The effects of zileuton and montelukast in reperfusion-induced arrhythmias in anesthetized rats

Abstract

Background: 5-Lipoxygenase is an enzyme involved in the synthesis of leukotriene eicosanoids from arachidonic acid. The therapeutic potential of zileuton, an inhibitor of 5-lipoxygenase, and montelukast, a cysteinyl leukotriene receptor antagonist, for the treatment of ischemia/reperfusion (I/R) injury of the heart has been proposed in a few studies. However, the effects of zileuton and montelukast on I/R-induced arrhythmias have not been determined.

Objective: We assessed the possible protective effects of zileuton and montelukast against I/R-induced arrhythmias.

Methods: Forty-five male Wistar albino rats were divided into 5 groups, each containing 9 rats. Group 1: control, Groups 2 and 3: rats treated with montelukast (10 and 30 mg/kg IP); and Groups 4 and 5: rats treated with zileuton (1 and 3 mg/kg IV) 15 minutes before the induction of ischemia. Ischemia and reperfusion were induced by occluding the left main coronary artery of anesthetized rats for 6 minutes followed by reopening the artery for 6 minutes.

Results: Both doses of zileuton decreased the mean [SE] arrhythmia score (zileuton 1 mg/kg: 1.4 [0.8]; zileuton 3 mg/kg: 1.3 [0.5] vs control: 2.9 [0.3]; P < 0.05), the duration of ventricular tachycardia, and the total length of arrhythmias, but montelukast was not effective to decrease the ventricular arrhythmias during the 6 minutes of reperfusion.

Conclusions: The results indicate for the first time that zileuton exerts an antiarrhythmic effect at different doses and that montelukast is not effective against I/R-induced arrhythmias. These results indicate that zileuton may be a candidate for drug treatment of I/R-induced arrhythmias.

Keywords: anesthetized rat; ischemia reperfusion arrhythmia; montelukast; zileuton.

Figure 1

Original electrocardiogram and blood pressure recordings, from (A) a control anesthetized rat, (B) a zileuton 1 mg/kg treated rat, (C) a zileuton 3 mg/kg treated rat, (D) a montelukast 10 mg/kg treated rat, and (E) a montelukast 30 mg/kg treated rat. BP = blood pressure; ECG = electrocardiogram; single = single extrasystole; ST = ST segment elevation; VF = ventricular fibrillation; VT = ventricular tachycardia.

Figure 2

The effect of drug treatments on the arrhythmia score during 6 minutes of reperfusion. Values are means [SD]. ^*P < 0.05 compared with control.

Figure 3

The effect of drug treatments on the total length of arrhythmias during 6 minutes of reperfusion. Values represent means [SE]. Other = other types of arrhythmias; VF = ventricular fibrillation; VT = ventricular tachycardia. ^*P < 0.05 compared with control.