 溝部 俊樹
    麻酔 62 11 1326 - 1335 克誠堂出版(株) 2013年11月
  • Yoshinobu Nakayama; Yasufumi Nakajima; Satoru Ogawa; Jun Iida; Toshiki Mizobe
    Japanese Journal of Anesthesiology 62 11 1326 - 1335 2013年11月 [査読有り]
     
    The number of patients with chronic kidney disease (CKD) continues to increase all over the world for the past ten years. It follows that we have more CKD patients with various complications who need perioperative management in Japan. Previous studies revealed that impaired renal function in preoperative period was the independent predictor of postoperative renal dysfunction. Safe comprehensive anesthetic management is required in order not to aggravate the preoperative CKD. In this review, we will take up some recent topics and novel concept in association with non-cardiac surgery for the perioperative management of CKD patients.
  • 中山 力恒; 中嶋 康文; 小川 覚; 溝部 俊樹
    Cardiovascular Anesthesia 17 Suppl. 110 - 110 (一社)日本心臓血管麻酔学会 2013年09月
  • 木下 真央; 竹下 淳; 中山 力恒; 清水 優; 加藤 秀哉; 安本 寛章; 中嶋 康文; 溝部 俊樹; 佐和 貞治
    Cardiovascular Anesthesia 17 Suppl. 253 - 253 (一社)日本心臓血管麻酔学会 2013年09月
  • 清水 優; 竹下 淳; 中山 力恒; 安本 寛章; 加藤 秀哉; 木下 真央; 中嶋 康文; 溝部 俊樹; 佐和 貞治
    Cardiovascular Anesthesia 17 Suppl. 261 - 261 (一社)日本心臓血管麻酔学会 2013年09月
  • 村瀬 百子; 中嶋 康文; 中山 力恒; 柴崎 雅志; 佐和 貞治; 溝部 俊樹
    Cardiovascular Anesthesia 16 2 23 - 30 (一社)日本心臓血管麻酔学会 2013年03月
  • Masayuki Shibasaki; Nobuaki Shime; Yasufumi Nakajima; Teiji Sawa
    Japanese Journal of Anesthesiology 62 3 368 - 375 2013年03月 [査読有り]
     
    Background : The goal of this investigation was to evaluate the details of preformed pediatric endotracheal tubes(PPETTs, I. D. 3.0-6.0 mm). Methods : Dimensions of all PPETTs were measured as follows : the distance from tube tip to the distal border of depth markings, length and the number of depth markings, outer diameter and length of the tubes, the distance from tube tip to the bent section, the number of the Murphy eyes and calculated cross sectional area of the Murphy eyes, the distance from tube tip to the distal/proximal border of the cuff, cuff diameter and cuff volume at 20 cmH2O cuff pressure. Results : A total of 80 PPETTs, including 18 brands from 5 manufacturers, were investigated, of which 30% of PPETTs are cuffed tubes. There are significant variability in the distance from tube tip to the bent section, the number and position of depth markings, the number of the Murphy eyes and position and diameter of cuff at 20 cmH2O cuff pressure for a given I. D. Conclusions : There are no uniformity in the details of PPETTs. The details of PPETTs including those with high volume low pressure cuff should be updated.
  • 中嶋 康文; 村瀬 百子; 小川 覚; 中山 力恒; 溝部 俊樹
    日本臨床麻酔学会誌 32 6 S239 - S239 日本臨床麻酔学会 2012年10月
  • Masayuki Shibasaki; Yasufumi Nakajima; Nobuaki Shime; Teiji Sawa
    Japanese Journal of Anesthesiology 61 9 1023 - 1029 2012年09月 [査読有り]
     
    Background: The goal of this investigation was to evaluate the details of cuffed pediatric endotracheal tubes (PCETTs, I. D. 3.0-6.0 mm) available in Japan. Methods: Following dimensions of all PCETTs were measured the distance from the tube tip to the distal/proximal border of cuff, cuff length, cuff volume and cuff diameter at 20 cmH2O cuff pressure, outer diameter and length of tubes, the distance from tube tip to the distal border of depth markings, length and the number of depth markings, calculated cross sectional area of the Murphy eyes, and the number of the Murphy eyes. Results: A total of 73 PCETTs, including 20 brands from 10 manufacturers, were investigated, in which 82.2% of PCETTs are larger than I. D. 5.0. There are significant differences in the distance from tube tip to the distal/proximal border of the cuff, and the cuff length at 20 cmH2O cuff pressure for a given I. D. Some tubes have no depth markings, others have multiple ones, and depth markings are positioned differently, Eighty-three point six % of PCETTs have one Murphy eye. Conclusions: There is no uniformity in the details of PCETTs available in Japan. The details of PCETTs including cuff design and depth marking should be updated.
  • Masayuki Shibasaki; Yasufumi Nakajima; Nobuaki Shime; Teiji Sawa; Daniel I. Sessler
    JOURNAL OF ANESTHESIA 26 4 536 - 540 2012年08月 [査読有り]
     
    Endotracheal tube intra-cuff pressure should be maintained between 20 and 30 cmH(2)O to prevent damage to the tracheal wall. However, cuff pressure is rarely measured, and clinicians estimate cuff pressure poorly. The goal of the present study was to predict the cuff volume that produces optimal cuff pressure either from tracheal diameter or from patient height and age. In the development phase, initial cuff pressure and cuff volume were measured in 240 patients. Optimal cuff volume, defined as the volume halfway between the volumes required to produce cuff pressures of 20 and 30 cmH(2)O, was determined in each patient. Then, regression equations relating optimal cuff volume to tracheal diameter on chest X-ray, and between optimal cuff volume and a combination of height and age, were calculated. The primary outcome was the proportion of patients in a validation set (n = 104) who achieved a cuff pressure of 20-30 cmH(2)O when cuff volume was selected by each regression formula. Only 28 % of the cuffs were optimally inflated using clinical criteria during the development phase. There was good correlation between optimal cuff volume and tracheal diameter and moderate correlation between optimal cuff volume and both height and age. Predicted cuff volume was more likely to provide optimal cuff pressure when based on tracheal diameter (65 % of patients) than when based on both height and age (45 % of patients). Optimal cuff volume was better estimated from tracheal diameter and patient height and age than from the manual palpation method.
  • 自己血輸血によってアナフィラキシー様の反応を引き起こした症例
    西田 智世里; 影山 京子; 木下 真央; 向井 信弘; 中嶋 康文; 佐和 貞治
    臨床麻酔 36 7 1025 - 1028 真興交易(株)医書出版部 2012年07月 [査読有り]
     
    脊椎側彎症患者の後方固定術において麻酔導入後にロクロニウムによるアナフィラキシーショックを呈した患者が、術翌日の自己血返血でもアナフィラキシー様の反応を呈した。保存自己血中のサイトカインによるアナフィラキシー様の反応と考え、自己血の貯血前に白血球除去を、返血を行う直前に遠心、洗浄を行い、それらの反応を回避した。自己血輸血時もアナフィラキシー様の反応は起こる可能性があり注意が必要である。(著者抄録)
  • 柴崎 雅志; 志馬 伸朗; 中嶋 康文; 石井 祥代; 溝部 俊樹; 佐和 貞治
    日本臨床麻酔学会誌 = The Journal of Japan Society for Clinical Anesthesia 32 3 371 - 374 THE JAPAN SOCIETY FOR CLINICAL ANESTHESIA 2012年05月 
    小児の気管チューブの挿入長は安全域が狭く，その決定に注意が必要である．現時点で利用可能な5つの挿入長決定法の有効性を比較し，不適切となる原因を調査した．適切な気管チューブの先端位置は「胸部X線写真による気管チューブの先端位置が両側鎖骨中線と気管分岐部より0.5cm頭側の間」と定義し，気管挿管後，胸部X線写真により気管チューブ先端の適切範囲を評価し，各種挿入長決定法に基づき算出した挿入長との関係を評価した．各種決定法で適切範囲内に収まる割合は56.0～64.0％，浅過ぎる割合は26.0～42.0％，深過ぎる割合は0.0～14.0％であった．現存する挿入長決定法では適切範囲内に収まる割合は低く，各種挿入長決定法により不適切な位置になる原因も異なっている．今後，より正確な挿入長決定法の構築が必要である．
  • 村瀬 百子; 中嶋 康文; 松田 直之; 中山 力恒; 柴崎 雅志; 溝部 俊樹; 佐和 貞治
    Cardiovascular Anesthesia 15 Suppl. 165 - 165 (一社)日本心臓血管麻酔学会 2011年10月
  • 中山 力恒; 前田 祥子; 安本 寛章; 竹下 淳; 中嶋 康文; 溝部 俊樹; 佐和 貞治
    Cardiovascular Anesthesia 15 Suppl. 180 - 180 (一社)日本心臓血管麻酔学会 2011年10月
  • 安本 寛章; 中嶋 康文; 中山 力恒; 前田 祥子; 竹下 淳; 溝部 俊樹; 佐和 貞治
    Cardiovascular Anesthesia 15 Suppl. 241 - 241 (一社)日本心臓血管麻酔学会 2011年10月
  • 竹下 淳; 中嶋 康文; 前田 祥子; 中山 力恒; 松山 広樹; 溝部 俊樹; 佐和 貞治
    日本臨床麻酔学会誌 31 6 S263 - S263 日本臨床麻酔学会 2011年10月
  • 飯田 淳; 影山 京子; 中山 力恒; 中嶋 康文; 佐和 貞治
    日本臨床麻酔学会誌 31 6 S503 - S503 日本臨床麻酔学会 2011年10月
  • 竹下 淳; 中嶋 康文; 中山 力恒; 安本 寛章; 柴崎 雅志; 溝部 俊樹
    Cardiovascular Anesthesia 15 1 195 - 198 (一社)日本心臓血管麻酔学会 2011年09月 
    症例1(62歳男性)。僧帽弁形成術後に人工心肺離脱時に僧帽弁前尖収縮期前方運動(SAM)を生じた。薬物療法および輸液負荷を行うも改善が得られず、再び人工心肺下に僧帽弁リングの抜去を行い、血行動態は安定した。症例2(72歳女性)。大動脈弁置換術後の人工心肺離脱時に左室流出路の圧負荷減少によるSAMを発症したが、薬物療法と輸液負荷にて改善が得られた。
  • 中山 力恒; 中嶋 康文; 竹下 淳; 溝部 俊樹; 佐和 貞治
    Cardiovascular Anesthesia 15 1 199 - 202 (一社)日本心臓血管麻酔学会 2011年09月 
    64歳男性。労作時息切れ、夜間起座呼吸を主訴に、精査の結果、陳旧性心筋梗塞と診断され、冠動脈バイパス術および僧帽弁輪形成術が施行された。だが、心臓手術終了直前に循環動態の悪化を認め、経食道心エコーを施行したところ、心膜横洞の限局性血腫が確認された。以後、再開胸にて血腫除去が行われ、術後は良好な経過を得ることができた。
  • 粟井 一博; 影山 京子; 山口 陽輔; 中嶋 康文; 橋本 悟
    日本臨床麻酔学会誌 = The Journal of Japan Society for Clinical Anesthesia 31 1 166 - 170 THE JAPAN SOCIETY FOR CLINICAL ANESTHESIA 2011年01月 
    腹臥位下に分離肺換気を行った胸椎腫瘍摘出術の麻酔を経験した．分離肺換気時の低換気，低酸素血症の対策として，4点支持フレームの除圧枕を使用し肺胸郭コンプライアンスを維持，頭部は三点支持固定とし分離肺換気操作が行いやすいようワーキングスペースを確保した．片肺換気時，非換気側肺のシャント血流残存効果による動脈血酸素飽和度（SpO2）の低下を認めたが，非換気側肺に持続陽圧呼吸（continuous positive airway pressure：CPAP）を行うことにより酸素化を維持した．腹臥位分離肺換気の呼吸生理を理解し，低酸素性肺血管収縮反応についての対策を考えた麻酔管理を行うことが必要である．
  • 志馬 伸朗; 細川 康二; 中嶋 康文
    日本集中治療医学会雑誌 18 4 661 - 662 一般社団法人 日本集中治療医学会 2011年
  • Kyoko Kageyama; Yuka Hayakawa; Yasufumi Nakajima; Satoru Hashimoto
    Japanese Journal of Anesthesiology 60 1 55 - 66 2011年01月 [査読有り]
     
