Annals of the Royal College of Sur(geons of England (I975) vol 57

Development

of the

right outflow tract and pulmonary arterial supply F D Skidmore

MD FRCS

British Heart Founldation Research Fellow1 and Hon. Senior Registrar in Cardiothlorat ic Suirgery, East Anglia Regionial Hos pital Board anzd United Camnbridge HospitaltsA

Summary The branchial arch vessels of the human embryo have been studied by histological and radiographic methods and the modelling that occurs (lurin the period Day 2 -Day 52 postfertilization is described. It has been shown that the myoendocardial reticulum is reamed out by blood flow and it is suggested that hydrodynamic force is the fundamental factor which determines chamber structure of the heart and flow pattern in the outflow tracts and great vessels. The sixth aortic arch vessels contribute tissue to the pulmonary trunk and proximal pulmonary arteries. The 'postbranchial pulmonary arteries' are morphologically distinct and form the pulmonary arteries at the lung hila. The primitile pulmonary plexus around the tips of the developing tracheobronchial primordia is formed from segmental vessels ar ising from the dorsal aorta. Bronchial arteries can be demonstrated only late in intrauterine life. The numerous bronichopulmonary precapillary anastomoses zwhich are found in the fetus at this time have

been dlemonstrated radiographically. Historical review The development of intracardiac operative

"Prcsent addlress: University Hospital of South Manchester, Manchester M20 8LR From ani Arris anid Gatle Lecture delivered at

techniques for the amelioration of congenital defects of the heart and great vessels has provided a stimulus for the re-examination of stages in human cardiac development. The embryologv of the human heart was first dlescribed before operative procedures on the heart were contemplated. Morphological features that received scant attention from the embryologists have been of great significance to the surgeon. Now that standardized techniques are available for the repair of atrial and ventricular defects the major challenge in aberrant cardiac morphology is provided by the complex disorders of the ventricular outflow tracts-that is, Fallot's tetralogy, pulmonary atresia, transposition of the great vessels, and truncus arteriosus. The pioneering work of Blalock in improving pulmonary oligaemia in Fallot's tetralogy has been folloved by other procedtures designed to provide better tissue oxygenation. There is now increasing emphasis on primary repair of defects in the first year of life. Subramanian' from New York has reviewed these advances in a recent Hunterian Lecture. The bronchial arteries The identification of the anatomical origin of these vessels is attributed to Galen in AD I62. In i878 Kiittner showed superficial connection between bronchial and pulmonary vessels and

Catmbridge

on IIth

Jllnc 1974

Development of the right outflow tract and pulmonary arterial supply Zuckerkandl in I 883 demonstrated deep intrapulmonary anastomoses between the pulmonary and systemic systems. In I 950 Marchand, Gilroy, and Wilson2 showed a precapillary anastomosis in neonates. Wagenvoort, Heath, and Edwards3 in I964 claimed that these anastomoses were rare by the age of 2 years.

Methods During the tenure of a British Heart Foundation Research Fellowship I studied the development of the ventricular outflow tracts and the formation of the pulmonary and bronchial vessels in the human fetus4. Sagittal and transverse sections of human embryos were examined serially. The specimens used were from the Boyd Collection in the Department of Anatomy at Cambridge and from the Carnegie Institute of Embryology in Baltimore. The age of embryos reviewed was in the range Day 25 Day 52 postfertilization with a crown-rump length of 3.2 6-2 I .33 mm (see table). The sections were 7 Vsm in thickness and stained with haematoxylin and eosin. Routine light microscopy was followed by photomicrography of selected slides. Absolute

and comparative measurements were made of the diameter of vessels and cardiac chambers. The number of circumferential lamellae of connective tissue cells around each vessel was noted at successive stages of development. The angles at vessel bifurcations were also recorded. In order to demonstrate the relationship of the bronchial and pulmonary circuits in the fetus and their anastomoses fresh human fetuses ranging from 40 mm to I 45 mm crown-rump length were also studied.

