tudy of therapeutic effect of sodium nitrite on crush syndrome

• Project/Area Number: 22592021
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Josai University
• Principal Investigator: KOBAYASHI Jun 城西大学, 薬学部, 教授 (20153611)
• Co-Investigator(Kenkyū-buntansha): OHTAKE Kazuo 城西大学, 薬学部, 助教 (50337482) ; MURATA Isamu 城西大学, 薬学部, 助手 (80610667)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: クラッシュ症候群 / 虚血再灌流 / 一酸化窒素 / 亜硝酸 / デキサメサゾン / 虚血再灌漑

Research Abstract

We developed crush syndrome (CS) rat model to evaluate the therapeutic effect of nitrite on crush syndrome. Intraperitoneal single injection of nitrite improved survival rate of this CS model from 25% to 64%, furthermore combined therapy of continuous infusion of nitrite with conventional therapies including massive fluid infusion and correction of acidosis resulted in 100% survival rate. This might be due to the tissue protective effect of nitrite-derived nitric oxide (NO) against ischemia/reperfusion injury. A 100% survival rate was also achieved by the treatment of the CS rat with single injection of dexamethasone through a mechanism involving NO production in the injured skeletal muscle．These results provide not only a new protective mechanism against ischemia/reperfusion injury in this syndrome, but also a simple and promising drug therapy especially useful in the field of disasters

Research Products

• [Journal Article] Acute lethal crush-injured rats can be successfully rescued by a single injection of high-dose dexamethasone through a pathway involving PI3K-Akt-eNOS signaling (2013)
  • Author(s): Isamu Murata, Kazuya Ooi, Shingo Shoji, Yohei Motohashi, Miwa Kan, Kazuo Ohtake, Soichiro Kimura, Hideo Ueda, GenyaNakano,Kunihiro Sonoda, Yutaka Inoue, Hiroyuki Uchida, Ikuo Kanamoto,Yasunori Morimoto, and Jun Kobayashi
  • Journal Title: Journal of Trauma and Acute Care Surgery Volume: (in press)
  • NAID: 120005539642
  • Peer Reviewed
• [Journal Article] Nitrite reduces ischemia/reperfusion-induced muscle damage and improves survival rates in rat crush injury model (2012)
  • Author(s): Isamu Murata, Ryo Nozaki, Kazuya Ooi,Kazuo Ohtake, Soichiro Kimura, Hideo Ueda,Genya Nakano, Kunihiro Sonoda, Yutaka Inoue, Hiroyuki Uchida, Ikuo Kanamoto,Yasunori Morimoto, Jun Kobayashi
  • Journal Title: Journal of Trauma Volume: Vol.72 Pages: 1548-1554
  • Peer Reviewed
• [Journal Article] Nitrite reduces ischemia/reperfusion-induced muscle damage and improves survival rates in rat crush injury model (2012)
  • Author(s): Isamu Murata
  • Journal Title: Journal of Trauma Volume: 72 Issue: 6 Pages: 1548-1554
  • DOI: 10.1097/ta.0b013e31824a76b5
  • Peer Reviewed
• [Journal Article] Nitrite reduces ischemia/reperfusion-induced muscle damage and improves survival rates in rat crush injury model (2012)
  • Author(s): Isamu Murata, Ryo Nozaki, Kazuya Ooi, Kazuo Ohtake, Soichiro Kimura, Hideo Ueda, Genya Nakano, Kunihiro Sonoda, Yutaka Inoue, Hiroyuki Uchida, Ikuo Kanamoto, Yasunori Morimoto, Jun Kobayashi
  • Journal Title: Journal of Trauma Volume: (In press)
  • Peer Reviewed
• [Journal Article] Characterization of systemic and histologicinjury following crush syndrome andintervals of reperfusion in a small animal model (2011)
  • Author(s): Isamu Murata, Kazuya Ooi, Hiromi Sasaki, Soichiro Kimura, Kazuo Ohtake, Hideo Ueda, Hiroyuki Uchida, Norikiyo Yasui,Yasuhiro Tsutsui, Naoya Yoshizawa, Ichiro Hirotsu, Yasunori Morimoto, Jun Kobayashi
  • Journal Title: Journal of Trauma Volume: Vol. 70 Pages: 1453-1463
  • Peer Reviewed
• [Journal Article] Characterization of systemic and histologic injury following crush syndrome and intervals of reperfusion in a small animal model (2011)
  • Author(s): Isamu Murata, Kazuya Ooi, Hiromi Sasaki, Soichiro Kimura, Kazuo Ohtake, Hideo Ueda, Hiroyuki Uchida, Norikiyo Yasui, Yasuhiro Tsutsui, Naoya Yoshizawa, Ichiro Hirotsu, Yasunori Morimoto, Jun Kobayashi
  • Journal Title: Journal of Trauma Volume: 70 Pages: 1453-1463
  • Peer Reviewed
• [Presentation] Crush syndrome ラットモデルに対する亜硝酸塩と輸液大量投与の相乗効果に関する研究 (2013)
  • Author(s): 鈴木隆太、村田勇、大竹一男、井上裕、小林順、金本郁男
  • Organizer: 日本薬学会 第133 年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-30
• [Presentation] Crush syndromeに対する筋肉内Dexamethazone 投与の効果に関する研究 (2013)
  • Author(s): 後藤麻依、村田勇、大竹一男、井上裕、小林順、金本郁男
  • Organizer: 日本薬学会 第133 年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-30
• [Presentation] Crush syndromeラットモデルに対する亜硝酸塩と輸液大量投与の相乗効果に関する研究 (2013)
  • Author(s): 小林 順
  • Organizer: 日本薬学会 第133年会
  • Place of Presentation: 横浜
• [Presentation] Crush syndromeに対する筋肉内Dexamethazone投与の効果に関する研究 (2013)
  • Author(s): 小林 順
  • Organizer: 日本薬学会 第133年会
  • Place of Presentation: 横浜
• [Presentation] Nitrite ameliorates ischemia/reperfusion injury of skeletal muscle in rat crush injury model (2011)
  • Author(s): Jun Kobayashi, Ryo Nozaki, Isamu Murata, Kazuo Ohtake, Kazuya Ooi, Kunihiro Sonoda, Genya Nakano, Soichiro Kimura, Hideo Ueda, Hiroyuki Uchida, Yasunori Morimoto
  • Organizer: Approaching the Clinic: Nitrite and Nitrate Pathophysiology and Therapy Conference
  • Place of Presentation: アトランタ 米国
• [Presentation] Nitrite ameliorates ischemia/reperfusion injury of skeletal muscle in rat crush injury model (2011)
  • Author(s): Jim Kobayashi, Ryo Nozaki, Isamu Murata, Kazuo Ohtake, Kazuya Ooi, Kunihiro Sonoda, Genya Nakano, Soichiro Kimura, Hideo Ueda, Hiroyuki Uchida, Yasunori Morimoto
  • Organizer: Fourth Bi-annual conference. Approaching the clinic : Nitrite and Nitrate Pathophysiology and Therapy
  • Place of Presentation: Emory Conference Center Hotel, Atlanta, Georgia, USA
• [Presentation] 亜硝酸剤によるcrush syndromeの治療に関する基礎的検討 (2011)
  • Author(s): 小林順, 他
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡グランシップ他