Li Yan, Sun Kai, An Meng-Yao, Pan Ying-Ying, Sun Tao, Yin Yong-Qiang, Kang Yi, Lou Jian-Shi
Department of Pharmacology, Basic Medical College, Tianjin Medical University, Tianjin 300070, China.
People's Hospital of Wuqing, Tianjin 301700, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2018 Feb 8;34(2):106-110. doi: 10.12047/j.cjap.5596.2018.026.
To investigate the effect of taurine magnesium coordination compound (TMCC) on torsades de pointes (TdP) in isolated guinea pig hearts.
Healthy male guinea pigs weighting 250300 g were randomly divided into 4 groups:①TdP model group (=7):Isolated hearts were perfused by normal K-H solution 20 minutes, then perfused by slowly activated delayed rectifier potassium current(IKs) blocker 10mol/L Chromanol 293B under hypokalemic solution(1.8 mmol/L) to establish TdP model;②④ TdP model + TMCC group (=6):Isolated hearts were perfused by normal K-H solution for 20 minutes, then perfused by IKs blocker 10mol/L Chromanol 293B 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 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.
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 293B under hypokalemic solution in TdP model group increased TDR(corrected) evidently(<0.01). Compared with the pre-drug, 1, 2, 4 mmol/L TMCC in TdP model + TMCC group could decrease the increased TDR(corrected) induced by Chromanol 293B under hypokalemic solution(>0.05). Compared with the TdP model group, 2, 4 mmol/L TMCC could evidently decrease the instability of QT interval induced by Chromanol 293B under hypokalemic solution(<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.
TMCC can play the role against TdP through decreasing TDR and instability of QT interval, and inhibiting early after depolarization(EAD).
研究牛磺酸镁配合物(TMCC)对离体豚鼠心脏尖端扭转型室性心动过速(TdP)的影响。
选取体重250300 g的健康雄性豚鼠,随机分为4组:①TdP模型组(n=7):离体心脏先用正常K-H液灌注20分钟,然后在低钾溶液(1.8 mmol/L)中用慢激活延迟整流钾电流(IKs)阻滞剂10μmol/L铬醇293B灌注以建立TdP模型;②④TdP模型+TMCC组(n=6):离体心脏先用正常K-H液灌注20分钟,然后在低钾溶液(1.8 mmol/L)中用IKs阻滞剂10μmol/L铬醇293B灌注60分钟,同时分别通过Langendorff逆行主动脉灌注法给予浓度为1、2、4 mmol/L的TMCC。用Biopac电生理记录仪采集并记录豚鼠心脏表面心电图。从Ⅱ导联心电图波形获取TdP发生率、复极跨壁离散度(TDR)、QT间期不稳定性,以描述TMCC对TdP模型的影响。数据在20分钟和TdP发作前采集,若未观察到TdP,则输入60分钟的值进行计算。
TdP模型组TdP发生率为6/7。1、2、4 mmol/L的TMCC可显著降低TdP发生率,分别为5/6、1/6、0/6。与用药前相比,TdP模型组低钾溶液中的铬醇293B明显增加了校正后的TDR(P<0.01)。与用药前相比,TdP模型+TMCC组中1、2、4 mmol/L的TMCC可降低低钾溶液中铬醇293B诱导的升高的校正后TDR(P>0.05)。与TdP模型组相比,2、4 mmol/L的TMCC可明显降低低钾溶液中铬醇293B诱导的QT间期不稳定性(P<0.05)。在建立TdP模型过程中,心电图中多个心动周期的P波持续消失。然而,在TdP模型+TMCC组采集的心电图中总能独立看到P波。
TMCC可通过降低TDR和QT间期不稳定性,抑制早期后除极(EAD),发挥抗TdP作用。