A median sternoPulmonary arteries tomy was performed on the fetus and the ductus arteriosus and the pulmonary trunk were ligated. The pulmonary artery was then injected with contrast medium using a 30gauge St Thomas's pattern lymphangiography needle.

Bronchial arteries The fetus was placed in the right lateral position and a standard left thoracotomy incision made. The posterior end of ribs 2-5 were divided and the airless lung retracted downwards. The ductus arteriosus and aortic arch proximal to the point of entry of the ductus were ligated. A separate Relation of age and size of embryo to stage left loin incision was used to gain access to of development (figures from the author's the abdominal aorta, and a fine cannula was statistical analysis of Carnegie Institute advanced into the descending thoracic aorta and ligated in place. Contrast medium was material) then injected retrograde into the aorta, filling Stage Days post- the intercostal arteries and their branches. Crown-rump length fertilization (mm) (mean) Radiographic and histological technique Postmortem microangiography II 3.26 25.3 12 was carried out with fine-grain X-ray film 3.79 27.9 30.2 4.73 13 and soft X rays. Micropaque was chosen as 6.49 14 34.0 the contrast medium and this was mixed 50/ 7.81 35.4 15 volume with double-strength recon50 by i6 9.48 39.0 stituted human plasma. After injection the 124I 17 42.5 i8 14.91 45.5 specimens were fixed in acid formol. DeI8.27 19 49.0 naturation of the plasma protein resulted 20 21.33 51.75 in Micropaque being fixed in the blood ves-

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sels, and the specimens were radiographed and serially sectioned. Certain specimens were treated in the following way. After routine histological fixation they were taken up into celloidin and alternate thick and thin sections at 375 ,um and 30 -Lm were cut. The thick slices were radiographed (Fig. I) and the thinner sections were photographed using dark-ground illumination. In this way it was possible to build up a picture of the constituent vessels in a block of tissues. The illustrations in this paper are taken from this material and the line drawings are my own interpretation of structural features in the early embryos.

Results Development of the ventricular outOn the 25th day after ferflow tracts tilization the human embryo has a crownrump length of about 3 mm (see table). The paired endocardial heart tubes have fused into a single canal, from the distal end of which the first branchial arch vessel emerges

and passes around the pharynx. Myoblasts in the 3-cell-thick ventricular wall start contracting at this time5. Between Day 25 and Day 35 all 6 pairs of branchial vessels appear, but Pairs I, 2, and 5 have only a transient existence. The position of the bulbus cordis and the sinoatrial portions of the tube are fixed on the ventral surface of the pharynx, and therefore increase in length causes the tubes to become curved (Fig. 2). The pericardial cavity is formed early in the development of the heart and exerts a restraining influence on the expanding cardiac tube. As a result of concertina folding within the pericardium the cardiac loop is asymmetrical and the common outflow tract passes dorsally and to the left. The right ventricular precursor is derived from bulboventricular tissue, whereas the left ventricle develops from the ventricular mass near to the atrioventricular constriction (Fig. 3). Partitioning of the blood which cmerges as a double spiral from the incompletely separated ventricles occurs between

