EFFECTS OF LIDOCAINE ON MULTIPLE ORGAN DYSFUNCTION : ELUCIDATION OF MECHANISM AND CLINICAL APPLICATION
| Project/Area Number |
09671561
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | KOBE UNIVERSITY |
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Principal Investigator |
MIKAWA Katsuya KOBE UNIV.SCH.MED.ASSISTANT PROF., 医学部・附属病院, 講師 (40229662)
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| 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)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| 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)
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| Keywords | Endotoxin / Multiorgan Failure / Local anesthetics / Hyperoxia / ARDS / Neutrophil / リドカイン / 肺障害 / 活性酸素 |
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| 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.
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Report
(3 results)
Research Products
(16 results)
