Development of Cardiac Dysfunction Induced by Repetitive Transient Myocardial Ischaemia 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.