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Morphologic features of the normal aortic arch in neonates, infants, and children pertinent to growth
Morphologic Features of the Normal Aortic Arch in Neonates, Infants, and Children Pertinent to Growth Masato Machii, MD, and Anton E. Becker, MD Department of Cardiovascular Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
Background. The aorta in n e w b o r n s rapidly adapts by growth to postnatal circulatory conditions. The question arises what structural features are associated with growth and whether differences occur b e t w e e n the various segments. Methods. N i n e t e e n specimens have b e e n studied: seven from babies less than I month, seven from I m o n t h to 1 year, and five from 1 to 4 years. In each b a b y the diameter of the aortic segments and its branches were measured. Histologically the n u m b e r of elastin lamellae was counted, and furthermore, collagen density was quantified at several m e a s u r e m e n t sites. Results. The diameter of each segment increases rapidly after birth and more so than that of the descending
aorta, except for the brachiocephalic artery a n d its branches and the left c o m m o n carotid artery, albeit not at the same rate. The ascending aorta is the only segment that shows a decrease in the ratio of elastin lamellae to diameter. Collagen density was always highest in the d e s c e n d i n g aorta. Conclusions. These observations show that postnatal growth of the thoracic aorta is associated with distinct structural r e m o d e l i n g soon after birth; these observations are of clinical relevance in case of aortic arch abnormalities.
he aorta in n e w b o r n babies rapidly adapts to postnatal circulatory conditions, which shows angiographically as an increase in diameter of the distal part of the transverse arch a n d in w i d e n i n g of the isthmus [1]. It has b e e n claimed that an increase in internal diameter of the ascending aorta is paralleled by an increase in the socalled packing density of the elastin lamellae [2]. This raises the question as to what are the basic structural features present at the time of adaptive vascular growth (ie, in the perinatal period a n d early infancy). U n d e r standing these aspects is relevant, as an a b n o r m a l aortic wall structure has b e e n d o c u m e n t e d in patients with hypoplastic transverse arch [3] a n d growth after end-toe n d repair for obstructive arch anomalies r e m a i n s controversial [4-6]. This study was u n d e r t a k e n to clarify the relationship b e t w e e n the diameter a n d the length of the various segments of the thoracic aorta a n d the microscopic features pertinent to growth.
ties. The specimens were g r o u p e d together according to age. Seven were obtained from babies less than 1 m o n t h of age (male/1 day, n = 2; female/1 day, n = 3; male/5 days, n = 1; female/25 days, n = 1), seven from 1 m o n t h to 1 year (male/1 month, n = 1; male/3 months, n = 3; male/4 months, n = 1; male/5 months, n = 1; female/8 months, n = 1), a n d five from I to 4 years (male/1 year, n = 3; male/2 years, n = 1; female/4 years, n = 1). All specimens were obtained from the Cardiovascular Registry a n d all had b e e n fixed in 4% formalin for a considerable length of time.
T
Material and Methods
Heart Specimens The study is based on 19 heart specimens, together with the thoracic aorta, of mature n e w b o r n babies, infants, a n d children. There were no cardiovascular a b n o r m a l i Accepted for publicationFeb 8, 1997. Address reprint requests to Dr Machii, Divisionof CardiovascularSurgery, Ebina General Hospital CardiovascularCenter, 1519Kawaraguchi, Ebina, Kanagawa24304,Japan. © 1997 by The Society of Thoracic Surgeons Published by Elsevier Science Inc
(Ann Thorac Surg 1997;64:511-5) © 1997 by The Society of Thoracic Surgeons
Morphometry The external diameters of the various segments of the thoracic aorta were m e a s u r e d as displayed in Figure 1. The d e s c e n d i n g aorta was m e a s u r e d at 2.5 cm distal to the insertion of the arterial duct or its ligament. The external diameters of the brachiocephalic artery, the right subclavian artery, the right a n d the left c o m m o n carotid artery, a n d the left subclavian artery were m e a s u r e d at 5 m m from their origin. To compensate for age, the diameter of each s e g m e n t was divided by that of the descending aorta a n d expressed as a ratio. The length of the proximal a n d distal transverse arch a n d that of the aortic isthmus were taken as shown in Figure 1.
