Development of The Heart: Cardiac Tube Development

I.

Development of the heart is first indicated at day 18 or 19, in the cardiogenic area
A.

CARDIAC TUBE DEVELOPMENT

1.

During the stage of gastrulation, angiogenetic cell clusters from the splanchnic
mesoderm layer of the late presomite embryo migrate from the primitive streak to
the area of the oropharyngeal membran They unite with comparable migrating
mesoderm from the opposite side to form a horseshoe-shaped plexus, the cardiac
primordium or cardiogenic cords
a.

Initially, the central portion of the horseshoe-shaped plexus is found anterior

to the prochordal plate and neural plat With closure of the neural plate and
formation of the brain vesicles, the CNS grows so rapidly in a cephalic
direction that it extends over the central cardiogenic area and the future
pericardial cavity

b.

During this growth, the expanding brain pulls the prochordal plate (future
buccopharyngeal membrane) and the central part of the cardiogenic plate
forward, rotating the plate and pericardial part of the intraembryonic
coelomic cavity so that the central portions of the cardiogenic plate and
pericardial cavity, initially rostral to the buccopharyngeal plate, are now
ventral and caudal to it

2.

Cleavage of the lateral plate by the coelom reaches this region, resulting in the
differentiation of the splanchnopleure and somatopleur These form the walls of the
future pericardial cavity

3.

Islands appear in the splanchnic mesoderm after day 20, and then by confluence,
the cords become 2 thin-walled endothelial tubes which are called the endocardial
heart tubes

4.

As the embryo undergoes cephalocaudal flexion, the endocardial tubes approach

each other in the midlin Closure of the foregut moves both tubes to a ventral
position

5.

The 2 endocardial tubes come together about day 22 and fuse, beginning at the
cephalic end of the original horseshoe-shaped structure and extending in a caudal
direction. Thus, a single endocardial tube is formed
a.

6.

The developing primitive heart tube, located in the splanchnic mesoderm of

the pericardial cavity, bulges gradually more and more into the pericardial
cavity and continues until the heart tube, with its investing layer, lies
completely in the cavity

The fusion of the 2 tubes is followed by disappearance of the ventral

mesocardiumand a temporary attachment to the dorsal side of the pericardial cavity
by a fold in mesodermal tissue, the dorsal mesocardium
a.

As the heart tubes fuse, the mesenchyme around them thickens to form the
myoepicardial mantle, which at first is separated from the endothelial wall of

the tube by the cardiac jelly (gelatinous connective tissue substance). The
jelly later is invaded by mesenchymal cells
b.

The inner endocardial tube will become the internal endothelial lining of the
heart, the endocardium; the myoepicardial mantle gives rise to the
myocardium (heart muscle) and epicardium or visceral pericardium

c.

The embryo is now about 23 days old, has 7 somites, and is 2 mm long

7.

The time between the first appearance of the intraembryonic vessels and the heart
tube formation is about 3 days. The resulting single median endocardial tube begins
to beat about day 22

8.

True embryonic circulation is established between days 27 and 29

Development of The Heart: Formation of The Heart Loop

I.

Formation of the heart loop: since the cardiac tube grows more rapidly than the pericardial cavity,
it must undergo a series of complex foldings to be accommodated
A.

THE SINGLE TUBULAR HEART elongates and develops dilatations and constrictions
1.

2.

B.

C.

D.

The intrapericardial part consists of the future bulboventricular portion (bulbus

cordis plus ventricle), whereas the atrial part and sinus venosus are still paired and
lie outside the pericardium in mesenchyme of the septum transversum
a.

The bulbus cordis, ventricle, and atrium appear first (day 22?1). The truncus
arteriosus and sinus venosus are seen a day later (day 23?1). The truncus is
continuous caudally with the bulbus cordis and cranially with the aortic sac
and aortic arches

b.

The sinus venosus (a large venous sinus) receives the umbilical, common
cardinal, and vitelline veins from the primitive placenta, body of the embryo
proper, and the yolk sac, respectively

During development, the bulboventricular part grows faster than the pericardial
cavity, and because its 2 ends are fixed to the surrounding tissue outside the
pericardial cavity (arterial end to the branchial arches, venous end to the septum
transversum), elongation cannot take place in a longitudinal direction

THE CEPHALIC END OF THE LOOP bends ventral and caudal and slightly to the right. As a
result, the bulboventricular sulcus (between bulbus cordis and ventricle) becomes visible on
the outside. Internally, it remains narrow as the primary interventricular foramen, with a
fold being formed, the bulboventricular fold
1.