FIG. I Radiograph of 375,um section of fetal lung with pulmonary arterial radicles outlined with Micropaque X 5. (See text for further descrip-

-

~~~~tion.)

Development of the right outflow tract and pulmonary arterial supply

Stage

II

Stage

12

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three principal vessels. These are the 3rd arch, destined to become the common carotid artery, the 4th arch, which becomes the aortic arch, and the 6th or pulmonary arch vessels. The major flow in this last vessel runs directly to the aorta in the ductus. Because of the asymmetrical nature of the cardiac loop previously mentioned the left-side vessels of each pair receive a greater flow than those of the right side (Fig. 4).

Predominance of left-sided sixth arch The bulbar ridges of cardiac vessels jelly become more prominent and develop in accord with the flow. The ridges also separate off the systemic 4th arch flow from that of the 6th arch vessels as they fuse in the midline of the truncus arteriosus. The paired 6th arch arteries arise close together from the Stage 13 posterior surface of the bulb, and by the 8-mm stage these vessels fuse proximally to form the pulmonary trunk, which is positioned in the left side of the developing mediastinum. /" Development of the sixth arch Figure 5 shows the arch vessels passing around the gut from the bulbus cordis at the 7-mm stage (Day 35 postfertilization). For the 6th arch are precursor blood islands in the mesothere Stage 14 derm surrounding the pharynx and these link up to form the early vessel. The proximal connection is to the posterior margin of the aortic sac. Distally a link with the dorsal aorta is soon formed. Study of sagittal sections of human embryos at 5 and 6 mm shows that there are two longitudinally-running angioblastic chains t Stage ventrolateral to the foregut (Fig. 6). These chains canalize and connect posteriorly with the pulmonary plexus described below. CranFIG. 2 Dotted line shows axis of outflow ially these vessels establish a direct connection with the 6th arch vessel where it passes tract from primitive ventricle running succesfrom the floor of the gut into the arch sively through branchial arch vessels as they mesoderm. I have designated this vessel the 'postbranchial pulmonary artery', which is develop in craniocaudal progression. lS

0go

F D Skidmore

FIG. 3 Stage-I3 embryo showing region of atrioventricular valve. Elongated valve cushions (AV) composed of cardiac jelly (C1) separate atrium (A) and ventricle (V). Bulbus cordis (BC) is seen sectioned above.

morphologically accurate and is identifiable mary connection. in the adult. This vessel is not derived from Bronchial arteries In fetuses examined arch vessels. there was no evidence of bronchial arteries Bronchial tree At the equivalent stage or bronchial circulation up to the I45-mm in development of the pharynx the tracheo- (20 weeks development) stage. It was not unbronchial primordium has become a ventral til the experimental techniques outlined above pouch of the primitive pharyngeal floor in were applied to fresh stillborn infants in the the same transverse plane of section as the 32-38-week age group that a bronchial cir6th arch vessels. The primitive trachea passes culation could be shown. Dissection of fetuses ventrally under the pharynx as an endo- in this age group reveals bronchial arteries dermal tubular process. It forms a Y-shaped arising as the first branch of proximal interfork into the two main bronchial precursors. costal arteries. The pattern is variable, but In the angle between the bronchi primitive usually such arteries arise from the first 3 blood islands develop which are the earliest pairs of intercostals. Subsequent radiographic analysis revealed a transbronchial flow intrapulmonary capillaries. sufficient to produce a pulmonary angiogram Pulmonary plexus Small capillaries (Fig. 7). It is emphasized that the ductus pass from the paired dorsal aortae to the arteriosus was ligated in these specimens to mesenchymatous tissue in the inferior tracheo- preclude any retrograde flow of contrast to bronchial angle. These vessels proliferate ven- the pulmonary circuit from the descending trally to form a primitive capillary network aorta. Thus in the human fetus there is late around the tip of the bronchial precursors. development of the entire bronchial circulaThis earliest bronchopulmonary plexus is tion and a precapillary bronchopulmonary splanchnic in nature and systemic in its pri- anastomosis.

