Investigations On The Effect Of Taurine-Magnesium Coordination Compound(TMCC) Against SQT2 In Cardiomyocytes And Isolated Hearts Of Guinea Pig

Objective:To investigate the effect of taurine-magnesium coordination compound（TMCC）on electrocardiogram of isolated guinea pig hearts,action potential of isolated guinea pig ventricular myocytes in the absence and presence of potassium channel opener pinacidil and trapidil,which hope to describe a primary research on its characteristic of anti-short QT syndrome.Methods:1.The isolated guinea pig heart was retrograde perfused by using Langendorff technique.In order to derermine the effects of taurine-magnesium coordination compound on heart rate,QT/QTc interval,transmural dispersion of repolarization,effective refractory period,instability of RR interval and instability of QT interval in the absence and presence of potassium channel opener pinacidil,the electrocardiogram of isolated guinea pig hearts was recorded by using Biopac physiological recorder.2.Single ventricular myocyte was isolated from guinea pig heart by enzymatic dissociation.Effects of taurine-magnesium coordination compound on action potential duration in the absence and presence of potassium channel opener trapidil were recorded by current clamp mode using whole patch clamp technique.Results:1.The effects of TMCC on the cardiac electrocardiogram of isolated hearts of guinea pigs.Results of the electrocardiogram measurement in isolated guinea pig hearts show that,compared with the control group,with 1,2 and 4 mM taurine-magnesium coordination compound,RR interval were prolonged from 275.71±8.45 ms to 282.50±8.80 ms（n=6,p<0.01）,323.03±12.72ms（n=6,p<0.01）and 331.93±9.28 ms（n=6,p<0.01）;heart rate were decreased from 218.89±6.85 beats/min to 213.51±7.22 beats/min（n=6,p<0.01）,187.20±7.45 beats/min（n=6,p<0.01）and 181.52±5.01 beats/min（n=6,p<0.01）;QT interval were prolonged from 175.88±5.22 ms to 182.30±6.09 ms（n=6,p<0.01）,200.67±7.56 ms（n=6,p<0.01）and 197.30±4.38 ms（n=6,p<0.01）;QTc interval were prolonged from 197.13±4.12 ms to 201.14±3.81 ms（n=6,p>0.05）,205.01±7.23 ms（n=6,p<0.01）and 199.04±4.02 ms（n=6,p<0.05）;effective refractory period were prolonged from 124.89±6.63 ms to 131.93±6.26 ms（n=6,p<0.01）,139.83±5.98 ms（n=6,p<0.01）and 143.17±5.93 ms（n=6,p<0.01）;transmural dispersion of repolarization and QRS interval were not influenced;the index of cardiac electrophysiological balance（iCEB）were increased from 3.81±0.13 to 4.06±0.12（n=6,p<0.05）,4.39±0.19（n=6,p<0.01）and 4.17±0.17（n=6,p<0.01）.2.The changes of electrocardiogram induced by pinacidil in SQT2 of isolated hearts of guinea pigs.Results of the electrocardiogram measurement in isolated guinea pig hearts show that,compared with the control group,with 20 μM pinacidil,RR interval and heart rate was not influenced;QT interval was shortened from 165.59±4.87 ms to 151.44±2.95 ms（n=6,p<0.01）;QTc interval was shortened from 192.29±3.07 ms to 172.45±2.33 ms（n=6,p<0.01）;the transmural dispersion of repolarization was increased from 60.01±4.69 ms to 70.08±6.29 ms（n=6,p>0.05）;effective refractory period was decreased from 112.87±6.55 ms to 88.84±5.78 ms（n=6,p<0.01）;QRS interval and the index of cardiac electrophysiological balance was not influenced;the total instability of RR interval（TIRR）was increased from 2.42±0.15 ms to 3.38±0.22 ms（n=6,p<0.01）;the total instability of QT interval（TIQT）was increased from 2.57±0.16 ms to 3.62±0.26 ms（n=6,p<0.01）;the short-term instability of RR interval（STIRR）was increased from 1.24±0.15 ms to 1.97±0.15 ms（n=6,p<0.05）;the short-term instability of QT interval（STIQT）was increased from 1.75±0.15 ms to 3.41±0.21ms（n=6,p<0.05）.3.The anti-arrhythmic effects of TMCC on SQT2 model induced by pinacidil in of isolated hearts of guinea pigs.Results of the electrocardiogram measurement in isolated guinea pig hearts show that,compared with the pinacidil group,with 1,2 and 4 mM taurine-magnesium