2005 Fiscal Year Final Research Report Summary
STUDY ON THE ENANTIO-SELECTIVITY OF S(+)-KETAMINE ON THE REGULATION OF CIRCULATION
| Project/Area Number |
14370493
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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 | Osaka City University |
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Principal Investigator |
NISHIKAWA Kiyonobu OSAKA CITY UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 大学院医学研究科, 助教授 (20145791)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Takashi OSAKA CITY UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, LECTURER, 大学院医学研究科, 講師 (00336786)
KARIYA Nobutaka OSAKA CITY UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, LECTURER, 大学院医学研究科, 講師 (20305642)
IKESHITA Kazutoshi OSAKA CITY UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, RESEARCH ASSOCIATE, 大学院医学研究科, 助手 (20288898)
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| Project Period (FY) |
2002 – 2005
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| Keywords | Optical enantiomer / S(+)-ketamine / Sympathetic nerve activity / ion channel / perfused heart / ATP |
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| Research Abstract |
The purpose of this study was to elucidate the mechanism on circulatory effects of epidural administration of racemic ketamine and S(+)-ketamine during concomitant use of general anesthesia. For whole animal study, rabbits anesthetized with 1 % (0.5MAC) isoflurane were used. Low thoracic epidural administration of racemic ketamine and S(+)-ketamine, 0.5 mg/kg and 1.0 mg/kg, both significantly reduced arterial pressure, renal sympathetic nerve activity. However, neither dose-dependency nor enantio-selectivity was demonstrated. Muscarinic M2 receptors and nitric oxide may not be involved in this hemodynamic change. High concentration of racemic ketamine or S(+)-ketamine (IC50 was approximately 300 uM) was required to suppress myocardial contractility. This effect is originated from the sodium channel blocking effects of these drugs. Similarly, high concentrations of ketamine at the perineurium may have blocked sympathetic nerve propagation thus no difference between the two drugs was detected.
Separation and culture of the cells from the intermediolateral cell columns in the spinal cord was difficult. Instead, rat microglial cell line was available so we did patch clamp study on these cells. Clinically relevant concentrations of thiopental enhanced P2X7 receptor currents, but clinically relevant concentrations of ketamine (100 M) did not significantly change P2X7 receptor currents. Real-time measurement of ATP as an extracellular transmitter was performed in the spinal cord using a biosensor which has high sensitivity and selectivity to ATP. Neural damage was induced by hypoxic challenge etc. ATP concentrations in the spinal cord and sympathetic nerve activity were measured and effects of S(+)-ketamine and racemic ketamine were studied. However, inclease in ATP concentrations was never observed with various conditions. Reevaluation of the reliability of the ATP biosensor was necessary.
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