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

Abstract

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. Key Words: chick embryo Ⅲ His-Purkinje system Ⅲ heart development Ⅲ optical mapping T he His-Purkinje system (HPS) is a specialized network of conduction tissues that ensures coordinated and reliable activation of the ventricular myocardium. Dysfunction of this essential network of specialized cardiac tissues is linked to ventricular arrhythmia and sudden cardiac death in both adults and children. To give a recent example, Purkinje fibers were mapped as the predominant origin of arrhythmias in human patients with recurrent idiopathic ventricular fibrillation. 1 The relationship between the anatomical structure of the HPS and its electrophysiological characteristics during the normal cardiac cycle has now been understood for nearly a century (summarized and put in perspective in Suma 2 ). After activation of the atria by the sinoatrial (SA) node, propagating electrical impulse exits from the atrioventricular (AV) node and is spread rapidly into the left and right ventricles via the bundle of His, its branched limbs and networks of Purkinje fibers ramifying from the bundle branches. The larger fascicles of the HPS (ie, the His bundle and bundle branches) are insulated from surrounding muscle as they course from the crest of the septum toward the ventricular apex. This insulation breaks down within the peripheral networks of Purkinje fibers, enabling direct electroton...

High‐frequency ultrasonographic imaging of avian cardiovascular development

“…Further validation of the utility of embryonic echocardiography is provided by its ability to detect structural and functional anomalies in the model of conotruncal banding (Clark et al, 1984); in particular, valve regurgitation, expected based on abnormal valvular morphology (Sedmera et al, 1999;Reckova et al, 2003), has not been documented before. Outflow tract regurgitation across the band, observed in a significant proportion of the banded embryos (Fig.…”

Abnormal Myocardial and Coronary Vasculature Development in Experimental Hypoxia

“…Embryonic days 5, 7, and 9 correspond to Hamburger-Hamilton stages 26/27, 31/32, and 37, respectively. tion from the norm, but at the latest sampling interval (ED7) there was a clear acceleration of the normal process of conversion toward mature apex-to-base activation pattern Reckova et al, 2003). This may be due to slowing of ventricular myocyte proliferation, known to be associated with differentiation of ventricular conduction system (Cheng et al, 1999;Thompson et al, 2003) or increased endothelial signaling from hyperplastic, overstimulated endocardium (Gourdie et al, 1998; through molecules such as endothelin.…”

What Is the Purpose of the Embryonic Heart Beat? or How Facts Can Ultimately Prevail over Physiological Dogma

“…For example, experiments in early chicken embryos involving explanted hearts suggest that heart beat is involved in the proper formation of the pacemaker and other cardiac conduction tissue (Tucker et al 1988). Also in chicken embryos, the creation of modified intracardiac blood flow patterns, subaortic ventricular septal defects, semilunar valve anomalies, atrioventricular anomalies, pharyngeal arch artery malformations, left heart hypoplasia, and modified His-Purkinje system development result from unilateral vitelline vein ligation or left atrial ligation (Hogers et al 1995(Hogers et al , 1997Broekhuizen et al 1999;Reckova et al 2003). Not surprisingly, these procedures affect cardiac performance (Tobita and Keller 2000;Ursem et al 2004).…”