Embryology of the Heart

Early Cardiac Development

angiogenic cell clusters (blood islands) are collections of angioblasts (mesodermal, mesenchymal) from

(1) splanchnopleure of yolk sac
(2) body stalk (allantois)
(3) somatopleure of chorion in the late presomite embryo

laterally located blood islands move cephalic and fuse forming a large meshwork of vessels

cardiogenic area—anterior central portion of cephalic plexus—adjacent coelom becomes pericardial cavity

angiogenic cells form heart tube

horns of the horseshoe develop into the inflow tract of the heart (sinus venosus)
central cresentic part forms the outflow tract and ventricular regions

other bilateral blood islands develop lumena forming longitudinal dorsal aortae (arches connect to heart)

Folding (day 23-28)

embryonic folding:

cranio-caudal causes anterior cardiogenic area to move ventrally
lateral-medial causes fusion of the cranial portions of horns of the cardiogenic area

dorsal mesocardium attaches heart tube to the dorsal side of pericardial cavity

disappears to form transverse pericardial sinus (passageway anterior to cardiac sac)
after dorsal mesocardium disappears, the heart is suspended by vessels at the cranial and caudal poles

folding of heart itself (day 23-28, due to rapid elongation of one side of tube):

cephalic (outflow) bends ventral, caudal, and to the right; caudal (inflow) bends dorsocranial and left
atria—initially paired structure located outside the pericardial cavity—which fuses to a single, common atrium and is incorporated into the pericardial cavity, subsequently divided by a septum

atrioventricular junction—forms atrioventricular canal connecting common atrium and primitive ventricle

bulbus cordis:

proximal one-third forms the trabeculated portion of the right ventricle

conus cordis—portion of bulbus cordis forming a common outflow tract for both ventricles

truncus arteriosis—distal portion of the bulbus cordis forming the proximal aorta and pulmonary artery

bulboventricular sulcus (primary interventricular foramen (PIF))—separates bulbus cordis and ventricle

trabeculated tissue forms proximal and distal to PIF forming the right and left ventricles.

Development of the Sinus Venosus (middle of the 5^th week, about day 30)

sinus venosus receives venous blood from right and left sinus horns, which receive blood from 3 systems:

(1) vitelline (omphalomesenteric) vein - returns blood from the yolk sac to sinus venosus

forms the portal and superior mesenteric veins (portal system drains GI blood, to liver

(2) umbilical vein - brings oxygenated blood from the chorion to the sinus venosus

in adults these become fibrous, forming ligamentum teres and ligamentum venosum

(3) common cardinal vein - returns blood from fetal body to sinus venosus

sinus-atrium entrance shifts to the right because of right-to-left shunt of blood (4-5 weeks)

left sinus horn is reduced and remnants include the oblique vein of left atrium and coronary sinus

right sinus horn enlarges forming sinus-right atrium connection and smooth part of right atrium

forms sinuatrial orifice, between right and left venous valves; inferior portion of right valve becomes valves of inferior vena cava and of the coronary sinus

Septa (wall) Formation in the Heart (day 27-37)

3 methods: actively growing or fusion of actively growing ridges, or growth of margins of adjacent cavities

complete closure occurs by secondary fusion with neighboring proliferating tissues

four septal locations in the heart:

(1) interatrial (end week 4): septum primum moves caudally to separate the atria

forms ostium primum (opening between limbs), later closed by endocardial cushions at AV margin
cell death forms ostium secundum then septum secundum grows cranially from endocardial cushion

foramen ovale (oval opening) forms between septum primum and secundum (fossa ovalis in adult)

(2) atrioventricular canal(week 4) atria into left then into both ventricles

superior/inferior atrioventricular endocardial cushions fuse to form canal and AV valves
(lateral cushions form interatrial and interventricular septa, above and below)

