Cardiovascular Development: Development of the Heart Development of the Vasculature Pamela Knapp, Ph.D. Professor, Dept. Anatomy & Neurobiology MSB1 - Rm. 411 6-7570 peknapp@vcu.edu

Extraembryonic blood vessels form during the early 3rd week Yolk Sac Yolk sac blood islands D.

Longitudinal (head) folding moves the developing heart region in a ventral direction

Transverse folding brings the right and left endocardial heart tubes into apposition, allowing them to fuse ~ beginning 4th week

Schematic showing relationship of parts of primitive heart tube, aortic arches and aortae in a mid-4th week embryo Note the 3 pairs of veins (vitelline, umbilical and cardinal) which empty intothe inflow end of the heart (sinus venosus). The aortic arches and dorsal aortae are paired structures. BLOOD FLOW THROUGH THE PRIMITIVE HEART Blood enters the caudal end of the tube, the sinus venosus. From the sinus venosus, blood flows cranially into the primitive atrium. From the atrium, blood enters the primitive ventricle. From the ventricle, blood is pumped to the bulbus cordis and then to the truncus arteriosus. The truncus is continuous cranially with the expanded aortic sac, from which arise the aortic arches. Blood flows from the aortic arches into the dorsal aortae.

Developing heart undergoes characteristic folding, because it is fixed in position at both ends while it elongates/grows RIGHT LEFT B-v sulcus RIGHT LEFT (Posterior /dorsal view) LEFT RIGHT RIGHT LEFT (Posterior /dorsal view) RIGHT LEFT Conus Cordis (dorsal view) (Posterior /dorsal view) LEFT RIGHT Primitive atrium forms portions of both adult atria -adult rt atrium also contains the rt horn of the sinus venosus -adult left atrium also contains exstrophied portions of the primitive pulmonary veins.

Exstrophy of the primitive pulmonary vein -Left auricle is rough/trabeculated -Rest of wall of the left atrium is smoother

What is happening to the heart cavities internally? Heart is still a tube! -Note opening between ventricles (interventricular foramen) -Note opening between ventricle and atrium (atrio-ventricular foramen) -Can’t see the foramen between the atria in these views … but it is there.

Partitioning the Primitive Heart: 4 walls separate atria from ventricles Separate right and left atria Separate right and left ventricles Pulmonary trunk from ascending aorta (1) Formation of the atrio-ventricular canals A V A V

(2) Formation of the atrial septum -2 phases: partial septum formed before birth is completed at/after birth B. A. Muscular interventricular septum The septum primum and secundum together make the inter-atrial septum. Prior to birth the pathway/opening between them is the foramen ovale. It allows blood flow between the atria before birth (mostly right-to-left) After birth, higher left side pressure closes the foramen by pushing the septum primum against the septum secundum.

Atrial Septal Defects Congenital anomalies of the heart and great vessels are overall relatively common (6-8 per thousand live births). -multiple causes - teratogens, environmental, genetic -isolated vs. grouped (ex. Tetralogy of Fallot) -may be well tolerated during fetal life 1. Patent foramen ovale - most common ASD -probe patent (25% of population) vs. fully patent -may be clinically insignificant -right to left shunt possible with other complications 2. Secundum ASDs - abnormally short septum secundum, or one with fenestrations. -left to right shunt under normal pressure conditions 3. Cor trioculare biventriculare - failure of interatrial septum formation. 3 heart chambers - 2 ventricles, 1 big atrium. 4. Premature closure of foramen ovale - usually results in heart muscle hypertrophy.

(3) Formation of the ventricular septum -2 parts: muscular & membranous Muscle cells in wall of bulbus cordis (rt v) and primitive ventricle (left v) proliferate and muscular septum increases in height. Approaches, but does not fuse with, endocardial cushions. Ridges of tissue growing out of the wall of the conus cordis (bulbar or conotruncal ridges) are referred to as the “membranous” component of the interventricular septum. They meet and fuse with the muscular septum AND with the endocardial cushions to complete the IVS.

Open communication between the 2 ventricules until the end of the 7th week through the interventricular foramen. Formen is closed by development of the membranous portion of the septum. Tissue of membranous septum: right and left conotruncal/bulbotruncal ridges & endocardial cushions Tissue of the muscular septum: floor of the ventricle/muscular interventricular septum

Ventricular Septal Defects -25% of all heart malformations are VSDs -can be membranous (common) or muscular (rare) in origin -With normal vascular pressure, always involve a left-to-right shunt of blood. -Large left-to-right shunts cause pulmonary hypertension. -Uncorrected VSDs can lead to death from congenstive heart failure. -Small defects can close spontaneously.

and truncus arteriosus) (4) Formation of the aortico-pulmonary septum (partitioning bulbus cordis and truncus arteriosus) Without partitoning, there would be only 1 outflow path from the 2 ventricle. Development of the aorticopulmonary septum creates 2 outflow paths, the aorta and the pulmonary trunk, one from each ventricle. Development is timed to coincide with the closure of the interventricular septum. Thus, and fortunately, at the time that there are 2 completely separate ventricles, there are also 2 completely separate outflow pathways! The aorticopulmonary septum forms a spiral, due to the position of the initial outgrowth of the swellings at successive levels. Instead of simply growing towards out towards each other from the same position all the way up to the aortic sac, the outgrowth region of the ridges spirals along opposite sides of the truncus.

- When the free edges of each ridge unite in the center of the truncus lumen, they form a spiraling wall, the septum. - A split develops in the medial plane of the septum, resulting in complete separation of the ascending aorta and pulmonary trunk with the pulmonary trunk twisting around the ascending aorta.

Anomalies of the great vessels Persistant truncus arteriosus -Failure of TA to divide along part/entire length. -Due to failure of conotruncal ridges to develop properly. -Pulmonary arteries and aorta may arise from common artery, or from the TA. Sometimes they are absent and bronchial arteries are only blood supply to the lungs Transposition of the Great Arteries/Vessels (TGA) -Most common cause of cyanotic disease in newborn. -Aorticopulmonary septum growns straight instead of spiraling. -Aorta arises from right ventricle and pulmonary trunk arises from left ventricle…thus 2 circulations. -MAY involve VSD. -Not immediately fatal due to mixing of blood through foramen ovale and ductus arteriosus. Overriding aorta or pulmonary trunk -Unequal TA division results in one great artery being larger than the other. Misplaced aorticopulmonary septum misaligns with intraventricular septum, causing VSD. Larger artery sits over (overrides) VSD. d. Tetralogy of Fallot -Group of 4 cardiac defect occurring together, driven by misplaced aorticopulmonary septum (overriding aorta), which causes VSD, stenosis in the outflow region of the right ventricle (pulmonary stenosis), and pulmonary hypertension.