Objectives: 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:①TdP 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 10μmol/L Chromanol 293B 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 IKs blocker 10μmol/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 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 293B under hypokalemic solution in TdP model group increased TDR(corrected) evidently(P<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(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 293B 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.
Conclusions: TMCC can play the role against TdP through decreasing TDR and instability of QT interval, and inhibiting early after depolarization(EAD).
Keywords: guinea pig; instability of QT interval; isolated heart perfusion; taurine magnesium coordination compound; torsades de pointes; transmural dispersion of repolarization.