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The roles of gaseous mediators during inflammatory cytokine induced cardiac depression

Research Project

Project/Area Number 14571471
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionNippon Medical School

Principal Investigator

SAKAMOTO Atsuhiro  Nippon Medical School, Department of Anesthesiology, Associate Professor, 医学部, 助教授 (30196084)

Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsnitric oxide / carbon monoxide / carboxy hemoglobin / inflammation / surgical insult / cardiac depression / 外科浸襲 / ヘムオキシゲナーゼ
Research Abstract

<Basic research> Using the rat working heart preperation, the role and relation of gaseous molecules (nitric oxide, NO ; carbon monoxide, CO) during tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-Iβ) induced cardiac depression. Administration of cytokines depressed the left ventricular work (LVW). Administrations of NO synthase (NOS) inhibitor, L-canavanin (CAN) and CO synthase (hemeoxygenase) inhibitor, zinc protoporphyrine (ZPP) improved the LVW. Gene expressions of inducible NOS (iNOS) and inducible HO (HO-1) in the left ventricle significantly increased 2 hours after perfusion. Administration of CAN inhibited the increase of HO-1 expression, and adminstration, of ZPP inhibited the HO-1 expression and promoted the INOS expression. These data suggest that NOS/NO systema and HO/CO system are interrelated at the gene ezpression levels even when those systems are highly promoted, however, the interaction of both systems on cardiac contractility did not make clear and other factors are speculated to be important under those situation. <Clinical research> Changes in CO generation during coronary artery bypass graft by measuring CO-Hb concentrations and the expression of HO in circulating blood as well as the expressions of TNF-α and IL-1β. CO-Hb significantly increased after surgery ; however, those values did not significantly change in patients who showed CO-Hb 【greater than or equal】1.0% before surgery. The expression ratios of HO-1, TNF-α, and IL-1β significantly increased after surgery. CO-Hb significantly correlated with the expression ratios of the inflammatory mediators ; however, the correlation was low in the patients who showed CO-Hb 【greater than or equal】1.0% before surgery. These data indicate that CO-Hb can, in general, reflect the surgical inflammatory response ; however, the usefulness of CO-Hb as a marker of surgical stress might be limited to certain patients.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Sakamoto A. et al.: "Different effects of inhalation anesthetics on calcium homeostasis in the cardiac muscle of isolated working heart"Biomedical Research. 24. 141-146 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sakamoto A. et al.: "Relationship between nitric oxide and carbon monoxide during inflammatory cytokine-induced cardiac depression"Biomedical Research. 25. 53-60 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 坂本篤裕: "医療ガスの現況と展望:一酸化炭素"医科器械学. 74. 111-119 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sakamoto A. et al.: "Prostaglandin E2 receptor subtype EP4 agonist attenuates cardiovascular depression in endotoxin shock by inhibiting inflammatory cytokine and nitric oxide production"Shock. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimizu, T., Sakamoto, A., Ogawa, R.: "Inhibition of inducible nitric oxide synthase attenuates interleukin-1β induced vascular hyporeactivitv in the rabbit."Journal of Nippon Medical School. 69. (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takeda, S., Nakanishi, K., Ikezaki, H., Kim, C., Sakamoto, A., Tanaka, K., Ogawa, R.: "Cardiac marker response to coronary artery bypass graft surgery with cardiopulmonary bypass and aortic cross-clamping."Journal of Cardiothoracic and Vascular Anesthesia. 16. 421-425 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takeda, S., Kim, C., Ikezaki, H., Nakanishi, K., Sakamoto, A., Okawa, K., Miyashita, M., Sasajima, K., Tajiri, T., Tanaka, K., Ogawa, R.: "Preoperative administration of methylprednisolone attenuates cytokine-induced respiratory failure after esophageal resection."Journal of Nippon Medical School. 70. 16-20 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sakamoto, A., Nishikawa, K., Ogawa, R: "Different effects of inhalation anesthetics on calcium homeostasis in the cardiac muscle of isolated working rat hearts."Biomedical Research. 24(3). 141-146 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsumura, J., Sakamoto, A., Ogawa, R.: "Transcriptional down-regulation of tumor necrosis factor-α gene by early given pentoxifylline : A quantitative demonstration in rats with peritoneal sepsis."Biomedical Research. 24. 187-194 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sakamoto, A., Matsumura, J., Shimizu, J., Ogawa, R.: "Relationship between nitric oxide and carbon monoxide during inflammatory cytokine-induced cardiac depression."Biomedical Research. 25. 53-60 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sakamoto, A., Matsumura, J., Mu, S., Gotoh, Y., Ogawa, R.: "A Prostaglandin E2 receptor subtype EP4 agonist attenuates cardiovascular depression in endotoxin shock by inhibiting inflammatory cytokine and nitric oxide production."Shock. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sakamoto A.et al.: "Different effects of inhalation anesthetics on calcium homeostasis in the cardiac muscle of isolated working rat hearts"Biomedical Research. 24・3. 141-146 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sakamoto A.et al.: "Relationship between nitric oxide and carbon monoxide during inflammatory cytokine-induced cardiac depression"Biomedical Research. 25・1. 53-60 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 坂本篤裕 他: "医療ガスの現況と展望:一酸化炭素"医療器械学. 74・3. 111-119 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sakamoto A.et al.: "Prostaglandin E2 receptor subtype EP4 agonist attenuates cardiovascular depression in endotoxin shock by inhibiting inflammatory cytokine and nitric oxide production."Shock. in press. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimizu T et al.: "Inhibition of inducible nicric oxide synthase attenuates interleukin-1 induced vascular hypo reactiviay in the rabbit"Journal of Nippon Medical School. 69・2. 149-153 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takeda S et al.: "Cardiac marker response to coronary arteybypdss gadft surgery with cardiopulmonary bypass and aortic-cross clamping"Journal of cardiothoracic and vascular anesthesia. 16. 421-425 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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