collateral arteries in pulmonary atresia with ventricular ... · * sghis partly supported bythe...

Br HeartJ 1980; 44: 5-13

Collateral arteries in pulmonary atresia withventricular septal defectA precarious blood supply

SHEILA G HAWORTH*

From the Department of Paediatric Cardiology, Institute of Child Health, Guilford Street, London

suMMARY In pulmonary atresia with ventricular septal defect and major aortopulmonary collateralarteries lung growth and survival depend on the size and continued patency of the collateral arteries.Arterial structure was examined in 13 collaterals, taken from the necropsy specimens of seven children,six ofwhom died during the first seven months of life. Serial reconstruction was made oftwo collaterals,from the aorta to the intrapulmonary vessels, and the other collaterals were examined by taking sectionsat intervals along the same course.

The collateral arteries arose from the aorta either as elastic vessels with a wide lumen or as musculararteries when they were stenosed. Nearly all vessels rapidly came to resemble muscular systemicarteries, the external and lumen diameter becoming smaller. All collateral arteries save one showedareas of intimal proliferation which varied in the extent to which they surrounded and encroached on

the lumen. In addition, four collaterals contained large intimal cushions which severely narrowed oreven occluded the lumen. At the anastomosis of collateral and intrapulmonary artery intimal cushionswere seen in all collaterals examined and the extent to which the structures reduced lumen diametervaried. The structure of collaterals is compared with that of growing systemic arteries and the ductusarteriosus, emphasis being given to the different types of intimal change. The clinical relevance of thesefindings is discussed.

The major aortopulmonary collateral arteries foundin pulmonary atresia with ventricular septal defecteither anastomose with a lobar pulmonary artery,with a segmental intrapulmonary artery or, lesscommonly, with a central pulmonary artery.' Thesegmental pulmonary arteries which anastomosewith collateral arteries have no connection withthe sixth arch or its branches within the lung.They do not differ either structurally or in theirbranching pattern from intrapulmonary arteriesconnected to central pulmonary arteries. Thus theterm collateral artery refers only to the vesselconnecting the aorta with the pulmonary segment.

Survival depends on the continued patency ofthe collateral arteries. In a large collateral somenarrowing is desirable to reduce the systemicarterial pressure to a level more appropriate to thepulmonary circulation, but the degree of stenosisis critical because lung growth depends on the

* SGH is partly supported by the British Heart Foundation.Received for publication 17 August 1979

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cross-sectional area of the collateral being adequate.Stenoses are seen radiologically and at necropsy,either as a localised constriction where the collateralarises from the aorta or where it anastomoses witha pulmonary artery, or as a narrowed segment.One collateral artery may be stenosed at severalpoints.Wall structure was examined in 13 collateral

arteries, taken from seven published cases of pul-monary atresia with ventricular septal defect andmajor aortopulmonary collateral arteries.' Thepurpose of the present study was to assess theprobability of collateral arteries remaining patentand growing as the child grows, the possibilityof collateral arteries being able to constrict, andhow their wall structure compared with that ofsystemic arteries and the ductus arteriosus. Inaddition, the structure of the collateral and largeintrapulmonary arteries was considered in relationto the most suitable site for insertion of an aorto-pulmonary anastomosis or a right ventricularconduit.

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Materials and methods

Collateral arterial structure was studied micro-scopically in 13 arteries taken at random fromseven cases of pulmonary atresia with ventricularseptal defect and major aortopulmonary collateralarteries. Serial reconstructions were made of two

collaterals from the aorta to the intrapulmonaryvessels, and the other collaterals were examinedby taking sections at intervals along the same

course (Table). The collaterals were always cut intransverse section, with the exception of one serialstudy in which a very tortuous artery was occasion-ally cut in longitudinal section. The sections were

stained with Miller's elastic van Gieson stain andwith a haematoxylin and eosin stain, except for theserial sections, all of which were stained withMiller's elastic van Gieson stain.Emphasis was given to the following features:

(1) the sequence of change in wall structure betweenthe aorta and the lung, (2) the amount and distri-bution of elastic tissue and smooth muscle cellsin the vessel wall, (3) intimal proliferation or

cushions, and (4) splitting and fragmentation of theinternal and external elastic laminae.

