摘要
目的在麻醉大鼠或离体灌流大鼠心脏建立缺血/再灌注(再灌注)性心律失常模型,应用心肌内向整流钾通道(La)激动剂扎考比利(Zacopride)缺血预处理观察Zacopride对再灌注性心律失常的效应并分析可能的机制。方法在体实验:结扎SD大鼠心脏冠状动脉左前降支,局部缺血15min,松扎后再灌15min,建立再灌注性心律失常模型。在缺血前3min(缺血预处理,pretreatment)分别给予1.5、15或50μg/kgZacopride。应用利多卡因(Lidocaine)做阳性对照药。全程连续记录心电图。离体实验:麻醉SD大鼠,开胸取出心脏,建立Tyrode液-Langendorff离体灌流系统,结扎SD大鼠心脏冠状动脉左前降支,局部缺血15min,松扎后再灌15min,建立离体再灌注性心律失常模型。缺血前3min分别给予0.1、1或10μmol/L Zacopride观察预处理对离体再灌注性心律失常的影响,IK1非特异性阻断剂BaCl2 1μmol/L拮抗Zacopride的效应。结果在体实验:应用1.5~50 Zacopride缺血预处理可显著抑制再灌注诱发的心律失常,最适剂量为15μg/kg(p<0.05),与利多卡因效应相仿(P>0.05);离体实验:Langendorff离体灌流心脏应用0.1~10μmiol/LZacopride缺血预处理可有效抑制再灌注心律失常的发生,1μmol/L为Zacopride作用最适浓度,其效应被1μmol/L BaCl2明显逆转。结论大鼠在体和离体实验证明,Zacopride预处理可有效抑制再灌注性心律失常;应用低剂量的BaCl2可消除Zacopride的抗心律失常作用,表明Zacopride抗缺血-再灌注性心律失常作用是通过其激动Ik1通道介导的。
Objective Establishing ischemia/reperfusion(reperfusion)arrhythmias in anesthetized rats in vivo or rat hearts in vitro.Pretreating the rats or rat hearts with the inward rectifier potassium channels (IK1) agonist,to observe the effects of Zacopride against reperfusion arrhythmias.Methods In vivo study:adult Sprague-Dawley (SD)rats were subjected to Ischemia/reperfusion by ligating and loosing the left main coronary artery for 15 min respectively.Zacopride at 1.5,15 or 50μg/kg (i.v.infusion)were applied respectively in the settings of pretreatment (Zacopride given 3 min prior to coronary occlusion).Each control rat received 0.2ml saline (i.v.).Lidocaine (7.5mg/kg)was used as a positive control drug.All the rats were monitored by ECG.In vitro study:In isolated and Langendorff-perfused rat hearts,the left main coronary artery was ligated across a small cotton roll for 15 min and loosen for 15min.Zacopride(i.v.infusion)at 0.1,1or 10μmol/L were applied respectively in the settings of pretreatment(Zacopride given 3min prior to coronary occlusion).BaCl2 was used as non-specific antagonist of IK1.Results In vivo study,Zacopride pre-treatment showed reliable protection against reperfusion arrhythmias.Zacopride (15μg/kg)significant decreased the premature ventricular contraction (PVC)and the duration and incidence of ventricular tachycardia (VT)or ventricular fibrillation (VF).The effects could be compared favorably with Lidocaine (P>0.05).In Langendorff perfused rat hearts,0.1-10μmol/L Zacopride pretreatment significantly inhibited reperfusion arrhythmias and the protection of 1μmol /L (optimal concentration)Zacopride was reversed by 1μmol/L BaCl2.Conclusion Data from In vivo and in vitro study show that Zacopride pretreatment could effectively inhibite reperfusion arrhythmias and the protection is mediated by agonizing cardiac IK1.
作者
赵晓泽
张研
李盼
乔希
李瑜
刘清华
ZHAO Xiao-ze;ZHANG Yan;LI Pan(Department of Pathophysiology,Shanxi Medical University, Taiyuan 030001,China)
出处
《中国心血管病研究》
CAS
2018年第11期1052-1056,共5页
Chinese Journal of Cardiovascular Research
基金
国家自然科学基金(项目编号:31200864)
山西省回国留学人员科研资助项目(项目编号:2016-059)
关键词
内向整流钾通道
再灌注
心律失常
预处理
Inward rectifier potassium channel
Reperfusion
Arrhythmia
Pretreatment