Development of the right outflow tract and pulmonary arterial supply

I9I

,__--__^ ~tube lumen. There is co-ordinated myoblastic contraction which compresses the cardiac jelly of the endocardial cushions. The jelly is G : ADA.C initially acellular; however, cellular infiltration occurs from the endothelium. Thus durI ll ing the 2o-day period under review the jelly changes from an amorphous substance into a definitive tissue. Initially it is passively reamed

---

--

11DC1;, 41 DC in outthe the direction and volume of the flow by primitive cardiac loop. Displacement IV |s @ 3 of jelly will be proportional to the flow in-

IV

-/-SC duced by contraction of the right and left

Dlavian artery;DA=dorsalaortDA

PBPA Q ~~~~~~0

1

0

VI

VI L

=

0W

R

FIG. 4 Dominance of left-side vessels at Stage i6 of development. ADAf C = anterior dorsal aorta destined to form carotid artery; G gut; DC = ductus caroticus; SC = subclavian artery; DA = dorsal aorta; IV = 4th arch; VI = 6th arch.

Hydrodynamic factors in development of ventricular outflow It is essential to discuss the significance of i the myoendocardial recticulum or cardiac jelly interposed between th.e endothelial y lining cells of the cardiac chambers andthes r s; BA cardiac myoblasts. Half the cardiac wall thickness at the 5-mm stage is cardiac jelly (see Fig. 3). High-resolution light micro-

VI (D)

6

IV DC B A

0

wl, I

DA

c V (D) I

.

p

scopy shows the jelly to be partly gelatinous FIG. 5 See text for description. C = foreand partly reticular in nature. It contains gut; DA = dorsal aorta; II, III, IV, V= mucopolysaccharides and hyaluronic acid','. successive branchial arch vessels; DC = In the absence of cardiac valves at this stage ducuts caroticus; VI (D) = ductus arterioof development onward flow in the vascular sus; B = bulbus cordis; PBPA= postsystem is achieved by occlusion of the heart branchial pulmonary artery. .

{

K

192

F D Skidmore

IV

-CP FIG. 6 Sagittal plane diagram of 6th arch vessel connections at Stage i6. B = bulbus cordis; IV = 4th arch vessel destined to become aortic arch; DL VI (D) = dorsal portion of 6th arch which forms ductus arteriosus (DA); PL VI = proximal left 6th arch; A = wall of common atrium; G = foregut; 0 = oesophagus; T = trachea; CP = capillary plexus; PBPA = postbranchial pulmonary artery; C = gill cleft; S = postbranchial segmented vessels.

ventricular precursors. However, as the jelly 'sets' with an increasing cellular density the size of the channel scoured out will be directly related to the number of myocardial cells and their physiological performance. Inadequate flow, even at this time, will result in a hypoplastic outflow tract. This type of explanation, invoking hydrodynamic principles for the manner of formation of the outflow tracts, is particularly attractive when we come to consider the causation of cardiac malformations. We need then only invoke cell death and subsequent hypoplasia or aplasia of recognizable tissue components of the heart as the final common pathway by which a whole spectrum of

malformations can be caused. Physical, chemical, and mechanical teratogenic factors could all play their part in cardiac malformation by affecting the delicate relationship between the normally balanced right and left ventricular outflows. I suggest that two factors-the development of increasing cardiac curvature and the craniocaudal development of successive branchial arch vessels-are causally related. Blood passing through the atrioventricular cushions is accelerated up the outflow tract by two separate ventricular components set at an angle to each other because of their successive position on the curve of the cardiac tube. This results in a double spiral vector

Development of the right outflow tract artd pulmonary arterial supply

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FIG. 7 Transbronchial pulmonary angiogram in infant at term showing bronchopulmonary anastomoses.

passing into the branchial arch vessels. It is my belief that this 'out of phase' twin spiral, passing clockwise distally, is the major factor responsible for the development of the outflow tract. De Vries and Sanders8 have shown an experimental model of this spiral flow. The increasing cardiac curvature selects more posterior branchial vessels for the vectored outflow from the chambers of the heart.