Because the bulbus cordis and ventricles grow faster than the other regions, the
heart tube bends on itself, forming a U-shaped bulboventricular loop

2.

As the heart bends, the atrium and sinus venosus come to lie dorsal to the bulbus
cordis, truncus arteriosus, and ventricl In addition, the sinus venosus at this stage
also develops lateral expansions, the right and left sinus horns

AS A SECONDARY SEQUENCE OF BENDING AND TORSION, the atrioventricular junction

comes to lie on the left side of the pericardial cavity, while the right side is occupied by the
greatly elongated bulbus cordis
1.

The cardiac loop thus consists of a cephalic or ascending limb (the bulbus) and a
descending limb formed by the embryonic ventricle

2.

The bulbus cordis is narrow except for its proximal one-third which will form
thetrabeculated part of the right ventricle. Its midportion, the conus cordis, forms
the outflow tracts of both ventricles. Its distal part, the truncus arteriosus, forms the
roots and proximal parts of the aorta and pulmonary artery

WHILE THE CARDIAC LOOP IS FORMING, changes occur throughout the length of the tube
1.

The atrial part, a paired structure outside the pericardial cavity, forms a common
atrium by fusion of the right and left sides. During fusion, it is incorporated into the

pericardial cavity and moves in a dorsocranial direction. The atrioventricular junction

assumes a cranial position and forms the atrioventricular canal, connecting the left
side of the common atrium with the embryonic ventricle
E.

WHEN LOOP FORMATION ENDS, the smooth-walled heart tube forms primitive trabeculae in
2 distinct areas: just proximal and distal to the primary interventricular foramen. The atrial
part and other parts of the bulbus remain temporarily smooth-walled

F.

THE PRIMITIVE VENTRICLE, now trabeculated, is called the primitive left ventricle since it
will form the major part of that definitive structure. The trabeculated proximal third of the
bulbus cordis is called the primitive right ventricle

G.

THE CONUS-TRUNCUS PART of the heart tube, initially on the right side of the pericardial
cavity, shifts to a medial position as a result of the formation of 2 transverse dilatations of
the atrium, which bulge on each side of the bulbus cordis
1.

As a result, the truncus is found in a depression between the right and left atria, and
the conus takes an oblique position between the roof of the primitive left ventricle
and the anteromedial wall of the atrium

Pericardial Cavity Development and Primitive Heart Circulation

I.

Pericardial cavity development

A.

B.

C.

II.

THE FIRST SIGN OF HEART FORMATION is found at the end of week 3. The first heartforming cells appear as irregular clusters and cords in the cephalic part of the embryo
between the entoderm of the yolk sac and the splanchnic mesoderm. These cell clusters
form solid strands across the midline in front of the neural plate and extend down on each
side of the embryo by the time the first somites appear
1.

As the head end of the embryo grows forward and folds off from the yolk sac, the 2
solid strands approach each other ventrally and also acquire a lumen lined by
endothelial cells. Thus, the 2 endocardial tubes are formed

2.

The lumen of each of the 2 tubes gradually extends cranially into the midline cell
strands and finally the 2 meet

3.

With further lateral folding of the embryo, the fusion of the 2 endocardial tubes then
progresses from the cephalic point in a caudal direction, thus forming a single
endocardial tube

SIMULTANEOUSLY, WITH LATERAL FOLDING and the medial migration and fusion of the
tubes, the intracoelomic cavities, right and left, also approach each other in the midline.
Initially, at the 4-somite state (about day 21), the primitive heart tubes are connected to
the anterior and posterior walls, between the right and left coelomic cavities, by
thedorsal and ventral mesocardium
1.

Whereas the ventral part disappears immediately after its early formation, the
dorsal mesocardium persists a little longer

2.

As the heart tube elongates, bends, and loops, it slowly sinks into the dorsal wall of
the pericardial cavity, which is formed from a fusion of the right and left
intraembryonic coelomic cavities

3.

