The Anatomy, Development, and Evolution of the Atrioventricular Conduction Axis

Abstract

It is now well over 100 years since Sunao Tawara clarified the location of the axis of the specialised myocardium responsible for producing coordinated ventricular activation. Prior to that stellar publication, controversies had raged as to how many bundles crossed the place of the atrioventricular insulation as found in mammalian hearts, as well as the very existence of the bundle initially described by Wilhelm His Junior. It is, perhaps surprising that controversies continue, despite the multiple investigations that have taken place since the publication of Tawara's monograph. For example, we are still unsure as to the precise substrates for the so-called slow and fast pathways into the atrioventricular node. Much has been done, nonetheless, to characterise the molecular make-up of the specialised pathways, and to clarify their mechanisms of development. Of this work itself, a significant part has emanated from the laboratory coordinated for a quarter of a century by Antoon FM Moorman. In this review, which joins the others in recognising the value of his contributions and collaborations, we review our current understanding of the anatomy, development, and evolution of the atrioventricular conduction axis.

Keywords: atrioventricular node; bundle of His; dead-end tract; retroaortic node; ventricular bundle branches.

Figure 1

The figure is prepared by scanning the figures from the original publication of His [6] (A) and the monograph of Tawara [1] (B). His’s figure is shown as seen from the right side, with the heart in “Valentine” orientation. Tawara’s figure is re-orientated to show the arrangement as seen in attitudinally appropriate fashion, with the endocardial surface of the right-sided chambers to the bottom of the picture. His’ image shows the penetrating portion of the atrioventricular (AV) conduction axis, whereas the figure of Tawara shows its overall extent.

Figure 2

The top panel shows the opened right atrium, revealing the landmarks of the triangle of Koch, namely the tendon of Todaro and the hinge of the septal leaflet of the tricuspid valve. The atrioventricular node (red star with white borders), located at the apex of the triangle, is more-or-less centrally positioned within the cardiac base as viewed from the internal aspect of the right-sided chambers. As is shown in the bottom panel, which is a dissection made by removing the floor of the triangle, the node lies directly adjacent to a cranial continuation of the inferior atrioventricular groove. This fibroadipose area forms the inferior pyramidal space. The cranial extent of the space is bounded by the atrioventricular component of the membranous septum. It is this area that is penetrated by the bundle of His.

Figure 2

The top panel shows the opened right atrium, revealing the landmarks of the triangle of Koch, namely the tendon of Todaro and the hinge of the septal leaflet of the tricuspid valve. The atrioventricular node (red star with white borders), located at the apex of the triangle, is more-or-less centrally positioned within the cardiac base as viewed from the internal aspect of the right-sided chambers. As is shown in the bottom panel, which is a dissection made by removing the floor of the triangle, the node lies directly adjacent to a cranial continuation of the inferior atrioventricular groove. This fibroadipose area forms the inferior pyramidal space. The cranial extent of the space is bounded by the atrioventricular component of the membranous septum. It is this area that is penetrated by the bundle of His.

Figure 3

The sections are from a series prepared from a human heart, showing the atrial components of the conduction axis, and its transition to the bundle of His. They are orientated in attitudinally appropriate fashion, but with the chambers of the right heart shown to the top of the images. Panel (A) shows the rightward and leftward inferior extensions from the compact node, which is seen in Panel (B). Panels (C,D) show how the axis becomes the penetrating bundle once it is insulated by the fibrous tissue of the central fibrous body from the atrial cardiomyocytes.

Figure 4

The left-hand image, prepared from a computed tomographic dataset obtained from an individual undergoing investigation for coronary arterial disease, shows how the location of the atrioventricular conduction axis can be predicted based on knowledge of the landmarks of the right atrial and right ventricular septal surfaces. The star shows the location of the atrioventricular node at the apex of the triangle of Koch. The red dotted line shows the location of the non-branching and branching components of the axis, which are carried on the crest of the muscular ventricular septum. The red arrow shows the site of emergence of the right bundle branch, marked by the medial papillary muscle of the tricuspid valve. The right-hand image is from the original monograph of Tawara [1]. It has been scanned and rotated through 90 degrees relative to the original, placing the image in more attitudinally appropriate orientation. The reconstructions made by Tawara show the origin and distribution of the left bundle branch within the left ventricle.

Figure 5

The images are from the same series as shown in Figure 4. Panel (A) shows the cranial continuation of the conduction axis, which has divided into the right and left bundle branches of the crest of the muscular ventricular septum. Panel (B) shows a section through the vestibule of the left atrium directly adjacent to the non-coronary sinus of the aortic root. The retroaortic node is seen on the atrial aspect of the insulating plane.

Figure 6

The domain of Tbx3-expressing myocardium partakes in dividing the heart in atrial and ventricular compartments, and also in the division of the atrial and ventricular compartment, respectively, by expression on the crests of the atrial and ventricular septum. Adapted from [58].

Figure 7

The identities of the myocardium of the atrioventricular junction of the formed murine heart. Adapted from [58].

Figure 8

Chronology of key studies in the molecular identification of the atrioventricular conduction axis. Cited studies: [9,13,21,24,32,33,34,36,37,38,47,56,58,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79]. There are recent and excellent reviews on the regulatory and transcriptional networks behind the formation of the cardiac conduction system [25,80].