Relationship between growth in thickness of vessel wall, diameter of lumen, and intravascular pressure Woods9 in I892 showed that the cardiac wall thickness was proportional to intramural tension. This is an example of Laplace's law, which states that the tension in the vessel wall is equal to twice the pressure multiplied by the radius. Thus the number of circumferential polarized layers of fibroblasts around a vessel are related to the force exerted on

the wall by the contained blood. Although it is impossible to make in-vivo measurements of flow in the embryonic heart, we can measure the number of cell layers around a vessel (Fig. 8). Inferences can be made about the relative flow beyond a bifurcation and the flow in separate vessels at the same point in time.

Morphology of the pulmonary artery Huntington"0 in 19I9 studied the embryology of the cat and showed that the intrapulmonary plexus established a connection with the 6th arch by a ventral longitudinal vessel and that this was followed by dissolution of the link between the pulmonary plexus and the dorsal aorta. The work reported in this paper provides evidence of the presence of identical vessels in the human fetus of 5-7 mm crownrump length. Once functional continuity has been estab-

F D Skidmore

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2

ducttus arteriosus-or it can pass caudoventrally in the postbranchial pulmonary artery to the lung plexus. The most proximal portion FIRST ARCH of the 6th paired arches fuse together to L form the pulmonary trunk (Fig. 9). The remainder of the proximal 6th arch is that tissue up to the point at which the postbranchial SECOND ARCHI pulmonary artery arises. The dorsal 6th arch runs up to the dorsal aorta. On the left side I this is the definitive ductus arteriosus. On the I I right the vessel involutes and disappears at the end of the 2nd month of development. THIRD MCH' The right ventral 6th arch vessel increases in length more than the left-side homologue r I___________________________________ Isince it crosses from the left side of the mediaI

2

4 3

2 4

RIGHT FOURTH ARCH

3~~~~~~~~~~~~~~~~~

|

2

2

FL IrTH

ARCH

m~--.-

I

RV VI

RD V+

PBP PBP FIG. 8 Increase inl cell layers in walls of 3rd and 4th arch vessels over a io-day period. L R The vestigial IIst, 2nd, and sth arch vessels remain ascapillaries. FIG. 9 Stage I6. Diagram of relationships of 4th and 6th arch vessels., bulbus cordis, and lished between the 6th arch and the post- postbranchial pulmonary arteries. G = gut; branchial artery the pulmonary arterial ves- DA = dorsal aorta; B = bulbus cordis; IV sel is complete. From the ventricles blood =4th arch vessel; RV VI = right ventral passes to the 6th arch vessels and runs in 6th arch. RD VI = right dorsal 6th arch; the pharyngeal floor to the angle at which LD VI (D) = left dorsal 6th arch (ductus it can either go towards the dorsal aorta in arteriosus); PBPA = postbranchial pulmonthe distal 6th arch- that is, the right and left ary artery.

Development of the right outflow tract and pulmonary arterial supply LV IV RV IV

R PPA

PB3PA

FIG. Io Morphological derivation of adult pulmonary arterial tree. FV VI = fused ventral 6th arches; PBPA = postbranchial pulmonary arteries (left and right). RV VI = right ventral 6th arch. LD VI = left dorsal 6th arch; LV IV = left ventral 4th arch; RV IV = right ventral 4th arch.

stinum to the right ventral aspect of the gut to link up with its postbranchial pulmonary artery and right ductus. Figure io shows the morphological derivation of the adult pulmonary arterial tree. On the left there is no cquivalent to the vessel labelled RV VI. In the embryo at the end of the 2nd month of development three routes exist for providing blood flow to the pulmonary plexus: (i) The 'normal' 6th arch flow via the postbranchial pulmonary arteries to the pulmonary plexus. (2) A reverse flow in the ductus arteriosus can connect with the postbranchial pulmonary artery and deliver a systemic flow to the lungs; this happens when there is aplasia of proximal 6th-arch tissue. (3) There is a possibility of flow occurring directly from the dorsal aorta at a distal level in vessels destined to become the bronchial arteries. Flow in the proximal pulmonary circuit Laplace's law has already been discussed in relation to the lamellar structure