Histology Transverse sections were taken at the measurements had been performed. The finely processed, e m b e d d e d in paraffin, thickness. The histologic sections were
sites where the blocks were rouand cut at 5-/~m stained with he-
0003-4975/97/$17.00 PII S0003-4975(97)00445-1
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MACHIIAND BECKER MORPHOLOGY OF NORMAL AORTIC ARCH GROWTH
Ann Thorac Surg 1997;64:511-5
sites. T h e a v e r a g e of t h e t w o c o u n t s w a s t h e n c a l c u l a t e d . To c o m p e n s a t e for a g e t h e n u m b e r of elastic l a m e l l a e w a s d i v i d e d b y t h a t of t h e d e s c e n d i n g a o r t a a n d exp r e s s e d as a ratio. B e c a u s e t h e n u m b e r of e l a s t i n l a r n e l l a e is c o n s i d e r e d to b e d i r e c t l y r e l a t e d to t h e d i a m e t e r [7], w e h a v e also c a l c u l a t e d t h e ratio n u m b e r of e l a s t i n l a m e l l a e to d i a m e t e r .
o r o x . TA
TA
~dist.
Collagen Density ii
T h e total a m o u n t of c o l l a g e n w a s q u a n t i f i e d w i t h t h e u s e of a m i c r o d e n s i t o p h o t o m e t e r , u s i n g s e c t i o n s s t a i n e d w i t h p i c r o s i r i u s r e d F3BA [8]. T h e m e a s u r e m e n t s w e r e p e r f o r m e d o n a V i c k e r s M85 s c a n n i n g a n d i n t e g r a t i n g m i c r o d e n s i t o m e t e r . In e a c h s e c t i o n 20 r a n d o m l y s e l e c t e d f r a m e s , w i t h i n t h e m i d d l e p a r t of t h e m e d i a , w e r e s c r e e n e d . T h e v a l u e s o b t a i n e d w e r e c o r r e c t e d for v a r i a t i o n s in t h i c k n e s s of t h e s e c t i o n s a n d s t a i n i n g c o n c e n t r a tions, u s i n g a r e f e r e n c e s e c t i o n . T h e a v e r a g e w a s calcul a t e d a n d e x p r e s s e d as a p e r c e n t a g e o f total c o l l a g e n in r e l a t i o n to total p r o t e i n .
s/
i,'
ist
Statistical Analysis Statistical a n a l y s i s w a s p e r f o r m e d as a m e a n + t h e s t a n d a r d d e v i a t i o n . D a t a w e r e a n a l y z e d b y a n a l y s i s of variance. Post-hoc intergroup comparisons were perf o r m e d u s i n g F i s c h e r ' s p r o t e c t e d l e a s t s i g n i f i c a n t differe n c e test. A p r i o r i l e v e l of s i g n i f i c a n c e w a s s e t at a p v a l u e of less t h a n 0.05.
Fig 1. Diagram of the thoracic aorta showing the various segments and the sites of measurements. (dist. TA = distal transverse arch; ist. = isthmus; prox. TA = proximal transverse arch.)
