title: Ischemic preconditioning enhances scavenging activity of reactive oxygen species and diminishes transmural difference of infarct size.
abstract: 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 microM) 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.
authors.affiliation: First Dept. of Internal Medicine, Asahikawa Medical College, Asahikawa, Hokkaido, 078-8510 Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Morihira
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Hasebe
authors.forename: Erdenechimeg
authors.initials: E
authors.lastname: Baljinnyam
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sumitomo
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Matsusaka
authors.forename: Kazuma
authors.initials: K
authors.lastname: Izawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fujino
authors.forename: Jun
authors.initials: J
authors.lastname: Fukuzawa
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kikuchi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D016166:Free Radical Scavengers / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006439:Hemodynamics; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005979:Glutathione Peroxidase; D003849:Deoxyguanosine; D005978:Glutathione