Effects of perindopril and spirolactone on plasma aldosterone and left atrial remodeling in a canine model of atrial fibrillation

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 07/2009; 37(7):626-9.
Source: PubMed


To investigate the effects of perindopril and spirolactone on plasma aldosterone (Ald) and left atrial remodeling and function in a canine model of atrial fibrillation (AF).
Adult dogs were randomly assigned to receive normal diet (group A), perindopril (group B, 1 mgxkg(-1)xd(-1)) and spironolactone (group C, 10 mgxkg(-1)xd(-1), n = 6 each) and rapid paced (500 beats/min) for 8 weeks. Plasma Ald levels as well as atrial dimension and function at baseline and at 4 and 8 weeks after pacing were measured by RIA and echocardiography, respectively. Incidence of maintained AF and AF duration were recorded when pacing was stopped after 8 weeks of pacing. Left and right atrial tissues were collected for measurements of tissue Ald levels and fibrosis.
Plasma Ald was similar among groups at baseline (P > 0.05) and significantly increased post 4 and 8 weeks pacing in group A (P < 0.05) while remained unchanged post pacing in group B and C (P > 0.05) compared to respective baseline level. Atrial Ald was significantly lower in group B and C compared that in group A post 8 weeks pacing (P < 0.05). Left atrial dimension, end-systolic and end-diastolic volume were significantly increased while left atrial ejection fraction (LAEF) was significantly reduced post pacing in group A (all P < 0.05 vs. baseline) and thses changes were significantly attenuated in group B and C (P < 0.05 vs. group A). Incidence of maintained AF and AF duration post pacing as well as interstitial collagen volume fraction were significantly lower in group B and C compared those in group A (P < 0.05).
Increased Ald might be an important pathogenesis for AF formation and progression, spironolactone and perindopril could attenuate atrial remodeling and improve atrial function by reducing plasma and tissue Ald levels in this model.

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    ABSTRACT: Atrial fibrillation (AF), the most common cardiac arrhythmia, is an electrocardiographic description of a condition with multiple and complex underlying mechanisms. Oxidative stress is an important driver of structural remodeling that creates a substrate for AF. Oxidant radicals may promote increase of atrial oxidative damage, electrical and structural remodeling, and atrial inflammation. AF and other cardiovascular morbidities activate angiotensin (Ang-II)-dependent and independent cascades. A key component of the renin-angiotensin-aldosterone system (RAAS) is the mineralocorticoid aldosterone. Recent studies provide evidence of myocardial aldosterone synthesis. Aldosterone promotes cardiac oxidative stress, inflammation and structural/electrical remodeling via multiple mechanisms. In HF patients, aldosterone production is enhanced. In patients and in experimental HF and AF models, aldosterone receptor antagonists have favorable influences on cardiac remodeling and oxidative stress. Therapeutic approaches that seek to reduce AF burden by modulating the aldosterone system are likely beneficial but underutilized.
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