Results
Morphometry m a t o x y l i n a n d e o s i n , a n elastic t i s s u e stain, a n d t h e p i c r o s i r i u s r e d F3BA stain. In e a c h c a s e t h e n u m b e r of m e d i a l e l a s t i n l a m e l l a e w a s c o u n t e d at t w o o p p o s i n g
T h e v a l u e s o b t a i n e d are s h o w n in T a b l e 1. T h e a v e r a g e a b s o l u t e d i a m e t e r of e a c h s e g m e n t i n c r e a s e d signific a n t l y w i t h age. O n c e d i a m e t e r s w e r e e x p r e s s e d as a ratio
Table 1. Morphometry of Different Segments of the Thoracic Aorta and its Branches a Age
I Measurement External diameter Ascending aorta Brachiocephalic artery Right subclavian artery Right common carotid artery Proximal transverse arch Left common carotid artery Distal transverse arch Left subclavian artery Aortic isthmus Descending aorta Length Proximal transverse arch Distal transverse arch Aortic isthmus
(<1 mo)
7.1 4.6 3.6 3.5
+ 0.5 + 0.6 + 0.6 -+ 0.7
6.5 + 0.5 3.4 + 0.7 5.9 3.4 5.1 6.7
-+ 0.5 -+ 0.3 -+ 0.7 + 0.8
1.1 + 0.3 1.8 - 0.8 3.1 -+ 0.6
II (1 mo to <1 y)
10.6 5.9 4.8 4.8
--- 1.4 -+ 0.8 -+ 0.4 -+ 0.5
10.4 -+ 1.5 4.9 -+ 0.3 8.5 4.7 7.8 8.1
-+ 1.2 -+ 0.7 + 1.5 + 1.4
0.7 + 0.5 3.4 + 2.0 3.1 --+ 1.2
II1 (>1 y)
p Values I vs II
II vs III
I vs III
-+ 2.0 -~ 0.8 ~ 0.4 -+ 0.6
0.0001 0.0034 0.0006 0.0010
0.0026 0.0005 <0.0001 0.0010
<0.0001 <0.0001 <0.0001 <0.0001
13.0 -~ 1.3 5.9 -+ 0.5
<0.0001 0.0001
0.0015 0.0107
<0.0001 <0.0001
~ 1.1 -+ 0.6 -+ 0.9 -~ 0.7
0.0001 0.0005 0.0004 0.0214
0.0020 0.0003 0.0048 0.0220
<0.0001 <0.0001 <0.0001 0.0002
0.8 -~ 0.8 3.6 + 1.6 5.0 + 1.6
0.2468 0.0728 1.000
0.7956 0.7899 0.0109
0.4166 0.0600 0.0109
13.4 7.8 6.4 6.2
10.6 6.2 9.9 9.7
a The mean -+ standard deviation of the absolute figures in millimeters are shown for each of the three age groups, together with the p values.
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513
Table 2. Ratio of the Different Segments of the Thoracic Aorta and its Branches a I (<1 mo)
Segment Ascending aorta Brachiocephalic artery Right subclavian artery Right common carotid artery Proximal transverse arch Left common carotid artery Distal transverse arch Left subclavian artery Aortic isthmus
1.08 0.68 0.54 0.52 0.98 0.50 0.88 0.52 0.78
Age II (1 mo to <1 y)
± 0.15 ± 0.08 ± 0.07 ± 0.10 _+ 0.12 ± 0.09 ± 0.11 ± 0.06 ± 0.15
1.33 0.72 0.60 0.60 1.29 0.62 1.06 0.58 0.96
_+ 0.17 _+ 0.09 -+ 0.09 ± 0.08 _+ 0.18 _+ 0.08 ± 0.13 ± 0.05 ± 0.13
III (>1 y) 1.38 0.81 0.66 0.64 1.34 0.61 1.09 0.64 1.02
± 0.12 ± 0.10 ± 0.06 ± 0.05 _+ 0.05 _+ 0.07 ± 0.05 ± 0.03 + 0.03
I vs II
p Values II vs III
I vs III
0.0067 0.2668 0.1894 0.1050 0.0005 0.0160 0.0066 0.0220 0.0107
0.5735 0.1864 0.1899 0.3734 0.5528 0.9013 0.5942 0.0722 0.4187
0.0035 0.0271 0.0186 0.0244 0.0003 0.0331 0.0037 0.0006 0.0032
a The ratio was obtained by dividing the diameter of each segment by the diameter of the descending aorta and expressed as a mean +- standard deviation, together with the p values.
