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Circulation
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Published Online
on December 26, 2006

Circulation. 2006
Published online before print December 26, 2006, doi: 10.1161/CIRCULATIONAHA.106.658807
A more recent version of this article appeared on January 2, 2007
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Submitted on August 28, 2006
Accepted on November 3, 2006

Persistence of Functional Atrioventricular Accessory Pathways in Postseptated Embryonic Avian Hearts. Implications for Morphogenesis and Functional Maturation of the Cardiac Conduction System

Denise P. Kolditz MSc, Maurits C.E.F. Wijffels MD, PhD*, Nico A. Blom MD, PhD, Arnoud van der Laarse MD, PhD, Roger R. Markwald MD, PhD, Martin J. Schalij MD, PhD, and Adriana C. Gittenberger-de Groot PhD

From the Department of Cardiology (D.P.K., M.C.E.F.W., A.v.d.L., M.J.S.), the Department of Pediatric Cardiology (N.A.B.) and Department of Anatomy and Embryology (A.C.G.-d.G.), Leiden University Medical Center, Leiden, the Netherlands; and the Department of Cell Biology and Anatomy (R.R.M.), Medical University of South Carolina, Charleston, SC.

* To whom correspondence should be addressed. E-mail: m.c.e.f.wijffels{at}lumc.nl.

Background--During heart development, the ventricular activation sequence changes from a base-to-apex to an apex-to-base pattern. We investigated the possibility of impulse propagation through remnants of atrioventricular (AV) connections in quail hearts.

Methods and Results--In 86 hearts (group A, HH30-34, n=15; group B, HH35-44, n=65; group C, 5 to 6 months, n=6) electrodes were positioned at the left atrium, right ventricular base, left ventricular (LV) base, and LV apex. In group A, LV base activation preceded LV apex activation in the majority of cases (60%; 9 of 15), whereas hearts in group B primarily demonstrated an LV apex-to-base activation pattern (72%; 47 of 65). Interestingly, in group B, the right ventricular base (17%; 11 of 65) or LV base (8%; 5 of 65) exhibited premature activation in 25% (16 of 65) of cases, whereas in 26% (17 of 65), the right ventricular base or LV base was activated simultaneously with the LV apex. Morphological analysis confirmed functional data by showing persistent muscular AV connections in embryonic hearts. Interestingly, all myocardial AV connections stained positive for periostin, a nonmyocardial marker. Longitudinal analysis (HH35-44) demonstrated a decrease in both the number of hearts that exhibited premature base activation (P=0.015) and the number (P=0.004) and width (P=0.179) of accessory AV pathways with developmental stage in a similar time course. In the adult quail hearts, accessory myocardial AV pathways were functionally and morphologically absent.

Conclusion--Thus, impulse propagation through persistent accessory AV connections remains possible at near-hatching stages (HH44) of development, which may provide a substrate for AV reentrant arrhythmias in perinatal life. Periostin positivity and absence of AV pathways in the adult heart suggest that these connections eventually lose their myocardial phenotype, which implicates ongoing AV ring isolation perinatally and postnatally.


Key words: arrhythmia • conduction • electrophysiology • morphogenesis




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