Anti-arrhythmic Effects Of Taurine-magnesium Coordination Compound On Type 1 Long QT Syndrome And Torsade De Pointes

Objective:To investigate the anti-arrhythmic effects of taurine–magnesium coordination compound（TMCC）on type 1 long QT syndrome（LQT1）and torsade de pointes（Td P）in isolated guinea pig hearts and observe the effects of TMCC on action potential of guinea pig ventricular myocytes in the absence and presence of Chromanol 293 B.Methods:1.Isolated spontaneously guinea pig hearts were perfused according to the Langendorff method.The electrocardiograms（ECG）of isolated guinea pig hearts were recorded by using Biopac physiological recorder.Firstly,the effect of TMCC on isolated guinea pig heart was evaluated by ECG parameters,including Heart rate,QT/QTc intervals,transmural dispersion of repolarization（TDR）,which were routinely measured from Lead Ⅱ ECG waveforms.Secondly,the anti-arrhythmic effect of TMCC was assessed on LQT1 model.I_Ks channel blocker Chromanol 293 B was used to mimic the LQT1 model.2.Isolated spontaneously guinea pig hearts were perfused according to the Langendorff method.The ECG of isolated guinea pig hearts were recorded by using Biopac physiological recorder.Instablity of RR interval,instablity of QT interval,TDR and incidence of Td P were acquired from Lead Ⅱ ECG waveforms to describe the effect of TMCC on Td P model which was established by Chromanol 293 B combined with hypokalemic solution（1.8 m M）.3.Single ventricular myocyte was isolated from guinea pig heart by enzymatic dissociation.Effects of TMCC on action potential duration（APD）of guinea pig ventricular myocytes in the absence and presence of I_Ks channel blocker Chromanol293 B were recorded by using whole patch clamp technique under the current clamp mode.Results:1.The effects of TMCC on isolated guinea pig hearts.1,2,4 m M TMCC significantly decreased the HR from 225.72±17.41,212.78±22.01,218.16±10.93beats/min to 213.51±17.69,187.20±18.25,181.52±12.27 beats/min（n=6,P<0.01）from baseline.1,2,4 m M TMCC remarkably prolonged QT interval from 174.37±4.63,178.30±6.77,174.97±4.27 ms to 182.30±6.09,200.67±7.59,197.30±4.37 ms（n=6,P<0.01）from baseline.But only TMCC at 2,4 m M increased QTc interval from196.23±5.90,196.06±3.94 ms to 205.01±7.23 ms（n=6,P<0.05）,199.04±4.02 ms（n=6,P<0.01）versus baseline.QTc intervals were not changed significantly with 1 m M TMCC.1,2,4 m M TMCC had no influence on TDR.1,2,4 m M TMCC remarkably prolonged PR interval from 65.50±0.81,60.25±2.75,58.33±3.45 ms to 77.67±2.12,75.75±2.56,71.83±3.34 ms（n=6,P<0.01）from baseline and also increased ERP from123.33±6.12,121.93±6.94,123.64±4.49 ms to 131.93±6.26 ms（n=6,P<0.01）,139.83±5.98 ms（n=6,P<0.05）,143.04±7.26 ms（n=6,P<0.01）.2.The anti-arrhythmic effects of TMCC on LQT1 model in isolated guinea pig hearts.10 μM Chromanol 293 B significantly prolonged QTc interval from191.58±3.51,193.12±3.82 ms to 203.07±4.44 ms（n=6,P<0.01）,202.96±4.35 ms（n=6,P<0.05）versus baseline.10 μM Chromanol 293 B also increased TDR from54.17±3.30,56.20±3.75 ms to 68.60±6.57 ms（n=6,P<0.05）,72.33±5.32 ms（n=6,P<0.01）versus baseline.Then,with 2 and 4 m M TMCC,the prolonged OTc interval could be shortened to 195.87±4.45,196.75±4.71 ms（n=6,P<0.05 vs LQT1 model group）.However,the increased TDR was not changed evidently.3.TMCC can resist the occurrence of Td P.In combined with the perfusion of hypokalemic solution（1.8 m M）,10 μM Chromanol 293 B caused Td P in 6 out of 7hearts.In the presence of 1,2 m M TMCC,Chromanol 293 B evoked Td P in 5 out of 6and 1 out of 6 respectively.With the 4 m M TMCC,Chromanol 293 B induced no Td P in all of test hearts.4.TMCC can shorten the APD of guinea pig ventricular mytocytes.Compared with the control group,0.01,0.1,1 m M TMCC shortened the APD.In the presence of0.01,0.1,1 m M TMCC,APD90 were decreased from 437.30±36.29 ms to268.55±32.42,199.19±24.31,313.23±31.80 ms（n=10,P<0.01）respectively.APD50 were decreased from 392.94±36.75 ms to 237.31±32.85 ms（n=10,P<0.01）,173.26±26.37 ms（n=10,P<0.01）,282.81±32.03 ms（n=10,P<0.05）respectively.5.TMCC can resist the APD prolongation caused by I_Ks channel blocker Chromanol 293 B.APD of control group was prolonged in the presence of 10 μM Chromanol 293 B.APD90 of control group was increased from 475.31±26.29 ms to525.33±28.38 ms（n=6,P<0.01）from baseline,about 12.58%;APD50 of control group was increased from 441.72±27.50 ms to 492.03±28.83 ms（n=6,P<0.01）from baseline,about 13.78%.The 0.01,0.1,1 m M TMCC group,which were incubated with the 0.01,0.1,1 m M TMCC in advance,only slightly prolonged the APD in the presence of 10 μM Chromanol 293 B.APD90 were increased from 357.41±26.97,275.25±39.88,349.56±65.05 ms to 374.17±26.86 ms（n=6,P<0.01）,281.57±40.24ms（n=6,P>0.05）,359.88±68.18 ms（n=6,P>0.05）from baseline,about 4.87%（n=6,P<0.05 vs control group）,2.56%（n=6,P<0.01 vs control group）,6.11%（n=6,P<0.05 vs control group）;APD50 were increased from 328.78±24.75,246.93±36.77,322.91±62.78 ms to 346.65±24.94 ms（n=6,P<0.05）,252.73±38.47 ms（n=6,P>0.05）,343.56±66.41 ms（n=6,P>0.05）from baseline,about 5.61%（n=6,P<0.05 vs control group）,1.94%（n=6,P<0.01 vs control group）,6.71%（n=6,P<0.05 vs control group）.Conclusions:1.TMCC shortens prolonged QTc interval caused by I_Ks channel blocker Chromanol 293 B.This result demonstrates that TMCC has anti-arrhythmic effect on LQT1.2.The increased instablity of RR/QT interval and TDR,which are induced by I_Ks channel blocker Chromanol 293 B under hypokalemic solution,can be decreased by TMCC.Besides,TMCC also decreases the high incidence of Td P caused by Chromanol 293 B in combine with hypokalemic solution.3.TMCC shortens the action potential duration of guinea pig ventricular myocyte and alleviates the prolongation of action potential duration caused by the perfusion of Chromanol 293B.