Difference in the Cardioprotective Mechanisms Between Ischemic Preconditioning and Pharmacological Preconditioning by Diazoxide in Rat Hearts

元データ 2004-01-20 社団法人日本循環器学会

概要

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.

著者

Satoh Hiroshi Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
KATOH Hideki Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
Katoh Hideki Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
Hayashi Hideharu Division Of Cardiology Internal Medicine Iii Hamamatsu University School Of Medicine
Hayashi Hideharu Department Of Internal Medicine Iii Hamamatsu University School Of Medicine
Terada Hajime Divisions Of Cardiology Department Of Internal Medicine Iii
Terada Hajime Department Of Medicine Iii Hamamatsu University Of Medicine
Uehara Akihiko Divisions Of Cardiology Department Of Internal Medicine Iii
Uehara Akihiko Department Of Internal Medicine Iii Hamamatsu University School Of Medicine
Hayashi Hideharu Department Of Cardiology Hamamatsu Medical Cente
Wakahara Nobuyuki Division of Cardiology, Department of Internal Medicine III, Hamamatsu University School of Medicine
Yaguchi Yasuhiro Division of Cardiology, Department of Internal Medicine III, Hamamatsu University School of Medicine
Fujise Yutaka Division of Cardiology, Department of Internal Medicine III, Hamamatsu University School of Medicine
Washiyama Naoki Cardiovascular Surgery Hamamatsu University School Of Medicine
Wakahara Nobuyuki Division Of Cardiology Department Of Internal Medicine Iii Hamamatsu University School Of Medicine
Fujise Yutaka Division Of Cardiology Department Of Internal Medicine Iii Hamamatsu University School Of Medicine
Yaguchi Yasuhiro Division Of Cardiology Department Of Internal Medicine Iii Hamamatsu University School Of Medicine
Uehara Akihiro 3rd Department Of Internal Medicine Hamamatsu University

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