Results

Seven of the 13 collateral vessels arose from theaorta as relatively thin-walled elastic arteries with

a large lumen (Table, Fig. 1). The remaining sixcollaterals were constricted, being thick-walled andmuscular near their origin. All the collaterals save

two had a predominantly muscular arterial wallstructure throughout most of their course betweenaorta and lung, the remaining two vessels havinga musculoelastic structure (Table). At the hilum ofthe lung 12 of the 13 collaterals connected with a

segmental intrapulmonary artery and provided theonly source of blood supply to those segments.As such a collateral artery approached a segmentalbronchus it dilated and the wall became elasticin structure (Fig. 1). The remaining collateralanastomosed with a lower lobe branch of a centrallyconnected pulmonary artery which supplied an

entire lung (Fig. 1). This collateral was thick-walled at the hilum and anastomosed with a thick-walled pulmonary artery.

Microscopically, the structure varied in eachcollateral artery along its course and in differentcollaterals, as shown by findings in two serialreconstructions.

SERIAL RECONSTRUCTION-CASE AThis collateral was not constricted at its originfrom the aorta and the vessel wall was composedlargely of long, unbroken elastic fibres (Fig. 2a).Gradually the elastic fibres became thinner andwere separated by smooth muscle cells whichoccupied a progressively greater proportion of the

Table Material. technique of examination, and summary of results

Intra-Case Age No. of Technique of Aortic origin Muscular mid-portion Collateral pulmonary

collaterals examination PA junction arterialstructure

A 12 days 1 Serial sections Not narrowed IP IC Normal

B 6 weeks 4 Step sections Not narrowed - IC NormalStep sections Not narrowed IP ? NormalStep sections Not narrowed IP ? NormalStep sections Not narrowed IP ? Normal

C 3 months 2 Step sections Narrowed IP + IC+ + NormalStep sections Narrowed IP+++ + IC+ + + Normal

IC

D 4 months 1 Step sections Narrowed IP+++ ? NormalICLumen obliterated

E 5 months 1 Serial sections Not narrowed IP + IC Normal

F 7 months 2 Step sections Narrowed IP+ + + IC NormalStep sections Narrowed IP + + IC Normal

IC

G 3 years 2 Step sections Narrowed Musculoelastic IC+ + + NorrnalIP

Step sections Not narrowed Musculoelastic ? ?IPIC

IP, intimal proliferation; IC, intimal cushion; ?, indicates structure not examined; PA, pulmonary artery; +, indicates size.

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Collateral arteries in pulmonary atresia with ventricular septal defect

vessel wall as the collateral proceeded towards the LUNG lo walllung. The subendothelial elastic fibres condensed E thicknessinto an internal elastic lamina, and short finefragmented fibres lay in the intima. The external 23elastic lamina did not entirely surround the circum-ference of the vessel. The majority of elastic fibresmerged into the adventitia. Thus, as the elastic . 44. 8lamellae disappeared a distinct media was formedand the elastic became a muscular artery. Theexternal diameter decreased, and relative wallthickness increased.

In the distal half of the collateral eccentric areas Mof intimal proliferation were superimposed onan expanded media (Fig. 2b). In this regionrelative wall thickness increased to 23-4 per cent.Intimal proliferation did not entirely surround thelumen of the collateral at any point along its lengthand decreased as the collateral approached the 38hilum of the lung. Nearing the hilum, the propor-tion of elastic to muscular tissue increased and thevessel dilated. At this point approximately one-fifthof its circumference was covered by an intimalcushion which did not significantly narrow thelumen. Within the lung no intimal cushions were

E +- 24

I ~~~~~~~a)I~~~~~~~~~~~~~L AORTA

I l \ Fig. 2 (a) Scale drawing of serial reconstruction-/ 1.' 1 \case A (magnification x 10) showing the reduction in/ _V,1 \external diameter in the muscular portion of the collateral/ /o,1 1_ Xwhich is exaggerated where intimal proliferation (------)

is most pronounced. X = plane of section of Fig. 2b.Abbreviations: E, elastic wall; M, muscular wall.

/t5/X{3I _ \ (b) Transverse section of collateral artery, showing a

muscular wall structure and an area of intimalproliferation (magnification x 45).Abbreviations: IL, internal elastic lamina; EL, externalelastic lamina; IP, intimal proliferation.

