Combined amiodarone and silymarin treatment, but not amiodarone alone, prevents sustained atrial flutter in dogs.
Combined amiodarone and silymarin treatment, but not amiodarone alone, prevents sustained atrial flutter in dogs.
复制标题
胺碘酮和水飞蓟素联合治疗（但不能单独使用胺碘酮）可以预防狗的持续性心房扑动。
DOI：
10.1046/j.1540-8167.2003.02446.x
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发表时间：
2003
影响因子：
2.7
通讯作者：
BeschJr,Henry
中科院分区：
文献类型：
--
作者：
Vereckei,András;Zipes,DouglasP;BeschJr,Henry
引言：由于胺碘酮产生的自由基可能介导胺碘酮的毒性，如果抗氧化剂不损害胺碘酮的抗心律失常作用，则与抗氧化剂同时治疗可能有益。我们测试了同时给予黄酮类抗氧化剂水飞蓟素是否会改变62只开胸犬的胺碘酮电生理（EP）作用，这些开胸犬具有通过Y形右心房切口产生的电诱导心房扑动。（600 mg/天）; 15只犬接受胺碘酮（600 mg/天）和水飞蓟素（70 mg bid）; 8只犬单独接受水飞蓟素（70 mg bid）。所有给药持续8周; 24只对照犬在诱导房扑前未接受药物。通过快速右心房起搏诱导房扑，并在创建Y形右心房切口之前（术前）和之后（术后）进行EP测量。胺碘酮治疗组（8/15 [53%]）、水飞蓟素治疗组（4/6 [67%]）和对照组（15/21 [71%]）持续>30分钟的房扑诱导频率无差异，而胺碘酮+水飞蓟素组犬的诱导频率（2/15 [13%]）与其他三组相比显著降低。与对照组相比，胺碘酮和胺碘酮+水飞蓟素治疗均延长了术前和术后右心房有效不应期;然而，胺碘酮+水飞蓟素治疗组与胺碘酮治疗组之间的任一参数均无显著差异。胺碘酮+水飞蓟素给药组和对照组犬的房扑平均周期长度（术后减去术前）的增加显著小于胺碘酮给药组犬（胺碘酮+水飞蓟素;对照组;胺碘酮给药组）。胺碘酮+水飞蓟素治疗导致术后右房不应期长于房扑平均周期长度，与可兴奋间隙的减少和/或消除一致。结论：胺碘酮在此心房扑动模型中没有预防性的抗心律失常作用，可能是因为它不能减少心房扑动的可兴奋间隙。然而，当与胺碘酮一起给药时，无直接抗心律失常作用的抗氧化剂水飞蓟素可增强胺碘酮的抗心律失常作用，并通过减少和/或消除可兴奋间隙来预防持续性房扑。（J.E. Vasc Electrophysiol，Vol. 14，pp. 861 - 867，2003年8月）
Introduction:Because amiodarone generates free radicals that may mediate amiodarone's toxicity, simultaneous therapy with an antioxidant might be beneficial if the antioxidant did not impair amiodarone's antiarrhythmic action. We tested whether simultaneous administration of a flavonoid antioxidant, silymarin, altered the electrophysiologic (EP) actions of amiodarone in 62 open chest dogs with electrically induced atrial flutter created by a Y‐shaped right atrial incision.Methods and Results:Fifteen dogs received oral amiodarone (600 mg/day); 15 dogs received amiodarone (600 mg/day) and silymarin (70 mg bid); and 8 dogs received silymarin (70 mg bid) alone. All dosing was for 8 weeks; 24 control dogs received no drugs prior to induction of atrial flutter. Atrial flutter was induced by rapid right atrial pacing, and EP measurements were made before (presurgical) and after (postsurgical) creation of a Y‐shaped right atrial incision. There was no difference in the frequency of induction of atrial flutter lasting >30 minutes among amiodarone‐treated (8/15 [53%]), silymarin‐treated (4/6 [67%]), and control (15/21 [71%]) groups, whereas the frequency of induction in the amiodarone+silymarin dogs (2/15 [13%]) was significantly reducedcompared with the other three groups. Both amiodarone and amiodarone+silymarin treatment prolonged the presurgical and postsurgical right atrial effective refractory periodcompared with control; however, there was no significant difference in either parameter between the amiodarone+silymarin–treated and amiodarone‐treated groups. The increase in atrial flutter mean cycle length (postsurgical minus presurgical) was significantlyless in the amiodarone+silymarin–treated and control dogs compared with the amiodarone‐treated dogs (for amiodarone+silymarin;for control; andfor amiodarone treatment). Amiodarone+silymarin treatment resulted in a longer postsurgical right atrial refractory periodthan atrial flutter mean cycle length, consistent with reduction and/or elimination of the excitable gap. Silymarin alone did not exert significant EP or antiarrhythmic action.Conclusion:Amiodarone exerted no preventative antiarrhythmic action in this atrial flutter model, probably because it could not reduce the excitable gap of atrial flutter. However, an antioxidant, silymarin, without a direct antiarrhythmic action, when administered together with amiodarone, potentiated amiodarone's antiarrhythmic actions and prevented sustained atrial flutter by reduction and/or elimination of the excitable gap.(J Cardiovasc Electrophysiol, Vol. 14, pp. 861‐867, August 2003)