摘要
目的应用哇巴因在大鼠离体心脏建立稳定的心律失常模型,观察KATP通道激动剂吡那地尔(pinacidil)对哇巴因诱发心律失常的影响。方法采用健康成年SD大鼠建立离体心脏Langendorff主动脉逆行灌流系统。实验分5组:正常对照组,哇巴因模型组和吡那地尔1,3,10μmol/L干预组。每组8只动物。应用5μmol/L哇巴因和低K+台式液([K+]o=2.7mmol/L)灌流心脏诱发室性心律失常,分别观察1,3,10μmol/L吡那地尔对药物性心律失常的影响,全程记录心电图的变化。结果在正常台式液中加入5μmol/L哇巴因灌流大鼠离体心脏仅引起一过性心律失常,而降低台式液中KCl浓度(2.7mmol/L),则相同浓度哇巴因可诱发出稳定的室性心律失常,包括室性早搏、室速和室颤。给药30min内,期前收缩(PVB)达到(386±49)个,室速(VT)和室颤(VF)发生率分别为100%(8/8)和87.5%(7/8)(n=8,P<0.01)。待哇巴因诱发出心律失常后立即应用吡那地尔可浓度依赖性抑制哇巴因诱发的期前收缩,降低室速和室颤的发生率(n=8,P<0.01)。结论作为KATP通道激动剂,1-10μmol/L吡那地尔可拮抗哇巴因所致心律失常,其电生理机制可能为增大心肌外向离子流,缩短动作电位时程并使心肌细胞膜超极化。
Objective To investigate the effect of ATP-sensitive potassium(KATP)channel opener pinacidil on ouabain-induced arrhythmia in isolated rat hearts. Methods Adult healthy Sprague-Dawley rats(weighed 220-250 g)were used to establish a Langendorff retrograde perfusion system.The rats were randomly divided into 5 groups:control group,ouabain model group and pinacidil treatment groups(1,3,10 μmol/L).Arrhythmia was elicited in isolated rat hearts by the perfusion of 5 μmol/L ouabain on the basis of low K+-Tyrode solution ([K+]o,2.7 mmol/L).Pinacidil (1,3,10 μmol/L)was given immediately after the development of fisrt sinus arrhythmia,respectively.The arrhythmias in each group were monitored and compared by simultaneous ECG recording for 30 min after application of ouabain. Results In Langendorff-perfused hearts,5 μmol/L ouabain based on low K+-Tyrode solution elicited singnificant ventricular arrhythmias.The total of premature ventricular beats(PVB)were 386±49.The incidence of ventricular tachycardia(VT)and ventricular fibrillation(VF)were 100%(8/8)and 87.5%(7/8),respectively(P0.01).At the concentration of 1-10 μmol/L,pinacidil inhibited a ouabain-induced arrhythmia in a concentration-dependent manner(n=8,P0.01). Conclusion The results indicate that the antiarrhythmic effect of pinacidil might be mediated by the hyperpolarization of resting membrane potential and the decrease of action potential duration.
出处
《山西医科大学学报》
CAS
2010年第6期501-503,共3页
Journal of Shanxi Medical University
关键词
心律失常
哇巴因
ATP敏感钾通道
吡那地尔
动作电位
超极化
arrhythmia
ouabain
ATP-sensitive potassium channel
pinacidil
action potential
hyperpolarization