title: Role of sarcoplasmic reticulum calcium in development of secondary calcium rise and early afterdepolarizations in long QT syndrome rabbit model.
abstract: BACKGROUND
  L-type calcium current reactivation plays an important role in development of early afterdepolarizations (EADs) and torsades de pointes (TdP). Secondary intracellular calcium (Cai) rise is associated with initiation of EADs.
  
  
  OBJECTIVE
  To test whether inhibition of sarcoplasmic reticulum (SR) Ca2+ cycling suppresses secondary Cai rise and genesis of EADs.
  
  
  METHODS
  Langendorff perfusion and dual voltage and Cai optical mapping were conducted in 10 rabbit hearts. Atrioventricular block (AVB) was created by radiofrequency ablation. After baseline studies, E4031, SR Ca2+ cycling inhibitors (ryanodine plus thapsigargin) and nifedipine were then administrated subsequently, and the protocols were repeated.
  
  
  RESULTS
  At baseline, there was no spontaneous or pacing-induced TdP. After E4031 administration, action potential duration (APD) was significantly prolonged and the amplitude of secondary Cai rise was enhanced, and 7 (70%) rabbits developed spontaneous or pacing-induced TdP. In the presence of ryanodine plus thapsigargin, TdP inducibility was significantly reduced (2 hearts, 20%, p = 0.03). Although APD was significantly prolonged (from 298 ± 30 ms to 457 ± 75 ms at pacing cycle length of 1000 m, p = 0.007) by ryanodine plus thapsigargin, the secondary Cai rise was suppressed (from 8.8 ± 2.6% to 1.2 ± 0.9%, p = 0.02). Nifedipine inhibited TdP inducibility in all rabbit hearts.
  
  
  CONCLUSIONS
  In this AVB and long QT rabbit model, inhibition of SR Ca2+ cycyling reduces the inducibility of TdP. The mechanism might be suppression of secondary Cai rise and genesis of EADs.
authors: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linko, Taoyuan, Taiwan; Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: Po-Cheng
authors: PC
authors: Chang
authors: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linko, Taoyuan, Taiwan.
authors: Hung-Ta
authors: HT
authors: Wo
authors: Department of Anesthesia, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors: Hui-Ling
authors: HL
authors: Lee
authors: Institute of Biomedical Engineering, National Chiao Tung University, Hsin Chu, Taiwan.
authors: Shien-Fong
authors: SF
authors: Lin
authors: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linko, Taoyuan, Taiwan; Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: Ming-Shien
authors: MS
authors: Wen
authors: Chang Gung University College of Medicine, Taoyuan, Taiwan; Division of Thoracic Surgery, Chang Gung Memorial Hospital, Linko, Taoyuan, Taiwan; Institute of Biomedical Engineering, National Chiao Tung University, Hsin Chu, Taiwan.
authors: Yen
authors: Y
authors: Chu
authors: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linko, Taoyuan, Taiwan; Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: San-Jou
authors: SJ
authors: Yeh
authors: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linko, Taoyuan, Taiwan; Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: Chung-Chuan
authors: CC
authors: Chou
mesh_terms: D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D008133:Long QT Syndrome / Q000378:metabolism* / Q000503:physiopathology*; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D016171:Torsades de Pointes / Q000378:metabolism / Q000503:physiopathology
chemical_list: D002118:Calcium