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Diaphragmatic fatigue during sepsis-Mechanisms and therapy

Research Project

Project/Area Number 09671579
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionSapporo Medical University, School of Medicine

Principal Investigator

WATANABE Hiroaki  Sapporo Medical University, Asso. Pro, 医学部, 助教授 (20113764)

Co-Investigator(Kenkyū-buntansha) NARIMATSU Eichi  Sapporo Medical University, Instructor, 医学部, 助手 (70295343)
SUMITA Shinzoh  Sapporo Medical University, Asso. Pro., 麻酔科, 非常勤講師 (70187805)
FUJIMURA Naoyuki  Sapporo Medical University, Training
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Keywordsdiaphragm / contractility / intra-abdominal sepsis / malondialdehyde / free radical / superoxide / dimethyl sulfoxide / catalase / 横隔膜収縮力低下 / malondialdehyde / hydroxyl radical / 過酸化水素 / catalase / superoxide / PEG-SOD / TBAR / 敗血症 / 呼吸筋疲労
Research Abstract

We investigated the alteration and mechanisms in diaphragmatic contractility in intra-abdominal sepsis in vitro. Intra-abdominal sepsis was produced using the cecal ligation and perforation technique (CLP). We assessed the diaphragmatic contractility by twitch characteristics and force-frequency curves in vitro. In the first study, we investigated the time course changes in diaphragmatic contractility after CLP. Diaphragmatic contractile dysfunction was began to develop 10hr after CLP and further reduction was observed 16hr after CLP. In the second study, we investigated the effects of PEG-SOD, PEG-CAT and DMSO on diaphragmatic contractility and MDA levels in septic peritonitis and the activities of two main antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPx) in vitro. PEG-SOD, PEG-CAT and DMSO were administered intraperitoneally 30 min before and 12h after CLP. Diaphragmatic MDA levels were significantly elevated after CLP. PEG=SOD, PEG-CAT and DMSO significantly improved diaphragmatic contractility and prevented the elevation in diaphragmatic MDA levels after CLP. Diaphragmatic SOD activities were significantly increased after CLP. These results suggest that several types of oxygen-derived free radicals play a role in the reduction in diaphragmatic contractility after CLP.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report

Research Products

(22 results)

All Other

All Publications (22 results)