195

around the developing blood vessels. The circumferential fibroblast layers around the endothelium of a developing vessel is the histological evidence of pressure in that structure. If one inspects the bifurcation of vessels the difference in wall thickness of the branches and the angle of the bifurcation tells of the intravascular pressure relationships between the two vessels and thus relates to flow. Cell counts and absolute measurements of the ductus arteriosus and postbranchial pulmoinary artery vessels reveals that the flow in the latter is relatively small. The left ductus carries more blood than its right homologue, and this can be understood when one studies the angle of the bifurcation from the posterior end of the bulbus cordis. In the I 2-mm human embryo the left ductus is I50 pm in diameter, whereas the right is only 40 ,um. Similarly the right dorsal aorta flow is diminished. The right ductus and right aorta disappear around Day 45. Throughout intrauterine life the right-toleft shunting across the ductus arteriosus avoids perfusion of functionless lung with deoxygenated blood and augments flow to the placenta via the dorsal aorta". The thickness of the right ventricular wall and the number of cell layers in the outflow tract suggest that there is equal right and left heart pressure in the fetus, a fact confirmed by the haemodynamic studies of Barclay, Franklin, and Pritchard in I 94512. The angle of the plane of the foramen ovale to the inferior vena caval flow ensures that blood shunts to the left heart as a proximal right-to-left shunt, thence passing via the left ventricle and its outflow to the central nervous system'3. In the fetus the right ventricular wall tension is developed in response to aortic pressure at the distal end of the ductus and pulmonary vascular resistance. The interlobular arteries are elastic arteries, while those

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F D Skidmore

in the lobes are of the muscular variety. The latter vessels have no lumen until birth'4. Identification of arterioles is not possible until the lungs have been aerated. Coincidentally with aeration of the lungs the pulmonary arterial pressure falls and there is a 6-io-fold increase in the pulmonary venous returnm5. This fall in pressure with rise in flow at birth is associated with 'maturation' in the pulmonary arterial structure'6. There is fragmentation of the lamellae in the pulmonary vessel walls. This fragmentation is related to the fall in right ventricular pressure in the neonatal period.

Bronchial arteries and bronchopulmonary anastomoses I agree with Boyden'7 that even at 13 weeks of intrauterine life it is impossible to show a peribronchial arterial plexus. These arteries appear in fetuses during the 2o-32-week stage of intrauterine life. Once the vessels ramify down the intrapulmonary bronchi they begin to form anastomoses with pulmonary circulation arterioles. Wagenvoort, Heath, and Edwards3 have shown that these anastomoses are rare in normal 2-year-old children, indicating that they have a short existence. However, in Fallot's tetralogy and other cyanotic heart disorders these anastomoses are grossly hypertrophied and allow oxygenation of the blood because of their precapillary connection with the pulmonary arterioles. What then is the haemodynamic significance of these bronchopulmonary anastomoses developing before birth in the normal human child and disappearing within 2 years? We know that with the major intraand postcardiac shunting occurring via the foramen ovale and ductus arteriosus the proximal perfusion pressures of the pulmonary artery and aorta are identical in the fetus'8. Right and left heart dissociation occurs as the shunts close and

