Protective Effects of Hydrogen Peroxide Against Ischemia/Reperfusion Injury in Perfused Rat Hearts

元データ 2003-02-20 社団法人日本循環器学会

概要

Among the several mechanisms proposed for ischemic preconditioning (IPC), generation of reactive oxygen species (ROS) is reported to be involved in the cardioprotective effects of IPC. The present study was designed to investigate whether repetitive exposure to hydrogen peroxide (H_2O_2) can protect the myocardium against subsequent ischemia/reperfusion injury, and whether the H_2O_2-induced cardioprotection is related to the preservation of energy metabolism. Langendorff-perfused rat hearts were exposed to two, 5min episodes of IPC or to various concentrations of H_2O_2 twice and then to 35min global ischemia and 40min reperfusion. Using 31P nuclear magnetic resonance (^<31>P-NMR) spectroscopy, cardiac phosphocreatine (PCr) and ATP and intracellular pH (pH_1) were monitored. IPC and the treatment with 2μmol/L H_2O_2 significantly improved the post-ischemic recovery of left ventricular developed pressure (LVDP) and the PCr and ATP compared with those of the control ischemia/reperfusion (LVDP : 36.9±7.4% of baseline in control hearts, 84.0+3.5% in IPC, 65.4±3.8% in H_2O_2 ; PCr: 51.1±5.3% in control hearts, 81.4+5.5% in IPC, 81.7±5.2% in H_2O_2 ; ATP_1 12.3+1.6% in control hearts ; 30.0+2.8% in IPC, 28.6+2.3% in H_2O_2, mean + SE, p<0.05). However, lower (0.5μmol/L) or higher (10μmol/L) concentration of H:0: had no effect. There were significant linear correlations between mean LVDP and high-energy metabolites after 40min reperfusion in H_2O_2-treated hearts. In IPC-treated hearts, the mean LVDP was greater than that in the 2μmol/L H_2O_2-treated hearts under similar levels of high-energy metabolites. IPC also ameliorated intracellular acidification (6.38±0.03 in control hearts, 6.65±0.04 in IPC, p<0.05), but treatment with H_2O_2 did not affect pH_1 during ischemia (6.40±0.05 in H_2O_2). In conclusion, H_2O_2 had protective effects against ischemia/reperfusion injury and the effects were related to the preservation of energy metabolism. IPC could have additional protective mechanisms that are associated with the amelioration of intracelluar acidosis during ischemia.

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
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
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
FUJISE Yutaka Department of Chemistry 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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