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EFFECTS OF LIDOCAINE ON MULTIPLE ORGAN DYSFUNCTION : ELUCIDATION OF MECHANISM AND CLINICAL APPLICATION

Research Project

Project/Area Number 09671561
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionKOBE UNIVERSITY

Principal Investigator

MIKAWA Katsuya  KOBE UNIV.SCH.MED.ASSISTANT PROF., 医学部・附属病院, 講師 (40229662)

Co-Investigator(Kenkyū-buntansha) NISHINA Kahoru  KOBE UNIV.SCH.MED.INSTRUCTOR, 医学部, 助手
志賀 真  神戸大学, 医学部, 助手 (10273773)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsEndotoxin / Multiorgan Failure / Local anesthetics / Hyperoxia / ARDS / Neutrophil / リドカイン / 肺障害 / 活性酸素
Research Abstract

Endotoxin or sepsis often causes multiple organ dysfunction syndrome (MODS) including acute lung injury. Neutrophils are thought to play a pivotal role in the pathogenesis of MODS through the release of reactive oxygen species (ROS). Lidocaine has been shown to inhibit production of ROS by neutrophils. We previously demonstrated that lidocaine is effective for attenuating acute lung injury induced by endotoxin. The first aim of this study was to assess the effect of pretreatment with lidocaine on endotoxin/sepsis- induced MODS using experimental models. The second aim was to determine the mechanism underlying attenuation of MODS by lidocaine. The final aim was to apply this pharmacological intervention to clinical settings.
[Experimental Study]
(A) in vitro
We measured NOx (nitrite + nitrate) production and expression of iNOS (inducible nitric oxide synthase) in Raw 264 cultured cell in the presence or absence of lidocaine. Lidocaine inhibited NOx production in a dose-dependent manner, but had no effect on expression of iNOS mRNA.
(B) in vivo
Light microscopic findings revealed that lidocaine infusion (2 mg/kg/hr) pathologically attenuated acute lung injury, renal failure, and hepatic failure induced by endotoxin. Furthermore, lidocaine attenuated progression of DIC.We have also shown that pre-treatment with lidocaine 2 mg/kg/hr but not 1 mg/kg/hr attenuated diaphragmatic dysfunction induced by sepsis or hyperoxia in hamsters assessed by contractile profiles and endurance capacity. Using immunohistochemistry we found that lidocaine attenuated stains of iNOS or nitrotyrosine expressed in alveolar and bronchial epithelial cells.
[Clinical Study]
We administered lidocaine to 5 adult patients (sepsis 1, acute pancreatitis 1, postoperation 3) who were thought to be at risk for MODS.No patients developed MODS.No adverse effects were observed.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] 三川勝也,他: "人工サーファクタント補充療法" 集中治療. 10. 43-54 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 三川勝也,他: "急性肺障害の病態" ICUとCCU. 23(印刷中). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mikawa K,et al: "Aminoguanidine attenuates endofoxin-indued acutelung injury" Crit Care Med. 26. 905-91 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Nishina, K.Mikawa, Y.Takao, et al.: "Inhaled nitric oxide does not prevent endotoxin-induced lung injury in rabbits." Acta Anaesthesiol Scand. 41. 399-407 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Mikawa, H.Akamatsu, K.Nishina, et al.: "Inhibitory effect of local anaesthetics on reactive oxygen species production by human neutrophils" Acta Anaesthesiol Scand. 41. 524-528 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Nishina, K.Mikawa, Y.Takao, et al.: "ONO-5046, an elastase inhibitor, attenuates endotoxin-induced acute lung injury in rabbits" Anesth Analg. 84. 1097-1103 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Nishina, Akamatsu H,K.Mikawa, et al.: "The inhibitory effects of thiopental, midazolam, and ketamine on human neutrophil functions." Anesth Analg. 86. 159-165 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Mikawa, K.Nishina, M.Tamada, et al.: "Aminoguanidine attenuates endotoxin-induced acute lung injury in rabbits." Crit Care Med. 26. 905-911 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Nishina, K.Mikawa, Y.Takao, et al.: "Intravenous lidocaine attenuates acute lung injury induced by hydrochloric acid aspiration in rabbits." Anesthesiology. 88. 1300-1309 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Mikawa, H.Akamatsu, K.Nishina, et al.: "Propofol inhibits human neutrophil functions." Anesth Analg. 87. 695-700 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Kiyonari, K.Nishina, K.Mikawa, et al.: "Lidocaine attenuates acute lung injury induced by combination of phospholipase A2 and trypsin." Crit Care Med. 27 (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 三川勝也,他: "人工サーファクタント補充療法" 集中治療. 10. 43-54 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 三川勝也,他: "急性肺障害の病態" ICUとCCU. 23(印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mikawa K, et al: "Amirognanidine attenuates endofoxin-indnced acute(Img injury)" Crit Care Med. 26. 905-911 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Katsuya Mikawa: "Inhibitory ettect of local anaesthetics on reactive organ species produced by human neutrophils." Acta Anaesthesiologica Scandinavica. 41・4. 524-528 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kahoru Nishina: "Intravenous liclocaine attenuates acute luug injury induced by hydrochloric acid aspiration in rabbits." Anesthesiology. 88・5(in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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