    Among all drugs used for general anesthesia, neuromuscular blocking agents (NMBAs) seem to play a predominant role in the incidence of severe adverse reactions. The overall incidence of perioperative anaphylaxis is estimated at 1 in 10,000-20,000 anesthetic procedures, whereas it is estimated at 1 in 6,500 administrations of NMBAs. After anaphylaxis, allergologic assessment is essential to identify the offending agent and to prevent recurrences. The estimated sensitivity of skin tests for muscle relaxants is approximately 94% to 97%. Prick testing is advised for the diagnosis of the NMBAs responsible for an anaphylactic reaction, and intradermal testing is preferred when investing cross-reaction. The choice of the safest possible anesthetic agents should be based on the result of a rigorously performed allergologic assessment.
  • Fumihiro Shimizu; Masayuki Shibasaki; Yasufumi Nakajima; Nobuaki Shime
    Japanese Journal of Anesthesiology 60 1 88 - 90 2011年01月 [査読有り]
     
    A neonate with transposition of the great arteries (TGA) was scheduled for arterial switch operation (ASO) and entered to Pediatric ICU on day 4. Although mainly fed with mother's and formula milk, the serum natrium concentration decreased extremely to 104 mEq·l-1 on day 9. We prioritized treatment of electrolyte disorders, and the operation was postponed on day 13. After the operation, he was diagnosed as syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and post operative course was uneventful. Electrolyte control is very important even if the infant is fed with mother's milk.
  • 松田 愛; 木村 みどり; 中山 力恒; 梅内 貴子; 天谷 文昌; 中嶋 康文; 溝部 俊樹
    日本臨床麻酔学会誌 30 6 S298 - S298 日本臨床麻酔学会 2010年10月
  • 竹下 淳; 中嶋 康文; 松田 愛; 安本 寛章; 中山 力恒; 柴崎 雅志; 溝部 俊樹; 橋本 悟
    Cardiovascular Anesthesia 14 Suppl. 121 - 121 (一社)日本心臓血管麻酔学会 2010年10月
  • 中山 力恒; 松田 愛; 安本 寛章; 竹下 淳; 柴崎 雅志; 中嶋 康文; 溝部 俊樹; 橋本 悟
    Cardiovascular Anesthesia 14 Suppl. 121 - 121 (一社)日本心臓血管麻酔学会 2010年10月
  • Masayuki Shibasaki; Yasufumi Nakajima; Sachiyo Ishii; Fumihiro Shimizu; Nobuaki Shime; Daniel I. Sessler
    ANESTHESIOLOGY 113 4 819 - 824 2010年10月 [査読有り]
     
    Background: Formulas based on age and height often fail to reliably predict the proper endotracheal tube ( ETT) size in pediatric patients. We, thus, tested the hypothesis that subglottic diameter, as determined by ultrasonography, better predicts optimal ETT size than existing methods. Methods: A total of 192 patients, aged 1 month to 6 yr, who were scheduled for surgery and undergoing general anesthesia were enrolled and divided into development and validation phases. In the development group, the optimal ETT size was selected according to standard age-based formulas for cuffed and uncuffed tubes. Tubes were replaced as necessary until a good clinical fit was obtained. Via ultrasonography, the subglottic upper airway diameter was determined before tracheal intubation. We constructed a regression equation between the subglottic upper airway diameter and the outer diameter of the ETT finally selected. In the validation group, ETT size was selected after ultrasonography using this regression equation. The primary outcome was the fraction of initial cuffed and uncuffed tube sizes, as selected through the regression formula, that proved clinically optimal. Results: Subglottic upper airway diameter was highly correlated with outer ETT diameter deemed optimal on clinical grounds. The rate of agreement between the predicted ETT size based on ultrasonic measurement and the final ETT size selected clinically was 98% for cuffed ETTs and 96% for uncuffed ETTs. Conclusions: Measuring subglottic airway diameter with ultrasonography facilitates the selection of appropriately sized ETTs in pediatric patients. This selection method better predicted optimal outer ETT diameter than standard age- and height-based formulas.
  • Masayuki Shibasaki; Yasufumi Nakajima; Akiko Kojima; Hirotoshi Kitagawa; Keiji Tanimoto; Toshiki Mizobe
    Japanese Journal of Anesthesiology 59 4 535 - 539 2010年04月 [査読有り]
     
    Background: In cardiac surgery, unfractionated heparin is widely used for anticoagulation. There are differences of heparin dosages among institutions for cardiac surgery with and without cardiopulmonary bypass (CPB). The aim of this clinical investigation is to find out the optimal dosage of heparin for initiation of CPB. Methods: In cardiac cases with CPB, patients' weight, initial dosage of heparin, ACT values after heparin administration, product name of heparin and ACT measurement devices were recorded. Results: There were significant differences in initial dosages of heparin, basal ACT values and increment of ACT values per units of heparin among institutions. Conclusions: A significant difference was revealed among institutions regarding the initial heparin dosage for CPB, in spite of the same target of ACT. There was no evidence to determine the optimal dosage of heparin for initiation of CPB.
  • Satoru Beppu; Yasufumi Nakajima; Masayuki Shibasaki; Kyoko Kageyama; Toshiki Mizobe; Nobuaki Shime; Naoyuki Matsuda
    ANESTHESIOLOGY 111 6 1227 - 1237 2009年12月 [査読有り]
     
    Background: Tissue damage during surgery activates platelets and provokes a prothrombic state. The current study attempted to determine the impact of phosphodiesterase 3 inhibitors on platelet activation, platelet-leukocyte aggregate formation, and monocyte tissue factor expression during and after total knee arthroplasty. Methods: Thirty-four patients undergoing scheduled total knee arthroplasty were randomly assigned to receive either the phosphodiesterase 3 inhibitor milrinone or the same amount of saline perioperatively. The effects of milrinone on platelet and leukocyte function hi vitro were then assessed in healthy volunteers. Results: Perioperative infusion of milrinone significantly attenuated platelet activation; phosphorylation of intraplatelet p38 mitogen-activated protein kinase, extracellular signal-regulated kinase 1/2, and Akt; and platelet-leukocyte aggregation. Furthermore, perioperative tissue factor expression on monocytes and fibrin monomer complex production were reduced by milrinone infusion in patients undergoing total knee arthroplasty. In vitro studies using adenosine diphosphate- and collagen-stimulated blood samples from healthy volunteers confirmed the antiplatelet effects; and reduced monocyte tissue factor expression by milrinone. These studies further showed that platelet aggregation and integrin alpha(IIB)beta(3) activation were modified by intraplatelet phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase/extracellular signal-regulated kinase pathways, and that P-selectin expression on platelets and platelet-leukoctye aggregation were modulated by intraplatelet p38 mitogen-activated protein kinase pathway. Conclusion: Continuous milrinone infusion has the potential to reduce platelet activation and monocyte tissue factor expression during the perioperative period in total knee arthroplasty. These events may be mediated in part by the ability of milrinone to reduce activation of intraplatelet mitogen-activated protein kinases and phosphatidylinositol 3-kinase. The clinical impact of phosphodiesterase 3 inhibition on perioperative hemostasis remains to be elucidated.
  • Masayuki Shibasaki; Yasufumi Nakajima; Naoko Inami; Fumihiro Shimizu; Satoru Beppu; Yoshifumi Tanaka
    Paediatric anaesthesia 18 10 997 - 8 2008年10月
  • Koji Hosokawa; Yasufumi Nakajima; Hiroki Matsuyama; Masayuki Shibasaki
    ANESTHESIA AND ANALGESIA 107 4 1158 - 1160 2008年10月 [査読有り]
  • Masayuki Shibasaki; Yasufumi Nakajima; Naoko Inami; Fumihiro Shimizu; Satoru Beppu; Yoshifumi Tanaka
    PEDIATRIC ANESTHESIA 18 10 997 - 998 2008年10月 [査読有り]
  • Koji Hosokawa; Yasufumi Nakajima; Satoru Hashimoto
    ANESTHESIOLOGY 109 2 355 - 355 2008年08月 [査読有り]
  • Masayuki Shibasaki; Yasufumi Nakajima
    CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE 55 4 245 - 246 2008年04月 [査読有り]
  • Mitsuhiko Mizuta; Hiroo Nakajima; Naruhiko Mizuta; Yoshihiro Kitamura; Yasufumi Nakajima; Soshi Hashimoto; Hiroki Matsuyama; Nobuaki Shime; Fumimasa Amaya; Hidefumi Koh; Akitoshi Ishizaka; Junji Magae; Sei-ich Tanuma; Satoru Hashimoto
    BIOLOGICAL & PHARMACEUTICAL BULLETIN 31 3 386 - 390 2008年03月 [査読有り]
     
