| Co-Investigator(Kenkyū-buntansha) |
DOMAE Naochika Osaka Dental University, Dept of Dent., professor, 歯学部, 教授 (60115889)
SUGIOKA Shingo Osaka Dental University, Dept of Dent., assist professor, 歯学部, 助手 (90278573)
KOTANI Junichiro Osaka Dental University, Dept of Dent., professor, 歯学部, 教授 (40109327)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
1. Is p38 MAPK involved in the cardioprotective effect of sevoflurane?
Isolated perfused guinea pig hearts underwent 30 min global ischemia and 120 min reperfusion. APC was elicited with 10 min of sevoflurane administration (1 MAC ; 2%) with a 10 min washout period prior to ischemia (SEV, n=10 ; control vehicle (CTL), n=10). SB203580 (2μM), a p38 MAPK inhibitor, was administered for 20 min, starting 10 min before sevoflurane (SEV+SB, n=10) or vehicle (CTL+SB, n=10) administration. A high dose SB group was also studied (10μM ; SEV+SB-H group, n=6). To inhibit p38 MAPK during sustained ischemia, SB203580 was administered for 30 min until the onset of ischemia with no washout in an additional group (SEV+SB-L group, n=6). Contractile recovery was monitored by left ventricular developed (LVDP) and end-diastolic (LVEDP) pressure. Infarct size was determined by triphenyltetrazolium chloride stain.
After ischemia/reperfusion, SEV, SEV+SB, SEV+SB-H and SEV+SB-L hearts had higher LVDP and lower LV
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EDP compared to CTL. Infarct size was significantly reduced in SEV compared to CTL (19±2% versus 39±2%, p<0.05). SB administration failed to abolish this cardioprotective effect of sevoflurane in SEV+SB, SEV+SB-H and SEV+SB-L.
p38 MAPK activation is not required as a trigger or mediator for sevoflurane-induced cardiac preconditioning.
2. Is there any interaction between ethanol induced and sevoflurane induced preconditioning?
The protocol of ischemia-reperfusion was same as above. Controls (CTL, n=10) were neither ethanol nor sevoflurane-treated. Ethanol-treated group (EtOH, n=10) received 2.5% ethanol in their drinking water for 6 weeks. The protocol of anesthetic preconditioning was also same as above in hearts from ethanol-treated (EtOH+SEVO, n=10) or non-ethanol-treated (SEVO, n=10) animals. To investigate the involvement of protein kinase C (PKC) and mitochondrial K_<ATP> channels, each inhibitor, chelerythrine (CHE, 10μM) and 5-hydroxydecanoate (5-HD, 200μM) respectively, were administered for 20 min, starting 10 min before sevoflurane (EtOH+SEVO+CHE, EtOH+SEVO+5-HD, n=10 each) or vehicle (CTL+CHE, CTL+5-HD, n=10 each) administration. After ischemia-reperfusion, EtOH, SEVO and EtOH+SEVO had higher LVDP and lower LVEDP compared to CTL. Infarct size was significantly reduced in EtOH and SEVO compared to CTL (27±2%, 23±2% vs 45±4%, respectively, p<0.05). Administration of sevoflurane to EtOH led to further reduction of infarct size to 15±2% in EtOH+SEVO. CHE and 5-HD administration abolished this cardioprotective effect of both sevoflurane and ethanol. Sevoflurane enhances cardiac preconditioning induced by low regular ethanol consumption. Activation of PKC activation and mitochondrial K_<ATP> channels are necessary in mediating this cardiac preconditioning. Less
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