Persistence of Functional Atrioventricular Accessory Pathways in Postseptated Embryonic Avian Hearts

Abstract

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, nϭ15; group B, nϭ65; group C, 5 to 6 months, nϭ6) 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 (Pϭ0.015) and the number (Pϭ0.004) and width (Pϭ0.179) 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.

Accessory Atrioventricular Myocardial Pathways in Mouse Heart Development: Substrate for Supraventricular Tachycardias

“…Recently, similar APs were demonstrated during normal quail heart development, where most APs were found at the posteroseptal aspect of the tricuspid valve orifice (12). In contrast, we demonstrated the majority of APs at the anterolateral aspect of mitral orifice in mouse.…”

“…It has been suggested that APs involved in these tachycardias are remnants of the primary AV canal myocardium, which disappear during development and maturation of the annulus fibrosus before and after birth (12,18). Although presence of APs has been demonstrated during normal cardiac development in human fetuses and neonates, their etiology and conducting properties as well as their causative role in AVRT are largely unrevealed (17)(18)(19)(20).…”

“…At later stages, ventricular conduction transforms into the mature apex-to-base activation. The switch from ventricular base-to-apex in apex-to-base activation is suggested to be closely related to the completion of ventricular septation and annulus fibrosus development (12,13). Nevertheless, contemporary electrophysiological studies in embryonic mouse hearts have shown that before ventricular septation is completed, a mature apex-to-base activation is already present, suggesting that the AV conduction axis is functional far before ventricular septation has finished (14,15).…”

“…Consequently, these transient APs may provide the substrate for AVRT in the perinatal period and explain its self-limiting character. Studies in avian demonstrated that antegrade conducting APs are present at late postseptated stages of heart development, which gradually diminish during fetal life (12). In mammalian hearts (15,16), including human (17,18), APs have also been described throughout cardiac development.…”

The Arterial Epicardium: A Developmental Approach to Cardiac Disease and Repair

“…Indirectly, the abnormal formation of the fibrous annulus with persisting accessory pathways can result in reentry tachycardias. PEO inhibition in chick embryos showed defective atrioventricular isolation, delaying the shift from a base-to-apex to an apex-to-base conduction [17].…”