(3) within truncus arteriosus and conus cordis (week 5)

opposing ridges expand into truncus and meet in lumen, other swellings from conus fuse with them
form spiral aorticopulmonary (AP) septum or conotruncal septum dividing pulm. trunk and aorta

if asymmetric – aortic or pulmonary stenosis or atresia
if no spiral – vessel transposition; incomplete – persistant truncus

(4) between ventricles (week 4) incomplete muscular wall remaining as right and left ventricles expand

closed by membranous outgrowth that fuses with conotruncal septum
ventricular valves formed at the bases of the aorta and pulmonary trunks from swellings in truncus

Aortic Arches

The brachial arches each contain an artery, collection of six pairs known as the aortic arch system

The 3rd, 4th, and 6th aortic arches are the most important developmentally, asymmetric fate

aortic arch derivatives

First mostly disappear; contribute to maxillary arteries; may contribute to external carotid arteries
Second part of stapedial arteries in ear
Third proximal portion: common carotid arteries; distal portion: internal carotid arteries
Fourth left: forms part of arch of aorta, right: proximal part of right subclavian artery
Fifth ~50% never develop; ~50% disappear without adult derivative
Sixth* left: proximal develops into proximal left pulmonary a; distal - ductus arteriosus

right: proximal develops into proximal right pulmonary a; distal degenerates
*Sixth arch is also known as Pulmonary Arch. It gives off a branch that develops towards and communicates with the developing lung bud forming the Pulmonary arteries

Adult Structure	Embryonic precursor
Roots of Pulmonary trunk and Ascending aorta	Truncus arteriosus
Proximal arch of Aorta	Aortic sac
Middle arch of Aorta	Left 4th aortic arch
Distal arch of Aorta and Descending aorta	Dorsal aorta
Apex of Pulmonary trunk and Ductus arteriosus	Left 6th aortic arch
Right Brachiocephalic artery	Aortic sac
Proximal portion of right Subclavian artery	Right 4th aortic arch
Intermediate portion of right Subclavian artery	Dorsal aorta
Distal portion of right Subclavian artery	Right 7th Intersegmental artery
Right Common Carotid artery and Proximal External Carotid artery	Right 3rd aortic arch
Left Common Carotid artery	Left 3rd aortic arch
Left Subclavian artery	Left 7th Intersegmental artery
Maxillary arteries and (??)some External Carotid arteries	1st aortic arch pair
Coronary Sinus and Oblique vein of left Atrium	Left horn of Sinus venosus
Superior Vena Cava	Right horn of Sinus venosus
Inferior Vena Cava	Right Vitelline vein
Pulmonary veins	Outgrowths from left Atrium

Fetal and Neonatal Circulation

gaseous exchange occurs in placenta, oxygenated blood to the fetus in umbilical vein

through ductus venosus through the liver, then joins the inferior vena cava, to right atrium

foramen ovale into left atrium, or recirculates with deoxygenated blood from head, through pulm. trunk

follows pulmonary arteries or ductus arteriosus into the aortic arch

in the left atrium, the oxygenated blood mixes with unsaturated blood returning from the lungs, through left ventricle, ascending aorta (coronary arteries), then lower limb and pelvic structures

some is then returned to the mother via the umbilical arteries (branches of the common iliac arteries)

Transition to Postnatal Circulation

gaseous exchange in lungs, sphincter of the ductus venosus closes preventing blood flow

umbilical vein and the ductus venosus no longer conduct blood, become fibrous, and form ligaments

umbilical vein becomes ligamentum teres (round ligament of the liver) which becomes free edge of the falciform ligament

ductus venosus becomes ligamentum venosum

The umbilical arteries become fibrous, and form ligaments known as the medial umbilical ligaments

pressure closes the foramen ovale

Local factors (O₂ concentration in the aorta caused by the release of bradykinin) causes constriction of the ductus arteriosus (2-3 months) – becomes fibrotic, forms the ligamentum arteriosum connecting the pulmonary trunk and the inferior margin of the aortic arch