( d i a m e t e r d i v i d e d b y t h e d i a m e t e r of t h e d e s c e n d i n g a o r t a ) a d i f f e r e n t p a t t e r n w a s o b s e r v e d ( T a b l e 2). A significant increase was observed in the two youngest age groups (<1 month and between 1 month and I year) w i t h r e s p e c t to t h e a s c e n d i n g a o r t a , t h e p r o x i m a l a n d d i s t a l t r a n s v e r s e a r c h , t h e a o r t i c i s t h m u s , t h e left c o m m o n c a r o t i d a r t e r y , a n d t h e left s u b c l a v i a n a r t e r y . I n t h e b r a c h i o c e p h a l i c a r t e r y a n d its b r a n c h e s , t h e r a t i o d i d n o t i n c r e a s e s i g n i f i c a n t l y i n t h i s p e r i o d . T h e d i a m e t e r of t h e a s c e n d i n g a o r t a w a s l a r g e r t h a n t h a t of t h e d e s c e n d i n g a o r t a a t all a g e s (ratio <1). In t h e p r o x i m a l a n d d i s t a l transverse arch, the ratio became larger than I only after 1 m o n t h of a g e a n d t h e a o r t i c i s t h m u s r a t i o r e a c h e d t h a t n u m b e r o n l y a f t e r I y e a r of a g e ( T a b l e 2). W i t h r e s p e c t to l e n g t h d i f f e r e n t r e s u l t s w e r e o b t a i n e d ( T a b l e 1). T h e l e n g t h of t h e a o r t i c i s t h m u s i n s p e c i m e n s m o r e t h a n I y e a r of a g e w a s s i g n i f i c a n t l y l o n g e r t h a n t h a t in s p e c i m e n s of y o u n g e r ages; b e t w e e n t h e t w o y o u n g e r age groups no significant increase in length was found. In c o n t r a s t , t h e d i s t a l t r a n s v e r s e a r c h b e c a m e l o n g e r at a n e a r l i e r stage, t h a t is a f t e r 1 m o n t h of age. T h e r e w a s n o
c h a n g e i n t h e l e n g t h of t h e p r o x i m a l t r a n s v e r s e a r c h at a n y age.
Histology T h e n u m b e r of e l a s t i n l a m e l l a e i n e a c h s e g m e n t is s h o w n i n T a b l e 3. I n all s e g m e n t s of a o r t a , e x c e p t t h e r i g h t s u b c l a v i a n a r t e r y , t h e n u m b e r of e l a s t i n l a m e l l a e w a s s i g n i f i c a n t l y h i g h e r i n t h e c a s e s of I m o n t h a n d b e y o n d , compared with the youngest specimens. Once expressed as a r a t i o ( n u m b e r of e l a s t i n l a m e l l a e d i v i d e d b y t h a t of the descending aorta) only the ascending aorta showed a s i g n i f i c a n t l y h i g h e r n u m b e r a n d o n l y i n s p e c i m e n s of less t h a n 1 m o n t h ( T a b l e 3). T h e r a t i o s o b t a i n e d b y d i v i d i n g t h e n u m b e r of e l a s t i n l a m e l l a e b y t h e d i a m e t e r a r e s h o w n i n T a b l e 4. T h e r a t i o o b t a i n e d for t h e a s c e n d i n g a o r t a i n b a b i e s less t h a n 1 m o n t h of a g e w a s s i g n i f i c a n t l y h i g h e r t h a n t h a t i n t h e descending aorta, thus indicating a relatively high numb e r of e l a s t i n l a m e l l a e . T h i s r a t i o d e c r e a s e d s i g n i f i c a n t l y i n t h e a s c e n d i n g a o r t a i n t h e e a r l y p e r i o d . T h e r a t i o s of o t h e r s e g m e n t s k e p t c o n s t a n t or d e c r e a s e d g r a d u a l l y
Table 3. Absolute Number of Elastin Lamellae +_ Standard Deviation ,for Each Age Group, Together With p Values and the Ratio a Age I
Segment Ascending aorta Right subclavian artery Distal transverse arch Left subclavian artery Descending aorta
(<1 mo) 58.7 (1.46 24.3 (0.61 41.7 (1.04 17.4 (0.43 40.4
+ 6.3 ± 0.17) ± 3.1 -+ 0.10) ± 8.3 ± 0.21) ± 1.6 ± 0.04) + 3.2
II (1 mo to <1 y) 69.3 (1.24 29.0 (0.52 52.9 (0.95 23.6 (0.43 55.4
± 7.0 ± 0.12) ± 4.8 _+ 0.07) ± 9.4 ± 0.15) ± 5.5 ± 0.09) ± 4.2
III (>1 y) 76.4 (1.24 39.2 (0.63 60.4 (0.98 26.4 (0.42 62.6
± 4.6 + 0.15) ± 6.1 ± 0.12) ± 4.0 +- 0.12) ± 4.9 ± 0.07) + 8.8
p Values I vs II
II vs III
I vs III
0.0058 (0.0211) 0.0739 (0.348) 0.0184 (0.3707) 0.0139 (0.9697) <0.0001
0.0683 (0.8526) 0.0016 (0.985) 0.1244 (0.8204) 0.2735 (0.9668) 0.0390
0.0002 (0.0226) <0.0001 (0.392) 0.0010 (0.5505) 0.0021 (0.9391) <0.0001
a These values were obtained by dividing the number of elastin lamellae of each case with that of the descending aorta, expressed as the mean -+ standard deviation.
