Rush Center for Congenital
and Structural Heart Disease




Ventricular septation

Ventricular septation is a complex process involving different septal structures from various origins and positioned at various planes [379-382].  These structures eventually meet to complete the separation of the right and left ventricles.

Muscular interventricular septum: 

During week 5 of development, around day 30, a muscular fold appears extending from the anterior wall of the ventricles to its floor, near the apex and grows towards the AV valves with a concave ridge.  This is known as the primary ventricular septum.  Most of the initial growth of this septum is achieved by enlargement of the two ventricles on either side of the septum.  The inlet ventricular septum is another contributor to the muscular ventricular septum, this septum forms from coalescing of trabeculations of the inlet region, first forming a muscular ridge, which then grows into the ventricular cavity at a slightly different plane than the primary ventricular septum.  The inlet ventricular septum has a special plane similar to that of the atrial septum.  The point of contact between the primary ventricular septum and the inlet ventricular septum will cause the edge of the primary septum to protrude slightly into the right ventricular cavity forming the trabecular septomarginalis.  The fusion of these two septa forms the bulk of the muscular interventricular septum.  This septum will then become in contact with the outflow septum (Figure 10).

The interventricular foramen, which is bordered by the concave upper ridge of the muscular interventricular septum and the fused AV canal endocardial tissue, closes at the end of week 7.  This is achieved by growth of three structures: the right and left bulbar ridges and the posterior endocardial cushion tissue.  This will close the interventricular communication and connect the ventricular septum to the outflow septum, thus connecting the right ventricle to the pulmonary trunk and the left ventricle to the aortic trunk.

Figure 10

Formation of ventricular septum:  The ventricular septum is complex in its formation.  Four separate components participate in partitioning the two ventricles and the outflow tract.  The primary septum and muscular ridge form the muscular interventricular septum.  The outflow septum divides the outflow tract into a right and left components and endocardial tissue completes the septation process


Outflow tract septum: 

Over the past 2 decades the role of cardiac neural crest cell migration and contribution to the outflow septation has been extensively studied [90, 372, 383-385, 387, 388].  The cardiac outflow tract includes the ventricular outflow tract and the aortopulmonary septum.  There has been much debate regarding this process, the following is a summary of various theories [383-385].

In 1942, Kramer [386] suggested that there are three embryological areas, the conus, the truncus and the aortopulmonary segments.  Each segment develops two opposing ridges of endocardial tissue, the opposing pair of ridges and those from various segments meet to form the septum separating the two outflow tracts, semilunar valves and the aortopulmonary trunks.  The aortopulmonary septum is formed by ridges separating the fourth (future aortic arch) and the sixth (future pulmonary arteries) aortic arches.  The truncus ridges are formed at the area where the semilunar valves are destined to be formed, therefore forming the septum between the ascending aorta and the main pulmonary artery.  The conus ridges form just below the semilunar valves and from the septation between the right and left ventricular outflow tracts.  Van Mierop [366] agreed that there are three pairs of ridges forming in the aortopulmonary, truncus and conus regions, however, he stated that each pairs of ridges fuse independently and later on fuse with other septa to complete septation.  His theory indicate that the truncus ridges form  first, and as they fuse they form a truncal septum which then fuses with the aortopulmonary septum which is formed by invagination of the dorsal wall of the aortic sac between the fourth and the sixth aortic arch arteries, figure 11.  Asami [386] followed Van Mierop’s theory; however, he stated that these ridge fuses in the opposite direction of what Van Mierop has indicated, i.e. from the outflow tract to the aortopulmonary region.  Pexieder [363, 384] and Orts Llorca et al [386] stated that there are only tow septa, a conotruncal (or bulbar) and an aortopulmonary septum (Figure 12).  Bartlings et al [386] introduced a new theory.  They stated that the septation process of the ventricular outflow tracts, pulmonary and aortic valves and the great vessels is mostly caused by a single septation complex, which they termed aortopulmonary septum.  This septation complex develops at the junction of the muscular ventricular outflow tract with the aortopulmonary vessel.  This junction has a saddle shape, i.e. not in one plane which would allow the right ventricular outflow tract to be long with a short main pulmonary artery, while the left ventricular outflow tract becomes short with a long ascending aorta (Figure 13).  The ventricular outflow septation is formed by condensed mesenchyme, embedded in the endocardial cushion tissue just proximal to the level of the aorto-pulmonary valves.  The condensed mesenchyme will come in close contact with the outflow tract myocardium, from the area just above the bulboventricular fold, and participate in the septation of the outflow tract by providing an analogue to muscle tissue.  [382, 386, 389, 391].  Myocardium in contact with the mesenchymal arch grow rapidly and form the bulk of the outflow septum and is continuous with the primary fold on the parietal  wall of the right ventricle and the myocardium on the right side of the primary septum.

Figure 11

Various orientations of outflow, semilunar valve and arterial septation create the spiral nature of these structures.




Kirby et al [90, 372, 387, 388] produced a wealth of literature studying the role of neural crest cells in the development of outflow septation.  These studies were based on a chick embryo model expressing conotruncal malformations such as persistent truncus arteriosus, double outlet right ventricle and others after ablation of a portion of the neural crest, later labeled cardiac neural crest.  Neural crest cells are ectodermal cells which detach from the lateral walls of the neural tube as it folds to close.  Neural crest cells migrate through pathways to various structures (Figure 13).  Those that migrate to and contribute in the development of vascular and outflow septum structures become mesenchymal cells.  The neural crest cells are crucial in the normal aorto-pulmonary septation.  Chick embryos with ablation of the neural crest almost always show significant outflow anomalies such as truncus arteriosus and double outlet right ventricle.  It is not clear if this is primarily dependent upon migrating neural crest cells or the effect of migrating neural crest on other migrating mesenchymal cells in the pharyngeal region.

In addition to Kirby’s vast contribution to our knowledge of outflow septation, she summarized the role of various factors involved in cardiac septation [388].  After looping of the single heart tube, the common atrium drains through a single atrioventricular canal into the presumptive left ventricle, which communicates widely through the interventricular foramen with the presumptive right ventricle.  The presumptive right ventricle in turn communicates through the conotruncus with the aortic sac.  Several septation processes result in the separation of the common atrioventricular canal into right and left atrioventricular valves and inflow regions.  Ventricular septation separates the right and left ventricle, while outflow septation divides the conotruncus into an aortic vestibule and a semilunar valve continuous with the left ventricle and pulmonary infundibulum and semilunar valve continuous with the right ventricle.  Cardiac looping may appear to be unrelated to outflow septation, however, it plays an important role in normal outflow tract development.  When the straight heart tube bends to form a rightward convexity, it allows convergence of the inflow and outflow regions.  The conotruncus which becomes situated ventral to the atrioventricular canal undergoes adjustment to allow the “wedging” of the conotruncus, such that the aortic side of it becomes in close proximity to the mitral and tricuspid valves.  Conotruncal septation occur simultaneous with the process of wedging, thus allowing the conotruncal septum at the base of the conus to properly align with the ventricular septum and endocardial cushion tissue, resulting in connecting the left ventricle to the aorta and the right ventricle to the pulmonary artery.  Improper wedging will cause failure of proper meeting of theses three components (base of conotruncal septum, ventricular septum and endocardial cushion tissue).  This will result in a number of outflow anomalies.


Figure 12

Diagram depicting a theory of ventricular outflow and great vessels’ septation: This diagram is similar though not a reproduction of those published by Bartlings, et al.  Numbers indicate specific aortic arch arteries.