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Congenital Defects Tutorial
Introduction Normal Cardiac Development Part 1 Normal Cardiac Development Part 2 Septal Defects Right Heart Lesions Left Heart Lesions Anomalies of Arteries and Veins Cardiac Transplantation References
Overview of Major Embryonic Regions Development Timeline of Human Heart Embryology Primary Heart Tube Systemic and Pulmonary Circulation

Primary Heart Tube

The formation of the linear heart tube is mostly initiated by the contribution of the first heart field, whereas the elongation during the looping is largely achieved by migrating cells from the second heart field.

Formation of the heart tube

The maturation of the heart starts approximately by day 15 of human development. By then the primitive streak has formed and the first mesodermal cells migrate through during early gastrulation. The mesodermal cells that become myocytes or heart cells migrate to an anterolateral portion of the embryo, forming the primary and secondary heart fields. By day 18 of human development, the lateral plate mesoderm splits into two layers–the somatopleuric and splanchnopleuric mesoderm.

The splanchnopleuric mesoderm contains the myocardial and endocardial cardiogenic precursors in the region of the first heart field and second heart field. Cells from the first heart field delaminate to form bilateral tubular structures surrounded by a myocardial layer. By day 21-22 of human development, lateral folding brings these tubes together to fuse in the midline, resulting in formation of the endothelial and myocardial components of the linear heart tube.

Then anterior/posterior folding of the embryo brings the heart tube to lie ventral to the foregut as the embryo takes on a convex shape. Next the primary heart tube sinks into what will become the pericardial cavity, fixed at cranial and caudal ends by the dorsal mesocardium. By day 22 of human development, the primary heart tube wall will consist of three components:

  • Endothelium (inner layer)
  • Myocardium (outer layer)
  • Cardiac jelly (middle layer; acellular extracellular matrix secreted from the myocardium)

Constrictions within the primary heart tube form five primary segments that outline critical future structures (from caudal to cranial):

  • Sinus venosus–receives venous inflow from right and left sinus horns
  • Primitive atrium–forms definitive right and left atria
  • Primitive ventricle–forms definitive left ventricle
  • Bulbus cordis–forms majority of definitive right ventricle
  • Conotruncal segment–outflow tract which is subdivided into two sections
    • Conus arteriosus–incorporated into right and left ventricles
    • Truncus arteriosus–divides to form ascending aorta and pulmonary trunk

These segments are additionally separated by two primary sulci:

  • Atrioventricular sulcus–separates the primitive atrium from primitive ventricle
  • Bulboventricular sulcus–separates the primitive ventricle from bulbus cordis

The aortic sac is located at the most cranial portion of the primitive heart tube and later gives rise to six pairs of aortic arches. Initial blood flow is directed from caudal to cranial. The sinus venosus receives blood from the bilateral vitelline veins (from yolk sac), the common cardinal veins (from embryo), and the umbilical veins (from primitive placenta) while the truncus arteriosus serves as the outflow tract of the developing heart.

By day 22 of human development, the heart tube begins to beat with peristaltic waves. The circulation can be recorded via Doppler by day 27-29 of human development.

Looping of the heart tube

By day 22-28 the primary heart tube begins the process of looping following an activation of gene cascade that determines right-left symmetry (Ashworth), whereas epicardial cells from proepicardial organ form the fourth outer layer of the linear heart tube. Cells migrate from the secondary heart field (splanchnic mesoderm) at the venous (caudal) and arterial (cranial) poles to contribute to growth of the heart tube. Clinical relevance of congenital heart defects is correlated to abnormalities in this heart field. The cells undergo epithelial-to-myocardial transformation at the outflow (arterial) pole and additional myocardial cells onto the then developing outflow tract creating the great vessels (aorta and pulmonary trunk) and right ventricle. Lengthening of the fixed heart tube and dissolution of dorsal mesocardium allow rightward bending and torsion to occur as the heart takes on a C-shaped formation. The process of looping reverses the positions of the primitive atrium and ventricle, modifying the initially C-shaped heart into more of an S-shape.

By day 28 of human development, elongation of the primary heart tube is commonly complete. Additional remodeling brings the primordial chambers into the final spatial arrangement. Migration of neural crest cells, combined with synthesis and expression of specific molecules by the myocardium into cardiac jelly, induces formation, migration, and proliferation of mesenchymal cells from endocardium forming endocardial cushion tissue. The endocardial cushion tissue is crucial for proper fibrous development of atrial and ventricular septa, forming bulbar ridges dividing the outflow tract into right and left sides, and forming the cardiac skeleton of the heart.

Formation of cardiac chambers

Both atria and ventricles form by ballooning growth from the primary heart tube. Expansions from the primitive atrium balloon to either side of the outflow tract occur to form the primordia of both right and left atrial appendages. The enlargement of that balloon outward from the ventricular loop forms the apical components of both the right and left ventricles, initially supporting the circumference of the outflow tract and atrioventricular canal.