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Eur Heart J ; 33(16): 2098-108, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21816854

RESUMO

AIMS: Hyperaldosteronism is associated with an increased prevalence of atrial fibrillation (AF). However, it is unclear whether this is the consequence of altered haemodynamics or a direct aldosterone effect. It was the aim of the study to demonstrate load-independent effects of aldosterone on atrial structure and electrophysiology. METHODS: Osmotic mini-pumps delivering 1.5 µg/h aldosterone were implanted subcutaneously in rats (Aldo). Rats without aldosterone treatment served as controls. After 8 weeks, surface electrocardiogram, the inducibility of AF, and atrial pressures were recorded in vivo. In isolated working hearts, left ventricular function was measured, and conduction in the right atrium (RA) and the left atrium (LA) was mapped epicardially. The atrial effective refractory period (AERP) was determined. Atrial tissue was analysed histologically. RESULTS: Neither systolic nor diastolic ventricular function nor atrial pressures were altered in Aldo rats. All Aldo (11/11) showed inducible atrial arrhythmias vs. two of nine controls (P = 0.03). In Aldo, the P-wave duration and the total RA activation time were longer. Prolongation of local conduction times occurred more often in Aldo, whereas the AERP did not differ between both groups. In Aldo, atrial fibroblasts and interstitial collagen were increased, active matrix metalloproteinase 13 was reduced, and atrial myocytes were hypertrophied. The connexin 43 content was unaltered. CONCLUSIONS: Aldosterone causes a substrate for atrial arrhythmias characterized by atrial fibrosis, myocyte hypertrophy, and conduction disturbances. The described model imputes atrial proarrhythmia directly to aldosterone, since ventricular haemodynamics appeared unaltered in this model. This mechanism may have therapeutical impact for primary and secondary prevention of AF.


Assuntos
Aldosterona/toxicidade , Fibrilação Atrial/induzido quimicamente , Animais , Fibrilação Atrial/fisiopatologia , Conexina 43/metabolismo , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Fibrose/induzido quimicamente , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Átrios do Coração/patologia , Sistema de Condução Cardíaco/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Hiperaldosteronismo/complicações , Metaloproteinase 13 da Matriz/metabolismo , Miócitos Cardíacos/patologia , Tamanho do Órgão , Ratos , Ratos Sprague-Dawley
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