Published Online
on February 6, 2006

A more recent version of this article appeared on February 14, 2006

This Article Full Text (PDF) All Versions of this Article: 113/6/806    most recent CIRCULATIONAHA.105.565804v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wiegerinck, R. F. Articles by Coronel, R. Search for Related Content PubMed PubMed Citation Articles by Wiegerinck, R. F. Articles by Coronel, R. Pubmed/NCBI databases Medline Plus Health Information Heart Failure Related Collections Animal models of human disease Heart failure - basic studies Hypertrophy Quantitative modeling

Submitted on May 31, 2005
Revised on December 7, 2005
Accepted on December 8, 2005

Larger Cell Size in Rabbits With Heart Failure Increases Myocardial Conduction Velocity and QRS Duration

Rob F. Wiegerinck MSc^*, Arie O. Verkerk PhD, Charly N. Belterman RA, Toon A.B. van Veen PhD, Antonius Baartscheer PhD, Tobias Opthof PhD, Ronald Wilders PhD, Jacques M.T. de Bakker PhD, and Ruben Coronel MD, PhD

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.

^* To whom correspondence should be addressed. E-mail: R.F.Wiegerinck{at}amc.uva.nl.

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.

Key words: hypertrophy • heart failure • electrocardiography • myocytes • conduction

This article has been cited by other articles:

				M. Hardziyenka, M. E. Campian, B. J. Bouma, A. C. Linnenbank, H.A.C.M. R. de Bruin-Bon, J. J. Kloek, A. C. van der Wal, J. Baan Jr, E. M. de Beaumont, H. J. Reesink, et al. Right-to-Left Ventricular Diastolic Delay in Chronic Thromboembolic Pulmonary Hypertension Is Associated With Activation Delay and Action Potential Prolongation in Right Ventricle Circ Arrhythm Electrophysiol, October 1, 2009; 2(5): 555 - 561. [Abstract] [Full Text] [PDF]

				M. Stein, T. A.B. van Veen, C. A. Remme, M. Boulaksil, M. Noorman, L. van Stuijvenberg, R. van der Nagel, C. R. Bezzina, R. N.W. Hauer, J. M.T. de Bakker, et al. Combined reduction of intercellular coupling and membrane excitability differentially affects transverse and longitudinal cardiac conduction Cardiovasc Res, July 1, 2009; 83(1): 52 - 60. [Abstract] [Full Text] [PDF]

				B. J.D. Boukens, V. M. Christoffels, R. Coronel, and A. F.M. Moorman Developmental Basis for Electrophysiological Heterogeneity in the Ventricular and Outflow Tract Myocardium As a Substrate for Life-Threatening Ventricular Arrhythmias Circ. Res., January 2, 2009; 104(1): 19 - 31. [Abstract] [Full Text] [PDF]

				S. Casini, A. O. Verkerk, M. M.G.J. van Borren, A. C.G. van Ginneken, M. W. Veldkamp, J. M.T. de Bakker, and H. L. Tan Intracellular calcium modulation of voltage-gated sodium channels in ventricular myocytes Cardiovasc Res, January 1, 2009; 81(1): 72 - 81. [Abstract] [Full Text] [PDF]

				S. Rossi, S. Baruffi, A. Bertuzzi, M. Miragoli, D. Corradi, R. Maestri, R. Alinovi, A. Mutti, E. Musso, A. Sgoifo, et al. Ventricular activation is impaired in aged rat hearts Am J Physiol Heart Circ Physiol, December 1, 2008; 295(6): H2336 - H2347. [Abstract] [Full Text] [PDF]

				A. O. Verkerk, A. C.G. van Ginneken, T. A.B. van Veen, and H. L. Tan Effects of heart failure on brain-type Na+ channels in rabbit ventricular myocytes: Reply Europace, February 1, 2008; 10(2): 257 - 258. [Full Text] [PDF]

				S. Casini, H. L. Tan, Z. A. Bhuiyan, C. R. Bezzina, P. Barnett, E. Cerbai, A. Mugelli, A. A.M. Wilde, and M. W. Veldkamp Characterization of a novel SCN5A mutation associated with Brugada syndrome reveals involvement of DIIIS4-S5 linker in slow inactivation Cardiovasc Res, December 1, 2007; 76(3): 418 - 429. [Abstract] [Full Text] [PDF]

				A. O. Verkerk, A. C.G. van Ginneken, T. A.B. van Veen, and H. L. Tan Effects of heart failure on brain-type Na+ channels in rabbit ventricular myocytes Europace, August 1, 2007; 9(8): 571 - 577. [Abstract] [Full Text] [PDF]

				G.-S. Hwang, H. Hayashi, L. Tang, M. Ogawa, H. Hernandez, A. Y. Tan, H. Li, H. S. Karagueuzian, J. N. Weiss, S.-F. Lin, et al. Intracellular Calcium and Vulnerability to Fibrillation and Defibrillation in Langendorff-Perfused Rabbit Ventricles Circulation, December 12, 2006; 114(24): 2595 - 2603. [Abstract] [Full Text] [PDF]