Protective Effect of FR 183998, a Na^+/H^+ Exchange Inhibitor, Against Postischemic Injury After Normothermic and Prolonged Hypothermic Ischemia in Isolated Perfused Rat Hearts
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概要
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Inhibition of Na+/H+ exchanger has been reported to protect hearts from ischemia and reperfusion injury. However, the effect of Na+/H+ exchange inhibition on hypothermic ischemic injury has not been extensively studied and the results are inconsistent. The purpose of this study was to investigate whether inhibition of Na+/H+ exchange with FR183998 (5-(2,5-dichlorothiphen-3-yl)-3-[(2-dimethylaminoethyl)carbamoyl]benzoylguanidine dihydrochloride), a potent Na+/H+ exchange inhibitor, would show protective effects against postischemic cardiac dysfunction after hypothermic as well as normothermic ischemia and furthermore, after hypothermic cardioplegic arrest in isolated rat hearts. FR183998 (3.2 × 10−8 – 3.2 × 10−7 M) improved post-ischemic recovery of left ventricular developed pressure and suppressed the increase of left ventricular end diastolic pressure in a dose-dependent manner, after not only 45 min of normothermic ischemia but also 6 h of hypothermic ischemia. Furthermore, FR183998 (10−7 – 10 −6 M) significantly reduced creatine kinase release during reperfusion after 3 h of hypothermic ischemia with cardioplegia. These results indicate that FR183998 has a potent protective effect on postischemic cardiac dysfunction after normothermic and hypothermic ischemia, and also on reperfusion injury after hypothermic cardioplegic arrest, suggesting that its effect would be additive to cardioplegia.
- 社団法人 日本薬理学会の論文
- 2001-10-01
著者
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Maeda K
Department Of Gastroenterology And Medicine Faculty Of Medicine Fukuoka University
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GOTO Toshio
Department of Quantum Engineering, Nagoya University
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Goto T
Graduate School Of Pharmaceutical Sciences Tohoku University
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Goto Takaaki
Department Of Electric Engineering Tokyo University Of Agriculture And Technology
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Maeda Kazuhiro
Department Of Gastroenterology Fukuoka University Hospital
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Ozaki Toru
Department of Materials Science, Faculty of Science, Hiroshima University
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Ozaki Toru
Department Of Cardiovascular Diseases Medical Biology Research Laboratories
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Seki Jiro
Department Of Cardiovascular Diseases Medical Biology Research Laboratories
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YAMAMOTO Nobuhiro
Department of Cardiovascular Diseases, Medicinal Biology Research Laboratories, Fujisawa Pharmaceuti
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Ohara Fumihiro
Department Of Cardiovascular Diseases Medical Biology Research Laboratories
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Goto Toshio
Department Of Electronics Faculty Of Engineering Nagoya University
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後藤 俊夫
Imram Tohoku University
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OHHARA Fumihiro
Department of Cardiovascular Diseases, Medical Biology Research Laboratories
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MAEDA Kazuhiro
Research Planning, Fujisawa Pharmaceutical Co., Ltd.,
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Yamamoto Nobuhiro
Department Of Cardiovascular Diseases Medical Biology Research Laboratories
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Goto Toshio
Department Of Electronic Mechanical Engineering Nagoya University
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Maeda Kazuhiro
Research Planning Fujisawa Pharmaceutical Co. Ltd.
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GOTO Toshio
Department of Agricultural Chemistry, Faculty of Agriculture, Nagoya University
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