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(Circulation. 2006;114:543-549.)
© 2006 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Atrioventricular Ring Reentry in Embryonic Mouse Hearts

Miguel Valderrábano, MD^*; Fuhua Chen, MD^*; Amish S. Dave, MD, PhD; Scott T. Lamp, MS; Thomas S. Klitzner, MD; James N. Weiss, MD

From the Departments of Medicine (Cardiology) (M.V., A.S.D., S.T.L., J.N.W.) and Pediatrics (F.C., T.S.K.) and the Cardiovascular Research Laboratory (M.V., F.C., A.S.D., S.T.L., T.S.K., J.N.W.), David Geffen School of Medicine at UCLA, Los Angeles, Calif. Dr Valderrábano is currently at the Methodist DeBakey Heart Center, Houston, Tex.

Correspondence to James N Weiss, MD, David Geffen School of Medicine at UCLA, 675 Charles Young Dr So, 3645 MRL, Los Angeles, CA 90095–1760. E-mail jweiss{at}mednet.ucla.edu

Received April 14, 2006; revision received May 24, 2006; accepted June 9, 2006.

Background— During development, AV conduction switches from base-to-apex to apex-to-base conduction after emergence of the conduction system. We hypothesize that after this transition, the bulk of the AV ring, although no longer required for AV conduction, remains transiently able to conduct, providing a potential arrhythmia substrate. We studied AV conduction during this transition and its sensitivity to autonomic modulation.

Methods and Results— Simultaneous voltage and Ca²⁺ mapping with RH-237 and Rhod-2 was performed with 2 CCD cameras in embryonic mouse hearts (n=43). Additionally, isolated calcium mapping was performed in 309 hearts with fluo-3AM. Propagation patterns in voltage and Ca²⁺ mapping coincided. Arrhythmias were uncommon under basal conditions, with AV block in 14 (4%) and junctional rhythms in 4 (1%). Arrhythmias increased after stimulation with isoproterenol—junctional rhythm in 9 (3%) and ventricular rhythms in 22 (6%)—although AV block decreased (3 hearts, 1%). Adding carbachol after isoproterenol caused dissociated antegrade and retrograde AV ring conduction in 30 (8.6%) of E10.5 and E11.5 hearts, occurring preferentially in the right and left sides of the ring, respectively. In 2 cases, reentry occurred circumferentially around the AV ring, perpendicular to normal propagation. Reentry persisted for multiple beats, lasting from 3 to 22 minutes. No episodes of AV ring reentry occurred in E9.5 hearts.

Conclusions— AV ring reentry can occur by spatial dissociation of antegrade and retrograde conduction during combined adrenergic and muscarinic receptor stimulation. Critical maturation (>E9.5) seems to be required to sustain reentry.

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