Eventually, beginning at the cranial end, the dorsal mesocardium also breaks down
and has entirely disappeared at the 16-somite stage; and the heart tube is then
freely suspended in the pericardial cavity and is attached to the surrounding tissues
only at its cephalic and caudal ends. The newly formed passage, dorsal to the
primitive heart tube, is the future transverse sinus of the pericardial cavity

IN WEEK 5, THE INTRAEMBRYONIC COELOM consists of a thoracic and abdominal

component, connected by a canal found on each side of the foregut. In the adult, the
intraembryonic coelom is divided into 3 well-defined compartments: the pericardial cavity
with the heart, the pleural cavities with the lungs, and the peritoneal cavity with the viscera
below the diaphragm. The diaphragm forms the septum between the thorax and abdomen;
the pleuropericardial membrane forms between the pericardial and pleural cavities (see
discussion on coelomic cavities and mesenteries)

Primitive heart circulation

A.

CONTRACTIONS OF THE HEART begin by day 22 and are of myogenic origin. The muscles of
the atrium and ventricle are continuous, and contraction, in peristaltic waves, begins in the
sinus venosus

1.

B.

C.

The circulation through the embryo and heart, at first, is an ebb-and-flow type, but
by the end of week 4, coordination of heart contractions creates a unidirectional flow

BLOOD RETURNS to the sinus venosus from

1.

The embryo proper via the common cardinal veins

2.

The developing placenta via the umbilical veins

3.

The yolk sac via the vitelline veins

THE SINOATRIAL VALVES control the blood flow from the sinus venosus into the atrium, and
the blood then passes through the atrioventricular canal into the ventricle. When the latter
contracts, blood is pumped through the bulbus cordis and truncus arteriosus into the aortic
sac and aortic arches of the branchial arches. Blood then passes to the dorsal aortae for
distribution to the embryo, yolk sac, and the placenta

Atrioventricular and Interatrial Septation and Development

I.

II.

Introduction: the cardiac tube is folded in the pericardial cavity by day 28 and consists of
A.

THE SINUS VENOSUS, into which enter the vitelline veins, the umbilical veins, and the
common cardinal veins

B.

THE ATRIAL REGION, which communicates with the ventricle via the atrioventricular canal

C.

THE VENTRICULAR REGION

D.

THE BULBUS CORDIS, which is a prolongation of the ventricle and is continuous with the
truncus arteriosus and gives rise to the aortic roots

E.

PARTITIONING of the atrioventricular canal, the atrium, and the ventricle begins about the
middle of week 4 and is essentially complete by the end of week 5 (days 27 to 37) when
the embryo grows in length from 5 mm to about 16 or 17 mm. Although described
separately, the processes take place concurrently

Atrioventricular canal septation: by day 28, the atrial region forms a large cavity dorsal (behind) to
the ventricular region and becomes divided into the right and left atria. Thus, at this time, the
ventricle is bounded ventrally by the bulbus cordis and the atria dorsally. The fold between the
ventricle and the bulbus rapidly disappears
A.

THE SEPARATION BETWEEN ATRIA AND VENTRICLE increases, resulting in a shrinkage of the
atrioventricular canal. On the ventral and dorsal walls of the canal, thickenings of
subendocardial tissue now appear, the 2 endocardial cushions, move toward each other,
and finally fuse (between days 35 and 40) to form the primitive interventricular septum
1.

III.

By day 40, the atrioventricular canal is divided into right and left atrioventricular
canals. The mesenchyme around each canal proliferates and forms the
atrioventricular valves (mitral valve at left and tricuspid valve at right)

Primitive interatrial septation begins during week 5. At this stage, one sees a single atrium,
common cardinal, vitelline, and umbilical veins
A.

A THIN, SICKLE-SHAPED MEMBRANE, the septum primum, appears on the posterosuperior

wall of the primitive atrial chamber and grows toward the endocardial cushions. A large,
temporary opening exists between the lower free edge of the septum primum and the
endocardial cushions called the foramen primum, which rapidly gets smaller

B.

BEFORE CLOSURE OF THE FORAMEN PRIMUM, small openings or perforations appear in the
upper central part of the septum primum, which merge to form another opening,
theforamen secundum. At the same time, the free edge of the septum primum fuses with
the left side of the fused endocardial cushions to obliterate the foramen primum
1.

C.

Thus, when the foramen (ostium) primum is closed, the foramen (ostium) secundum
remains patent and affords free access between the 2 atria

A NEW CRESCENTERIC MEMBRANE appears to the right of the "delicate" septum primum,
on the antero-superior wall of the atrium, near the end of week 5. It converges toward the
endocardial cushions as the septum secundum

D.

1.

The septum secundum enlarges, covers the foramen secundum in the septum
primum, but remains as an incomplete partition which results in an oval-shaped
passageway, the foramen ovale, in the interatrial septum directly in the path of the
blood coming from the inferior vena cava

2.

