Osaka Kyoiku University Researcher Information
日本語 | English
健康安全教育系
基本情報
- 所属
- 大阪教育大学 健康安全教育系 教授
- 学位
- Ph.D.(Kyoto University)医学博士(京都大学)
- 研究者番号
- 20298821
- J-GLOBAL ID
- 200901018715925421
- researchmap会員ID
- 1000229740
研究キーワード
3経歴
4-
2008年4月 - 2015年3月
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1997年4月 - 2008年3月
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1994年8月 - 1997年3月
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1990年4月 - 1994年7月
学歴
1-
1978年4月 - 1984年3月
論文
42-
INTERNATIONAL JOURNAL OF CARDIOLOGY 176(3) 822-827 2014年10月 査読有りBackground: Increased activated Akt and eNOS expression coincide with this persistent cardioprotection. Emergent coronary reperfusion therapies are rarely carried out before considerable myocardial injury has occurred. Moreover, reperfusion after prolonged ischemia produces paradoxical ischemia-reperfusion injury, attenuating the efficacy of reperfusion therapies. This has provided impetus for identifying chronic therapies to protect against ischemia-reperfusion injury in those at risk. We previously found that regular dipyridamole therapy produces a chronic preconditioning-like effect mediated through adenosine A1 receptors. Methods: To determine how long this chronic preconditioning effect of dipyridamole remains present after discontinuing therapy, guinea pigs received 4 mg/kg/day in their water for 6 weeks. Ischemia-reperfusion was performed at 0, 2, 3, and 4 days after dipyridamole discontinuation (0 day, 2 days, 3 days and 4 days; n = 8 per group). Left ventricular developed pressure (LVDP), end-diastolic pressure (LVEDP), coronary flow (CF), infarct size, and western blot analyses for Akt and endothelial nitric oxide synthase (eNOS) were studied. Results: After ischemia-reperfusion, 0 day, 2 days and 3 days, but not 4 days, had significantly higher LVDP and lower LVEDP compared to control. Myocardial infarct size was significantly reduced at 0 day, 2 days and 3 days, but not 4 days, compared to control. Western blot analyses demonstrated upregulation of phospho-Akt and phospho-eNOS expression at 0 day, 2 days, and 3 days, but not 4 days. Conclusions: A chronic preconditioning-like cardioprotection by regular dipyridamole treatment persists for 3 days after discontinuing therapy. Increased activated Akt and eNOS expression may play a role in this persistent cardioprotection. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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JOURNAL OF ANESTHESIA 28(4) 593-600 2014年8月 査読有りSevoflurane increases reactive oxygen species (ROS), which mediate cardioprotection against myocardial ischemia-reperfusion injury. Emerging evidence suggests that autophagy is involved in cardioprotection. We examined whether reactive oxygen species mediate sevoflurane preconditioning through autophagy. Isolated guinea pigs hearts were subjected to 30 min ischemia followed by 120 min reperfusion (control). Anesthetic preconditioning was elicited with 2 % sevoflurane for 10 min before ischemia (SEVO). The ROS-scavenger, N-(2-mercaptopropionyl) glycine (MPG, 1 mmol/l), was administered starting 30 min before ischemia to sevoflurane-treated (SEVO + MPG) or non-sevoflurane-treated (MPG) hearts. Infarct size was determined by triphenyltetrazolium chloride stain. Tissue samples were obtained after reperfusion to determine autophagy-related protein (microtubule-associated protein light chain I and II: LC3-I, -II) and 5' AMP-activated protein kinase (AMPK) expression using Western blot analysis. Electron microscopy was used to detect autophagosomes. Infarct size was significantly reduced and there were more abundant autophagosomes in SEVO compared with control. Western blot analysis revealed that the ratio of LC3-II/I and phosphorylation of AMPK were significantly increased in SEVO. These effects were abolished by MPG. Sevoflurane induces cardioprotection through ROS-mediated upregulation of autophagy.
