Background: This study aims to evaluate the effects of zileuton on myocardial ischemia/reperfusion injury and ischemia-induced ventricular arrhythmias and to investigate the role of 5-lipoxygenase pathway in the pathogenesis of myocardial ischemia/reperfusion injury.

Methods: In anesthetized rats, myocardial ischemia was induced by the ligation of the left main coronary artery for 30 min before 120-min reperfusion period. Zileuton was given both at the doses of 3 and 10 mg/kg 15 min before the ligation. During the experiment, electrocardiography, blood pressure, and heart rate were recorded. The duration of arrhythmia types were determined during the ischemic period. To evaluate the ischemia/reperfusion injury in the myocardial tissue, histopathological examination was performed and the infarct size was determined by 2,3,5-triphenyltetrazolium chloride staining.

Results: Zileuton at a dose of 3 mg/kg significantly decreased the infarct size and the tissue injury score obtained using histopathological examinations (infarct size [% of the area at risk]: zileuton 3 mg/kg 36±7% versus control 66±6%, p<0.05). Zileuton 10 mg/kg was found to be ineffective. Both 3 and 10 mg/kg doses of zileuton did not shorten the duration of arrhythmias during the ischemic period.

Conclusion: Our study results showed that 3 mg/kg dose of zileuton protected the heart against myocardial ischemia/ reperfusion injury. However, it was ineffective to reduce the ischemia-induced ventricular arrhythmias. Based on these results, zileuton may be a promising drug for the treatment of myocardial ischemia/reperfusion injury.

Keywords : Myocardial ischemia/reperfusion injury; rat model; ventricular arrhythmias; zileuton