    Alveolar epithelial cell death plays a crucial role in the progression of acute lung injury. We have demonstrated up-regulation of Fas expression on alveolar epithelial cells, and soluble Fas ligand secretion from inflammatory cells upon acute lung injury. Here we show that the lipopolysaccharide-stimulated human monocyte cell line THP-1 releases Fas ligand, and that conditioned medium from lipopolysaccharide-stimulated THP-1 cells induces apoptosis of the human pulmonary adenocarcinoma cell line A549. Activation of caspase-3 and -8 is associated with the apoptosis. Gene targeting on Fas in A549 cells by specific small interfering RNA impairs apoptosis induced by conditioned medium from activated THP-1, while that on Fas ligand in THP-1 cells impairs the apoptosis-inducing activity of the conditioned medium produced by lipopolysaccharide-stimulated cells. These results suggest that Fas ligand released by monocytes causes alveolar epithelial cell death through a Fas-dependent apoptotic mechanism in the development of acute lung injury.
  • Koji Hosokawa; Yasufumi Nakajima
    Anesthesia and analgesia 106 1 61 - 2 2008年01月
  • Koji Hosokawa; Yasufumi Nakajima
    ANESTHESIA AND ANALGESIA 106 1 61 - 62 2008年01月 [査読有り]
  • Kyoko Kageyama; Soshi Hashimoto; Yasufumi Nakajima; Nobuaki Shime; Satoru Hashimoto
    Paediatric anaesthesia 17 11 1071 - 7 2007年11月 
    BACKGROUND: The present study aimed to elucidate the pathophysiological roles of endothelin (ET)-1 in patients with pulmonary hypertension and pulmonary vascular obstructive disease secondary to congenital heart disease and compare the plasma levels of ET-1 between children with and without Down syndrome. METHODS: Subjects comprised 32 children with congenital heart disease aged 0.5-14 months. Patients were classified into two groups: those with Down syndrome (Group D, n = 16); and those with nonDown syndrome (Group ND, n = 16). Heparinized blood samples were taken from a radial arterial line and plasma ET-1 levels were measured preoperatively, during cardiopulmonary bypass (CPB), a few minutes after termination of CPB, and 2, 6 and 24 h after discontinuation of CPB. RESULTS: Plasma ET-1 levels were significantly higher in Group D than in Group ND at all times except for a few minutes after termination of CPB. In both groups, peak ET-1 values were obtained at 6 h after CPB. At 24 h after CPB, ET-1 concentrations returned to baseline levels before CPB in Group ND, but not in Group D. A correlation was identified between preoperative pulmonary to systemic pressure ratio and ET-1 concentration before and after CPB in both groups. CONCLUSIONS: Pre- and postoperative plasma ET-1 concentrations reflect pre- and postoperative pulmonary artery conditions in both groups. Specific features in Down syndrome could be associated with ET injury and might cause persistent increases in ET concentration and prolong artificial respiration.
  • Kyoko Kageyama; Soshi Hashimoto; Yasufumi Nakajima; Nobuaki Shime; Satoru Hashimoto
    PEDIATRIC ANESTHESIA 17 11 1071 - 1077 2007年11月 [査読有り]
     
    Background: The present study aimed to elucidate the pathophysiological roles of endothelin (ET)-1 in patients with pulmonary hypertension and pulmonary vascular obstructive disease secondary to congenital heart disease and compare the plasma levels of ET-1 between children with and without Down syndrome. Methods: Subjects comprised 32 children with congenital heart disease aged 0.5-14 months. Patients were classified into two groups: those with Down syndrome (Group D, n = 16); and those with nonDown syndrome (Group ND, n = 16). Heparinized blood samples were taken from a radial arterial line and plasma ET-1 levels were measured preoperatively, during cardiopulmonary bypass (CPB), a few minutes after termination of CPB, and 2, 6 and 24 h after discontinuation of CPB. Results: Plasma ET-1 levels were significantly higher in Group D than in Group ND at all times except for a few minutes after termination of CPB. In both groups, peak ET-1 values were obtained at 6 h after CPB. At 24 h after CPB, ET-1 concentrations returned to baseline levels before CPB in Group ND, but not in Group D. A correlation was identified between preoperative pulmonary to systemic pressure ratio and ET-1 concentration before and after CPB in both groups. Conclusions: Pre- and postoperative plasma ET-1 concentrations reflect pre- and postoperative pulmonary artery conditions in both groups. Specific features in Down syndrome could be associated with ET injury and might cause persistent increases in ET concentration and prolong artificial respiration.
  • K. Hosokawa; Y. Nakajima; T. Umenai; H. Ueno; S. Taniguchi; T. Matsukawa; T. Mizobe
    BRITISH JOURNAL OF ANAESTHESIA 98 5 575 - 580 2007年05月 
    Background. Postoperative atrial fibrillation (AF) is one of the most common complications after cardiothoracic surgery and is associated with an increased risk of stroke, and longer hospital stay. The pathophysiology of postoperative AF is uncertain, and its prevention remains unsatisfactory. Many previous studies have examined the predictors of AF after on-pump coronary artery bypass graft surgery (CABG), but there are few reports after off-pump CABG. Methods. The aim of the present prospective observational study, in which 296 consecutive patients were enrolled, was to elucidate the predictors of AF after off-pump CABG. The association of perioperative factors with AF was investigated using univariate analysis. Significant variables were included into a stepwise logistic regression model to ascertain their independent influence on the occurrence of AF. Results. The incidence of AF was 32%. AF prolonged the time until patients were fit for discharge by 3 days (P < 0.01). Stepwise multivariate analysis identified increasing age [odds ratio (OR) 1.44 per 10-yr increase; 95% confidence interval (CI) 1.06-1.95], intraoperative average core temperature (OR 1.64; 95% CI 1.05-2.56), the average cardiac index in the intensive care unit (OR 0.37; 95% CI 0.19-0.71), and intraoperative fluid balance (OR 0.96 per 100-ml increase; 95% CI 0.93-0.99) as independent predictors of postoperative AF. Conclusion. Our present findings indicate that ageing, the intraoperative fluid balance, and postoperative cardiac index are associated with the onset of AF after off-pump CABG.
  • K. Kageyama; Y. Nakajima; M. Shibasaki; S. Hashimoto; T. Mizobe
    JOURNAL OF THROMBOSIS AND HAEMOSTASIS 5 4 738 - 745 2007年04月 
    Background: Orthopedic surgery, especially total knee and total hip arthroplasty, is considered a risk factor for peri-operative venous thromboembolism. Objectives: This study evaluates how accelerated inflammatogenic cellular interactions and the subsequent production of tissue factor and CD40 ligand play an important role in the pathogenesis of venous thromboembolism. Patients and methods: Twenty-four patients undergoing total knee arthroplasty were randomly assigned to groups with (Ti; n = 12) and without (Tn; n = 12) pneumatic tourniquet inflation. Results: Numbers of leukocyte-platelet aggregates, especially those comprising monocytes-platelets in central venous blood from the Ti group, were increased during the peri-operative period (P < 0.01), and returned to the baseline level at 24 h after starting surgery. Levels of PAC-1, P-selectin, CD40 ligand, tissue factor, Mac-1 expression on monocytes including monocyte-platelet aggregates, and the number of microparticles including those of endothelial cell origin were noticeably increased in central venous blood from the Ti group (P < 0.01). Whole blood coagulability was also obviously increased in central venous blood from the Ti group (P < 0.01). Furthermore, the concentrations of venous plasma tissue factor antigen, CD40 ligand, platelet factor 4, beta-thromboglobulin, the soluble fibrin monomer complex and prothrombin fragment 1+2 were also increased (P < 0.05). Conclusions: This study showed that platelet, leukocyte and endothelium activities as well as their interactions are enhanced during the peri-operative period of total knee arthroplasty, particularly in venous blood from the lower half of the body, which consequently augments blood coagulability. Further, tourniquet inflation during surgery exaggerates these responses.
  • Toshiki Mizobe; Yasufumi Nakajima
    Japanese Journal of Anesthesiology 56 3 305 - 316 2007年03月 [査読有り]
     
