| Project/Area Number |
10671441
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | Jichi Medical School |
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Principal Investigator |
AKAZAWA Satoshi Jichi Medical School, Dept. of Medicine, Assistant Professor, 医学部, 助教授 (10184079)
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| Co-Investigator(Kenkyū-buntansha) |
SEKIGUCHI Masato Jichi Medical School, Dept. of Medicine, Clinical Assistant, 医学部, 助手 (80322395)
池野 重雄 自治医科大学, 医学部, 助手 (60265270)
石井 良介 自治医科大学, 医学部, 講師 (50222956)
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| Project Period (FY) |
1998 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2000: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1999: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | K_<ATP> channel / agonist / volatile anesthetics / glyburide / sevoflurane / antagonist / regional myocardial function / myocardial stunning / KATPチャネル / 局所心筋収縮機能 / 再灌流障害 / 抗虚血作用 / 心機能 / 虚血プレコンディショニング / K_<ATP>チャネル開口薬 / マグネシウムイオン / K_<AIP>チャネル開口薬 / ニコランジル / エピネフリン / 抗不整脈作用 |
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| Research Abstract |
Background : Volatile anesthetics have been shown to protect against myocardial ischemia and reperfusion injury in animals. However, the mechanism of the protective actions of these agents has not been elucidated. This study investigated the role of myocardial adenosine triphosphate-regulated potassium [K_<ATP>] channels in sevoflurane-induced enhancement of regional myocardial contractile function after multiple brief occlusions and reperfusion of the left anterior descending coronary artery (LAD) in fentanyl-anesthetized dogs.
Methods : Twenty-one dogs were allocated to one of three groups (n = 7 for each). In control group, dogs received drug vehicle alone. In the other two groups, dogs received vehicle or glyburide (a non-selective K_<ATP> channel antagonist (1.0 mg/kg i.v.) immediately before inhalation of 1 minimum alveolar concentration of sevoflurane administered for 30 min before and during ischemia. Sevoflurane was discontinued at the onset of the final reperfusion period. Reg
… More
ional myocardial contractile function was assessed with percent segment shortening (%SS). Measurements of hemodynamics and %SS were made before and during ischemia, and during 180 min of reperfusion.
Results : LAD occlusion caused regional dyskinesia during ischemia in all dogs. Dogs receiving glyburide plus sevoflurane showed poor recovery of %SS by 180 min after reperfusion (approximately 50 % of baseline). In contrast, dogs receiving vehicle plus sevoflurane demonstrated almost complete recovery of %SS by 180 min after reperfusion (90 % of baseline). Control dogs showed an intermediate recovery of %SS between the other two groups. Sevoflurane reduced myocardial oxygen demand through decreases in aortic pressure and heart rate in vehicle-pretreated dogs.
Conclusion: The results indicate that sevoflurane protect against regional myocardial contractile dysfunction caused by myocardial stunning. These actions result in enhanced recovery of contractile function of post-ischemic, reperfused myocardium and are mainly mediated by sevoflurane-induced activation of K_<ATP> channels. Cardioprotective interaction between sevoflurane and magnesium should be determined in a further study. Less
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