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EUROPEAN JOURNAL OF PHARMACOLOGY 724 58-66 2014年2月 査読有りSevoflurane preconditioning against myocardial ischemia-reperfusion injury is lost if the ischemic insult is too long. Emerging evidence suggests that induction of autophagy may also confer cardioprotection against ischemia-reperfusion injury. We examined whether induction of autophagy prolongs sevoflurane preconditioning protection during a longer ischemic insult. Isolated guinea pigs hearts were subjected to 30 or 45 mm ischemia, followed by 120 min reperfusion (control). Anesthetic preconditioning was elicited with 2% sevoflurane for 10 min prior to ischemia (SEVO-30, SEVO-45). Chloramphenicol (autophagy upregulator, 300 mu M) was administered starting 20 min before ischemia and throughout reperfusion in SEVO-45 (SEVO-45 + CAP). To inhibit autophagy, 3-methyladenine (10 mu M) was administered during sevoflurane administration in SEVO-45 + CAR Infarct size was determined by triphenyltetrazolium chloride stain. Tissue samples were obtained before ischemia to determine autophagy-related protein (microtubule-associated protein light chain I and II: LC3-I, II), Ala and glycogen synthase kinase 3 beta (GSK3 beta) expression using Western blot analysis. The effect of autophagy on calcium-induced mitochondrial permeability transition pore (MPTP) opening in isolated calcein-loaded mitochondria was assessed. Electron microscopy was used to detect autophagosomes. Infarct size was significantly reduced in SEVO-30, but not in SEVO-45. Chloramphenicol restored sevoflurane preconditioning lost by 45 min ischemia. There were more abundant autophagozomes and LC3-II expression was significantly increased in SEVO-45 + CAP. Induction of autophagy before ischemia enhanced GSK3 beta phosphorylation and inhibition of calcium-induced MPTP opening. These effects were abolished by 3-methyladenine. Pre-ischemic induction of autophagy restores sevoflurane preconditioning lost by longer ischemic insult. This effect is associated with enhanced inhibition of MPTP by autophagy. (C) 2013 Elsevier B.V. All rights reserved.
MISC
5-
Current Drug Abuse Reviews 3(1) 39-48 2010年 査読有りEpidemiological studies demonstrate that excessive drinking is associated with hypertension, cerebral bleeding and loss of cardiac contractility. Conversely, studies have shown that mortality rates for people who regularly drink ethanol in moderation are lower than in abstainers, primarily due to decreased fatal ischemic heart disease. Further, moderate ethanol consumers have lower rates of myocardial infarction compared with abstainers. These beneficial cardiac effects may be due to pleiotropic effects of ethanol on lipids, platelets, and fibrinolytic activity. During the past decade, studies conducted in several animal models have revealed that light to moderate regular ethanol consumption renders hearts more tolerant to myocardial ischemia-reperfusion injury to a degree similar to cardiac ischemic preconditioning (brief episodes of ischemia dramatically limit infarct size following prolonged ischemia). Recent clinical evidence suggests that light to moderate ethanol consumption in the year prior to myocardial infarction is associated with reduced mortality following myocardial infarction. These findings suggest that light to moderate ethanol consumption not only prevents myocardial infarction but also improves survival after myocardial infarction. Proposed mechanisms of cardioprotection by regular ethanol consumption include activation of adenosine A1 receptors, 1-adrenoceptors, protein kinase C-δ and ε, adenosine triphosphate-dependent potassium (KATP) channels, nitric oxide synthase and reduced leukocyte-endothelial cell adhesive interactions. In this review, we focus on the recent progress in elucidating the endogenous myocyte signaling mediating cardioprotection by light to moderate ethanol consumption. © 2010 Bentham Science Publishers Ltd.
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Anesthesia 21 Century 11(3-35) 49-57 2009年
講演・口頭発表等
22-
Annual Meeting of American Society of Anesthesiologist, San Francisco, USA 2013年10月13日
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9th International Congress on Coronary Artery Disease (ICCAD) from prevention to intervention, Venice, Italy 2011年10月24日
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2011 Annual Meeting of American Society of Anesthesiologist, Chicago, USA 2011年10月18日
共同研究・競争的資金等の研究課題
12-
2020年 - 2023年
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日本学術振興会 科学研究費補助金(基盤C) 2014年4月 - 2017年3月
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日本学術振興会 科学研究費補助金(基盤C) 2011年4月 - 2014年3月
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日本学術振興会 科学研究費補助金(基盤C) 2008年4月 - 2011年3月
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日本学術振興会 科学研究費補助金(基盤C) 2006年4月 - 2008年3月