title: Electrophysiological effect of rotigaptide in rabbits with heart failure.
abstract: BACKGROUND
  Rotigaptide is a new anti-arrhythmic peptide, which has recently been found to increase junctional conductance and prevent ischemia-induced ventricular tachycardia. In this study, we attempted to investigate the effects and mechanisms of rotigaptide on the vulnerability to ventricular arrhythmias in rabbits with heart failure (HF).
  
  
  METHODS
  Chronic volume-pressure overload was used to induce HF. After rotigaptide infusion, an electrophysiological study was performed to record monophasic action potential (MAP), determine the effective refractory period (ERP) and ventricular fibrillation threshold (VFT), and assess the susceptibility to ventricular arrhythmia. Finally, real-time PCR was used to detect the changes of connexin 43 (Cx43) mRNA expression.
  
  
  RESULTS
  HF rabbits exhibited significant down-regulation of Cx43 mRNA, increase of effective refractory period (ERP) and decrease of VFT (p < 0.05, respectively). These changes resulted in an increase of vulnerability to ventricular tachyarrhythmias (VT/VF). Rotigaptide administration shortened ERP (113.3 ±8.6 ms vs. 131.7 ±12.5 ms, p < 0.05), restored VFT (15.0 ±2.0 V vs. 6.3 ±1.4 V, p < 0.05), and decreased the vulnerability to VT/VF. However, short-term rotigaptide treatment had no significant effect on MAP duration (MAP duration at 90% repolarization: 169.3 ±6.0 ms vs. 172.7 ±6.2 ms, p > 0.05) or connexin 43 mRNA expression (p > 0.05).
  
  
  CONCLUSIONS
  Rotigaptide decreases the ERP, elevates VFT, and reduces the vulnerability to ventricular arrhythmias without changing Cx43 expression in rabbits with HF. It may be a promising antiarrhythmic drug for preventing ventricular arrhythmia in HF.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xia
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Shengbo
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Congxin
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: He
authors.initials: H
authors.lastname: Huang
keywords: connexin 43; heart failure; rotigaptide; ventricular arrhythmias