This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 93/1/77    most recent 01.RES.0000079488.91342.B7v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Reckova, M. Articles by Sedmera, D. Search for Related Content PubMed PubMed Citation Articles by Reckova, M. Articles by Sedmera, D. Related Collections Electrophysiology Cardiac development Animal models of human disease Arrythmias-basic studies

(Circulation Research. 2003;93:77.)
© 2003 American Heart Association, Inc.

Integrative Physiology

Hemodynamics Is a Key Epigenetic Factor in Development of the Cardiac Conduction System

Maria Reckova, Carlin Rosengarten, Angela deAlmeida, Chiffvon P. Stanley, Andy Wessels, Robert G. Gourdie, Robert P. Thompson, David Sedmera

From the Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, SC.

Correspondence to David Sedmera, Department of Cell Biology and Anatomy, Medical University of South Carolina, 173 Ashley Ave, BSB 601, Charleston, SC 29425. E-mail sedmerad{at}musc.edu

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.

Key Words: chick embryo • His-Purkinje system • heart development • optical mapping

This article has been cited by other articles:

				J. T. Butcher, T. C. McQuinn, D. Sedmera, D. Turner, and R. R. Markwald Transitions in Early Embryonic Atrioventricular Valvular Function Correspond With Changes in Cushion Biomechanics That Are Predictable by Tissue Composition Circ. Res., May 25, 2007; 100(10): 1503 - 1511. [Abstract] [Full Text] [PDF]

				A. Gurjarpadhye, K. W. Hewett, C. Justus, X. Wen, H. Stadt, M. L. Kirby, D. Sedmera, and R. G. Gourdie Cardiac neural crest ablation inhibits compaction and electrical function of conduction system bundles Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1291 - H1300. [Abstract] [Full Text] [PDF]

				D. P. Kolditz, M. C.E.F. Wijffels, N. A. Blom, A. van der Laarse, R. R. Markwald, M. J. Schalij, and A. C. Gittenberger-de Groot Persistence of Functional Atrioventricular Accessory Pathways in Postseptated Embryonic Avian Hearts: Implications for Morphogenesis and Functional Maturation of the Cardiac Conduction System Circulation, January 2, 2007; 115(1): 17 - 26. [Abstract] [Full Text] [PDF]

				P. P. Sengupta, J. Korinek, M. Belohlavek, J. Narula, M. A. Vannan, A. Jahangir, and B. K. Khandheria Left Ventricular Structure and Function: Basic Science for Cardiac Imaging J. Am. Coll. Cardiol., November 21, 2006; 48(10): 1988 - 2001. [Abstract] [Full Text] [PDF]

				K. Tobita, L. J. Liu, A. M. Janczewski, J. P. Tinney, J. M. Nonemaker, S. Augustine, D. B. Stolz, S. G. Shroff, and B. B. Keller Engineered early embryonic cardiac tissue retains proliferative and contractile properties of developing embryonic myocardium Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1829 - H1837. [Abstract] [Full Text] [PDF]

				D. Sedmera, A. Wessels, T. C. Trusk, R. P. Thompson, K. W. Hewett, and R. G. Gourdie Changes in activation sequence of embryonic chick atria correlate with developing myocardial architecture Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1646 - H1652. [Abstract] [Full Text] [PDF]

				B. Swynghedauw Phenotypic plasticity of adult myocardium: molecular mechanisms J. Exp. Biol., June 15, 2006; 209(12): 2320 - 2327. [Abstract] [Full Text] [PDF]

				M. Schmelter, B. Ateghang, S. Helmig, M. Wartenberg, and H. Sauer Embryonic stem cells utilize reactive oxygen species as transducers of mechanical strain-induced cardiovascular differentiation FASEB J, June 1, 2006; 20(8): 1182 - 1184. [Abstract] [Full Text] [PDF]

				P. P. Sengupta, B. K. Khandheria, J. Korinek, J. Wang, A. Jahangir, J. B. Seward, and M. Belohlavek Apex-to-Base Dispersion in Regional Timing of Left Ventricular Shortening and Lengthening J. Am. Coll. Cardiol., January 3, 2006; 47(1): 163 - 172. [Abstract] [Full Text] [PDF]

				D. Sedmera Form follows function: developmental and physiological view on ventricular myocardial architecture Eur. J. Cardiothorac. Surg., October 1, 2005; 28(4): 526 - 528. [Abstract] [Full Text] [PDF]

				F. Rothenberg, V. P. Nikolski, M. Watanabe, and I. R. Efimov Electrophysiology and anatomy of embryonic rabbit hearts before and after septation Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H344 - H351. [Abstract] [Full Text] [PDF]

				I. R. Efimov, V. P. Nikolski, and G. Salama Optical Imaging of the Heart Circ. Res., July 9, 2004; 95(1): 21 - 33. [Abstract] [Full Text] [PDF]

				C. E. Hall, R. Hurtado, K. W. Hewett, M. Shulimovich, C. P. Poma, M. Reckova, C. Justus, D. J. Pennisi, K. Tobita, D. Sedmera, et al. Hemodynamic-dependent patterning of endothelin converting enzyme 1 expression and differentiation of impulse-conducting Purkinje fibers in the embryonic heart Development, February 1, 2004; 131(3): 581 - 592. [Abstract] [Full Text] [PDF]