Fig. 1 Diagram to illustrate the possible variation incollateral arterial structure showing, in the right lowerlobe from above downwards, a branching collateral artery fJ:, 'Vwith a relatively large lumen, a collateral with a wideorigin but thick muscular wall distally with intimalproliferation, and a collateral stenosed at its origin from ILthe aorta. In the left lung a large collateral anastomosis E-+ h f...;#7v.*+X.cZ--7 Zh;7S1rt ................nt.-k..EL.wztn tne iower sove pulmonary artery. 3otia tines inaicareintrapulmonary arteries, the solid outlines indicatemuscular walled collateral arteries, and the interruptedlines indicate the elastic portion of a collateral arteryand the aorta.

(b)

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seen and the vessel had a structure of a normallyconnected pulmonary artery.

SERIAL RECONSTRUCTION-CASE EThe structural features of this collateral are illustra-ted in Fig. 3. Intimal cushions were found at eachbranching point, becoming smaller with eachsuccessive division (Fig. 3c and d).The small collateral destined to join the upper

lobar pulmonary artery had a thick media withinternal and external elastic laminae. Intimalproliferation covered approximately half the cir-cumference and consisted of an inner layer of fineelastic fibres and an adluminal layer of relativelyacellular amorphous material (Fig. 3d). The largeparent collateral artery divided again. One vesselremained thick-walled, and in the other intimalcushions developed and beyond this the arterial wallbecame thin, the proportion of elastic fibres in-creasing in relationito the amount of smooth muscle.

a) b)

At this point the vessel became a segmental pul-monary artery of the left lower lobe (Fig. 3d).

ADDITIONAL FEATURES PRESENT IN THESEAND OTHER COLLATERAL ARTERIES(1) Aortic originSix collateral arteries were narrowed at theiraortic origin. At this point, all showed an extremelythick muscular media from which fleshy tongues ofmuscle encroached on the lumen (Fig. 4). Thickbundles of longitudinal muscle cells lay in theouter half of the media and circumferentially andobliquely orientated muscle cells lay beneath areduplicated internal elastic lamina.

(2) Mid sectionIn the mid section of all save two collaterals thearterial wall changed from an elastic to a muscularstructure approximately 1-5 to 2 cm from the aorta.External diameter decreased and relative wall

ULPA__W

LLPA

c) d)

Length after fixation = 1. 8 cm

Fig. 3 Serial reconstruction-case E. Line drawing of acollateral artery, from the aorta to where its branches joinsegmental intrapulmonary arteries. Photomicrographs (a)-(d) aresections taken at the points indicated on the diagram.(a) collateral arising from the aorta ( x 13-4), showing itselastic structure. (b) Muscular mid portion, showing thick mediabetween internal and elastic laminae and intimal proliferation.Note variation in structure around circumference of vessel,particularly in amount of elastic material in media and intima( x 28). (c) Intimal cushions protrude into lumen at a branchingpoint. Internal elastic lamina splits at edge oJ cushions ( x 28).(d) Lowest branch of collateral joins segmental intrapulmonaryartery, beyond intimal cushions ( x 13). All sections stainedwith Miller's elastic stain. Abbreviations: ULPA, upper lobepulmonary artery; LLPA, lower lobe pulmonary artery;IL, internal elastic lamina; EL, external elastic lamina;IP, intimal proliferation; IC, intimal cushion.

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branchtoUPA

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thickness increased (Fig. 2, 3, 5, and 6), causingsegmental narrowing in all instances, sometimesof a severe degree (Fig. 5 and 6).The remaining two collateral arteries (case G)

had a large lumen. Both had a musculoelastic wallstructure. A broken external elastic lamina and abroken, frequently splitting internal elastic laminabounded a media composed of smooth muscle cells

Fig. 4 Transverse sections of a collateral narrowed atits aortic origin, showing a thick media, extensions ofwhich project into the lumen (Miller's elastic stain x 29).

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interspersed with long, fine elastic' fibres, forming4 to 8 elastic laminae.

All the collateral arteries save one showed areasof intimal proliferation and, in four, intimalcushions projected into the lumen (Table).

(3) Collateral-pulmonary artery anastomosisIn all vessels in which the structure of the collateral-pulmonary artery anastomosis was examined, nearor within the hilum of the lung intimal cushionsprojected into the lumen, reducing its cross-sectional area (Fig. 3d). In three collaterals, largecushions were covered by a thick layer ofamorphousmaterial. Beyond this point the muscular wallgradually became elastic, until within the lungparenchyma the wall structure was that of anelastic pulmonary artery (Fig. 7). The pulmonaryarteries were dilated where they connected with acollateral artery, occasionally producing a sinusoidalcavity from which arose abnormally small segmentalarteries.

