牛磺酸镁抗豚鼠尖端扭转型室速的作用研究

Anti-arrhythmic effects of taurine-magnesium coordination compound on torsades de pointes

目的:研究牛磺酸镁配位化合物(TMCC)抗豚鼠心脏尖端扭转型室速(TdP)的作用。方法:取健康、体重250~300 g的成年雄性豚鼠,随机分为4组:(1)TdP模型组(n=7):离体心脏以K-H灌流液灌流20 min,然后使用IKs阻滞剂10μmol/L Chromanol 293B合并低钾(钾离子浓度为1.8 mmol/L)进行灌流,建立TdP模型。(2)^(4)TdP模型+TMCC低中高浓度组(n=6):正常灌流稳定20 min后,在建立TdP模型的同时分别给予1、2、4 mmol/L TMCC。采用Langendorff逆行主动脉灌流法灌流豚鼠离体心脏,利用Biopac电生理记录仪采集并记录豚鼠离体心脏表面心电图。从心电图第Ⅱ导联图形获取各组豚鼠离体心脏TdP发生率、跨室壁复极离散度、QT间期不稳定性,以观察TMCC对TdP的影响。观测指标量取时间分别为:豚鼠离体心脏正常灌流20 min时、TdP发生前及给药60 min时。结果:TdP模型组的TdP发生率为6/7。1、2、4mmol/L TMCC可降低TdP发生率,三组TdP发生率分别为5/6、1/6、0/6。与给药前相比,TdP模型组中Chromanol 293 B合并低钾可使豚鼠离体心脏校正后的跨室壁复极离散度显著增大(P<0.01);与TdP模型组相比,TdP模型+1、2、4mmol/L TMCC组可明显减弱Chromanol 293B合并低钾导致的豚鼠离体心脏校正后的跨室壁复极离散度增大(P>0.05)。与模型组相比,2、4mmol/L TMCC明显降低Chromanol 293B合并低钾导致的QT间期不稳定增大(P<0.05)。在TdP模型建立过程中,从心电图中可观察到连续多个心动周期的P波消失,而在TdP模型+TMCC组中,心电图始终拥有独立P波。结论:TMCC可通过降低离体心脏跨室壁复极离散度和QT间期不稳定性以及抑制早后除极的发生而发挥抗TdP作用,降低TdP发生率。

Objective： To investigate the effect of taurine – magnesium coordination compound（ TMCC） on torsades de pointes（ TdP） in isolated guinea pig hearts. Methods： Healthy male guinea pigs weighting 250 ～ 300 g were randomly divided into 4 groups：（1）TdP model group（ n = 7） ： Isolated hearts were perfused by normal K-H solution 20 minutes,then perfused by slowly activated delayed rectifier potassium current（ IKs） blocker 10 μmol/L Chromanol 293 B under hypokalemic solution（ 1. 8 mmol/L） to establish TdP model;（2） ～（4） TdP model ＋ TMCC group（ n = 6） ： Isolated hearts were perfused by normal K-H solution for 20 minutes,then perfused by IKsblocker 10 μmol/L Chromanol 293 B under hypokalemic solution（ 1. 8 mmol/L） for 60 minutes,at the same time TMCC which concentration was 1,2,4 mmol/L was administered respectively by Langendorff retrograde aortic perfusion method. Cardiac surface electrocardiogram of guinea pigs in vitro was collected and recorded by Biopac electrophysiological recorder. Incidence of TdP,transmural dispersion of repolarization（ TDR）,instability of QT interval were acquired from Lead Ⅱ electrocardiograph（ ECG） wave forms to describe the effect of TMCC on TdP model. Datas were acquired at the time of 20 min and pre-TdP,in case there was no TdP observed,a value of 60 min was entered for calculation purpose. Results： Incidence of TdP in TdP model group was 6/7. TdP incidence could be decreased significantly by 1,2,4 mmol/L TMCC,and was 5/6,1/6,0/6 respectively. Compared with the pre-drug,Chromanol 293 B under hypokalemic solution in TdP model group increased TDR（ corrected） evidently（ P〈0. 01）. Compared with the predrug,1,2,4 mmol/L TMCC in TdP model ＋ TMCC group could decrease the increased TDR（ corrected） induced by Chromanol293 B under hypokalemic solution（ P〈0. 05）. Compared with the TdP model group,2,4 mmol/L TMCC could evidently decrease the instability of QT interval induced by Chromanol 293 B under hypokalemic solution（ P〈0. 05）. During the establishment of TdP model,P waves in more than one cardiac cycle continuously were disappeared in ECG. However,P wave could always be seen independent in ECG acquired from TdP model ＋ TMCC group. Conclusion： TMCC can play the role against TdP through decreasing TDR and instability of QT interval,and inhibiting early after depolarization（ EAD）.