Sridhar A, Nishijima Y, Terentyev D, Khan M, Terentyeva R, Hamlin RL, Nakayama T, Gyorke S, Cardounel AJ, Carnes CA
Chronic Heart Failure and the Substrate for Atrial Fibrillation. [JOURNAL ARTICLE]
Cardiovasc Res 2009 Jun 30.
AIMS: We sought to define the underlying mechanisms for atrial fibrillation during chronic heart failure (HF).
Methods: Preliminary studies showed that 4 months of HF resulted in irreversible systolic dysfunction (n=9) and a substrate for sustained inducible atrial fibrillation (> 3 months, n=3). We used a chronic (4 month) canine model of tachypacing-induced heart failure (n=10) to assess atrial electrophysiologic remodeling, relative to controls (n=5).
RESULTS: Left ventricular fractional shortening was reduced from 37.2+/-0.83% to 13.44+/-2.63% (p<0.05). Left atrial contractility (fractional area change) was reduced from 34.9+/-7.9 to 27.9+/-4.23% (p<0.05). Action potential durations (APD) at 50 and 90% repolarization were shortened by approximately 60% and 40%, respectively, during heart failure (p<0.05). Heart failure-induced atrial remodeling included increased fibrosis, increased I(to) and decreased I(K1), I(Kur) and I(Ks) (p<0.05). Heart failure induced increases in left atrial Kv channel interacting protein 2 (p<0.05), no change in K(v)4.3, K(v)1.5, or Kir2.3, and reduced Kir2.1 (p<0.05). When I(CaL) was elicited by action potential clamp, heart failure action potentials reduced the integral of I(Ca) in control myocytes, with a larger reduction in heart failure myocytes (p<0.05). I(CaL) measured with standard voltage clamp was unchanged by heart failure. Incubation of myocytes with N-acetylcysteine (glutathione precursor) attenuated HF-induced electrophysiologic alterations. Left atrial angiotensin-1 receptor expression was increased in heart failure.
CONCLUSIONS: Chronic heart failure causes alterations in ion channel expression and ion currents, resulting in attenuation of the APD and atrial contractility and a substrate for persistent atrial fibrillation.
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