Irrespective of the severity of luminal narrowingproduced by the intimal mounds, the distal pul-monary arteries were invariably patent.

STRUCTURE OF INTIMAL CUSHIONSThe type of intimal change varied along thecourse of each collateral and also in the sameregion of different collaterals. In the muscular

IL-IMElELv

IC

->PA

Fig. 5 Transverse section of the mid portion of acollateral at a region of segmental narrowing. The lumenof this muscular artery is almost totally obliterated byintimal proliferation and cushion formation, and a layerof amorphous material containing no elastic tissue(Miller's elastic stain x 17).Abbreviations: IL, internal elastic lamina; EL, externalelastic lamina; M, media; IC, intimal cushion; PA,pulmonary artery.

Fig. 6 Transverse section of the mid portion of acollateral at a region of segmental narrowing, showing athick media and narrowing of the lumen by intimalproliferation and mound formation. Intimal moundscontain fine elastic fibres and are covered with a layer ofacellular material (Miller's elastic stain x 38).

mid-section two types of intimal change occurred,either small areas of intimal proliferation or largeintimal cushions. Small areas of proliferation werepresent in nearly all cases, even at 12 days of age(Fig. 2b). They varied in size, but did not causesignificant narrowing of the lumen. By contrast,large intimal cushions occurred in only fourcollaterals, but in all they narrowed or even obliter-ated the lumen (Fig. 5 and 6). At the margin of allareas of intimal proliferation and cushion forma-tion, the dense internal elastic lamina usually split,a larger proportion continuing as a broken internalelastic lamina, the adluminal part splitting into finefragmented fibres lying within the expandedintima.The cushions contained many collagen fibres.

Towards the lumen of the vessel the cushionsbecame progressively less cellular, contained fewerelastin and collagen fibres, and were frequentlycovered by amorphous and relatively acellularmaterial. No subendothelial elastic lamina waspresent. Beneath the cushion the smooth muscleof the media was often thinned and the cells were

no longer arranged in a regular concentric manner,but ran in an oblique, irregular fashion betweenbroken internal and external elastic laminae(Fig. 5). Bundles of longitudinal muscle fibres

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frequently lay on either side of the internal elasticlamina. The number of elastic fibres usuallyincreased considerably in relation to the amountof smooth muscle.

In three of the four collateral arteries containinglarge cushions the outer third of the media showedhyaline change, and at this point the lumen wasentirely surrounded by intimal proliferation andcushion formation.At the branching point of a collateral artery the

intimal cushions were more clearly defined struc-tures than those described above (Fig. 3c). Theyconsisted of long thin branching elastic fibres,generally running circumferentially around thelumen. They did not have a thick subendothelialelastic lamina, and were not covered by layers ofamorphous material. The intimal cushions presentat the junction of a collateral and a segmentalpulmonary artery were smaller than those foundat the branching points, but had a similar discreteappearance (Fig. 3d). In this position, occasionallya thick layer of intimal proliferation, sometimeswith a layer of amorphous material, was super-imposed on a well-defined intimal cushion.

Discussion

Findings in the present study help to explain theradiological appearances of the collateral arteriesduring life. As they arose from the aorta somevessels generally had an elastic wall structureand a wide lumen, but others were constricted attheir origin because of a thick muscle wall. Theexternal and lumen diameter of the collaterals

Fig. 7 Cross-section of lung showing an intrapulmonaryartery which was connected proximally to a collateralartery. The vessel has the elastic wall structure of atypical pulmonary artery (Miller's elastic stain x 21).Abbreviations: Br, bronchus; PA, pulmonary artery.

narrowed as the elastic vessels came to resemblemuscular systemic arteries. Four vessels containedan extremely narrow segment composed of a thickmuscle wall with intimal proliferation and cushionformation. At the anastomosis of a collateral witha pulmonary artery intimal cushions were seen inall the collaterals examined, but the extent to whichthese structures reduced the lumen diametervaried. Distally the pulmonary artery was large,irrespective of the severity of stenosis, and some-times showed post-stenotic dilatation.

