title: Function of the CaMKII-ryanodine receptor signaling pathway in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia.
abstract: BACKGROUND
  Calcium calmodulin-dependent kinase II (CaMKII) can be more active in patients with left ventricular hypertrophy (LVH), which in turn causes phosphorylation of ryanodine receptors, resulting in inactivation and the instability of intracellular calcium homeostasis. The present study aimed to determine the effect of CaMKII-ryanodine receptor pathway signaling in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia.
  
  
  METHODS
  Forty New Zealand rabbits were randomized into four groups (10 per group): sham group, LVH group, KN-93 group (LVH+KN-93), and ryanodine group (LVH+ryanodine). Rabbits in the LVH, KN-93, and ryanodine groups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta, while those in the sham group did not undergo the coarctation. After eight weeks, action potentials (APs) were recorded simultaneously in the endocardium and epicardium, and a transmural electrocardiogram (ECG) was also recorded in the rabbit left ventricular wedge model. Drugs were administered to the animals in the KN-93 and ryanodine groups, and the frequency of triggered APs and ventricular tachycardia was recorded after the rabbits were given isoprenaline (1 μmol/L) and high-frequency stimulation.
  
  
  RESULTS
  The frequency (animals/group) of triggered APs was 0/10 in the sham group, 10/10 in the LVH group, 4/10 in the KN-93 group, and 1/10 in the ryanodine group. The frequencies of ventricular tachycardia were 0/10, 9/10, 3/10, and 1/10, respectively. The frequencies of polymorphic ventricular tachycardia or ventricular fibrillation were 0/10, 7/10, 2/10, and 1/10, respectively. The frequencies of triggered ventricular arrhythmias in the KN-93 and ryanodine groups were much lower than those in the LVH group (P<0.05).
  
  
  CONCLUSIONS
  KN-93 and ryanodine can effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH. The CaMKII-ryanodine signaling pathway can be used as a new means of treating ventricular arrhythmia.
authors.affiliation: Department of Emergency Internal Medicine, Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University, Fuzhou 350001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ke
authors.affiliation: Integrated Department, Tongji Hospital Affiliated to Tongji Medical College of Huazhong Science Technology University, Wuhan 430030, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Emergency Internal Medicine, Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University, Fuzhou 350001, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Tongji Hospital Affiliated to Tongji Medical College of Huazhong Science Technology University, Wuhan 430030, China.
authors.forename: Li
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Emergency Internal Medicine, Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University, Fuzhou 350001, China.
authors.forename: Mu-Sen
authors.initials: MS
authors.lastname: Dai
authors.affiliation: Department of Emergency Internal Medicine, Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University, Fuzhou 350001, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Wang
authors.affiliation: Department of Emergency Internal Medicine, Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University, Fuzhou 350001, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Emergency Internal Medicine, Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University, Fuzhou 350001, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Integrated Department, Tongji Hospital Affiliated to Tongji Medical College of Huazhong Science Technology University, Wuhan 430030, China.
authors.forename: Cun-Tai
authors.initials: CT
authors.lastname: Zhang
keywords: CaMKII; Left ventricular hypertrophy; Ryanodine receptors; Signaling transduction pathway; Triggered action potential; Ventricular arrhythmia