title: Effects of spironolactone on electrical and structural remodeling of atrium in congestive heart failure dogs.
abstract: BACKGROUND
  Renin-angiotensin-aldosterone system has been demonstrated to be associated with both congestive heart failure (CHF) and atrial fibrillation (AF). This study investigated the effects of spironolactone, a kind of aldosterone antagonist, on atrial electrical remodeling and fibrosis in CHF dogs induced by chronic rapid ventricular pacing.
  
  
  METHODS
  Twenty one dogs were randomly divided into sham-operated group, control group, and spironolactone group. In control group and spironolactone group, dogs were ventricular paced at 220 beats per minute for 6 weeks. Additionally, spironolactone at 15 mg x kg(-1) x d(-1) was given to dogs 1 week before rapid ventricular pacing until pacing stopped. Transthoracic and transoesophageal echocardiographic examinations were performed to detect structural and functional changes of the atrium. Swan2 Ganz floating catheters were used to measure hemadynamics variances. Atrial effective refractory period (AERP), AERP dispersion (AERPd), intra- and inter-atrium conduction time (CT) and intra-atrium conduction velocity (CV) were determined. The inducibility and duration of AF were also measured in all groups. Finally, atrial fibrosis was quantified with Masson staining.
  
  
  RESULTS
  AERP did not change significantly after dogs were ventricular paced for 6 weeks. However, AERPd, intra- and inter-atrium CT increased significantly, and CV decreased apparently, which was negatively correlated to the atrial fibrosis (r = -0.74, P < 0.05). Simultaneously, left atriums were enlarged and cardiac hemadynamics worsened in pacing dogs. Although spironolactone could not affect cardiac hemadynamics effectively, it can obviously improve left atrial ejection fraction (P < 0.05). Spironolactone treatment did not alter AERP duration, but this medicine dramatically decreased AERPd (P < 0.05), shortened intra- and inter-atrium conduction time (P < 0.05), and increased atrium CV. Moreover, spironolactone decreased the inducibility and duration of AF (P < 0.05), as well as atrial fibrosis (P < 0.01) induced by chronic rapid ventricular pacing.
  
  
  CONCLUSIONS
  Spironolactone contributes to AF prevention in congestive heart failure dogs induced by chronic rapid ventricular pacing, which is related to atrial fibrosis reduction and independent of hemadynamics.
authors.affiliation: Department of Cardiology, First Clinical College of Harbin Medical University, Harbin, Heilongjiang 150001, China.
authors.forename: Shu-sen
authors.initials: SS
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Hong-yan
authors.initials: HY
authors.lastname: Zhou
authors.forename: Guo
authors.initials: G
authors.lastname: Dong
authors.forename: Bai-chun
authors.initials: BC
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Huo
authors.forename: Na
authors.initials: N
authors.lastname: Wei
authors.forename: Yong
authors.initials: Y
authors.lastname: Cao
authors.forename: Guo
authors.initials: G
authors.lastname: Zhou
authors.forename: Chun-hong
authors.initials: CH
authors.lastname: Xiu
authors.forename: Wei-min
authors.initials: WM
authors.lastname: Li
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000517:prevention & control; D002306:Cardiac Volume; D003094:Collagen / Q000032:analysis; D004285:Dogs; D006325:Heart Atria / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D013148:Spironolactone / Q000627:therapeutic use*
chemical_list: D013148:Spironolactone; D003094:Collagen