| Project/Area Number |
18592210
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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 |
Surgical dentistry
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| Research Institution | Osaka Dental University |
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Principal Investigator |
MIYAMAE Masami Osaka Dental University, Dept of Dent., assist professor (20298821)
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| Co-Investigator(Kenkyū-buntansha) |
DOMAE Naochika Osaka Dental University, Dept of Dent., professor (60115889)
SUGIOKA Shingo Osaka Dental University, Dept of Dent., assist professor (90278573)
KOTANI Junichiro Osaka Dental University, Dept of Dent., professor (40109327)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,750,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | sevoflurane / apoptosis / Preconditioning / alcohol / Akt / heart / mitochondrial KATP channel / ischemia-reperfusion / heart / Bcl-2 / Bax |
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| Research Abstract |
1. Is Akt, antiapoptotic kinase, involved in the cardioprotective effect of sevoflurane ?
It has been reported that isoflurane-induced myocardial preconditioning is dependent on phosphatidylinositol-3-kinase (PI3K)/Akt signaling which plays a central role of reperfusion injury salvage kinase cascade. It remains unclear whether this signaling cascade is involved in sevoflurane-induced preconditioning. Isolated perfused guinea pig hearts underwent 30 min global ischemia and 120 min reperfusion (CTL). Sevoflurane-induced preconditioning was elicited by administration of 10 min of sevoflurane (1 MAC; 2%) with 10 min washout before ischemia (SEVO). Phosphorylation of Akt was assessed by western blot. After ischemia-reperfusion, SEVO had higher left ventricular developed and lower end-diastolic pressure versus CTL. Infarct size was significantly reduced in SEVO compared to CTL. Akt phosphorylation was not increased during ischemia and 10 min after reperfusion, which is in contrast to the find
… More
ings previously demonstrated in isoflurane-induced preconditioning. Other reperfusion injury salvage kinases such as mitogen-activated protein kinase/extracellular signal-regulated kinases (MEK) and extra-cellular signal-regulated kinase (ERK) may be more important in sevoflurane-induced preconditioning.
2. Is there any interaction between ethanol-and sevoflurane-induced preconditioning ?
We investigated whether sevoflurane enhances ethanol preconditioning and whether inhibition of protein kinase C (PKC) and mitochondrial KATP channels attenuated this enhanced cardioprotection. Isolated perfused guinea pig hearts underwent 30 min global ischemia and 120 min reperfusion (Control: CTL). The ethanol group (EtOH) received 2.5% ethanol in their drinking water for 6 weeks. Anesthetic preconditioning was elicited by 10 min exposure to sevoflurane (1 MAC; 2%) in ethanol (EtOH+SEVO) or non-ethanol (SEVO) hearts. PKC and mitochondrial KATP channels were inhibited with chelerythrine (CHE) and 5-hydroxydecanoate (5-HD) pretreatment, respectively. After ischemia-reperfusion, EtOH, sevoflurane (SEVO), and EtOH+SEVO groups had higher LVDP and lower LVEDP compared with CTL. Infarct size was reduced in EtOH and SEVO hearts compared with CTL. Sevoflurane further reduced infarct size in EtOH hearts. CHE and 5-HD abolished cardioprotection in both SEVO and EtOH cardioprotected hearts. iNOS expression was reduced and eNOS expression was increased in EtOH hearts. Sevoflurane enhances cardiac preconditioning induced by regular EtOH consumption. This effect is mediated in part by modulation of PKC and mitochondrial K_<ATP> channels, and possibly by altered modulation of NOS expression. Less
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