The effects of zileuton and montelukast in reperfusion-induced arrhythmias in anesthetized rats.
The effects of zileuton and montelukast in reperfusion-induced arrhythmias in anesthetized rats.
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DOI：
10.1016/j.curtheres.2013.06.001
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发表时间：
2013-12
影响因子：
1.9
通讯作者：
Gonca, Ersoz
中科院分区：
文献类型：
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作者：
Gonca, Ersoz
5-脂氧合酶是一种参与花生四烯酸合成白三烯类二十烷酸的酶。一些研究已经提出了5-脂氧合酶抑制剂zileuton和半胱氨酸白三烯受体拮抗剂孟鲁司特治疗心脏缺血/再灌注（I/R）损伤的治疗潜力。然而，zileuton和孟鲁司特对I/ r诱发的心律失常的影响尚未确定。我们评估了zileuton和孟鲁司特对I/ r诱发的心律失常可能的保护作用。选取雄性Wistar白化大鼠45只，随机分为5组，每组9只。1组：对照组，2、3组：孟鲁司特（10、30 mg/kg）；4、5组：在缺血诱导前15分钟给予紫优通（1、3 mg/kg IV）。麻醉大鼠冠状动脉左主干闭塞6分钟，再开放6分钟，诱导缺血再灌注。两种剂量的zileuton均可降低心律失常平均[SE]评分（zileuton 1 mg/kg: 1.4 [0.8]; zileuton 3 mg/kg: 1.3 [0.5] vs对照组：2.9 [0.3];P < 0.05）、室性心动过速持续时间和心律失常总长度，但孟鲁司特在再灌注6分钟内对室性心律失常没有降低效果。结果首次表明，zileuton在不同剂量下具有抗心律失常作用，而孟鲁司特对I/ r诱发的心律失常无效。这些结果表明zileuton可能是治疗I/ r致心律失常的候选药物。
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. We assessed the possible protective effects of zileuton and montelukast against I/R-induced arrhythmias. 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. 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. 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.