    After the ingestion or infusion of nutrients, there is an increase in energy expenditure which has been referred to as dietary or nutrient-induced thermogenesis. This thermogenesis induced by protein or amino acids is well known to be largest and most prolonged. According to these physiological backgrounds, preoperative amino acid infusion was reported to prevent postoperative hypothermia during general anesthesia and spinal anesthesia. Also, perioperative amino acid infusion is reported to improve the outcome of the patients undergoing off-pump CABG. Amino acid infusion was observed to shift upward the threshold core temperature for thermoregulatory vasoconstriction as well as to increase energy expenditure. Fructose also prevents perioperative hypothermia during surgery by the same mechanisms.
  • Takako Umenai; Yasufumi Nakajima; Daniel I Sessler; Satoshi Taniguchi; Hitoshi Yaku; Toshiki Mizobe
    Anesthesia and analgesia 103 6 1386 - 93 2006年12月 
    Perioperative amino acid infusion helps maintain core temperature and improves patient outcomes after gynecologic and orthopedic surgery. In the present study we prospectively determined the effect of amino acid infusion on esophageal core temperature and postoperative outcomes during off-pump coronary artery bypass grafting (CABG). One-hundred-eighty consecutive patients undergoing primary elective or urgent off-pump CABG were randomly divided into two groups: the i.v. amino acid infusion group (4 kJ kg(-1) h(-1) starting 2 h before surgery) and the saline infusion group (similar period and volume of saline infusion). The esophageal core temperature at the end of surgery was 35.6 (35.3-35.8) degrees C [mean (95% confidence interval)] in the saline infusion group and 36.1 degrees C (35.9-36.3) degrees C in the amino acid infusion group (P = 0.01). Kaplan-Meier analysis demonstrated that patients given amino acids required a significantly shorter duration of postoperative mechanical ventilation than patients given saline [median (95% confidence interval), 3.0 (2.5-3.9) vs 4.5 (3.8-5.8) h; P = 0.01]. Furthermore, intensive care unit stay [20 (19.5-38.4) vs 44 (21-45) h; P = 0.001] and days until fit for discharge from hospital [10 (9-11) vs 12 (11-13) days; P = 0.004] were significantly shorter in patients given amino acid. Perioperative amino acid infusion in patients undergoing off-pump CABG effectively minimizes intraoperative hypothermia and improves postoperative recovery.
  • Takako Umenai; Yasufumi Nakajima; Daniel I. Sessler; Satoshi Taniguchi; Hitoshi Yaku; Toshiki Mizobe
    ANESTHESIA AND ANALGESIA 103 6 1386 - 1393 2006年12月 
    Perioperative amino acid infusion helps maintain core temperature and improves patient outcomes after gynecologic and orthopedic surgery. In the present study we prospectively determined the effect of amino acid infusion on esophageal core temperature and postoperative outcomes during off-pump coronary artery bypass grafting (CABG). One-hundred-eighty consecutive patients undergoing primary elective or urgent off-pump CABG were randomly divided into two groups: the IV amino acid infusion group (4 kJ kg(-1) h(-1) starting 2 h before surgery) and the saline infusion group (similar period and volume of saline infusion). The esophageal core temperature at the end of surgery was 35.6 (35.3-35.8)degrees C [mean (95% confidence interval)] in the saline infusion group and 36.1 degrees C (35.9-36.3)degrees C in the amino acid infusion group (P = 0.01). Kaplan-Meier analysis demonstrated that patients given amino acids required a significantly shorter duration of postoperative mechanical ventilation than patients given saline [median (95% confidence interval), 3.0 (2.5-3.9) vs 4.5 (3.8-5.8) h; P = 0.01]. Furthermore, intensive care unit stay [20 (19.5-38.4) vs 44 (21-45) h; P = 0.001] and days until fit for discharge from hospital [10 (9-11) vs 12 (11-13) days; P = 0.004] were significantly shorter in patients given amino acid. Perioperative amino acid infusion in patients undergoing off-pump CABG effectively minimizes intraoperative hypothermia and improves postoperative recovery.
  • K. Hosokawa; Y. Nakajima; H. Yaku; T. Mizobe
    ANAESTHESIA 61 8 814 - 815 2006年08月 [査読有り]
  • T Mizobe; Y Nakajima; H Ueno; DI Sessler
    ANESTHESIOLOGY 104 6 1124 - 1130 2006年06月 [査読有り]
     
    Background: The authors tested the hypothesis that intravenous fructose ameliorates intraoperative hypothermia both by increasing metabolic rate and the vasoconstriction threshold (triggering core temperature). Methods: Forty patients scheduled to undergo open abdominal surgery were divided into two equal groups and randomly assigned to intravenous fructose infusion (0.5 g center dot kg(-1) center dot h(-1) for 4 h, starting 3 h before induction of anesthesia and continuing for 4 h) or an equal volume of saline. Each treatment group was subdivided: Esophageal core temperature, thermoregulatory vasoconstriction, and plasma concentrations were determined in half, and oxygen consumption was determined in die remainder. Patients were monitored for 3 h after induction of anesthesia. Results: Patient characteristics, anesthetic management, and circulatory data were similar in the four groups. Mean final core temperature (3 h after induction of anesthesia) was 35.7 degrees +/- 0.4 degrees C (mean +/- SD) in the fructose group and 35.1 degrees +/- 0.4 degrees C in the saline group (P = 0.001). The vasoconstriction threshold was greater in the fructose group (36.2 degrees +/- 0.3 degrees C) than in the saline group (35.6 degrees +/- 0.3 degrees C; P < 0.001). Oxygen consumption immediately before anesthesia induction in the fructose group (214 +/- 18 ml/min) was significantly greater than in the saline group (181 +/- 8 ml/min; P < 0.001). Oxygen consumption was 4.0 l greater in the fructose patients during 3 h of anesthesia; the predicted difference in mean body temperature based only on the difference in metabolic rates was thus only 0.4 degrees C. Epinephrine, norepinephrine, and angiotensin H concentrations and plasma renin activity were similar in each treatment group. Conclusions: Preoperative fructose infusion helped to maintain normothermia by augmenting both metabolic heat production and increasing the vasoconstriction threshold.
  • Masayuki Shibasaki; Keiko Okano; Kyoko Kageyama; Yasufumi Nakajima; Takae Ibuki; Yoshifumi Tanaka
    Japanese Journal of Anesthesiology 54 11 1302 - 1305 2005年11月 [査読有り]
     
    We gave anesthesia to a neonate with a retroperitoneal giant teratoma who underwent its extirpation. Even if patients have a prenatal diagnosis of teratoma like this case, there are many patients, especially infants, with severe general condition. We report the difficulty for management during anesthesia because of severe respiratory acidosis due to pressure from diaphragmatic pleura by tumor, severe circulatory disorder due to massive bleeding during operation and severe hyperkalemia due to renal failure.
  • T Mizobe; Y Nakajima; M Sunaguchi; H Ueno; DI Sessler
    BRITISH JOURNAL OF ANAESTHESIA 94 4 536 - 541 2005年04月 [査読有り]
     
    Background. Perioperative hypothermia is common and results from anaesthesia-induced inhibition of thermoregulatory control. Hypothermia is blunted by baroreceptor unloading caused by positive end-expiratory pressure (PEEP), and is mediated by an increase in the vasoconstriction threshold. Premedication with clonidine impairs normal thermoregulatory control. We therefore determined the effect of clonidine on PEEP-induced hypothermia protection. Methods. Core temperature was evaluated in patients undergoing combined general and epidural anaesthesia for lower abdominal surgery. They were assigned to an end-expiratory pressure of zero (ZEEP) or 10 cm H2O PEEP. The PEEP group was divided into three blinded subgroups that received placebo (Cl-0), clonidine 150 mu g (Cl-150) and clonidine 300 mu g (Cl-300) respectively. Placebo or clonidine was given orally 30 min before surgery. We evaluated core temperature and thermoregulatory vasoconstriction. We also determined plasma epinephrine, norepinephrine, angiotensin II concentrations and plasma renin activity. Results. Core temperature after 180 min of anaesthesia was 35.1 (0.4)degrees C in the ZEEP group. PEEP significantly increased final core temperature to 35.8 (0.5)degrees C (Cl-0 group). Clonidine produced a linear, dose-dependent impairment of PEEP-induced hypothermia protection: final core temperatures were 35.4 (0.3)degrees C in the Cl-150 group and 35.0 (0.6)degrees C in the Cl-300 group. Similarly, clonidine produced a linear and dose-dependent reduction in vasoconstriction threshold: Cl-0, 36.4 (0.3)degrees C; Cl-150, 35.8 (0.3)degrees C; Cl-300, 35.4 (0.6)degrees C. Plasma norepinephrine, angiotensin II concentrations and renin activity were consistent with the thermoregulatory responses. Conclusion. Baroreceptor unloading by PEEP normally moderates perioperative hypothermia. However, clonidine premedication produces a linear, dose-dependent reduction in this benefit.
  • Y Nakajima; A Takamata; T Matsukawa; DI Sessler; Y Kitamura; H Ueno; Y Tanaka; T Mizobe
    ANESTHESIOLOGY 100 3 634 - 639 2004年03月 
    Background. Administration of protein or amino acids enhances thermogenesis, presumably by stimulating oxidative metabolism. However, hyperthermia results even when thermoregulatory responses are intact, suggesting that amino acids also alter central thermoregulatory control. Therefore, the authors tested the hypothesis that amino acid infusion increases the thermoregulatory set point. Methods. Nine male volunteers each participated on 4 study days in randomized order: (1) intravenous amino acids infused at 4 kJ(.)kg(-1.)h(-1) for 2.5 h combined with skin-surface warming, (2) amino acid infusion combined with cutaneous cooling, (3) saline infusion combined with skin-surface warming, and (4) saline infusion combined with cutaneous cooling. Results: Amino acid infusion increased resting core temperature by 0.3 +/- 0.1 degreesC (mean +/- SD) and oxygen consumption by 18 +/- 12%. Furthermore, amino acid infusion increased the calculated core temperature threshold (triggering core temperature at a designated mean skin temperature of 34 degreesC) for active cutaneous vasodilation by 0.3 +/- 0.3 degreesC, for sweating by 0.2 +/- 0.2 degreesC, for thermoregulatory vasoconstriction by 0.3 +/- 0.3 degreesC, and for thermogenesis by 0.4 +/- 0.5 degreesC. Amino acid infusion did not alter the incremental response intensity (i.e., gain) of thermoregulatory defenses. Conclusions: Amino acid infusion increased the metabolic rate and the resting core temperature. However, amino acids also produced a synchronous increase in all major autonomic thermoregulatory defense thresholds; the increase in core temperature was identical to the set point increase, even in a cold environment with amble potential to dissipate heat. in subjects with intact thermoregulatory defenses, amino acid-induced hyperthermia seems to result from an increased set point rather than increased metabolic rate per se.
  • Kyoko Kageyama; Toshiki Mizobe; Shinji Nozuchi; Noriko Hiramatsu; Yasufumi Nakajima; Hiroshi Aoki
    Journal of anesthesia 18 2 107 - 12 2004年 
    PURPOSE: We investigated the inhibitory effects of toborinone and olprinone on human platelet aggregation and calcium mobilization.Abstract Copyright: METHODS: Washed human platelets were preincubated with toborinone or olprinone, then exposed to 0.015 U.ml-1 of thrombin. Aggregation curves were measured using an aggregometer. Effects of toborinone or olprinone on changes in intracellular calcium concentration ([Ca2+]i) were measured fluorometrically using fura-2 acetoxymethyl ester (fura-2). Levels of intracellular cyclic 3",5"-adenosine monophosphate concentration ([cAMP]i) were also measured, using enzyme-linked immunosorbent assay (ELISA) techniques. RESULTS: The concentrations required to cause 50% inhibition of aggregation (IC50) induced by thrombin were 9.7 +/- 0.9 micro M for toborinone and 3.6 +/- 0.2 micro M for olprinone. Both drugs at IC50 significantly elevated [cAMP]i levels and significantly inhibited Ca2+ release from intracellular stores. Release of [Ca2+]i induced by thrombin was 272.9 +/- 87.1 nM, 153.3 +/- 28.7 nM, and 138.9 +/- 58.2 nM in the control, toborinone, and olprinone groups, respectively ( P < 0.02). Calcium influx through calcium channels in the plasma membrane was also suppressed by toborinone and olprinone. CONCLUSION: Toborinone (9.7 micro M) and olprinone (3.6 micro M) inhibit human platelet aggregation, though these concentrations are higher than their therapeutic plasma concentrations. The inhibitory effects of both drugs are related to the inhibition of both Ca2+ release and Ca2+ entry through [cAMP]i elevation.
  • Kyoko Kageyama; Toshiki Mizobe; Shinji Nozuchi; Noriko Hiramatsu; Yasufumi Nakajima; Hiroshi Aoki
    Journal of Anesthesia 18 2 107 - 112 2004年 [査読有り]
     
