title: Chronic heart failure and the substrate for atrial fibrillation.
abstract: OBJECTIVE
  We sought to define the underlying mechanisms for atrial fibrillation (AF) during chronic heart failure (HF).
  
  
  RESULTS
  Preliminary studies showed that 4 months of HF resulted in irreversible systolic dysfunction (n = 9) and a substrate for sustained inducible AF (>3 months, n = 3). We used a chronic (4-month) canine model of tachypacing-induced HF (n = 10) to assess atrial electrophysiological remodelling, relative to controls (n = 5). Left ventricular fractional shortening was reduced from 37.2 +/- 0.83 to 13.44 +/- 2.63% (P < 0.05). Left atrial (LA) contractility (fractional area change) was reduced from 34.9 +/- 7.9 to 27.9 +/- 4.23% (P < 0.05). Action potential durations (APDs) at 50 and 90% repolarization were shortened by approximately 60 and 40%, respectively, during HF (P < 0.05). HF-induced atrial remodelling included increased fibrosis, increased I(to), and decreased I(K1), I(Kur), and I(Ks) (P < 0.05). HF induced increases in LA Kv channel interacting protein 2 (P < 0.05), no change in Kv4.3, Kv1.5, or Kir2.3, and reduced Kir2.1 (P < 0.05). When I(Ca-L) was elicited by action potential (AP) clamp, HF APs reduced the integral of I(Ca) in control myocytes, with a larger reduction in HF myocytes (P < 0.05). I(CaL) measured with standard voltage clamp was unchanged by HF. Incubation of myocytes with N-acetylcysteine (a glutathione precursor) attenuated HF-induced electrophysiological alterations. LA angiotensin-1 receptor expression was increased in HF.
  
  
  CONCLUSIONS
  Chronic HF causes alterations in ion channel expression and ion currents, resulting in attenuation of the APD and atrial contractility and a substrate for persistent AF.
authors: Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors: Arun
authors: A
authors: Sridhar
authors: Yoshinori
authors: Y
authors: Nishijima
authors: Dmitry
authors: D
authors: Terentyev
authors: Mahmood
authors: M
authors: Khan
authors: Radmila
authors: R
authors: Terentyeva
authors: Robert L
authors: RL
authors: Hamlin
authors: Tomohiro
authors: T
authors: Nakayama
authors: Sandor
authors: S
authors: Gyorke
authors: Arturo J
authors: AJ
authors: Cardounel
authors: Cynthia A
authors: CA
authors: Carnes
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D016279:Atrial Function, Left; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling; D002304:Cardiac Pacing, Artificial; D002908:Chronic Disease; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005355:Fibrosis; D006329:Heart Conduction System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D006333:Heart Failure / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010865:Pilot Projects; D015221:Potassium Channels / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012032:Refractory Period, Electrophysiological; D013997:Time Factors; D016277:Ventricular Function, Left
chemical_list: D020746:Calcium Channels, L-Type; D015221:Potassium Channels; D044140:Receptor, Angiotensin, Type 1; D000111:Acetylcysteine