| Project/Area Number |
08457405
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Gifu University |
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Principal Investigator |
DOHI Shuji Gifu University School of Medicine, Department of Anesthesiology & Critical Care Medicine, Professor and Chair, 医学部, 教授 (40155627)
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| Co-Investigator(Kenkyū-buntansha) |
ASANO Toshio Department of Anesthesiology & Critical Care Medicine, Gifu University, 医学部・附属病院, 助手 (80231893)
IIDA Hiroki Department of Anesthesiology & Critical Care Medicine, Gifu University, 医学部, 講師 (30159561)
竹田 智雄 岐阜大学, 医学部・附属病院, 助手 (30252141)
太田 宗一郎 岐阜大学, 医学部・附属病院, 講師 (50144027)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1996: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Keywords | Alpha-2 adrenergic receptors / Clonidine / Dexmedetomidine / Alpha-2 adrenoceptor / Spinal Antinociception / Receptor bindings / Signal transduction / Opioid tolerance / α2-adrenergic agonists / 局所麻酔薬 / Extracelluallr Signal-regulated Kinase / Ouabain / ペントバルビタール / プロポホール / イソフルラン / 細胞内情報伝達 / mRNA / 脳 / 腎 / 静脈麻酔薬 / プロポフォール / 吸入麻酔薬 / イソフルレン / α2-アドレナリン受容体 / PKC / c-fos |
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| Research Abstract |
For the last decade, alpha-2 adrenergic agonists such as clonidine have been extensively used for clinical anesthesia to provide better patients' care in perioperative periods. When given clonidine preoperatively as a premedicant for patients undergoing anesthesia and surgery it Would reduce requirements of inhalational and intravenous anesthetic agents, and opioids, provide stable hemodynamics, and enhance the action of vasopressors such as phenylephrine. When clonidine given intrathecally, it would produce a potent spinal antinociception and prolonged spinal anesthesia with local anesthetics. To elucidate some of mechanism(s) and roles for clinical efficacy of alpha-2 adrenoceptor agonists, we have done several studies, Using the cranial window technique, we found that clonidine produces cerebral vasoconstriction via activation of alpha-2 adrenoceptors of the pial vessels in a dose-related manner. When alpha-2 adrenoceptor agonists, clonidine, dexmedetomidine and tizanidine, were given into the epidural space or intravenously in rats, they produced almost 5 times greater antinociception with epidural administration as compared with those with their intravenous administration. The rank of order for their spinal antinociceptive action was identical with those of alpha-2 adrenergic receptor binding affinity of spinal' cord and brain. Brain alpha-2-adrenoceptors are up-regulated in morphine dependent guinea pigs and clonidine could reduced opiate withdrawal sings in morphine-dependent animals. We also found that patients given clonidine as premedicant showed a significantly augmented responses to ephedrine in propofol anesthesia to reduce epinephrine test dose for epidural anesthesia. Also we found that clonidine premedication modifies responses to alpha1- and beta-_2 adrenoceptor agonists and baroreflex sensitivity.
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