    Purpose. We investigated the inhibitory effects of toborinone and olprinone on human platelet aggregation and calcium mobilization. Methods. Washed human platelets were preincubated with toborinone or olprinone, then exposed to 0.015 U·ml-1 of thrombin. Aggregation curves were measured using an aggregometer. Effects of toborinone or olprinone on changes in intracellular calcium concentration ([Ca2+]i) were measured fluorometrically using fura-2 acetoxymethyl ester (fura-2). Levels of intracellular cyclic 3′,5′-adenosine monophosphate concentration ([cAMP]i) were also measured, using enzyme-linked immunosorbent assay (ELISA) techniques. Results. The concentrations required to cause 50% inhibition of aggregation (IC50) induced by thrombin were 9.7 ± 0.9 μM for toborinone and 3.6 ± 0.2 μM for olprinone. Both drugs at IC50 significantly elevated [cAMP]i levels and significantly inhibited Ca2+ release from intracellular stores. Release of [Ca2+]i induced by thrombin was 272.9 ± 87.1 nM, 153.3 ± 28.7 nM, and 138.9 ± 58.2 nM in the control, toborinone, and olprinone groups, respectively (P < 0.02). Calcium influx through calcium channels in the plasma membrane was also suppressed by toborinone and olprinone. Conclusion. Toborinone (9.7μM) and olprinone (3.6μM) inhibit human platelet aggregation, though these concentrations are higher than their therapeutic plasma concentrations. The inhibitory effects of both drugs are related to the inhibition of both Ca2+ release and Ca2+ entry through [cAMP]i elevation. © JSA 2004.
  • Nesidioblastosisに対する膵亜全摘術の麻酔経験
    谷口 知史; 梅内 貴子; 中嶋 康文; 廣瀬 宗孝; 田中 義文
    日本臨床麻酔学会誌 23 8 S337 - S337 日本臨床麻酔学会 2003年09月
  • Yuko Katoh; Yasufumi Nakajima; Masaaki Yamagishi; Toshiki Mizobe
    Paediatric anaesthesia 13 5 461 - 3 2003年06月
  • Y Katoh; Y Nakajima; M Yamagishi; T Mizobe
    PAEDIATRIC ANAESTHESIA 13 5 461 - 463 2003年06月 [査読有り]
  • T Kasai; Y Nakajima; T Matsukawa; H Ueno; M Sunaguchi; T Mizobe
    BRITISH JOURNAL OF ANAESTHESIA 90 1 58 - 61 2003年01月 [査読有り]
     
    Background. Intravenous amino acid infusion during general anaesthesia prevents decreases in core temperature resulting from increased energy expenditure and heat accumulation. Methods. We investigated whether such stimulation also occurs during spinal anaesthesia, which blocks sympathetic nervous activity. We examined the effect of i.v. amino acid infusion on changes in core temperature during spinal anaesthesia. Thirty-five patients were divided into two groups: an i.v. amino acid infusion group (4 kJ kg(-1) h(-1) starting 2 h before surgery); and a saline infusion group. Tympanic membrane core temperature, forearm-fingertip temperature gradient (an index of peripheral vasoconstriction) and mean skin temperature were measured for 90 min after the onset of spinal anaesthesia. Results. Changes in mean arterial pressure and heart rate did not differ significantly between the groups during the study period. Mean final core temperature 90 min after induction of spinal anaesthesia was 35.8 (sem 0.1)degreesC in the saline group and 36.6 (0.1)degreesC in the amino acid group (P<0.05). The increased level of oxygen consumption in the amino acid group compared with the saline group was preserved even after the onset of spinal anaesthesia. The thermal vasoconstriction threshold, defined as the tympanic membrane temperature that triggered a rapid increase in forearm-fingertip temperature gradient, was increased in the amino acid group [36.8 (0.1)&DEG;C] compared with the saline group [36.5 (0.1)&DEG;C] (P<0.05). Conclusions. Preoperative infusion of amino acids effectively prevents spinal anaesthesia-induced hypothermia by maintaining a higher metabolic rate and increasing the threshold core temperature for thermal vasoconstriction.
  • Yasufumi Nakajima; Akira Takamata; Tomoyuki Ito; Daniel I Sessler; Yoshihiro Kitamura; Goshun Shimosato; Satoshi Taniguchi; Hiroki Matsuyama; Yoshifumi Tanaka; Toshiki Mizobe
    Anesthesia and analgesia 94 6 1646 - 51 2002年06月 
    UNLABELLED: We recently reported that baroreceptor-mediated reflexes modulate thermoregulatory vasoconstriction during lower abdominal surgery. Accordingly, we examined the hypothesis that postural differences and the related alterations in baroreceptor loading similarly modulate the thermogenic (i.e., shivering) response to hypothermia in humans. In healthy humans (n = 7), cold saline was infused IV (30 mL/kg at 4 degrees C) for 30 min to decrease core temperature. Each participant was studied on 2 separate days, once lying supine and once sitting upright. Tympanic membrane temperature and oxygen consumption were monitored for 40 min after each saline infusion. The decrease in core temperature upon completion of the infusion in the upright posture position was 1.24 degrees C +/- 0.07 degrees C, which was significantly greater than the 1.02 degrees C +/- 0.06 degrees C seen in the supine position. The core temperature was reduced by 0.59 degrees C +/- 0.07 degrees C in the upright position but only by 0.37 degrees C +/- 0.05 degrees C in the supine position when the increase in oxygen consumption signaling thermogenic shivering occurred. Thus, the threshold temperature for thermogenesis was significantly less in the upright than the supine position. The gain of the thermogenic response did not differ significantly between the positions (363 +/- 69 mL. min(-1). degrees C(-1) for upright and 480 +/- 80 mL. min(-1). degrees C(-1) for supine). The skin temperature gradient was significantly larger in the upright than in the supine posture, suggesting that the peripheral vasoconstriction was augmented by upright posture. Plasma norepinephrine concentrations increased in response to cold saline infusion under both conditions, but the increase was significantly larger in the upright than in the supine posture. Baroreceptor unloading thus augments the peripheral vasoconstrictor and catecholamine response to core hypothermia but simultaneously reduces thermogenesis, which consequently aggravated the core temperature decrease in the upright posture. IMPLICATIONS: Upright posture attenuates the thermogenic response to core hypothermia but augments peripheral vasoconstriction. This divergent result suggests that input from the baroreceptor modifies the individual thermoregulatory efferent pathway at a site distal to the common thermoregulatory center or neural pathway.
  • Y Nakajima; A Takamata; T Ito; DI Sessler; Y Kitamura; G Shimosato; S Taniguchi; H Matsuyama; Y Tanaka; T Mizobe
    ANESTHESIA AND ANALGESIA 94 6 1646 - 1651 2002年06月 [査読有り]
     
