title: Development of cardiac dysfunction induced by repetitive transient myocardial ischemia is inhibited by edaravone in conscious rats.
abstract: 1. In the present study, we investigated the effects of treatment with the hydroxyl radical scavenger 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone) on myocardial dysfunction induced by transient but frequent ischaemia in conscious rats. 2. Conscious male Wistar rats were subjected to repetitive ischaemia (RI; 40 s ischaemia every 20 min for 72 h). After the ninth episode of RI, edaravone (1 mg/kg, i.v., at each ischaemic event) or vehicle control (acetate buffer solution, i.v.) was administered. Dilation of the left ventricle (LV) after the eighth RI (fractional area change; %FAC(initial)) and after the final RI (%FAC(final)) was determined by comparing measurements (12 MHz echocardiogram) at these time-points with baseline LV area prior to RI. 3. In controls, %FAC(final) was correlated with %FAC(initial) (r = 0.98; P < 0.0001), making %FAC(initial) a predictor of %FAC(final). Edaravone treatment shifted the %FAC(initial)–%FAC(final) relationship downward (P < 0.0001), indicating that edaravone inhibited progression of LV dilation. In addition, %FAC(final) was correlated with myocardial generation of reactive oxygen species (ROS) in control samples (r = 0.88, P = 0.008), although both %FAC(final) and ROS were suppressed by edaravone treatment (P = 0.016). 4. We conclude that repetitive transient ischaemia in conscious rats induced development of cardiac dysfunction and that this phenomenon was inhibited by edaravone. We speculate that edaravone is a potential therapeutic agent that may interfere with the progression of cardiac dysfunction in high-risk patients with RI.
authors.affiliation: Department of Cardiology, Kawasaki Medical School, Kurashiki, Japan. toyota@kyokuto.or.jp
authors.forename: Eiji
authors.initials: E
authors.lastname: Toyota
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Koichiro
authors.initials: K
authors.lastname: Imai
authors.forename: Yoji
authors.initials: Y
authors.lastname: Neishi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003243:Consciousness; D004195:Disease Models, Animal; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D014463:Ultrasonography; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D000077553:Edaravone; D000983:Antipyrine