title: Aldosterone promotes atrial fibrillation.
abstract: OBJECTIVE
  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.
authors.affiliation: Klinik für Innere Medizin III (Kardiologie, Angiologie, Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Kirrberger Straße, D-66421 Homburg/Saar, Germany. reil@med-in.uni-saarland.de
authors.forename: Jan-Christian
authors.initials: JC
authors.lastname: Reil
authors.forename: Mathias
authors.initials: M
authors.lastname: Hohl
authors.forename: Simina
authors.initials: S
authors.lastname: Selejan
authors.forename: Peter
authors.initials: P
authors.lastname: Lipp
authors.forename: Fabian
authors.initials: F
authors.lastname: Drautz
authors.forename: Andrey
authors.initials: A
authors.lastname: Kazakow
authors.forename: Benedikt M
authors.initials: BM
authors.lastname: Münz
authors.forename: Patrick
authors.initials: P
authors.lastname: Müller
authors.forename: Paul
authors.initials: P
authors.lastname: Steendijk
authors.forename: Gert-Hinrich
authors.initials: GH
authors.lastname: Reil
authors.forename: Maurits A
authors.initials: MA
authors.lastname: Allessie
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.forename: Hans-Ruprecht
authors.initials: HR
authors.lastname: Neuberger
mesh_terms: D000450:Aldosterone / Q000633:toxicity*; D000818:Animals; D001281:Atrial Fibrillation / Q000139:chemically induced* / Q000503:physiopathology; D018031:Connexin 43 / Q000378:metabolism; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D005355:Fibrosis / Q000139:chemically induced; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006325:Heart Atria / Q000473:pathology; D006329:Heart Conduction System / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006929:Hyperaldosteronism / Q000150:complications; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000473:pathology; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018031:Connexin 43; D000450:Aldosterone; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D053509:Matrix Metalloproteinase 13