Effects of spironolactone on electrical and structural remodeling of atrium in congestive heart failure dogs.
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.
Yang
Shu-sen
SS
Department of Cardiology, First Clinical College of Harbin Medical University, Harbin, Heilongjiang 150001, China.
Han
Wei
W
Zhou
Hong-yan
HY
Dong
Guo
G
Wang
Bai-chun
BC
Huo
Hong
H
Wei
Na
N
Cao
Yong
Y
Zhou
Guo
G
Xiu
Chun-hong
CH
Li
Wei-min
WM
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*
D013148:Spironolactone; D003094:Collagen