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GW24-e1724 Verapamil reduces transmural dispersion of repolarisation and prevents Torsade de Pointes in LQT2 model of the long QT syndrome
  1. Liu Yang1,2,
  2. Xue Yu-mei1,
  3. Zhang Cun-tai3,
  4. Wang Lin2,
  5. Wu Shu-lin1,
  6. Bai Rong4
  1. 1Cardiovascular Department, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangzhou, China 510080
  2. 2Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 430030
  3. 3Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 430030
  4. 4Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China 100029

Abstract

Objectives To investigate the effects of verapamil on LQT2 models and its electrophysiologic mechanism by which verapamil suppresses torsades de pointes (TdP) in a developed left ventricular wedge model of LQT2.

Methods Transmembrane action potentials of epicardial (Epi) and endocardial (Endo) cells were recorded simultaneously at a basic cycle length of 2000 ms from an arterially perfused wedge of rabbit left ventricle together with a transmural ECG. E-4031 (0.5 μmol/L) was used to block IKr (LQT2 model). We examined the effect of verapamil on action potential duration (APD), transmural dispersion of repolarisation (TDR) and the development of TdP in LQT2 model of LQTS.

Results In LQT2 models, E-4031 preferentially prolonged APD in Endo rather than Epi, thereby dramatically increasing the QT interval and TDR. Spontaneous or Programmed electrical stimulation-induced early afterdepolarisation (EAD) was observed in Endo, and subsequent TdP occurred. Verapamil (0.5 to 2.5 μmol/L) dose-dependently abbreviated APD in Endo more than in Epi, thereby significantly decreasing the QT interval, TDR, and suppressing EAD and TdP.

Conclusions Our data suggest that verapamil prevents TdP in LQT2 Model of the LQTS by reducing TDR. These results indicate a possible therapeutic role of verapamil in the treatment of LQT2 patients.

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