title: Apamin-sensitive potassium current modulates action potential duration restitution and arrhythmogenesis of failing rabbit ventricles.
abstract: BACKGROUND
  Apamin-sensitive K currents (I(KAS)) are upregulated in heart failure. We hypothesize that apamin can flatten action potential duration restitution (APDR) curve and can reduce ventricular fibrillation duration in failing ventricles.
  
  
  RESULTS
  We simultaneously mapped membrane potential and intracellular Ca (Ca(i)) in 7 rabbit hearts with pacing-induced heart failure and in 7 normal hearts. A dynamic pacing protocol was used to determine APDR at baseline and after apamin (100 nmol/L) infusion. Apamin did not change APD(80) in normal ventricles, but prolonged APD(80) in failing ventricles at either long (≥300 ms) or short (≤170 ms) pacing cycle length, but not at intermediate pacing cycle length. The maximal slope of APDR curve was 2.03 (95% confidence interval, 1.73-2.32) in failing ventricles and 1.26 (95% confidence interval, 1.13-1.40) in normal ventricles at baseline (P=0.002). After apamin administration, the maximal slope of APDR in failing ventricles decreased to 1.43 (95% confidence interval, 1.01-1.84; P=0.018), whereas no significant changes were observed in normal ventricles. During ventricular fibrillation in failing ventricles, the number of phase singularities (baseline versus apamin, 4.0 versus 2.5), dominant frequency (13.0 versus 10.0 Hz), and ventricular fibrillation duration (160 versus 80 s) were all significantly (P<0.05) decreased by apamin.
  
  
  CONCLUSIONS
  Apamin prolongs APD at long and short, but not at intermediate pacing cycle length in failing ventricles. I(KAS) upregulation may be antiarrhythmic by preserving the repolarization reserve at slow heart rate, but is proarrhythmic by steepening the slope of APDR curve, which promotes the generation and maintenance of ventricular fibrillation.
authors: Department of Medicine, Division of Cardiology, Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors: Yu-Cheng
authors: YC
authors: Hsieh
authors: Po-Cheng
authors: PC
authors: Chang
authors: Chia-Hsiang
authors: CH
authors: Hsueh
authors: Young Soo
authors: YS
authors: Lee
authors: Changyu
authors: C
authors: Shen
authors: James N
authors: JN
authors: Weiss
authors: Zhenhui
authors: Z
authors: Chen
authors: Tomohiko
authors: T
authors: Ai
authors: Shien-Fong
authors: SF
authors: Lin
authors: Peng-Sheng
authors: PS
authors: Chen
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D011817:Rabbits; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D001030:Apamin; D011188:Potassium