coordination compound,the shortened QT interval could be prolonged to 175.77±5.22 ms（n=6,p<0.01）,159.27±5.75 ms（n=6,p<0.01）and 165.93±3.91 ms（n=6,p<0.01）;the shortened QTc interval could be prolonged to 182.88±1.55 ms（n=6,p>0.05）,174.59±5.59 ms（n=6,p>0.05）and 165.40±3.82 ms（n=6,p>0.05）;the increased transmural dispersion of repolarization could be decreased to 61.50±7.46 ms（n=6,p<0.05）,68.76±6.29 ms（n=6,p>0.05）and 60.55±3.35 ms（n=6,p<0.05）;the shortened effective refractory period could be prolonged to 113.50±6.78 ms（n=6,p<0.01）,94.00±9.22 ms（n=6,p<0.01）and 106.03±5.11 ms（n=6,p<0.01）;the increased TIRR could be decreased to 3.14±0.20 ms（n=6,p<0.01）,2.27±0.09 ms（n=6,p<0.01）and 1.63±0.36 ms（n=6,p<0.01）;TIQT could be decreased to 3.41±0.20 ms（n=6,p<0.01）,2.89±0.19 ms（n=6,p<0.01）and 2.41±0.45 ms（n=6,p<0.01）;STIRR could be decreased to 1.83±0.14 ms（n=6,p<0.05）,1.16±0.10 ms（n=6,p<0.01）and 0.77±0.25ms（n=6,p<0.05）;STIQT could be decreased to 1.69±0.19 ms（n=6,p<0.05）,1.65±0.19 ms（n=6,p<0.05）and 1.15±0.43 ms（n=6,p<0.05）.4.Effects of TMCC on action potential duration in ventricular myocytes of guinea pigs.Results of the action potential measurement in single guinea pig ventricular myocyte show that,compared with the control group,with 10,100 and 1000 μM taurine-magnesium coordination compound,the resting membrane potential（RMP）were increased from-80.18±0.53 mV to-83.23±0.81 mV（n=10,p<0.05）,-83.39±0.91 mV（n=10,p<0.05）and-85.54±1.05 mV（n=10,p<0.01）;the action potential amplitude（APA）were increased 148.49±3.11 mV（n=10,p>0.05）,150.77±3.85 mV（n=10,p>0.05）and 149.98±3.13 mV（n=10,p>0.05）;APD50 were decreased from 400.73±39.70 ms to 237.32±32.85 ms（n=10,p<0.01）,196.01±26.41ms（n=10,p<0.01）and 265.54±28.83ms（n=10,p<0.01）;APD90 were decreased from 445.84±38.99 ms to 68.55±32.42 ms（n=10,p<0.01）,239.77±27.21ms（n=10,p<0.01）and 295.86±29.45ms（n=10,p<0.01）.5.Effects of TMCC on shortened action potential duration induced by trapidil in ventricular myocytes of guinea pigs.Results of the action potential measurement in single guinea pig ventricular myocyte show that,compared with the control group,the resting membrane potential（RMP）was decreased from-73.51±1.05 mV to-69.53±1.21 mV（n=12,p<0.05）by 1 mmol·L^-1 trapidil,then the decreased RMP could be increased to-74.97±1.10 mV（n=12,p<0.01）,-73.89±0.60 mV（n=12,p<0.05）and-74.99±0.53 mV（n=12,p<0.01）by 10,100 and 1000 μM TMCC;compared with the control group,the action potential amplitude（APA）was decreased from 131.48±2.48 mV to 129.39±1.42 mV（n=12,p>0.05）by 1 mmol·L^-1 trapidil,then the decreased APA could be increased to 136.77±2.19 mV（n=12,p>0.05）,129.41±3.15 mV（n=12,p>0.05）and 135.11±3.10 mV（n=12,p>0.05）by 10,100 and 1000 μmol·L^-1 TMCC;compared with the control group,APD50 was decreased from 289.52±14.19 ms to 248.22±10.81 ms（n=12,p<0.05）by 1 mmol·L^-1 trapidil,then the decreased APD50 could be increased to 265.49±24.86 ms（n=12,p>0.05）,269.39±21.98ms（n=12,p>0.05）and 299.94±16.00ms（n=12,p<0.05）by 10,100 and 1000 μM TMCC;compared with the control group,APD90 was decreased from 326.15±16.67 ms to 274.54±7.00 ms（n=12,p<0.05）by 1 mmol·L^-1 trapidil,then the decreased APD90 could be increased to 300.84±24.13 ms（n=12,p>0.05）,322.37±20.92ms（n=12,p>0.05）and 331.14±7.96 ms（n=12,p<0.05）by 10,100 and 1000 μmol·L^-1 TMCC.Conclusion:1.TMCC decreases the heart beat,prolongs the QT interval and the effective refractory period,the shortened QT interval and the effective refractory period which were induced by pinacidil could be reversed by TMCC;the increased transmural dispersion of repolarization which was induced by pinacidil could be decreased by TMCC;The increased instability of RR and QT interval which were induced by pinacidil could be decreased by TMCC.2.TMCC increases the resting membrane potential and increases its decreases which is induced by trapidil.the shortened action potential duration which was induced by trapidil could be reversed by TMCC.