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This Article Full Text Full Text (PDF) All Versions of this Article: 290/2/H577    most recent 00817.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Morihira, M. Articles by Kikuchi, K. Search for Related Content PubMed PubMed Citation Articles by Morihira, M. Articles by Kikuchi, K.

Ischemic preconditioning enhances scavenging activity of reactive oxygen species and diminishes transmural difference of infarct size

First Department of Medicine, Asahikawa Medical College, Asahikawa, Japan

Submitted 11 August 2004 ; accepted in final form 13 July 2005

Reactive oxygen species (ROS) enhance myocardial ischemia-reperfusion (I/R) injury. Ischemic preconditioning (PC) provides potent cardioprotective effects in I/R. However, it has not been elucidated whether PC diminishes ROS stress in I/R and whether PC protects the myocardium from ROS stress transmurally and homogeneously. Isolated rabbit hearts perfused with Krebs-Henseleit buffer underwent 30 min of ischemia and 60 min of reperfusion. Hemodynamic changes and myocardial damage extent were analyzed in four groups. The control group underwent I/R alone. The H₂O₂ group underwent I/R with H₂O₂ infusion (50 µM) in the first minute of reperfusion to enhance oxidative stress. The PC and H₂O₂+PC groups underwent 5 min of PC before control and H₂O₂ protocols, respectively. Extracted myocardial DNA was analyzed for 8-hydroxydeoxyguanosine (8-OHdG), an indicator of oxidative DNA damage, with the use of the HPLC-electrochemical detection method. Glutathione peroxidase (GPX) activity and the reduced form of GSH were measured by spectrophotometric assays. The myocardial infarct size was significantly reduced in the PC group (19 ± 2%) compared with the control group (37 ± 4%; P < 0.05), particularly in the subendocardium. H₂O₂ transmurally increased the infarct size by 59 ± 4% (P < 0.05), which was significantly diminished in the H₂O₂+PC group (31 ± 4%; P < 0.01). The GSH levels, but not GPX activity, were well preserved transmurally in protocols with PC. The 8-OHdG levels were significantly decreased in PC and were significantly enhanced in H₂O₂ (P < 0.01). These changes in oxidative DNA damage were effectively diminished by PC. In conclusion, PC enhanced the scavenging activity of GSH against ROS transmurally, reduced myocardial damage, particularly in the subendocardium, and diminished the transmural difference in myocardial infarct size.

reperfusion injury; 8-hydroxydeoxyguanosine; glutathione