MECHANISM OF TORSADE DE POINTES IN SOTALOL-INDUCED LONG QT SYNDROME MODEL

BothacquiredandcongenitalLong QTSyndrome(LQTS)ischaracterizedbypolymorphousventriculartachycardia (PMVT ) ,Torsadedepointets(Tdp)andsuddencardiacdeath (SCD) .ThemechanismsofarrhythmiasinLQTScomefromdrug mimicingLQTSmodels1 ] .Studiesshowedthatadecreaseofinwardcurrentand /oranincreaseofoutwardcurrentduring phase 2and 3repolarization prolongaction potentialduration(APD )andincreasetransmuraldispersionofrepolarization (TDR) ,whichactsasaprimarystepforthe generationofearlyafterdepolar…

MECHANISM OF TORSADE DE POINTES IN SOTALOL-INDUCED LONG QT SYNDROME MODEL

Objective To study the role of early afterdepolarizations(EAD) in producing a trigger to initiate Torsade de pointes(Tdp) with QT prolongation induced by D-sotalol,and to examine the contribution of transmural dispersion of repolarization(TDR) to transmural propagation of EAD and maintenance of Tdp. Methods Transmembrane action potentials from epicardium and endocardium were recorded simultaneously by using floating glass microelectrode,together with a transmural ECG,in arterially perfused rabbit left ventricular preparations.The role of D-sotalol on action potential duration(APD) of different layer myocytes,TDR,EAD,R-on-T extrasystole and polymorphous ventricular tachycardia(PMVT) were observed. Results In arterially perfused rabbit left ventricular wedge preparations,D-sotalol(100umol*L-1) preferentially prolong APD of endo-myocytes,leading to QT interval prolongation and an increase of TDR.The incidence of EAD,R-on-T premature beats and spontaneous Tdp are 7/7,7/7 and 3/7(P＜0.05) respectively. Conclusion Using an LQT2 model in arterially perfused rabbit left ventricular wedge preparations,we find that in intact ventricular wall,EAD can be generated and a trigger to initiate the onset of Tdp can be produced.Increasing TDR not only facilitates transmural propagation of EAD but also contribute to the maintenance of Tdp.