Restitution properties and occurrence of ventricular arrhythmia in LQT2 type of long QT syndrome

Introduction: The aim of this study was to clarify the ventricular tachyarrhythmia mechanism induced by the I-Kr-blocking agent E4031, simulating the LQT2 form. Electrophysiologic properties were examined in 13 canines before and after administration of E4031. Method and Results: Thirty-six needle electrodes were inserted into the anterior left ventricular wall. From each needle, local unipolar electrograms were obtained from four intramural sites. Activation time (AT) and activation-recovery interval (ARI) were measured. To evaluate the susceptibility to ventricular arrhythmia, intramural ARI dispersions and the restitution relationship between ARI and diastolic interval were calculated. After E4031 administration, ARI prolonged uniformly in each myocardial layer. However, ARI dispersion was not augmented compared with control. The slope of the ARI restitution curve after E4031 was significantly steeper than control. A steep slope may result from augmented ARI alternans. In 11 of the 13 canines, ventricular tachyarrhythmia was induced by programmed stimulation after E4031, whereas no arrhythmia was induced by the same protocol in control. Conclusion: Steepness of electrical restitution may play a major role in arrhythmogenicity in LQT2 hearts.