Fundamental research on new cardioprotection by inhalational general anesthetics

• Project/Area Number: 15592143
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kanagawa Dental College
• Principal Investigator: NISHIDA Naofumi Kanagawa Dental College, Dentistry, Lecturer, 歯学部, 助手 (10350539)
• Co-Investigator(Kenkyū-buntansha): YOSHIDA Kazu-ichi Kanagawa Dental College, Dentistry, Professor, 歯学部, 教授 (50200978) ; FURUYA Munetaka Kanagawa Dental College, Dentistry, Assistant Professor, 歯学部, 講師 (90318890)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥3,200,000 (Direct Cost: ¥3,200,000); Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000); Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: preconditioning / myocardial protection / infarct size / sevoflurane / 5-hydroxydecanoate / isoflurane / KATP channel / TTC

Research Abstract

BACKGROUND : Recent investigations showed that isoflurane can induce pharmacological preconditioning in myocardium. The present study aimed to compare the cardioprotection potency of two different halogenated anaesthetics and ischemic preconditioning. Moreover, we investigated if there is an additive effect of sevoflurane on IP induced cardioprotection.
METHODS : Anaesthetized open-chest rabbits underwent 30 min of coronary artery occlusion followed by 3 h of reperfusion. Before this, rabbits were randomized into one of eight groups and underwent a treatment period consisting of either no intervention for 45 min (control;n=5), 5 min coronary artery occlusion followed by 10 min of reperfusion before subjecting to prolonged ischemia/reperfusion as in control(IP;n=5), or 30 min of halogenated anaesthetic inhalation exposure, respectively, followed by 15 min of washout. End-tidal concentrations of halogenated agents were 1.5% for sevoflurane (n=5), and 1.1% for isoflurane (n=11). The KATP c hannel blocker, 5-hydroxydecanoate (5HD,5 mg/kg) was given intravenously 10 min before ischemic preconditioning, sevoflurane and isoflurane exposure, respectively, (5HD+IP;n=5,5HD+S;n=5,5HD+I;n=5) and 1.5% for sevoflurane followed by ischemic preconditioning(S+IP;n=5).
Area at risk and infarct size were assessed by blue dye injection and tetrazolium chloride staining. Infarct size was compared among groups (mean +/- SD).
RESULTS : Mean (SD) infarct size was 67.4±1.5% of the risk area in untreated controls and mean infarct size was significantly smaller in the ischemic preconditioning, sevoflurane, isoflurane and sevoflurane plus ischemic preconditioning groups:41.2±0.9%,49.7±4.6%,50.4±4.9% and 40.9±3.6%, respectively (P<0.05 vs control).
In contrast, mean infarct size was 56.7±2.1% in the 5HD+IP,61.6±2.8% in the 5HD+S and 59.8±1.8% in the 5HD+I groups(P>0.05,ns).
CONCLUSIONS : Sevoflurane and isoflurane induced pharmacological preconditioning. Sevoflurane exposure confers cardioprotection through opening of mitochondrial KATP channels. There is no additive effect of sevoflurane on IP induced cardioprotection.