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Table 4. Ratio Obtained by Dividing the Number of Elastin Lamellae by Diameter Expressed as a Mean +_ Standard Deviation for Each Age Group, Together With p Values
Segment Ascending aorta Right subclavian artery Distal transverse arch Left subclavian artery Descending aorta
I (<1 mo) 8.24 ± 6.63 ± 7.19 ± 5.44 ± 6.01 ±
0.90a 1.73 1.73b 1.34 0.72
Age II (1 mo to <1 y)
III (>1 y)
I vs II
p Values II vs III
I vs III
6.55 _+0.67 6.06 ± 0.84 6.27 _+ 1.18 4.81 _+ 1.14c 6.94 ± 0.96
5.83 + 1.10 6.13 ÷ 0.89 5.77 _+0.86 4.31 ÷ 1.00~ 6.51 _+ 1.19
0.0025 0.4104 0.2236 0.3371 0.1109
0.1779 0.9328 0.5308 0.4828 0.4467
0.0003 0.5026 0.0913 0.1244 0.4580
a Significant (p < 0.05) compared with all segments except distal transverse arch. c Significant (p < 0.05) compared with all segments.
with age, although they did not reach levels of statistical significance. C o m p a r i n g these ratios in each age group, the ratios in the a s c e n d in g aorta w e r e significantly greater than those in other s e g m e n t s except the distal transverse arch in the y o u n g e s t age group, and this t e n d e n c y d i m i n i s h e d in the two older age groups. Moreover, the right subclavian artery h a d a significantly smaller ratio c o m p a r e d with other s e g m e n t s in these periods (Table 4).
Collagen Density The collagen density is shown in Table 5. The values obtained for the d e s c e n d i n g aorta w e r e significantly higher than those for the ascending aorta and the distal transverse arch at all ages. The collagen density in each s e g m e n t kept constant with aging (Table 5). Comment This study shows that neonatal growth of the thoracic aorta is not uniformly distributed over the different segments. Two observations are outstanding. First, it appears that the diameters of the ascending aorta, the proximal and distal aortic arches, the aortic isthmus, left c o m m o n carotid artery, and the left subclavian artery show a significant increase c o m p a r e d with the growth in d i a m e t e r of the d e s c e n d i n g aorta. Second, the absolute n u m b e r of elastin lamellae in the ascending aorta already reaches adult levels before 1 year of age. The n u m b e r is also relatively high at birth, c o m p a r e d with its diameter. H o w e v e r , very soon a relative decrease occurs so that the
b Significant (p < 0.05) compared with left subclavian artery.
ascending aorta w i d e n s out of proportion with its n u m ber of elastin lamellae. W h a t could be the explanation for these p h e n o m e n a ? O n e could hypothesize that the increased v o l u m e of blood to be c o n v e y e d by the ascending aorta and aortic arch after birth causes the increase in diameter. The significant increase in d i a m e t e r of the left subclavian artery also suggests redistribution of blood toward this vessel. Indeed, it is generally accepted that arterial growth (ie, diameter) relates to b l o o d flow [9-11]. This is nicely illustrated also by c o m p a r i n g the ascen d ing aorta and the p u l m o n a r y trunk. During the gestational perio d - i n general t e r m s - - l e f t ventricular output is less than that of the right ventricle, but these differences gradually increase an d at the time of birth both ascen d i n g aorta a nd p u l m o n a r y trunk have almost similar d i am et ers a nd a similar configuration of elastin lamellae [12, 13]. However, the p r e s e n t study also shows that the n u m b er of elastin lamellae is not d e t e r m i n e d on the basis of flow only, as the d e s c e n d i n g aorta has significantly less elastin lamellae than the ascen d i n g aorta despite an almost eq u al d i a m e t e r at birth. Moreover, as p o i nt e d out before, after birth the ascen d i n g aorta shows a rapid relative decrease in the n u m b e r of elastin lamellae, which surely cannot be attributed to a decrease in flow. It is tempting, therefore, to consider other rheologic factors as well. For instance, after birth the p e a k blood velocity in the ascending aorta changes from approximately 90 cm/s in fetuses to approximately 140 cm/s at 6 m o n t h s of age [13, 14]. At the same time the absolute output from the left ventricle increases with b o d y growth. However,
Table 5. The Mean Values +_ Standard Deviation of the Collagen Density Using the Picrosirius Red Stain, Quantified Densitophotometn'cally and Expressed as a Percentage of Total Protein for Each Group, Together With the p Values Age Segment Ascending aorta Distal transverse arch Descending aorta
p Values
I (<1 mo)
II (1 mo to <1 y)
III (>1 y)
I vs II
II vs III
I vs III
26.9 ± 2.0 25.3 ± 2.0 42.1 +_ 7.4a
24.8 ± 2.3 24.8 ± 3.4 36.3 ± 5.0~
25.0 +- 2.2 26.1 _+ 3.5 36.8 ± 4.8a
0.0805 0.7228 0.0878
0.8824 0.4662 0.9056
0.1400 0.6822 0.1432
a Significant (p < 0.05) compared with ascending aorta and distal transverse arch in each age group.