In pulmonary atresia with ventricular septaldefect and major aortopulmonary collateral arteries,survival depends on the collateral arteries. Intimalproliferation and cushion formation was found inthe majority of collaterals examined and in severalthe lumen was almost or totally occluded. Not allthe intimal change, however, was necessarilypathological. The small areas of intimal proliferationfound in the muscular mid-section of the collateralswere structurally similar to those described byRobertson2 in the brachial, popliteal, and coronaryarteries of the fetus and by Dock,3 in the coronaryarteries of the newborn. Robertson2 4 did notregard these fetal cushions as pathological. Thenormal development of intimal pads in systemicarteries might explain their presence in the col-lateral arteries of young infants. In systemicarteries, the function of intimal pads is not under-stood, but they may represent growing points andmight also strengthen the vessel wall. Pulsatilestress is thought to stimulate cushion formation,stimulating longitudinal orientation of medialmuscle and the formation of muscle in theintima.2 4 Collateral arteries are, of course, subjectto the pulsatile stress of the thoracic aorta.As in the present study, intimal cushions or

pads have been described at the branching points ofbrachial, popliteal, and cerebral arteries in thefetus and are thought to have a supportive func-tion.2 46 They have not been described in thefetal and newborn lung (A Hislop, 1980, personalcommunication), but in the adult they are presentat the mouths of lateral branches arising from thesegmental axial artery.6

Intimal cushions were also present at the site ofanastomosis between a collateral and intrapul-monary artery, the site at which these vessels areprobably normally connected in early fetal lifeand then, presumably, in the normal fetus, arelater disconnected when the intrapulmonary ar-teries become exclusively connected to the sixtharch. In this position, the intimal cushions werefrequently covered by a thick layer of intimalproliferation and a superficial relatively structure-less layer. This appearance suggests that super-

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imposed on discrete intimal cushions, layers ofintimal proliferation caused progressive narrowingof the vessel lumen.

It may be that intimal pads develop in utero incollateral and in normal arteries, and in both are thesite of early obliterative change.3 The intimalcushions present in the muscular mid-section ofseveral collaterals were larger than those previouslydiscussed and less discrete. In some collateralsremnants of intimal cushions could be seen beneatha less structured layer of intimal proliferationcontaining relatively little elastic material. Thebasic structure of collateral arteries may predisposethem to obliterative change. The collateral arteriesdescribed in the present study had a thick muscularwall, whereas large conducting arteries so close tothe thoracic aorta normally have a predominantlyelastic wall structure. The muscular collateralarteries are presumably less distensible and arealso capable of contracting in response to a highdistending pressure. When the lumen is narrowedthe velocity of flow increases, increasing theshearing stress on the endothelium and the likeli-hood of producing intimal damage and pro-liferative change.7The structure of the narrowed collateral arteries

resembled that of a normally closing ductusarteriosus.8 Like the ductus, the collaterals re-sembled muscular systemic arteries and severalcontained intimal cushions structurally similarto ductal cushions. Like the normally closingductus arteriosus, no subendothelial elastic laminawas present. In both collateral arteries and theductus arteriosus areas of cytolytic necrosis andmucoid lakes occurred in the inner media and baseof the intimal cushions. These similarities mayindicate only that the structural mechanism bywhich these muscular arteries, or indeed anymuscular artery, are obliterated is similar, irres-pective of the functional stimulus which provokesthe change. Alternatively, the structural similaritiesbetween the narrowed collateral arteries andclosing ductus arteriosus and the propensity forboth channels to close in early postnatal life mayimply that both structures are persistent fetalchannels which are destined to close. Boyden9suggested that collateral arteries are persistentsegmental arteries which normally close about 50days after ovulation. We might therefore be wit-nessing delayed "normal" closure of segmentalarteries in infants with pulmonary atresia andventricular septal defect. This could explain whysevere obliterative change was found in such younginfants. A high transmural pressure alone might notbe sufficient to produce such severe obliterativechange so rapidly.

