title: Hemodynamics is a key epigenetic factor in development of the cardiac conduction system.
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.
authors.affiliation: Department of Cell Biology and Anatomy, Medical University of South Carolina, 173 Ashley Ave, BSB 601, Charleston, SC 29425, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Reckova
authors.forename: Carlin
authors.initials: C
authors.lastname: Rosengarten
authors.forename: Angela
authors.initials: A
authors.lastname: deAlmeida
authors.forename: Chiffvon P
authors.initials: CP
authors.lastname: Stanley
authors.forename: Andy
authors.initials: A
authors.lastname: Wessels
authors.forename: Robert G
authors.initials: RG
authors.lastname: Gourdie
authors.forename: Robert P
authors.initials: RP
authors.lastname: Thompson
authors.forename: David
authors.initials: D
authors.lastname: Sedmera
mesh_terms: D000818:Animals; D002642:Chick Embryo; D006329:Heart Conduction System / Q000196:embryology / Q000502:physiology* / Q000503:physiopathology; D006352:Heart Ventricles / Q000196:embryology / Q000503:physiopathology; D006439:Hemodynamics; D018636:Hypoplastic Left Heart Syndrome / Q000196:embryology / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D009206:Myocardium / Q000737:chemistry; D039842:Neural Cell Adhesion Molecule L1 / Q000032:analysis; D011690:Purkinje Fibers / Q000196:embryology / Q000502:physiology* / Q000503:physiopathology; D012794:Sialic Acids / Q000032:analysis; D016276:Ventricular Function
chemical_list: D039842:Neural Cell Adhesion Molecule L1; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule