Difference in the Cardioprotective Mechanisms Between Ischemic Preconditioning and Pharmacological Preconditioning by Diazoxide in Rat Hearts
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概要
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Background Recent studies have implicated the opening of mitochondrial KATP (mitoKAip) channels and the production of reactive oxygen species (ROS) in the cardioprotective mechanism of ischemic preconditioning (IPC). Methods and Results The involvement of mitoKATP channels and ROS in the cardioprotective effects of both IPC and the mitoKATP channel opener diazoxide (DZ) was investigated in ischemic/reperfused rat hearts. The effects of IPC and DZ on myocardial high-energy phosphate concentrations and intracellular pH (pHi) were also examined using ^<31>P nuclear magnetic resonance spectroscopy. Although both the mitoKATP channel inhibitor 5-hydroxydecanoate and the antioxidant A^-acetylcysteine abolished the postischemic recovery of contractile function by DZ, neither of them inhibited that by IPC. IPC attenuated the decline in pHi during ischemia, but DZ did not (6.28±0.04 in IPC, p<0.05, and 6.02±0.05 in DZ vs 6.02±0.06 in control hearts). DZ, but not IPC, reduced the decrease in ATP levels during ischemia (ATP levels at 20-min ischemia: 26.3±3.4% of initial value in DZ, p<0.05, and 8.1±3.0% in IPC vs 15.1±1.3% in control hearts). Conclusions These results suggest that DZ-induced cardioprotection is related to ROS production and reduced ATP degradation during ischemia, whereas attenuated acidification during ischemia is involved in IPC-induced cardioprotection, which is not mediated through mitoKATP channel opening or ROS production.
- 社団法人日本循環器学会の論文
- 2004-01-20
著者
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Satoh Hiroshi
Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
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KATOH Hideki
Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
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Katoh Hideki
Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
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Hayashi Hideharu
Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
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Hayashi Hideharu
Department Of Internal Medicine Iii Hamamatsu University School Of Medicine
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Terada Hajime
Divisions Of Cardiology Department Of Internal Medicine Iii
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Terada Hajime
Department Of Medicine Iii Hamamatsu University Of Medicine
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Uehara Akihiko
Divisions Of Cardiology Department Of Internal Medicine Iii
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Uehara Akihiko
Department Of Internal Medicine Iii Hamamatsu University School Of Medicine
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Hayashi Hideharu
Department Of Cardiology Hamamatsu Medical Cente
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Wakahara Nobuyuki
Division of Cardiology, Department of Internal Medicine III, Hamamatsu University School of Medicine
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Yaguchi Yasuhiro
Division of Cardiology, Department of Internal Medicine III, Hamamatsu University School of Medicine
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Fujise Yutaka
Division of Cardiology, Department of Internal Medicine III, Hamamatsu University School of Medicine
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Washiyama Naoki
Cardiovascular Surgery Hamamatsu University School Of Medicine
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Wakahara Nobuyuki
Division Of Cardiology Department Of Internal Medicine Iii Hamamatsu University School Of Medicine
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Fujise Yutaka
Division Of Cardiology Department Of Internal Medicine Iii Hamamatsu University School Of Medicine
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Yaguchi Yasuhiro
Division Of Cardiology Department Of Internal Medicine Iii Hamamatsu University School Of Medicine
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Uehara Akihiro
3rd Department Of Internal Medicine Hamamatsu University
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