1. In the present study, we investigated the effect of
3-methyl-1-phenyl-2-pyrazolin-5-one (
edaravone), a
free radical scavenger, on
myocardial infarct (MI) size and cardiac function in an in vivo model of MI in rabbits. We further investigated the contribution of
hydroxyl radicals,
superoxide and
nitric oxide (NO) to its effects. 2. Anaesthetized open-chest Japanese white male rabbits were subjected to 30 min
coronary occlusion and 48 h reperfusion. The control group (n = 10) was injected with saline 10 min before reperfusion. The
edaravone group (n = 10) was injected with a bolus of 3 mg/kg
edaravone 10 min before reperfusion. The
edaravone +
N(G)-nitro-L-arginine methyl ester (
L-NAME) group (n = 5) was given 10 mg/kg, i.v.,
L-NAME 10 min before the administration of 3 mg/kg
edaravone. The
L-NAME group (n = 5) was given 10 mg/kg, i.v.,
L-NAME 20 min before reperfusion.
Infarct size was measured using the triphenyl tetrazolium
chloride method and is expressed as a percentage of area at risk. Cardiac function was assessed by echocardiography 14 days after
infarction. 3. In another series of experiments, rabbits were subjected to 30 min
coronary occlusion and 30 min reperfusion and myocardial interstitial
2,3-dihydroxybenzoic acid (DHBA) and 2,5-DHBA levels, indicators of
hydroxyl radical, were measured using a microdialysis technique. 4.
Infarct size in the
edaravone group was significantly reduced compared with that in the control group (27.4 +/- 6.8 vs 43.4 +/- 6.8%, respectively; P < 0.05). The
edaravone-induced reduction of
infarct size was abolished by pretreatment with
L-NAME. Myocardial interstitial levels of 2,3-DHBA and 2,5-DHBA increased 20 and 30 min after ischaemia and peaked
at 10 min reperfusion in the control group.
Edaravone significantly inhibited the increase in 2,3-DHBA and 2,5-DHBA levels seen during reperfusion.
Dihydroethidium staining showing in situ detection of
superoxide was less intense in ischaemic myocardium in the
edaravone-treated group compared with the control group.
Edaravone improved cardiac function and left ventricular remodelling 14 days after
infarction. 5. In conclusion,
edaravone significantly reduces MI size and improves cardiac function and LV remodelling by decreasing
hydroxyl radicals and
superoxide in the myocardium and increasing the production of NO during reperfusion in rabbits.