DEVELOPMENT OF THE Angiogenic clusters • Cells that give rise to the cardiovascular system first appear in week 3.

• Mesenchymal cells from the splanchnic mesoderm, divide and form cell clusters called the angiogenic clusters.

• These clusters initially located on the lateral sides of the embryo but later migrate to the cephalic direction also forming the cardiogenic plate Location of the cardiogenic area • The cardiogenic area is initially located anterior to the prochordal plate (future buccopharyngeal membrane) and the neural plate. • When the neural tube closes and brain vesicles form, the CNS grows very rapidly cephalically and extends over the central cardiogenic area and the future pericardial cavity. • With forward pulling and rotation at about 180°C along the transverse axis, the cardiogenic plate and pericardial cavity become located ventrally and caudally to the buccopharyngeal membrane.

Formation of the endocardial tubes • The angiogenic cell clusters coalesce to form the right and left endocardial tubes laterally and the paired aortae dorsally.

• Each tube is continuous cranially with a dorsal (outflow tract) and caudally with a vitelloumbilical vein (inflow tract).

• Due to folding of the embryo, the endocardial tubes come closer and fuse cephalocaudally to form primitive heart tube

Primitive heart tube • The newly formed heart tube bulges into the pericardial cavity attached to the dorsal wall by a fold of tissue, the dorsal mesoderm (mesocardium). • This tissue will rupture leaving the heart tube suspended in the pericardial cavity anchored cephalically by the dorsal aortae and caudally by the vitelloumbilical veins.

• The ventral mesocardium is never formed.

Primitive heart tube • Becomes invested in a layer of myocardium (from mesoderm surrounding the heart tube). • A layer of acellular matrix, the cardiac jelly, separates the myocardium and the endothelial heart tube. • The cells from the endothelium invade the cardiac jelly to form the .

• From the inflow to the outflow, it consists of , , the , the , and .

Regions of the primitive heart tube

• Outflow • Bulbus cordis which may be divided as follows: • bulbus cordis - forms the trabeculated part of right ventricle • conus cordis (mid portion) • truncus arteriosus • Interventricular sulcus divides the primitive ventricle and the bulbus cordis • Primitive ventricle expands to become the left ventricle • Atrioventricular sulcus divides the atria and the primitive ventricle. • paired Primitive atria. These structures will later fuse together to form common atrium • Sinus venosus - consists of right and left horns Inflow Bending of the primitive heart tube (PHT) • Part of the PHT is outside and part inside the pericardial cavity

• The heart tube bends in such a way that the cephalic portion bends in ventral and caudal directions and to the right. • The caudal atrial portion moves in the dorsocranial direction and to the left. • This forms the cardiac loop. • The primitive ventricles expand. • The paired atria fuse and expand and become located in the pericardial cavity. • The atrioventricular junction remains narrow forming the atrioventricular canal.

Bulbous cordis • The bulbous cordis is divided into 1. the proximal third which forms part of the right ventricle. 2. the mid portion (conus cordis) forms the outflow tracts of both ventricles. 3. the distal part (truncus arteriosus) forms the roots and proximal portion of the aorta and . Trabeculated ventricles • The smooth-walled heart tube forms primitive trabeculae in two areas on either side of the primary interventricular foramen. • This forms the left primitive and trabeculated ventricle and the right primitive and trabeculated ventricle (previously bulbous cordis). • The loop formation continues until the atria bulge on either side of the bulbous cordis.

Fate of the sinus venosus • The left sinus horn of the sinus venosus degenerates due to obliteration of its blood vessels • The right sinus horn enlarges and is incorporated into the right atrium to form the smooth-walled part of the right atrium and the two communicate via the sinuatrial orifice. Formation of cardiac septae

• The septae formed are; 1. Septum in the common atrium. 2. Septum in the atrioventricular canal 3. Septum dividing the ventricles

Septum in the common atrium • grows from dorsal wall roughly mid-point downwards towards the in the atrioventricular canal • Space is left between the septum primum and cushions called ostium primum. • Tissue from the endocardial cushions grows dorsally and close ostium primum • At the first part to grow, septum primum gets perforated to form ostium secundum –blow shunt

Septum in the common atrium • As the right sinus horn fuses with the right atrium, it introduces a fold to divide the common atrium • This is called • The septum secundum does not completely seal, leaving an opening called the oval foramen where the blood from the right atrium flows to the left atrium. • The remaining part of septum primum acts as a valve of the oval foramen. The valve of the oval foramen closes after birth by the increase of pressure in the left atrium.

Septum in the atrioventricular canal • Two endocardial cushions of mesenchymal origin appear at the superior and inferior borders of the atrioventricular canal. • In addition, the lateral atrioventricular cushions (right and left) appear. • The superior and inferior cushions grow and project into the lumen and fuse dividing the canal into right and left atrioventricular orifices. Septum in the atrioventricular canal • The atrioventricular valves are formed when the tissue of the orifices is hollowed out and thinned by the blood flow. • The valves remain attached to the thickened trabeculae on the wall of the ventricles (papillary muscles) by the chordae tendineae. • Two cusps are formed in the left atrioventricular orifice and three cusps in the right.

Septum dividing the ventricles

• The two primitive ventricles grow. • The medial walls of the enlarging ventricles fuse and grow to form the muscular interventricular septum. • A space remains between the muscular interventricular septum and the fused endocardial cushions and allows communication between the two ventricles. • This opening is later closed by the membranous interventricular septum formed by the endocardial cushions of the atrioventicular canal.

