| Project/Area Number |
16390451
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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 University |
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Principal Investigator |
HAYASHI Yukio Osaka University, Graduate School of Medicine, Associate professor, 医学系研究科, 助教授 (60294063)
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| Co-Investigator(Kenkyū-buntansha) |
KAMIBAYASHI Takahiko Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (10273640)
MASHIMO Takashi Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (60157188)
MATSUDA Naoyuki University of Toyama, School of Medicine, Department of Pharmacology, Associate Professor, 医学薬学研究部, 助教授 (50332466)
HATTORI Yuichi University of Toyama, School of Medicine, Department of Pharmacology, Professor, 医学薬学研究部, 教授 (50156361)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2006: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2005: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2004: ¥6,200,000 (Direct Cost: ¥6,200,000)
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| Keywords | Brain death / Cardiac function / Arrhythmias / Volatile anesthetics / ATP sensitive K channel / 麻酔薬 |
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| Research Abstract |
The brain death is a condition where regulation by the central nervous system was lost. We investigated effect of the central nervous system as well as the brain death on cardiac function.
1) The central regulation of cardiac function
The activation of the vagal nerve by stimulation of the central imidazoline 1 receptors facilitates acetylcholine (Ach) release. Ach stimulates myocardial muscarinic receptors following activation of pertussis toxin sensitive G protein, protein kinase C and opening ATP-sensitive K channels and produces antiarrhythmic action on halothane-epinephrine arrhythmias in rats. In addition, the mechanism requires endogenous nitric oxide (NO), because specific NO synthesis inhibitors (L-NAME, L-NMMA) abolished the antiarrhythmic effect. These results suggest that the cardiac protective effect by the vagal nerve abolished in the brain death condition.
2) Myocardial sensitization of volatile anesthetics in brain death
Brain death was induced by the modified method of Pra
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tschke et al. (Transplantation 67:343-8, 1999) in rats. We examined the arrhythmogenic dose of epinephrine in the presence of 0.3 MAC of halothane, isoflurane and sevoflurane and compared these values with that in the absence of anesthetics in brain death rats. Halothane reduced arrhythmogenic dose of epinephrine compared with rats with no anesthetics, while sevoflurane and isoflurane also reduced the arrhythmogenic dose of epinephrine compared with rats with no anesthetics, but the difference was not significant. In addition, the differences of arrhythmogenic dose between halothane and isoflurane and between halothane and sevoflurane in the brain death rats were smaller than those in naive rats. These results suggest that the central nervous system may play a part in the myocardial sensitization of volatile anesthetics.
3) Cardiac function following brain death
We performed continuous measurement of cardiac function using conductance catheter technique in rats. Arterial blood pressure did not reduce until about 6 hours following brain death. However, ejection fraction did reduce 2 or 3 hours following brain death. These results suggested that cardiac dysfunction occurred much earlier than the significant blood pressure reduction. Nicorandil, an ATP sensitive K channel opener, prolonged the time interval to reduction of ejection fraction and improve the survival following brain death. ATP sensitive K channel may play a role in cardiac dysfunction following brain death. Less
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