    We recently reported that baroreceptor-mediated reflexes modulate thermoregulatory vasoconstriction during lower abdominal surgery. Accordingly, we examined the hypothesis that postural differences and the related alterations in baroreceptor loading similarly modulate the thermogenic (i.e., shivering) response to hypothermia in humans. In healthy humans (n = 7), cold saline was infused W (30 mL/kg at 4degreesC) for 30 min to decrease core temperature. Each participant was studied on 2 separate days, once lying supine and once sitting uptight. Tympanic membrane temperature and oxygen consumption were monitored for 40 min after each saline infusion. The decrease in core temperature upon completion of the infusion in the upright posture position was 1.24degreesC +/- 0.07degreesC, which was significantly greater than the 1.02degreesC +/- 0.06degreesC seen in the supine position. The core temperature was reduced by 0.59degreesC +/- 0.07degreesC in the upright position but only by 0.37degreesC +/- 0.05degreesC in the supine position when the increase in oxygen consumption signaling thermogenic shivering occurred. Thus, the threshold temperature for thermogenesis was significantly less in the upright than the supine position. The gain of the thermogenic response did not differ significantly between the positions (363 +/- 69 mL.min(-1).degreesC(-1) for upright and 480 +/- 80 mL . min(-1) . degreesC(-1) for supine). The skin temperature gradient was significantly larger in the upright than in the supine posture, suggesting that the peripheral vasoconstriction was augmented by upright posture. Plasma norepinephrine concentrations increased in response to cold saline infusion under both conditions, but the increase was significantly larger in the upright than in the supine posture. Baroreceptor unloading thus augments the peripheral vasoconstrictor and catecholamine response to core hypothermia but simultaneously reduces thermogenesis, which consequently aggravated the core temperature decrease in the upright posture.
  • Yasufumi Nakajima; Toshiki Mizobe; Takashi Matsukawa; Daniel I Sessler; Yoshihiro Kitamura; Yoshifumi Tanaka
    Anesthesia and analgesia 94 1 221 - 6 2002年01月 
    UNLABELLED: Thermoregulation interacts with cardiovascular regulation within the central nervous system. We therefore evaluated the effects of head-down tilt on intraoperative thermal and cardiovascular regulation. Thirty-two patients undergoing lower-abdominal surgery were randomly assigned to the 1) supine, 2) 15 degrees -20 degrees head-down tilt, 3) leg-up, or 4) combination of leg-up and head-down tilt position. Core temperature and forearm minus fingertip skin-temperature gradients (an index of peripheral vasoconstriction) were monitored for 3 h after the induction of combined general and lumbar epidural anesthesia. We also determined cardiac output and central-venous and esophageal pressures. Neither right atrial transmural pressure nor cardiac index was altered in the Head-Down Tilt group, but both increased significantly in the Leg-Up groups. The vasoconstriction threshold was reduced in both leg-up positions but was not significantly decreased by head-down tilt. Final core temperatures were 35.2 degrees C +/- 0.2 degrees C (mean +/- SEM) in the Supine group, 35.0 degrees C +/- 0.2 degrees C in the Head-Down Tilt group, 34.2 degrees C +/- 0.2 degrees C in the Leg-Up group (P < 0.05 compared with supine), and 34.3 degrees C +/- 0.2 degrees C when leg-up and head-down tilt were combined (P < 0.05 compared with supine). These results confirm that elevating the legs increases right atrial transmural pressure, reduces the vasoconstriction threshold, and aggravates intraoperative hypothermia. Surprisingly, maintaining a head-down tilt did not increase right atrial pressure. IMPLICATIONS: Intraoperative hypothermia is exaggerated when patients are maintained in the leg-up position because the vasoconstriction threshold is reduced. However, head-down tilt (Trendelenburg position) does not reduce the vasoconstriction threshold or aggravate hypothermia. The head-down tilt position thus does not require special perioperative thermal precautions or management unless the leg-up position is used simultaneously.
  • Y Nakajima; T Mizobe; T Matsukawa; DI Sessler; Y Kitamura; Y Tanaka
    ANESTHESIA AND ANALGESIA 94 1 221 - 226 2002年01月 [査読有り]
     
    Thermoregulation interacts with cardiovascular regulation within the central nervous system. We therefore evaluated the effects of head-down tilt on intraoperative thermal and cardiovascular regulation. Thirty-two patients undergoing lower-abdominal surgery were randomly assigned to the 1) supine, 2) 15degrees-20degrees head-down tilt, 3) leg-up, or 4) combination of leg-up and head-down tilt position. Core temperature and forearm minus fingertip skin-temperature gradients (an index of peripheral vasoconstriction) were monitored for 3 h after the induction of combined general and lumbar epidural anesthesia. We also determined cardiac output and central-venous and esophageal pressures. Neither right atrial transmural pressure nor cardiac index was altered in the Head-Down Tilt group, but both increased significantly in the Leg-Up groups. The vasoconstriction threshold was reduced in both leg-up positions but was not significantly decreased by head-down tilt. Final core temperatures were 35.2degreesC +/- 0.2degreesC (mean +/- SEM) in the Supine group, 35.0degreesC 0.2degreesC in the Head-Down Tilt group, 34.2degreesC +/- 0.2degreesC in the Leg-Up group (P < 0.05 compared with supine), and 34.3&DEG;C &PLUSMN; 0.2&DEG;C when leg-up and head-down tilt were combined (P < 0.05 compared with supine). These results confirm that elevating the legs increases right atrial transmural pressure, reduces the vasoconstriction threshold, and aggravates intraoperative hypothermia. Surprisingly, maintaining a head-down tilt did not increase right atrial pressure.
  • Y Nakajima; T Mizobe; A Takamata; Y Tanaka
    AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY 279 4 R1430 - R1436 2000年10月 
    Mild hypothermia is a major concomitant of surgery under general anesthesia. We examined the hypothesis that baroreceptor loading/unloading modifies thermoregulatory peripheral vasoconstriction and, consequently, body core temperature in subjects undergoing lower abdominal surgery with general anesthesia. Thirty-six patients were divided into four groups: control group (C), applied positive end-expiratory pressure (PEEP; 10 cmH(2)O) group (P), applied leg-up position group (L), and a group of leg-up position patients with PEEP starting 90 min after induction of anesthesia (L + P). The esophageal temperature (T-es) and the forearm-fingertip temperature gradient, as an index of peripheral vasoconstriction, were monitored for 3 h after induction of anesthesia. Mean arterial pressure and pulse pressure did not change during the study in any group. The change in right atrial transmural pressure from the baseline value was 0.3 +/- 0.1 mmHg in C, -3.0 +/- 0.5 mmHg in P, and 2.3 +/- 0.4 mmHg in L (P < 0.01). The change in Tes at the end of the study was -1.7 +/- 0.1 (35.1 +/- 0.1)degrees C in C, -1.1 +/- 0.1 (35.7 +/- 0.1)degrees C in P, and -2.7 +/- 0.1 (34.1 +/- 0.1)degrees C in L, showing significant differences (P < 0.01). The Tes threshold for thermal peripheral vasoconstriction was 35.6 +/- 0.1 degrees C in C, 36.2 +/- 0.2 degrees C in P, and 34.8 +/- 0.2 degrees C in L (P, 0.01). Excessive Tes decrease in the leg-up-position operation was attenuated by applying PEEP (L + P group; P < 0.05). Our data indicate that baroreceptor loading augments and unloading prevents perioperative hypothermia in anesthetized and paralyzed subjects by reducing and increasing the body temperature threshold for peripheral vasoconstriction, respectively.
  • Y Nakajima; H Nose; A Takamata
    JAPANESE JOURNAL OF PHYSIOLOGY 49 1 121 - 124 1999年02月 [査読有り]
     
    Tail skin blood flow (TBFu) was directly measured in anesthetized and passively heated rats by ultrasonic Doppler flowmetry during heating, and the values were compared to those (TBFp) simultaneously measured by venous-occlusion plethysmography. TBFp was estimated from the values per unit tissue multiplied by the tail volume, the shape of which was assumed to be a cone. TBFp was highly correlated with TBFu, with a regression equation of TBFp=0.7TBF(u)+0.1 (r(2)=0.94, p<0.001). Although TBFp was slightly lower than TBFu, the equation is useful to estimate the absolute values of tail skin blood flow from the values of plethysmography in awake rats.
  • Y Nakajima; H Nose; A Takamata
    AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY 275 5 R1703 - R1711 1998年11月 
    To gain better insights into the effect of dehydration on thermal and cardiovascular regulation during hyperthermia, we examined these regulatory responses during body heating in rats under isosmotic hypovolemia and hyperosmotic hypovolemia. Rats were divided into four groups: normovolemic and isosmotic (C), hypovolemic and isosmotic [L, plasma volume loss (Delta PV) = -20% of control], hypovolemic and less hyperosmotic [HL1, increase in plasma osmolality (Delta P-osm) = 23 mosmol/kgH(2)O, Delta PV = -16%], and hypovolemic and more hyperosmotic (HL2, Delta P-osm = 52 mosmol/kgH(2)O, Delta PV = -17%). Hyperosmolality was attained by subcutaneous injection of hypertonic saline and hypovolemia by intra-arterial injection of furosemide before heating, Then rats were placed in a thermocontrolled box (35 degrees C air temperature, similar to 20% relative humidity) for 1-2 h until rectal temperatures (T-re) reached 40.0 degrees C. Mean arterial pressure in L decreased with rise in T-re (P < 0.001), whereas mean arterial pressure remained constant in the other groups. Maximal tail skin blood flow in L, HL1, and HL2 was decreased to similar to 30% of that in C (P < 0.001). T-re threshold for tail skin vasodilation (TVD) was not changed in L, whereas the threshold shifted higher in the HL groups. T-re threshold for TVD was highly correlated with P-osm (r = 0.94, P < 0.001). Heart rate in the HL groups increased with rise in T-re (P < 0.001), whereas it remained unchanged in C and L. Cardiovascular responses to heating were not influenced by V-1 antagonist in C, L, and HL2. Thus isotonic hypovolemia attenuates maximal tail skin blood flow, whereas hypertonic hypovolemia causes an upward shift of T-re threshold for TVD and an increase in heart rate during hyperthermia. These results suggest that plasma hyperosmolality stimulates presser responses in the hypovolemic condition that subsequently contribute to arterial pressure regulation during heat stress.
  • 能勢 博; 広瀬 宗孝; 中嶋 康文; 鷹股 亮; 陳 勉
    日本臨床麻酔学会誌 17 10 585 - 588 THE JAPAN SOCIETY FOR CLINICAL ANESTHESIA 1997年

MISC

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    研究期間 : 2020年04月 -2023年03月 
    代表者 : 中嶋 康文; 竹下 淳; 影山 京子
     
