Development of cardiac dysfunction induced by repetitive transient myocardial ischemia is inhibited by edaravone in conscious rats.
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.
Toyota
Eiji
E
Department of Cardiology, Kawasaki Medical School, Kurashiki, Japan. toyota@kyokuto.or.jp
Miyamoto
Yoshinori
Y
Imai
Koichiro
K
Neishi
Yoji
Y
Kawamoto
Takahiro
T
Okura
Hiroyuki
H
Yoshida
Kiyoshi
K
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
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D000077553:Edaravone; D000983:Antipyrine