Fate of truncus arteriosus • Two truncus swellings/cushions (the right superior and the left inferior swellings) grow and fuse forming the dividing the truncus arteriosus into an aortic and pulmonary channels.

• As they grow, the swellings twist around each other. The twisting makes the aorta to connect to the left ventricle and the pulmonary artery to the right ventricle Division of the conus cordis • Two swellings also appear in the right dorsal and left ventral walls of conus

cordis. • The conus swellings grow and fuse to form a septum dividing the conus into the anterolateral portion (outflow tract for the right ventricle) and the posteromedial portion (outflow tract for the left ventricle).

Formation of the semilunar valves • After the partitioning of the truncus, tubercles on the main truncus swellings appear. One pair of tubercles for the pulmonary channel and one pair for aortic channel. A third tubercle appears in both channels. The tubercles get hollowed out at their upper surfaces to form the semilunar valves.

Atrial septal defects (ASD)

1. Failure of ostium secundum to close. This may cause significant shunting of blood from the left to right after birth. 2. Complete absence of atrial septum (called common atrium or cor triloculare biventriculare) 3. Failure of oval foramen to close. 4. Prenatal/premature closure (in the uterus) of the . This leads to severe hypertrophy of the right atrium and ventricle and underdevelopment of the left atrium and ventricle. This usually leads to death soon after birth.

Atrioventricular canal defects

1. Persistent atrioventricular canal due to failure of the endocardial cushions to develop and fuse. 2. Patent ostium primum. Failure of the atrioventricular canal cushions to grow and close the ostium primum. 3. Closure of the right atrioventricular orifice due to absence or fusion of tricuspid valves. This defect is associated with patent oval foramen, ventricular septal defect, underdevelopment of the right ventricle and hypertrophy of the left ventricle.

Interventricular septal defect

• The membranous part fails to develop due to failure of the atrioventricular cushions to grow downwards. This is the most common heart defect

• More blood carried by the pulmonary artery than normal Abnormality of the truncus and conus • Teratology of Fallot. Pulmonary infundibular stenosis and narrow right ventricular outflow due to unequal division of the conus. This is accompanied by a large interventricular septal defect. The aorta is directly above the septal defect from both ventricle cavities. Blood moves from left to right after birth causing hypertrophy of the right ventricle. Teratology of fallot is the most important defect causing cyanosis. Abnormality of the truncus and conus

• Persistent truncus arteriosus. The aorta and pulmonary artery share one origin. Associated with the interventricular septal defect

• Transposition of great vessels. The truncoconal septum fails to spiral. The aorta originates from the right ventricle and the pulmonary artery from the left ventricle Abnormalities of semilunar valves

1. Valvular stenosis of the pulmonary artery. This a narrowed origin of the pulmonary artery. It can even be atretic. 2. Aortic valvular stenosis due to fusion of the thickened valves, leaving a very small opening. 3. If fusion is complete, the result is aortic valvular atresia. The left side of the heart and the aorta are underdeveloped. Associated with patent

Abnormalities of heart position

1. Ectopia cordis. The heart is located outside the thoracic cavity due to failure of the embryo to close in the midline (sternal defect).

2. Dextrocardia. The most common anomaly of position. Due to the formation of the cardiac loop to the left hence the heart is located to the right of the thoracic cavity • Oxygenated blood from delivered to the fetus through . • Much of this blood by-passes the liver through the which joins the inferior vena cava

• Small amount of this blood enters the liver and mixes with blood from portal circulation

• Oxygenated blood from placenta and deoxygenated blood from the fetal lower limbs mix in the inferior vena cava Fetal circulation

• Mixed blood enters the right atrium

• Much of the blood passes through the oval foramen to the left atrium, guided by the valve of inferior vena cava.

• Some blood remains in the right atrium and mixes with deoxygenated blood returning from the head, neck and arms via the superior vena cava

• In the left atrium, blood mixes with small amount of deoxygenated blood from the lungs

Fetal circulation • Blood in the left atrium enters the left ventricle and into the aorta.

• Some of the well oxygenated blood in aorta branch to the heart wall via coronary artery and to the brain via the carotid arteries.

• The deoxygenated blood that remains in the right atrium, enters the right ventricle and into the pulmonary artery. Much of this blood is shunted by ductus arteriosus into the descending aorta, by- passing the lungs. • Blood from ductus arteriosus and ascending aorta mix in the descending aorta Fetal circulation • Blood from the descending aorta runs to other parts.

• Some of the blood in the descending aorta with less oxygen is returned to the placenta via the umbilical arteries that branch off from the iliac arteries • The blood is again oxygenated in the placenta and the cycle repeats. Cardiovascular changes that occur at/afterbirth 1. Closure of umbilical arteries by contraction of smooth muscle to form medial umbilical ligaments. 2. Closure of umbilical vein and ductus venosus. The umbilical veins forms ligamentum teres hepatis in the lower margin of the falciform ligament. The ductus venosus form the ligamentum venosus that joins ligamentum teres to the inferior vena cava Cardiovascular changes that occur at/afterbirth 3. Closure of ductus arteriosus by contraction of muscular wall immediately after birth. In the adult, the obliterated ductus arteriosus forms the ligamentum arteriosum 4. Closure of the oval foramen by the septum primum that is pressed against septum secundum by the high pressure on the left atrium. First deep breath contributes to high pressure. Crying of the infant reduces pressure on the left and transiently opens the oval foramen hence right-left shunt and transient cyanosis. Complete sealing happens about 1 year later