    健康成人被験者から、1回20ｍｌのクエン酸採血を行い、遠心操作にてHistopaque等を用いて好中球の分離を行った。好中球の培養実験 糖濃度の異なる培養液を用いた好中球の培養系において、LPSを含有する培養液で24-48時間培養後、ホルボール12-ミリスチン酸13-酢酸塩（PMA）負荷し、好中球の脱顆粒化、NETs、ヒストンを蛍光色素染色後、蛍光倒立顕微鏡で観察、または培養後の回収液をフローサイトメーターで定量化し、対象群と比較検討した。（Joshi MB, et al. FEBS Letters 2013； 587) 好中球検体からmirVanaTM miRNA Isolation Kit 等を用いてmiRNAを抽出した。 １）包括的miRNAの発現プロファイリング 定量性のある網羅的miRNAプロファイリングを、従来のマイクロアレイ法よりも、優れた次世代高速シーケンサーIon PGMシステム（Life Technology社)を用いた。２）Small RNAのライブラリ作成 Ion Total RNA-Seq Kitを用いる３）cDNAに変換、増幅 逆転写後、エマルジョンPCR法で、cDNAを増幅 ４）シーケンシング（３時間）シーケンサーによるmiRNA発現定量 ５）データ解析（１時間）サーバーにSFFまたはFASTQ形式データの転送 統計学的な有意差検定を伴う発現定量解析には、CLCバイオ社の解析ソフト（Genomic Work Bench）を使用した。その中で、複数のmiRNA Prediction Tool（Miranda, Target Scan Human5.0, PicTar, miRBase Targets Version 5.0）より、特にNETsを含む、細胞死・炎症惹起物質に関連する伝達RNAに相補配列のあるmiRNAを選別した。しかし、次世代シーケンサーのキットが旧世代で、高濃度のmiRNAを必要とするため思ったような結果が出なかったため、外部委託業者に、新しい試薬と次世代シーケンサーを用いてmRNAおよびmiRNAの網羅的解析を依頼することになった。
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2019年04月 -2023年03月 
    代表者 : 影山 京子; 中嶋 康文
     
    敗血症時の血小板と好中球の相互作用において、血小板由来miRNAの役割を、ヒト正常血小板、好中球を用いた共培養実験系（In Vitro系）で、施行した。 健康成人被験者約２０名から、各々1回20ｍｌの採血を行う。クエン酸採血後、遠心操作にて洗浄血小板溶液作成、及びHistopaque等を用いて好中球の分離を行った。（miRNAの分 離と濃縮）血小板、好中球、及び還流液検体から、miRNeasy Mini Kit等を用いてmiRNAを含むTotal RNAを抽出した。自身が所有する次世代シーケンサーで解析を試みたが性能が悪いためか思ったような実験結果が出なかったため、再度、別の検体を用いて、次世代シーケンサーによる網羅的解析を外部委託会社に依頼することにした。
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2019年04月 -2023年03月 
    代表者 : 竹下 淳; 中嶋 康文
     
    miRNAの網羅的解析による敗血症における血小板が関与する機序を検証するためヒト正常血小板及び、培養細胞用いた以下の実験系（In Vitro）を施行した。 健康成人の被験者の末梢静脈から、1回20ｍｌの採血を行った。a.RNAの分離と濃縮 クエン酸採血後、遠心操作にて多血小板血漿作成後、洗浄血小板溶液の作成。血小板内miRNA変化を観察する目的で、敗血症病態の主因となるリポ多糖体、ヒストン、HMGB1等の DAMPs投与前後の洗浄血小板検体から、miRNA Easy Mini Kit 等を用いてTotal RNAを抽出した。b.包括的miRNAの発現プロファイリング 次に、定量性のある網羅的miRNAプロファイリングを、従来のマイクロアレイより優れた次世代高速シーケンサーIon PGMシステム (Life Technology社) を用いて絶対的な定量法を施行。１．Small RNAのライブラリ作成 Ion TotalRNASeqKitを用いてフラグメント化 ２．cDNAに変換 逆転写酵素を用いる。３．ビース調整（４時間）エマルジョンPCR法を用いて、cDNAを増幅 ４．シーケンシング（３時間） シーケンサーによるmiRNA発現定量 ５．データ解析の順で行った。 しかし、次世代シーケンサーの性能が悪いためか、実験結果が芳しくなかったため、外部委託業者に、次世代シーケンサーによるmRNAおよびmiRNAの網羅的発現解析を依頼した。
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2016年04月 -2018年03月 
    代表者 : 徳平 夏子; 中嶋 康文; 黄瀬 ひろみ; 中山 力恒
     
    本研究では、AKIを発症しやすい心臓血管手術患者周術期や、集中治療を要する重症症例の尿中、血液中からエクソソーム、クロマチンを抽出し、次世代シーケンサーを用いてmiRNA、及びceRNA発現の網羅的解析を行った。具体的には、RIFLE 及びAKIN criteriaを用いて、周術期のAKIの重症度をステージ分類し、急性腎障害時に変化するmiRNAおよびceRNAの発現を多変量解析により選出した。現在、統計的有意差を得るため、症例収集している。さらに、データベースを用いてmiRNA-ceRNA, miRNA-ncRNAのネットワークを探索する事に、主眼を置いた。 今回使用する次世代シーケンサーは、網羅的なmiRNAプロファイリングを未知のnon-cording RNAの発現に対してだけでなく、miRNA発現の絶対的定量評価が行える点で、従来のマイクロアレイ法と比べ、感度、正確性、再現性などにおいて優れている。近年、miRNAは抗体医薬と異なり開発に特別なノウハウが不必要なため、遺伝子治療として核酸創薬の対象になっている。早期診断マーカーに有用性の高いmiRNAのターゲットが、急性腎障害抑制に有用なタンパク質であった場合、今後の遺伝子治療に展開出来る可能性があると考えている。 また、一方で研究手法が次世代シーケンサーを用いた研究手法で同様であるため、共同研究を行った研究課題”次世代シーケンサーを用いた、チアノーゼ先天性心疾 患における血球異常症の発症メカニズムに関与する赤血球中microRNAの網羅的解析”に関してh、共同演者として2017年度の日本麻酔科学会で報告し、最優秀演題を受賞した。さらに2018年度の日本麻酔科学会においても、”保存赤血球製剤中における赤血球内microRNA経時変化の網羅的解析”を報告した。
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2015年04月 -2018年03月 
    代表者 : 影山 京子; 棚橋 俊仁; 徳平 夏子; 中嶋 康文; 中山 力恒
     
    心臓血管手術患者を対象に、周術期の急性腎障害（AKI: Acute Kidney Injury）発症の早期診断バイオマーカーの探索を目的に、血液中、尿中エクソソーム中のmicroRNA(miRNA)を網羅的に解析し、AKI発症の早期検出に特異度、感度何れも優れているmiRNAを検討した。また、統計解析で有意に変化があると判明したmiRNAのターゲットとなるタンパク質を同定する事で、AKI発症の新しい機序、及びmiRNAのAKI発症における役割を探求することを主眼において研究を行った。
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2014年04月 -2018年03月 
    代表者 : 佐和 貞治; 天谷 文昌; 中嶋 康文
     
    高齢化社会の進行の中で、免疫力の低下した高齢者を対象に多剤耐性緑膿菌による重症肺炎が増加している。今回、緑膿菌の主要な病原性であるⅢ型分泌システムを阻害できるモノクローナル抗体m166のハイブリドーマ細胞よりクローニングした抗体遺伝子をテンプレートとして、遺伝子遺伝子組換え抗PcrV単鎖抗体scFv::m166-HLLを作成した。さらにこの抗体をヒト化する改変を加えて、緑膿菌肺炎の予防・治療薬として気管内投与による効果をマウス緑膿菌肺炎モデルで検討した。この研究を通じて、細菌性肺炎に対する吸入抗体医薬品としての遺伝子組換え単鎖抗体の可能性が示唆された。
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2014年04月 -2018年03月 
    代表者 : 中嶋 康文; 佐和 貞治; 石井 祥代; 溝部 俊樹; 小川 覚; 中山 力恒
     
    人工心肺下心臓手術後の血小板機能低下の機序は、未だ解明の余地がある。無核細胞の血小板にも、種々の刺激で、有核細胞同様にアポトーシスが誘導される。人工心肺下手術周術期に起きる血小板機能障害の原因として、アポトーシスに関連する細胞内情報伝達系が関与している可能性があるとの仮説で実験を行った。血小板は、また、転写、翻訳機能を有し、RNAを含有している。本研究において、幾つかのmicroRNAが周術期に変化し、その結果、ターゲットとなるmRNAとタンパク質が低下することで、血小板の機能低下をもたらすとの仮説の元、実験を行った。手法として、次世代シーケンサーでmicroRNAの変化を網羅的に解析した。
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2014年04月 -2017年03月 
    代表者 : 中山 力恒; 佐和 貞治; 溝部 俊樹; 小川 覚; 中嶋 康文
     
    現在、患者予後と明らかな関連があると報告が認められる血小板機能モニタリングは、ごく僅かである。 今回、我々は、周術期抗血小板薬効モニタリングのために有用な血小板由来microRNA明らかにするために研究を行った。まず、第一段階として、薬物及びずり応力を用いた血小板刺激を行い、最も鋭敏に反応するmicroRNAを同定することを行った。実際には、刺激前後の血小板由来microRNAを次世代シーケンサーを用いて網羅的に解析した。その結果、mir-155を含むいくつかのmicroRNAに有意差を認めており、実際に抗血小板薬を用いた次の研究段階に移る予定である。
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2012年04月 -2017年03月 
    代表者 : 橋本 悟; 志馬 伸朗; 佐和 貞治; 柴崎 雅志; 足立 孝臣; 橋本 壮志; 徳平 夏子; 中嶋 康文; 金子 猛; 成宮 博理; 天谷 文昌; 松山 広樹
     
    肺および腎の双方に影響すると考えられるHO-1（Heme Oxygenase-1, 以下HO-1）の関与に着目して研究を進め重症患者ほどHO-1の血中濃度は有意に高値を示し、腎機能も障害を示すことが判明した。また緑膿菌を用いた敗血症マウスモデルにおいて抗PcrV抗体を含むガンマグロブリン投与等が肺腎等の全身臓器傷害に対して防御的に作用することを示した。これらの結果は肺における障害が遠隔臓器に影響を及ぼすいわゆる臓器間クロストークの存在を示唆するものであると考えられた。
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2013年04月 -2016年03月 
    代表者 : 影山 京子; 佐和 貞治; 中嶋 康文
     
