Published online before print February 6, 2006, doi: 10.1161/CIRCULATIONAHA.105.565804
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(Circulation. 2006;113:806-813.)
© 2006 American Heart Association, Inc.
Heart Failure |
Larger Cell Size in Rabbits With Heart Failure Increases Myocardial Conduction Velocity and QRS Duration
From the Departments of Experimental Cardiology (R.F.W., A.O.V., C.N.B., A.B., T.O., J.M.T.d.B., R.C.) and Physiology (A.O.V., R.W.), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; the Department of Medical Physiology (T.A.B.v.V., T.O., J.M.T.d.B.), University Medical Center Utrecht, Utrecht, the Netherlands; and the Interuniversity Cardiology Institute of the Netherlands (J.M.T.d.B.), Utrecht, the Netherlands.
Correspondence to Rob F. Wiegerinck, MSc, Department of Experimental Cardiology, Molecular & Experimental Cardiology Group, Academic Medical Center, Room M0-109, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E-mail R.F.Wiegerinck{at}amc.uva.nl
Received May 31, 2005; revision received December 7, 2005; accepted December 8, 2005.
Background— Patients with heart failure (HF) have an increased QRS duration, usually attributed to decreased conduction velocity (CV) due to ionic remodeling but which may alternatively result from increased heart size or cellular uncoupling. We investigated the relationship between QRS width, heart size, intercellular coupling, and CV in a rabbit model of moderate HF and in computer simulations.
Methods and Results— HF was induced by pressure-volume overload. Heart weight (21.1±0.5 versus 10.2±0.4 g, mean±SEM; P<0.01) and QRS duration (58±1 versus 50±1 ms; P<0.01) were increased in HF versus control. Longitudinal CV (
L; 79±2 versus 67±4 cm/s; P<0.01) and transversal subepicardial CV (T; 43±2 versus 37±2 cm/s; P<0.05) were higher in HF than in controls. Transmural CV (TM) was unchanged (25±2 versus 24±1 cm/s; P=NS). Patch-clamp experiments demonstrated that sodium current was unchanged in HF versus control. Immunohistochemical experiments revealed that connexin43 content was reduced in midmyocardium but unchanged in subepicardium. Myocyte dimensions were increased in HF by 
30%. Simulated strands of mammalian ventricular cells (Luo-Rudy dynamic model) revealed increased L and T with increased myocyte size; however, increased CV could not compensate for increased strand size of longitudinally coupled cells, and consequently, total activation time was longer.
Conclusions— Increased myocyte size combined with the observed expression pattern of connexin43 yields increased L and T and unchanged TM in our nonischemic model of HF. A hypertrophied left ventricle together with insufficiently increased L and unaltered TM results in a prolonged QRS duration.
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