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Hemodynamics is a key epigenetic factor in development of the cardiac conduction system
Maria Reckova1, Carlin Rosengarten, Angela deAlmeida
1Department of Cell Biology and Anatomy, Medical University of South Carolina, 173 Ashley Ave, BSB 601, Charleston, SC 29425, USA.
Insights
Hemodynamic load critically influences the maturation of the His-Purkinje system (HPS) in chick embryos. Increased load accelerates HPS development, while reduced load delays the shift to mature ventricular activation patterns.
Area of Science:
- Cardiovascular Physiology
- Developmental Biology
- Cardiac Electrophysiology
Background:
- The His-Purkinje system (HPS) coordinates ventricular contraction.
- HPS maturation involves a shift from base-to-apex to apex-to-base activation.
- Hemodynamics and mechanical forces are proposed epigenetic factors in HPS development.
Purpose of the Study:
- To investigate the hypothesis that hemodynamic load affects the timing of the HPS maturation topological shift.
- To determine if variations in hemodynamic load alter the sequence of ventricular activation during embryonic development.
Main Methods:
- Mapping spatiotemporal patterns of ventricular activation using high-speed imaging of voltage-sensitive dye in chick embryos.
- Modulating hemodynamic load via conotruncal banding (CTB) for increased load and left atrial ligation (LAL) for reduced load.
- Comparing activation patterns in control, CTB, and LAL embryonic hearts during normal development.
Main Results:
- The timing of the shift to mature ventricular activation patterns exhibits significant plasticity.
- Conotruncal banding (CTB) resulted in precocious emergence of mature His-Purkinje system function.
- Left atrial ligation (LAL) was associated with a delay in the conversion to apical initiation of activation.
Conclusions:
- Biophysical factors, specifically hemodynamic load, play a critical role in the differentiation of specialized cardiac tissues.
- This study provides a basis for a new model to investigate the molecular mechanisms of His-Purkinje system induction and patterning in vivo.
Abstract:
The His-Purkinje system (HPS) is a network of conduction cells responsible for coordinating the contraction of the ventricles. Earlier studies using bipolar electrodes indicated that the functional maturation of the HPS in the chick embryo is marked by a topological shift in the sequence of activation of the ventricle. Namely, at around the completion of septation, an immature base-to-apex sequence of ventricular activation was reported to convert to the apex-to-base pattern characteristic of the mature heart. Previously, we have proposed that hemodynamics and/or mechanical conditioning may be key epigenetic factors in development of the HPS. We thus hypothesized that the timing of the topological shift marking maturation of the conduction system is sensitive to variation in hemodynamic load. Spatiotemporal patterns of ventricular activation (as revealed by high-speed imaging of fluorescent voltage-sensitive dye) were mapped in chick hearts over normal development, and following procedures previously characterized as causing increased (conotruncal banding, CTB) or reduced (left atrial ligation, LAL) hemodynamic loading of the embryonic heart. The results revealed that the timing of the shift to mature activation displays striking plasticity. CTB led to precocious emergence of mature HPS function relative to controls whereas LAL was associated with delayed conversion to apical initiation. The results from our study indicate a critical role for biophysical factors in differentiation of specialized cardiac tissues and provide the basis of a new model for studies of the molecular mechanisms involved in induction and patterning of the HPS in vivo.