| Project/Area Number |
17591648
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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 | Osaka City University |
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Principal Investigator |
ODA Yutaka Osaka City University, MEDICINE, ANESTHESIOLOGY, ASSOCIATE PROFESSOR (70214145)
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| Co-Investigator(Kenkyū-buntansha) |
HAMAOKA Naoya OSAKA CITY UNIVERSITY, MEDICINE, ANESTHESIOLOGY, LECTURER (80347492)
ASADA Akira OSAKA CITY UNIVERSITY, MEDICINE, ANESTHESIOLOGY, PROFESSOR (00047367)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥180,000)
Fiscal Year 2007: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | PHARAMCOKINETICS / BRAIN / LIDOCAINE / LOCAL ANESTHETICS / MICRODIALYSIS / PROTEIN-UNBOUND / EPINEPHRINE / CONVULSIONS / 脳波 / 中枢神経毒性 / 非コンパートメント解析 / 側座核 / エピネフィリン |
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| Research Abstract |
BACKGROUND : Local anesthetics exert central nervous system (CNS) toxicity by inhibiting intracerebral neuronal activity, while epinephrine augments the CNS toxicity of intravenously administered local anesthetics. Viewed together, increases of extracellular concentrations of local anesthetics in the brain may be directly associated with increased CNS toxicity. The authors examined the hypothesis that epinephrine enhances the CNS toxicity of lidocaine by increasing the extracellular concentration in the brain. METHODS : An awake, spontaneously breathing rat model was used. Twenty male Sprague-Dawley rats received an intravenous infusion of lidocaine (3 mg x kg x min ; group C) or lidocaine with epinephrine (3 mg x kg x min and 2 microg x kg x min, respectively ; group E) for 10 min (n = 10 in each group). Effects of epinephrine on the convulsive dose and concentrations of total (protein-bound and unbound) and unbound lidocaine in plasma were examined. Concentrations of extracellular lidocaine in the cerebral nucleus accumbens were quantitatively determined by a microdialysis method. RESULTS : The convulsive dose of lidocaine was significantly lower in group E than in group C (22.4+/-5.5 vs. 27.9+/-3.1 mg/kg, respectively ; P<0.05). Overall concentrations and area under the plasma concentration-versus-time curve of unbound lidocaine in group E were significantly higher than those in group C. Concentrations of extracellular lidocaine in the nucleus accumbens in group E were comparable to those of unbound fraction in plasma and were also significantly higher than those in group C. CONCLUSIONS : Concomitant administration of epinephrine significantly enhanced the CNS toxicity of intravenously administered lidocaine. Increased extracellular concentration in the brain would be related to this mechanism.
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