Rush Center for Congenital
and Structural Heart Disease




The primitive heart:

The first intraembryonic blood vessels are noted at day 20, and one to three days later the formation of the single median heart tube is complete.  The heart starts to beat at day 22, but the circulation does not start until days 27 to 29 [364].

The single tubular heart develops many constrictions outlining future structures.  The cranial most area is the bulbus cordis which extends cranially into the truncus arteriosus, which in turn is connected to the aortic sac and through the aortic arches to the dorsal aortae [364].  The primitive ventricle is caudal to the bulbus cordis and the primitive atrium is the caudal-most structure of the tubular heart (Figure 5).  The atrium which is paired connects to the sinus venosus which receives the vitelline veins which drain the yolk sac, common cardinal veins which drain the embryo and the umbilical veins which drain the primitive placenta (figure 6b & 7a).  The primitive atrium and sinus venosus lay outside the caudal end of the pericardial sac, while the truncus arteriosus is outside the cranial end of the pericardial sac. Terminology describing the segments of the primitive heart tube changed over the past two decades, Wenink supports the use of inlet, outlet and arterial segments as proposed by Anderson and Becker [367-370]. 

Figure 5

The single heart tube shows constriction outlining future structures.  The cranial most area becomes the truncus arteriosus which connects the cranial end of the single heart tube to the aortic arch arteries.  Caudal to the truncus arteriosus is the bulbus cordis which eventually develops into the right ventricle and outflow tract of both ventricles.  Caudal to the bulbus cordis is the primitive ventricle which later develops into the left ventricle.  The atrium is the caudal most part of the single heart tube which connects to the pair of sinus horns which in turn connects to 3 pairs of systemic veins.


Looping of the primitive heart occur at about 23 days of development [371].  It was initially suggested that this occurs due to faster growth of the bulboventricular portion of the heart in comparison to the pericardial sac and the rest of the embryo [364].  However, it has been shown that the heart will loop even when the pericardial sac is removed, after enzymatic removal of the cardiac jelly and without blood circulating as seen when the heart is cultured in vitro [366, 372].  It seems that the process of looping is a genetic property of the myocardium [366].  This is further supported by the observation of the consistency of rightwards looping of the primitive heart tube in vertebrates, which suggest that the process is genetically controlled [373].  Abnormal looping results in heterotaxy as demonstrated in the homozygous iv/iv mice (inversus viscerum).  In these mice, the genetic abnormality results in a wide range of heterotaxy abnormalities similar to what is seen in humans such as situs inversus of the heart with or without abnormal cardiac defects, visceral situs inversus, duplication or reversal of right-left sidedness of bronchial pattern, visceral situs inversus, polysplenic abdominal viscera and aspelnic abdominal viscera.


Figure 6

Looping of the single endocardial heart tube transforms it into a complex four chamber structure.  Looping starts at day 23 of development, and the four chambered heart is evident at day 27.  The rightwards bending of the single heart tube causes the bulbus cordis to occupy a rightward position while the primitive ventricle is to the left.  The atrium, which initially is caudal to the primitive ventricle, becomes dorsal to the ventricles.


Situs inversus is also noted, however without additional cardiac defects, in some patients with the immotile cilia syndrome.  In such patients there is a defect in dynein arms.  Dynein is responsible for ciliary motility.  It is not clear how this would result in situs inversus since there is no known role for cilia in looping of the heart [373].

As the heart tube loops, the cephalic end of the heart tube will bend ventrally, caudally and slightly to the right (Figure 6).  The bulboventricular sulcus will become visible from the outside, and from the inside there will be a primitive interventricular foramen.  The internal fold formed by the bulboventricular sulcus is known as the bulboventricular fold.  The bulboventricular segment of the heart is now U-shaped, bulbus cordis is on the right arm of the U-shape and the primitive ventricle is on the left arm.  The looping of the bulboventricular segment of the heart will cause the atrium and sinus venosus to become dorsal to the heart loop [366].  At this stage the paired sinus venosus extends laterally and give rise to the sinus horns.

As the cardiac looping progresses the paired atria form a common chamber and move into the pericardial sac, it now occupies a more dorsal and cranial position and the common atrio-ventricular junction becomes the atrioventricular canal, this connects the left side of the common atrium to the primitive ventricle [364].  At this stage the heart has a smooth lining except for the area just proximal and just distal to the bulboventricular foramen, where trabeculations form.  This is followed by trabeculations of the primitive ventricle which will form most of the left ventricle.  The proximal portion of the bulbus cordis will form the right ventricle.  The distal part, an elongated structure, will form the outflow tract of both ventricles and the truncus arteriosus will form the roots of both great vessels.  The bulbus cordis gradually acquires a more medial position due to the growth of the right atrium, forcing the bulbus to be in the sulcus in-between the two atria [374].  (Figure 6)



Figure 7

Development of the systemic venous drainage:  These are dorsal views of the heart.  (a) At week 4 of development, depicts symmetrical systemic venous drainage into the two sinus venosus horns. (b) At week 7 of development, depicts degeneration of some of the systemic veins.  (c)  At week 8 of development, depicts the central systemic venous anatomy as seen in a born child.