Clearly, not all collateral arteries become severelynarrowed because some children with pulmonaryatresia, ventricular septal defect, and major aorto-pulmonary collateral arteries reach adolescence.There is evidence to suggest that the variablenatural history might be a result of a basic structuraldifference in the collateral arteries. In the presentstudy two thin-walled collateral arteries presentin the 3-year-old child contained a greater amountof elastic tissue than did the collaterals of theyounger cases. Two large collateral arteries in a7-year-old child, not included in the presentseries, had a wall composed of densely packedelastic laminae. In these four collaterals, intimalchange was less frequent and less severe than in themuscular collateral arteries and though the mid-section of one collateral contained a large intimalcushion this did not produce significant narrowingof the wide lumen.The difference between the wall structure of

collaterals with a relatively large lumen found inolder children and that in the majority of collateralarteries in the infant group is similar to thatbetween the persistently patent and normallyclosing ductus arteriosus. A persistent ductusarteriosus usually contains more elastic tissuethan a normally closing ductus, sometimes showinglamella formation.8 A patent ductus is, however,characterised by a wavy unfragmented subendothe-lial elastic lamina which continues as a thick fibreon top of the cushions, while in the collateral arteriesthis elastic lamina became fragmented within thecushions.These observations suggest that collateral arteries

containing a greater proportion of elastic ratherthan smooth muscle tissue are larger and remainpatent for a longer period of time than do muscularcollateral arteries. It is also possible that an increasein elastin is secondary to prolonged patency. Inthe ductus arteriosus, however, there was no relationbetween age and the occurrence of a subendotheliallamina and the amount of elastic material in theductus wall.8 Further studies of collateral arterialstructure in older patients are obviously necessary.

CLINICAL IMPLICATIONSThe question arises as to whether any pharma-cological agent might encourage the collateralarteries to remain patent. Prostaglandin E1 dilatesthe normally closing ductus, but a structuralsimilarity between the closing ductus and a closingcollateral artery does not necessarily imply afunctional similarity. Moreover, to be effectiveprostaglandins would have to be given prophylacti-cally from birth since once fibrous obliterativechange is present and the media is thinned the

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vessel is unlikely to respond to any vasodilatordrug.A necropsy study obviously gives a biased

impression of the natural history of any condition.Findings in the present study, however, indicatethat in young infants with pulmonary atresia,ventricular septal defect, and major aortopulmonarycollateral arteries, the collateral arteries can undergoobliterative change, and are unlikely to increasein size as the child grows. These observations helpexplain why infants with this anomaly frequentlybecome increasingly cyanosed during the firstmonths of life. Furthermore, quantitative morpho-metric analysis of areas of lung periphery perfusedby the collateral arteries described in the presentseries, showed impaired lung growth, usuallybecause of hypoperfusion.1 Because large occlusiveintimal cushions can develop at the junction ofcollateral and intrapulmonary arteries, an aorto-pulmonary anastomosis or a right ventricularconduit should be inserted beyond the collateralartery, at the origin of the intrapulmonary vessel.The author thanks Professor C Berry for advice inthe preparation of this manuscript, and Dr Gitten-berger-de Groot for stimulating and helpfuldiscussion.

References1 Haworth SG, Macartney FJ. Growth and develop-ment of pulmonary circulation in pulmonary atresia

with ventricular septal defect and major aorto-pulmonary collateral arteries. Br Heart J 1980; 44:14-24.

2 Robertson JH. Stress zones in foetal arteries. J ClinPathol 1960; 13: 133-9.

3 Dock W. The predilection of atherosclerosis for thecoronary arteries. JAMA 1946; 131: 875-8.

4 Robertson JH. The influence of mechanical factorson the structure of the peripheral arteries and thelocalization of atherosclerosis. J Clin Pathol 1960; 13:199-204.

5 Stebhens WE. Focal intimal proliferation in thecerebral arteries. Am Jf Pathol 1960; 36: 289-302.

6 Elliott FM. The pulmonary artery system in normaland diseased lungs-structure in relation to patternof branching. University of London: PhD Thesis,1964: 261-71.

7 Fry DL. Acute vascular endothelial changes associatedwith increased blood velocity gradients. Circ Res1968; 22: 165-97.

8 Gittenberger-de Groot AC. Persistent ductus arterio-sus: most probably a primary congenital malformation.Br Heart J7 1977; 39: 610-8.

9 Boyden EA. The time lag in the development ofbronchial arteries. Anat Rec 1970; 168: 611-4.

Requests for reprints to Dr S G Haworth, Depart-ment of Paediatric Cardiology, The Hospital forSick Children, Great Ormond Street, LondonWC1N 3JH.

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