Edaravone prevented deteriorated cardiac function after myocardial ischemia-reperfusion via inhibiting lipid peroxidation in rat

Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has potent effects in the brain as a free radical scavenger in ischemia-reperfusion as well as in ischemic injuries. However, whether this free radical scavenger prevents deterioration of cardiac function and lethal ventricular arrhythmias after ischemia-reperfusion in rat heart is not clear. We aimed to assess whether free radical scavenging by edaravone maintains cardiac function and suppresses life-threatening ventricular tachyarrhythmia after myocardial ischemia-reperfusion. Twenty-nine 7-week-old male Sprague-Dawley rats had acute myocardial ischemia induced by ligation of the left coronary artery for 5 minutes followed by reperfusion. Eleven were treated by intravenous injection of edaravone at 3 mg/kg 2 minutes after coronary ligation, and 18 were left untreated. The index of systolic function (contractility; end-systolic elastance, Ees) and hemodynamics were measured by pressure-volume relationships every 5 minutes before ligation to 25 minutes after reperfusion. Blood levels of malondialdehyde (MDA) and the ischemic areas were also measured 25 minutes after reperfusion. There were no differences in the ischemic areas between the groups. Lethal reperfusion tachyarrhythmia was observed in 5 untreated rats but not in those having edaravone treatment. Ees was significantly greater in the edaravone-treated than in untreated rats from 5 to 25 minutes after reperfusion (1789 866 in untreated versus 2809 +/- 273 mm Hg/mL in edaravone-treated rats at 25 minutes, P < 0.001). MDA level was significantly lower in edaravone-treated than in untreated rats (1.44 +/- 0.29 nmol/L in edaravone-treated versus 1.90 +/- 0.28 nmol/L in untreated group, P < 0.05). The results suggest that edaravone treatment before reperfusion prevented lethal reperfusion ventricular tachyarrhythmias and deteriorated cardiac function with ischemia and ischemia-reperfusion injuries through inhibiting lipid peroxidation in terms of scavenging for free radicals.