Atrioventricular ring reentry in embryonic mouse hearts.
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.


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.
Valderrábano
Miguel
M
Department of Medicine, David Geffen School of Medicine at UCLA, 675 Charles Young Dr So, 3645 MRL, Los Angeles, Calif. 90095-1760, USA.
Chen
Fuhua
F
Dave
Amish S
AS
Lamp
Scott T
ST
Klitzner
Thomas S
TS
Weiss
James N
JN
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D001283:Atrioventricular Node / Q000502:physiology*; D002118:Calcium / Q000032:analysis; D002217:Carbachol / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000196:embryology* / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D009206:Myocardium / Q000737:chemistry; D011941:Receptors, Adrenergic / Q000032:analysis / Q000502:physiology; D011976:Receptors, Muscarinic / Q000032:analysis / Q000502:physiology; D013611:Tachycardia, Atrioventricular Nodal Reentry / Q000503:physiopathology*
D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D011941:Receptors, Adrenergic; D011976:Receptors, Muscarinic; D002217:Carbachol; D007545:Isoproterenol; D002118:Calcium