The upper portion of the septum primum, which is attached to the roof of the left
atrium, gradually disappears, but the rest of the septum becomes the valve of the
foramen ovale

COMPLETE FUSION OF THE SEPTUM PRIMUM to the septum secundum forms the definitive
interatrial septum, obliterating the foramen ovale
1.

Traces of the former passage are often seen

2.

A depression, the fossa ovalis, is evident on the right side of the interatrial septum

3.

The crest of the septum secundum becomes the limbus of the fossa ovalis

I.

The sinus venosus contributes to the definitive form of the atrium. It maintains its paired condition
longer than any other part of the heart tube, and in the 4 mm embryo consists of asmall
transverse part, opening into the center of the primitive atrium, and the right and left sinus horns.
Each horn receives blood from 3 major veins: the vitelline (omphalomesenteric), umbilical, and
common cardinal veins
A.

THE COMMUNICATION BETWEEN THE SINUS VENOSUS AND ATRIUM, which at first is wide,
becomes narrow and shifts to the right as a result of development of a deep fold,
the sinoatrial fold, which separates the left part of the sinus from the left side of the atrium.
In addition, the right horn enlarges due to 2 left-to-right shunts of blood, and by the end of
week 4, the right horn is much larger than the left. Thus, the sinoatrial opening shifts to the
right and opens into the future right atrium
1.

2.

The first left-to-right shunt of blood results from transformation of the vitelline and
umbilical veins
a.

The vitelline veins enter the embryo with the yolk stalk, pass through the
septum transversum, and enter the sinus venosus. Between the yolk sac and
the septum, the paired vitelline veins are connected via anastomoses. In the
septum, the veins are broken up into sinusoids by the developing cords of
liver cells, which later become the hepatic sinusoids

b.

The terminal part of the inferior vena cava forms from the right vitelline vein
between the liver and right horn of the sinus venosus. The hepatic veins form
from the remains of the right vitelline vein in the area of the developing liver.
The portal vein forms from the anastomotic network formed around the
duodenum by the vitelline veins

c.

The umbilical veins

i.

The right umbilical vein and the part of the left between the liver and
the sinus venosus degenerate

ii.

The persistent part of the left umbilical vein carries all the blood from
the placenta to the fetus

iii.

The ductus venosus forms in the liver and connects the left umbilical
vein with the inferior vena cav The ductus serves as a bypass through
the liver, enabling blood to bypass the liver and go from the placenta
to the heart

The second left-to-right shunt of blood occurs when the anterior cardinal veins
become connected by an oblique anastomosis which shunts blood from the left to
right anterior cardinal vein. The anastomosis becomes the left brachiocephalic vein
a.

The right anterior cardinal and right common cardinal veins become
thesuperior vena cava

b.

The right posterior cardinal vein forms the root of the azygos vein

c.

The posterior cardinal vein contributes to the formation of the left superior
intercostal vein

B.

d.

The left anterior cardinal vein vanishes

e.

The left common cardinal vein is greatly reduced at week 10 to form

theoblique vein of the left atrium

DUE TO THE SHUNTS AND OBLITERATION of the left umbilical vein at the 5 mm stage and
the left vitelline vein at the 7 mm stage, the left horn of the sinus decreases greatly in size
and loses its importance. The right horn enlarges to receive all the blood from the head and
neck via the superior vena cava and from the lower body region and the placenta via the
inferior vena cava. When the left common cardinal vein is finally obliterated at week 10, the
distal part of the left sinus horn remains as the oblique vein of Marshall, while the proximal
part of the horn and transverse part of the sinus become the coronary sinus
1.

Due to obliteration of the veins on the left side, the right sinus horn and veins
greatly enlarg Subsequently, the right horn, the only connection between the
original sinus venosus and atrium, is slowly incorporated into the right atrium

I.

Interventricular septation
A.

B.

A MUSCULAR CREST (ridge or fold) appears on the anterior ventricular wall near its floor
and almost in a median plane near the apex, at the same time that the interatrial septum is
forming, at about week 5. This is the interventricular septum primordium
1.

The interventricular septum is incomplete and has an upper free concave edge

2.

Most of its increase in length, at first, is the result of dilatation of the ventricles on
each side of the septum, which produces an external interventricular groove

3.

With active growth, the septum forms the muscular portion of the interventricular
septum

4.