  • [Publications] Fujimura N, Sumita S, Narimatsu E, Nakayama Y, Shitinohe Y, Namiki A: "Effects of Isoproterenol on Diaphragmatic Contractility in Septic Peritonitis"Am J Respir Crit Care Med. 161. 440-446 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fujimura N, Sumita S, Narimatsu E: "Alteration in diaphragmatic contracitility during septic peritonitis in rats Effect of poiyethyiene glycol absorbed superoxide dism utase"Crit Care Med. in press. (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Natimatsu E, Nkayama Y, Sumita S, Iwasaki H, Fujimura N, Sato K, Namiki A: "Sepsis attenuates the intensity of the neuromuscular effect of d-Tubocurarine and the antagonistic actions of neostigmine and edrophonium"Acta Anaesth Scand. 43. 196-201 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Narimatsu E, Nkayama Y, Aimono M, Fujimura N, Iwasaki H, Namiki A: "Milrinone, a Phosphodiesterase III inihibitor, antagonizes the neuromuscular blocking effect of a non-depolarizing muscle relaxant"Res Commun Mol Pathol Pharmacol. 104. 219-228 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakayama Y, Narimatsu E, Sumita S, Fujimura N, Satoh K, Iwasaki H, Namiki A: "Propofol enhances a d-tubocurarine-induced twitch depression in septic rat diaphragm"Anesth Analg. 90. 80-84 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Narimatsu E, Nakayama Y, Sumita S, Iwasaki H, Fujimura N, Satoh K, Namiki A: "Sepsis attenuates the intensity of the neuromuscular blocking effect of d-tubocurarine and the antagonisitic a ctions of neostigmine and edrophonium accompanying depression of muscle contractility of the diaphragm"Acta Anaesthesiol Scand. 43. 196-201 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] FUJIMURA,N., SUMITA,S., NARIMATSU,E., NAKAYAMA,Y., SHITINOHE,Y., NAMIKI,A.: "Effects of Isoproterenol on Diaphragmatic Contractility in Septic Peritonitis."Am J Respir Crit Care Med. 161(2). 440-446 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] NARIMATSU,E., NAKAYAMA,Y., SUMITA,S., IWASAKI,H., FUJIMURA,N., SATOH,K., NAMIKI,A.: "Sepsis attenuates the intensity of the neuromuscular effect of d-Tubocurarine and the antagonistic actions of neostigmine and edrophonium."Acta Anaesth Scand. 43. 196-201 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] NARIMATSU,E., NAKAYAMA,Y., AIMONO,M., FUJIMURA,N., IWASAKI,H., NAMIKI,A.: "Milrinone, a Phosphodiesterase III inhibitor, antagonizes the neuromuscular blocking effect of a non-depolarizing muscle relaxant."Res Commun Mol Pathol Pharmacol. 104. 219-228 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] NAKAYAMA,Y., NARIMATSU,E., SUMITA,S., FUJIMURA,N., SATOH,K., IWASAKI,H., NAMIKI,A.: "Propofol enhances a d-tubocurarine-induced twitch depression in septic rat diaphragm."Anesth Analg. 90(1). 80-84 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] NARIMATSU,E., NAKAYAMA,Y., SUMITA,S., IWASAKI,H., FUJIMURA,N., SATOH,K., NAMIKI,A.: "Sepsis attenuates the intensity of the neuromuscular blocking effect of d-tubocurarine and the antagonistic actions of neostigmine and edrophonium accompanying depression of muscle contractility of the diaphragm."Acta Anaesthesiol Scand. 43(2). 196-201 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakayama Y,Narimatsu E,Sumita S et al: "Propofol enhances a d-tubocurarine-induced twitch depression in septic rat diaphnagm"Anesthesia and Analgesia. 90. 80-84 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fujimura N,Sumita S,Narimats E et al: "Effect of isoproferenol on diaphragmatic contractility in septic peritonitis"American Journal of Respiratory and Critial Care Medicine.

    • Related Report
      1999 Annual Research Report
  • [Publications] Fujimura N,Sumita S,Narimatsu E: "Atteration in diaphragmatic contractility doring septic peritonitic in rats:Effect of polyethylene glyool absorbed soperoxide dismutael"Critical Core Medicine.

    • Related Report
      1999 Annual Research Report
  • [Publications] Narimatsu E,Nakayama Y,Aimono M: "Phosphodiesterase III,inhibitor,antagonizes the neuromuscular blocking effect of a non-depolarizing muscle reloxant"Res Commun Mol Pathol Pharmacol. 104. 219-228 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Watanabe H,Watanabe Y,Ichikawa et al: "A New Skin-Protective Sphygnomanometer Antf"Anesthesia and Analgesia. 89. 1240-1242 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] E.Narimatsu et al: "Sepsts attenuates the intensity of the neuromuscular blocking effect of d-Tubocurarine and the antagonistic actions of neostigmine and edrophanion accoinparying depression of mosdle contractility of the diaphragm" Acta.Anesthesiologica Scandinavica. 43. 196-201 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 住田臣造、並木昭義: "Molecular biologyからみたショックの病態-heat shock proteinを中心に" 集中治療. 10. 377-385 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 住田臣造、七戸康夫ら: "敗血症と熱ショック蛋白質" 日本ショック学会雑誌. 13. 40-44 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Itoh: "The effect of fentanyl on d-Tuborakne-induced onkcle pilaxution in septic rat chaphragin" Anesthesiology. 87・3A. A857 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] N.Fujimura: "Isoproterenol improves sepsis-induced diaphragmcitic dyshmction in rats" Critical Care Medicine. 25-1sup. A115 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 住田臣造: "Molecular biologyからみたショックの病態ーheat shock proteinを中心に" 集中治療. 10・4. (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-03-31   Modified: 2016-04-21  

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