Inhibition by KB-R7943 of the Reverse Mode of the Na^+/Ca^<2+> Exchanger Reduces Ca^<2+> Overload in Ischemic-Reperfused Rat Hearts
スポンサーリンク
概要
- 論文の詳細を見る
Ca^<2+> influx via the Na^+/Ca^<2+> exchanger (NCX) may lead to Ca^<2+> overload and myocardial injury in ischemia-reperfusion. Direct evidence that increased cytoplasmic Ca^<2+> concentration ([Ca^<2+>]_i) is mediated by the reverse mode of the NCX is limited, so in the present study the [Ca^<2+>]_i dynamics and left ventricular pressure were monitored in perfused beating hearts. The effects of KB-R7943 (KBR), a selective inhibitor of the NCX in the reverse mode, were analyzed during low-Na^+ exposure and ischemia-reperfusion. Hearts from Sprague-Dawley rats were retrogradely perfused and loaded with 4μmol/L fura-2 to measure the fluorescence ratio as an index of [Ca^<2+>]_i. To evaluate KBR effects on the reverse mode exchanger, the increase in [Ca^<2+>]_i induced by low-Na^+ exposure (Na^+: 30mmol/L, 10mmol/L caffeine pre-treatment) was measured with and without 10μmol/L KBR (n=5). In another series, the hearts were subjected to 10min of low-flow ischemia with pacing, followed by reperfusion in the absence (n=6) or in the presence of 10μmol/L KBR (n=6). Background autofluorescence was subtracted to estimate the ratio in the ischemia-reperfusion protocol. KBR significantly suppressed the increase in [Ca^<2+>]_i induced by low-Na^+ (40.2±11.2% of control condition, p=0.014), as well as on increase in diastolic [Ca^<2+>]_i during ischemia (% increase from pre-ischemia in [Ca^<2+>]_i at 10min: KBR, 17.9+6.4% no KBR, 44.4±7.7%; p=0.024). After reperfusion, diastolic [Ca^<2+>]_i normalized more rapidly in KBR-treated hearts (% increase at 1 min: KBR, 4.5±7.0%; no KBR, 39.8±12.2%; p=0.03). Treatment with KBR also accelerated recovery of the rate-pressure product on reperfusion (1min: KBR, 8,944±1,554min^<-1> no KBR, 4,970±1,325; p<0.05). Thus, inhibition of the reverse mode exchanger by KBR reduced ischemic Ca^<2+> overload and possibly improved functional myocardial recovery during reperfusion in a whole heart model.
- 社団法人日本循環器学会の論文
- 2002-03-20
著者
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Mochizuki Seibu
Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine
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NAGAI Makoto
Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine
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SEKI Shingo
Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine
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TANIGUCHI Ikuo
Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine
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Tanaka Hiroyuki
Division Of Cardiology Department Of Internal Medicine The Jikei University School Of Medicine
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TAKEDA Hiroshi
Division of Nephrology and Metabolism, Department of Internal Medicine, Tokai University School of M
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Taniguchi Masayuki
Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine
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Nagai Makoto
Division Of Cardiology Department Of Internal Medicine The Jikei University School Of Medicine
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Nagano M
Department Of Medicine Jikei Aoto Hospital
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Taniguchi M
Fac. Engineering Niigata Jpn
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Taniguchi Masayuki
Division Of Cardiology Department Of Internal Medicine The Jikei University School Of Medicine
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Taniguchi Masayuki
Department Of Food Science And Technology Faculty Of Agriculture Kyoto University
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Taniguchi Masayuki
Department Of Medicine The Jikei University School Of Medicine Aoto Hospital
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Mochizuki Seibu
Division Of Cardiology Department Of Internal Medicine Jikei Univerisity School Of Medicine
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Nagano M
Division Of Cardiology Department Of Internal Medicine The Jikei University School Of Medicine
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Takeda Hiroshi
Division Of Cardiology The Jikei University School Of Medicine
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Taniguchi Masayuki
Gaduate School Of Science And Technology Niigata University:food Research Center Niigata Agricultura
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Takeda Hiroshi
Division Of Cardiology Department Of Internal Medicine The Jikei University School Of Medicine
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Taniguchi Ikuo
Division Of Cardiology Department Of Internal Medicine The Jikei University School Of Medicine
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Seki Shingo
Division Of Cardiology Department Of Internal Medicine The Jikei University School Of Medicine
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