    研究課題に基づき、炎症消退脂質分子の周術期病態下における炎症消退反応やオートファジーの誘導について、術後回復力(ERAS)に関連するメカニズムを解明することを目的とした。最初のステップとして、C57BL/6マウスをコントロール群と飢餓群に設定し、肝細胞の変化を観察した。生理活性脂質であるレゾルビン投与で、飢餓状態の肝細胞内のオートファジーの進行が抑制される可能性を見出した。また、オートファジーに関連する可能性のあるmicroRNAを肝細胞内のmicroRNAの網羅的発現解析から探求した。結果、候補と考えられていたmicroRNAについて、有意差を得るには至っていない。
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2010年04月 -2013年03月 
    代表者 : 早川 由夏; 中嶋 康文; 志馬 伸朗; 加藤 祐子; 木村 みどり; 岡野 佳子
     
    本年度実験経過においては、ラット心筋細胞を用いたIn Vitro系でヒトを対象とした臨床実験(In vitro系)系と同様に心筋障害とアポトーシス及びオートファジーの関係を解明する事、β-blockerまたは吸入麻酔薬を培養液に添加する事で、アポトーシス及びオートファジーの発現変化を観察する事を目標にしていた。しかし、ヒトを対象とした臨床研究で研究結果の進展をみたので、ラット心細胞を用いた実験系を中断した。 去年度の報告書において、 1.心拍動下冠動脈バイパス手術症例における心筋保護作用を目的とした短時間作用型β-blocker(ランジオロール)投与に、一部有効性を示すことができた。人工心肺下冠動脈バイパス手術症例においては、心筋障害が高度に発現している可能性があるのでより有用性を示す可能性がある、と記載した。 この仮説に従い術前からのβ遮断経口薬のみならず、術中の短時間作用型β遮断薬投与により、人工心肺下冠動脈バイパス手術において心筋細胞内の小胞体ストレス(CHOP発現)と細胞死(Caspase3発現)の発現が抑制されることで、周術期の心筋障害(血漿中H-FABP濃度)が抑制されることが分かった。また、これら術中の短時間作用型β遮断薬投与によるCHOP及びCaspase3発現抑制効果は心拍動下冠動脈バイパス手術においては確認されなかったことから、より心筋に侵襲の高い環境において短時間作用型β遮断薬の効果が見られる事が示唆された。
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2011年 -2013年 
    代表者 : 中嶋 康文; 柴崎 雅志; 溝部 俊樹; 橋本 悟; 佐和 貞治
     
    血小板は止血凝固系の働き以外に、炎症制御にも深く関与している事が最近知られている。敗血症病態において、血小板は好中球との相互作用により好中球よりNETsを産生させる事で炎症消退機構に寄与している。しかし、NETsが過剰に産生されると毛細血管が閉塞することで、臓器不全を来す可能性がある。我々は炎症、細胞死に関与するタンパク質遺伝子のノックダウン血小板細胞を作成し、好中球との共培養を実験を行った。実験結果より、細胞死の過程にある血小板と好中球の共培養ではNETsの産生が抑制されるが、過度な血小板活性化がNETsを過剰に産生させるため、適度な血小板活性化が炎症消退に重要である可能性が示唆された。
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2009年 -2011年 
    代表者 : 影山 京子; 中嶋 康文; 溝部 俊樹; 谷口 文香
     
    人工心肺使用下の開心術の周術期では,血小板機能低下が原因で止血に難じる事がある.本研究は血小板細胞内p38MAPK経路を中心とした細胞内情報伝達系の経時的変化とその役割について研究を行った.結果,人工心肺離脱後からGPIbやPAR-1など,トロンビン受容体の発現低下を認めた.また,細胞死シグナルである血小板内Baxの上昇とミトコンドリア内シトクロムCの低下を認め, Baxのミトコンドリアへの移行が関連していることが示唆された.血小板の機能維持のためには,血小板内のBaxの制御が重要であると考えた.
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2008年 -2010年 
    代表者 : 中嶋 康文; 上野 博司; 溝部 俊樹; 橋本 悟
     
    血液単球系細胞からのTissue Factor(組織因子)の放出にRaf-MEK-ERK1/2pathway 及びその下流の転写因子Egr-1の関与がRNA 干渉法による遺伝子ノックダウン手技を用いて示唆された。クロドロネート前処理することで、血液中の単球系細胞を抑制したマウスにこれらの遺伝子ノックダウン単球系細胞を注入後、肺梗塞モデルマウスを用いて、肺梗塞の重症度及び生存率を検討したところ、Tissue Factorの発現、炎症系が抑制されることで重症度と生存率が改善した。
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2006年 -2007年 
    代表者 : 中嶋 康文; 溝部 俊樹; 橋本 悟
     
    我々は、人工膝関節手術患者を対象にした臨床研究において、特に下大静脈血内の血小板活性化による血漿Tissue Factor濃度、血液凝固能の亢進が静脈血栓塞栓症の病態生理に重要な役割を果たしている可能性を論文に報告した。(J Thromb Haemost.,2007;5:738-45.) また、その研究過程において周術期PDE3 inhibitor投与が血小板活性を抑制しその結果血液凝固能充進を抑制することを見いだした。さらにPDE3 inhibitorによる血小板機能抑制のメカニズムとして血小板内シグナリングに注目し、p38MAPK signaling抑制がLeukocyte Platelet Conjugate生成の抑制に、MEK/ERK,PI3/Akt signaling抑制が血小板凝集能抑制に働くことにより、周術期の血漿Tissue Factor濃度、血液凝固能の亢進を抑制していることを学会報告した。現在これらの内容を投稿予定している。 培養細胞を用いての実験においては、siRNAによる遺伝子ノックダウン実験により活性化血小板による単球からのTissue Factor放出にp38MAPK pathway及びMEK/ERK path wayが主に関与していることが分かった為、今後さらにヒト単球等を用いて深く探求していく予定である。
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2005年 -2006年 
    代表者 : 溝部 俊樹; 中嶋 康文; 影山 京子; 谷口 知史
     
    前年度において、我々は膝関節全景換手術症例を対象にした臨床実験により、Flow-Cytometry法,ELISA法,Whole Blood Impedance法等を用いて、下半身から還流された下大静脈内において、白血球(主に単球)、血小板、血管内皮細胞が相互作用を及ぼし互いに活性化される事によりLeukocyte-Platelet Conjugate, Microparticleの形成Tissue Factor, CD40Ligand等サイトカインの産生か行われ、それらがFibrin MonomerComplexの生成及び血液凝固亢進を引き起こす事を明らかにし、肺梗塞発生との関係を示唆した。それらの主な結果は、論文として本年度に公表した。(J Throrab Haemost.2007Apr;5(4):738-45,)本年度は、更にこれら血液細胞の相互作用のメカニズムをIn Vitroにおいて観察すべく、培養細胞、及びPrimary Cellを用いてRNAi法による遺伝子ノックダウンにより白血球-血小板間の相互作用が弱められることを明らかにした。具体的には、THP-1細胞及びヒト単球表面抗原のCD162(P-selectin glycoprotein-1),またはCD40をNucleofection法を用いてsiRNAを導入し、72時間後に表面抗原がノックダウンされていることを確認した細胞と血小板を共培養して、Leukocyte-Platelet Congugate産生の低下、Soluble Tissue Factor、CD142発現の低下、Microparticle産生の低下を確認した。また、血小板機能も抑制されることを確認した。
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2004年 -2005年 
    代表者 : 中嶋 康文
     
    (研究計画)心臓血管手術に於いては虚血再還流障害等が原因で、高サイトカイン血症によりSIRSに陥る危険性が知られている。従って適度な炎症性サイトカイン産生抑制は患者に利益をもたらす可能性がある。よって心臓血管外科周術期においてグルココルチコイド投与がサイトカインバランスを修飾し、患者のOutcomeを改善するか否かを検討する事が一つの目的であった。またラットを用いた実験に於いて同様の結果が得られる実験系を確立する事がもう一つの目的であった。 (研究経過及び成果)ストレス用量のHydrocortisoneの投与(2-3mg/kg)により血漿中及び肺胞上皮被覆液中のIL6,IL8,CD40,MMP9産生の抑制,IL10濃度の上昇と共に、血漿中Fatty Acid Binding Protein, NT-proBNP, Troponin I濃度の低下を認めた。よってストレス用量のグルココルチコイド投与が心筋保護に働いている事が示唆された。ラットを用いた動物実験においては、冠状動脈前下行枝結紮モデルに於いてIL10発現アデノウイルス(Ad-IL10)を尾静脈より注入することにより、冠状動脈前下行枝結紮による心筋梗塞発症後の血漿中Troponin I濃度の上昇が抑制された。従って、ステロイド投与による血漿中IL10上昇が心筋保護に作用していることが示唆された。これらの結果は学会にて発表予定である。また、心拍動下冠動脈バイパス術における術後心房細動の予測因子の解析研究発表は2004年の国際心臓血管麻酔学会において藤田昌雄賞にノミネートされた。
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2001年 -2001年 
    代表者 : 中嶋 康文
     
    申請者らは、体温調節系に影響を及ぼす系として循環制御系を中心に研究を行ってきた。即ち、血圧の変動により体温調節機能が変化する事を高体温側及び低体温側において発見したが、研究途中に置いてアミノ酸輸液が体温調節中枢に影響を及ぼすことを発見した。血中アミノ酸濃度が上昇すると代謝量が上昇し体温が上昇することは既知の事実であったが、熱放散が上昇すれば体温は一定に保たれるはずである。これらの事実より、我々は体温調節機能が高体温側にシフト、即ちアミノ酸が発熱物質のように体温調節中枢に作用しているのではないかという仮定の基、健康被験者を用いて実験を行った。被験者に2時間、体重あたり一定量のアミノ酸輸液を投与後、下半身40度温浴または、water-perfused suitに約15度の冷水を還流し中枢温を上昇または低下させその時の体温調節反応を測定した。その結果、皮膚血管拡張、発汗および皮膚血管収縮、ふるえすべての反応が高体温側にシフトしていることが分かった。また、ふるえに於いてはアミノ酸輸液により上昇する事が分かった。これらの現象に交感神経系が関与していることを我々は発見したが詳細は今後の研究課題である。
  • The effect of cytokine balance on cardiovascular disease
    研究期間 : 2001年
  • 周術期の血小板細胞内シグナリングの変化と血小板機能
  • Study for the interaction between thermoregulction and cardiovascularregulertion

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