A crescenteric interventricular foramen is seen between the free edge of the septum
and the fused endocardial cushions, allowing for communication between the right
and left ventricles, until about the end of week 7

SEPTUM FORMATION in the truncus arteriosus and bulbus cordis

1.

During week 5, aortic arch VI appears and contributes to the formation of the
pulmonary arteries. Just cephalic to arch VI, the subendocardial tissue in the bulbus
cordis thickens into 2 opposing ridges called the truncoconal or bulbar ridges.
Semilunar ridges also form in the truncus arteriosus and are continuous with those
in the bulbus cordis

2.

The bulbar ridges soon fuse with those of the truncus arteriosus
a.

3.

4.

As a result of the spiral orientation of the septum, the aorta and pulmonary artery
twist around each other
a.

Blood from the aorta now passes into the third and fourth parts of the aortic
arches

b.

Blood from the pulmonary trunk flows into the sixth pair of aortic arches

The bulbus cordis is gradually incorporated into the walls of the ventricles
a.

C.

The fusion takes a spiral orientation, possibly due to the streaming of blood
from the ventricles, and forms the aorticopulmonary septum, which
definitively separates the aorta and the pulmonary artery

In the adult right ventricle, the bulbus cordis is seen as the conus arteriosus
or infundibulum; and in the left ventricle, it is seen as the aortic vestibule

CLOSURE OF THE INTERVENTRICULAR FORAMEN and completion of the interventricular

septum
1.

Ventricular septation is completed by closure of the interventricular communication

(foramen) around the end of week 7, as the bulbar ridges fus Closure from fusion of
subendocardial tissue is from 3 sources
a.

A proliferation of the right bulbar ridge near the tricuspid orifice

2.

b.

A proliferation of the left bulbar ridge near the mitral orifice

c.

A proliferation of the posterior (atrioventricular) endocardial cushion

Fusion of the two ridges and the endocardial cushion outgrowth forms
themembranous portion of the interventricular septum and is completed toward the
end of month
a.

This tissue fuses with the aorticopulmonary septum and muscular portion of
the interventricular septum, thus, the pulmonary trunk communicates with
the right ventricle and the aorta with the left ventricle

The Right and Left Atrial Walls and The Venous Valves
I.

The right atrial walls

A.

THE SINUS VENARUM (smooth part of the wall of the right atrium into which the great veins
open) is derived from the sinus venosus
1.

B.

The rest of the atrium and its muscular extension, the auricle, have a rough
trabeculated surface and are derived from the primitive right atrium

THE SINUS VENARUM AND THE PRIMITIVE ATRIUM are demarcated internally by a vertical
ridge, the crista terminalis, and externally, by an inconspicuous groove, the sulcus
terminalis
1.

Thus, the crista represents the cranial part of the right sinoatrial valve
a.

2.

II.

The left sinoatrial valve fuses with the septum secundum and is incorporated into
the interatrial septum

The left atrial walls

A.

III.

The lower portion of the right sinoatrial valve forms the valves of the inferior
vena cava and coronary sinus

MOST OF THE LEFT ATRIUM is smooth and is derived from the primitive pulmonary vein,
which develops as an evagination from the dorsal wall of the atrium in the sinoatrial region
1.

Initially, the single common pulmonary vein opens into the primitive left atrium, but
as the latter expands, parts of the vein are gradually absorbed into the wall of the
left atrium

2.

Progressively, the proximal parts of the branches of the pulmonary vein are also
absorbed, thus, the 4 pulmonary veins all open independently into the left atrium

3.

Only the left auricle (derived from the primitive atrium) has a rough, trabeculated
appearance

The venous valves

A.

THE ENTRANCE OFTHE SINOATRIAL OPENING is flanked on each side by a valvular fold,
the right and left venous valves
1.

On the right, this fold is formed by a sinoatrial fold

2.

On the left, there is a smaller fold, called the left venous valve

B.

DORSOCRANIALLY, THE VALVES FUSE to form a ridge called the septum spurium

C.

INITIALLY, THE VALVES ARE LARGE, but when the right horn is incorporated into the atrial
wall, the left sinus venosus valve and septum spurium fuse with the developing atrial
septum

1.

The superior portion of the right venous valve disappears completely, while its
inferior part fuses with the septum that develops between the orifice of the right
vitelline vein (inferior vena cava) and the orifice of the coronary sinus. The
remainder of the valve is divided into 2 parts: valve of the inferior vena cava and
valve of the coronary sinus