systemic bronchial flow supplies oxygenated blood to the parenchyma. Rudolph'3 has shown that in the fetus the lung flow is only 6% of total cardiac output, but within the first 2 weeks of life this figure rises to approximately 50% of the total cardiac output. In the normal infant the anastomoses between pulmonary and systemic circulations probably act as an equilibration mechanism. The pulmonary vascular resistance is high initially and there is a safety valve at a precapillary level which prevents right ventricular failure, until the pulmonary vascular resistance falls and the pulmonary circuit becomes a low-pressure, high-flow system. Once maturation has occurred the pulmonary circuit represents the low-pressure run-off to the left atrium, and so the need for the anastomosis is reduced. However, in cases of pulmonary oligaemia due to congenital right outflow tract obstruction the anastomoses increase in size and their flow is augmented both by humoral and systemic pressure mechanisms. Thus we find that in Fallot's tetralogy and pulmonary atresia systemic vessels track directly into the lung substance and fuse in angiomatous fashion with minute vessels at the distal end of the pulmonary pathways". The survival of children with a defective circulation shows the capacity of the circuit to undergo dynamic adjustments to mitigate the disadvantages imposed by morphological variations.

Conclusions i) Once the fetal heart

starts

contracting

its development and that of the circulation result from the interaction of two factors: (a) continuing cell growth and maintained physiological performance of myoblasts and (b) the effect of the stroke volume outflow on the connective tissue cells surrounding the

endothelium.

Development of the right

outflow tract and pulmonary arterial supply

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2) In the heart the cardiac jelly interposed 4 Skidmorc, F D (I973) MD Thesis, University of Cambridge. between myoblasts and endothelium takes part in the modelling process. 5 Challice, C E, and Edwards, G A (I96I) in The Specialized Tissues of the Heart, ed. A 3) Abnormal channels imprinted into the Paes de Carvatho, W C de Mello, and B R cardiac jelly persist. Later cardiac growth Hoffman. Amsterdam, Elsevier. is simply an increase in size of the organ whose 6 Barry, A (I95I) Anatomical Record, 11I, 22!. structure has been determined as above. 4) The pulmonary circuit in the fetus car- 7 Ortiz, E C (1958) Archivos del Instituto de cardiologia de Mexico, 28, 244. ries only 6% of the cardiac output. The late development of the bronchial circulation and 8 De Vries, P A, and Sanders, J D de C M (I962) Contributions to Embryology of the Carnegie its anastomoses with the pulmonary vessels Institute of Washington, 37, 87. enable rapid safe conversion from the fetal high-pressure to the infant high-flow situa- 9 Woods, R H (I892) Journal of Anatomy and Physiology, 26, 262. tion in the pulmonary artery. 5) In infants with right outflow tract ob- io Huntington, G S (I9I9) Anatomical Record, struction the rapid augmentation of the I7, i65. bronchial arterial tree is the means by which ii Wagenvoort, N (I966) The Heart and Circulamany survive. tion in the Foetus and Newborn, p. 207. New I should like to acknowledge the help given by members of the audiovisual aids section in the Department of Anatomy, Cambridge University, in preparing the diagrams, radiographs, and photomicrographs. My special thanks are due to Professor Richard Harrison FRS and Dr J E Ebert for providing facilities in Cambridge and Baltimore respectively during the tenure of the British Heart Foundation Research Fellowship.

I2

References

i6

Subramanian, S (I974) Annals of the Royal College of Surgeons of England, 54, I76. 2 Marchand, P, Gilroy, J C, and Wilson, V H (1950) Thorax, 5, 207. 3 Wagenvoort, N, Heath, D, and Edwards, J E (1964) The Pathology of the Pulmonary Vasculature. Springfield, Ill., Thomas.

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York, Grune and Stratton. Barclay, A E, Franklin, K G, and Pritchard, M L L (I945) The Foetal Circulation. Oxford, Blackwell. Rudolph, A M (I969) in Foetal Anatomy ed. G Wolstenholme. London, Churchill. Civin, W H, and Edwards, J E (I95i) Archives of Pathology, 51, 192. Dawes, G S, and Mott, J C (I953) Journal of Physiology, I2I, 141. Heath, D (I969) in Anatomy of the Developing Lung ed. J Emery. London, Heinemann. Boyden, E A (1970) Anatomical Record, I66, 6i i. Adams, F M, and Lind, J (I957) Pediatrics, I9, 421.

I9 Turner-Warwick, M (I96I) MD Thesis, University of London.

Development of the right outflow tract and pulmonary arterial supply.

The branchial arch vessels of the human embryo have been studied by histological and radiographic methods and the modelling that occurs during the per...
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