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...

Specialized conduction tissues mediate coordinated propagation of electrical activity through the adult vertebrate heart. Following activation of the atria, the activation wave is slowed down in the atrioventricular canal or node, after which it spreads rapidly into the left and right ventricles via the His-Purkinje system (HPS). This results in the ventricles being activated from the apex toward the base, which is a hallmark of HPS function. The development of mature HPS function follows significant phases of cardiac morphogenesis. Initially, the cardiac impulse propagates in a slow, linear, and isotropic fashion from the sinus venosus at the most caudal portion of the tubular heart. Although the speed of impulse propagation gradually increases as it travels toward the anterior regions of the heart tube, the actual sequence of ventricular activation in the looped heart proceeds in the same direction as blood flow. Eventually, the immature base-to-apex sequence of ventricular activation undergoes an apparent reversal, changing to the mature apex-to-base pattern. Using an optical mapping approach, we demonstrate that the timing of this last transition shows striking dependence on hemodynamic loading of the ventricle, being accelerated by pressure overload and delayed in left ventricular hypoplasia. Comparison of chick and mammalian hearts revealed some striking similarities as well as key differences in the timing of such events during cardiac organogenesis.