Ebselen protects against ischemia-reperfusion injury in a canine model of myocardial infarction.
We investigated the infarct-limiting effect of a selenoorganic compound, ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], in a canine coronary artery occlusion-reperfusion model of myocardial infarction. Ebselen, administered 1 h before coronary artery occlusion (50 mg/kg po), significantly reduced infarct size resulting from 90-min coronary artery occlusion followed by 5-h reperfusion (P < 0.05). When we examined the relation between infarct size and plasma ebselen level, infarct size in dogs with plasma ebselen level > 5 microM before reperfusion was significantly smaller (P < 0.05) than that in dogs with plasma ebselen level < or = 5 microM or in the control dogs. This infarct limitation produced by ebselen treatment was associated with an increase in reduced glutathione content and a reduction in myeloperoxidase activity in the ischemic myocardium. No differences between the control and treated groups were found in hemodynamic parameters or regional myocardial blood flow in the course of the experiment. The findings of this study demonstrate that ebselen effectively reduced the myocardial ischemia-reperfusion injury associated with preservation of the glutathione redox state and a reduction in neutrophil infiltration into the ischemic myocardium.
Hoshida
S
S
Division of Cardiology, Osaka University School of Medicine, Suita, Japan.
Kuzuya
T
T
Nishida
M
M
Yamashita
N
N
Hori
M
M
Kamada
T
T
Tada
M
M
D000818:Animals; D001393:Azoles / Q000627:therapeutic use*; D001794:Blood Pressure; D003250:Constriction; D003326:Coronary Circulation; D003331:Coronary Vessels; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006339:Heart Rate; D054833:Isoindoles; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D017202:Myocardial Ischemia; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D016566:Organoselenium Compounds / Q000627:therapeutic use*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D009195:Peroxidase / Q000378:metabolism
D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D009195:Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione