Human Cardiogenesis
Introduction
Placental vascularisation and embryo development occur in unison. In the human embryo, blood from the neo-placenta enters the embryonic heart tube via developing vitelline veins from three weeks (stage HH8 in chicken embryo surrogate model).
Blood flow is laminar and the bilateral vitelline inflows retain separate streams through the heart tube and into the paired pharyngeal arches. The circulating blood is of very low oxygenation and the growing embryo initially sources its energy from glycolysis.
In the blood-electric cardiogenesis model, from approximately four weeks gestation (HH14-16), when the heart tube and its caudal venous inflow and cephalad truncal outflow is established and blood is seen moving unidirectionally forward, the co-developing vitelline plexus begins to indraw maternal oxygen and a nascent oxygenated stream of vitelline blood enters the heart tube streaming alongside along the dorsal aspect of the deoxygenated blood from the embryo corpus.
It is hypothesised that at this microfluidic scale (less than 1mm diameter heart tube), the differential electromagnetic forces generated by placental oxy- and embryo de-oxygenated blood streaming side-by-side through the single lumen heart tube has a direct effect on cardiogenesis.
The paramagnetic properties of deoxygenated haem are exploited in plethysmography, magnetophoresis and MRI but the notion of biomagnetic fluid dynamics has until recently been overlooked in nanoscale circulatory physiology [Tzirtzilakisa, 2005].
It is assumed that, despite water (H2O) taking the position of oxygen (O2) in the heme cavity, there exists a 2 electron difference between oxygenated and deoxygenated blood, given the strongly paramagnetic nature, or high spin state of deoxygenated blood. Because the Reynolds and Womersley numbers are low (<1) in sub-millimeter lumens, blood inertia forces (pressure, gravity) are not significant until the four-chambered heart has taken shape.
On account of its opposite polarity and that both streams, carrying some burden of unpaired electrons and subjected to an external magnetic field, create perpendicular forces and are mutually repellent, the red thread takes up an axially rotated attitude along the dorsal aspect of its blue host.
Posterior (dorsal) view of the developing heart tube. The endothelium is drawn in black. The venous pole (left and right common cardinal veins) is caudal and the arterial pole (bulbo-truncal outlet) cephalad. Atrioventricular and truncal orifices are shown as black rings, with the primitive ventricle between. The dashed line indicates the mid-ventricular region and the fold-line that occurs in heart tube C-looping.
With C-looping, the middle of the heart tube bends forward, or ventrally (into the page). This brings the A-V and truncal orifices into apposition dorsally. The (ventricular) loop of the red thread is cantilevered leftward and its outward stream rightward, the atrio-ventricular and truncal orifices acting as fulcrums.
In both mammals and birds, the next stage of cardiogenesis is described as S-looping. In this stage, changes in the growth and patterning of the vitelline veins of the chorioallantoic membrane/yolk sac are associated with alterations in the intracardiac route of blood. This is seen as a consistent phenomenon in the chicken embryo model from HH16 onwards. Caudal vitelline blood is seen to course through the left side of the atrioventricular canal (the future mitral ostium) and the canal shifts from a circular shape to oval. Similarly, the paired pharyngeal arches are seen to lose their bisymmetry, with changes in the diameters of arch vessels.
Atrial and ventricular septae develop through day 46 (HH34). Atrioventricular and conotruncal septae fill in along the spiraled line of separation. The head and upper body preferentially gets oxygenated blood. Deoxygenated blood is preferentially directed into the lower arch branches to drive pulmonary trunk development and via the ductus arterious to supply the lower body. The distal embryo is relatively hypoxic.
With further strengthening of the oxygenated stream, the repellant loop-in-loop scissors apart at the truncal fulcrum to achieve a perpendicular parity. Remarkably, in the human adult heart, the aortic and pulmonary valves are offset 90 degrees of each other.
At birth and with closure of the ductus arteriousus, transition to a double-looped circulation is complete with the lungs now in series as an interposed pathway in the primary loop.
The blood-based mechanism allows correlation with many other extant findings in the adult human heart. Right-hand spiralled blood flow is seen through the mitral annulus and ascending aorta whereas flow through the pulmonary trunk is laminar. The right ventricular outflow is at a reverse forty-five degree angle, as is the left, etc.
After approximately eight weeks (HH35), and with completion of common outflow tract septation into aortic and pulmonary trunks, the fetal four-chambered heart emerges.