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w i t h i n t h e aorta flow v e l o c i t y a n d oscillation d e c r e a s e with increasing distance from the pumping chamber, w h e r e a s t h e p r e s s u r e p u l s e i n c r e a s e s [15]. H e n c e , o n e m a y s p e c u l a t e that t h e s e factors c o n t r i b u t e to the g e n e s i s of elastin l a m e l l a e , b u t b e c a u s e of the differences b e t w e e n the a s c e n d i n g a n d d e s c e n d i n g aorta, t h e s e factors also c a u s e a r e l a t i v e d e c r e a s e in the n u m b e r of elastin l a m e l l a e in the a s c e n d i n g aorta c o m p a r e d w i t h that in t h e d e s c e n d i n g aorta. O u r o b s e r v a t i o n s of n o r m a l g r o w t h characteristics rev e a l distinct r e m o d e l i n g of t h e a s c e n d i n g aorta a n d t h e aortic arch s o o n after birth, that is b e f o r e I m o n t h of age. In this p a r t i c u l a r p e r i o d the p o t e n t i a l for g r o w t h and, m o s t likely, a d a p t a t i o n to s e c o n d a r y c h a n g e s , s u c h as t h o s e i n d u c e d b y c o n g e n i t a l h e a r t defects, is high. T h e s e o b s e r v a t i o n s , t h e r e f o r e , m a y s e r v e as r e f e r e n c e o n c e c o n f r o n t e d w i t h a b n o r m a l i t i e s of the aortic arch.
transverse arch and coarctation in neonates. Surgical reconstruction of the aortic arch: a study of sixty-six patients. J Thorac Cardiovasc Surg 1990;100:808-16. Siewers RD, Ettedgui J, Pahl E, Tallman T, del Nido PJ. Coarctation and hypoplasia of the aortic arch: will the arch grow? Ann Thorac Surg 1991;52:608-14. Brouwer MHJ, Cromme-Dijkhuis AH, Ebels T, Eijgelaar A. Growth of the hypoplastic aortic arch after simple coarctation resection and end-to-end anastomosis. J Thorac Cardiovasc Surg 1992;104:426--33. Wolinsky H, Glagov S. A lamellar unit of aortic medial structure and function in mammals. Circ Res 1967;20:99-111. James J, Bosch KS, Zuyderhoudt FMJ, Houtkooper JM, Van Gool J. Histophotometric estimation of volume density of collagen as an indication of fibrosis in rat liver. Histochemistry 1986;85:129-33. Kamiya A, Togawa T. Adaptive regulation of wall shear stress to flow changes in the rabbit carotid artery. Am J Physiol 1980;239(Heart Circ Physiol 8):H14-H21. Langille BL, Bendeck MP, Keeley FW. Adaptations of carotid arteries of young and mature rabbits to reduced carotid blood flow. Am J Physiol 1989;256(Heart Circ Physiol 25): H931-9. Guyton JR, Hartley CJ. Flow restriction of one carotid artery in juvenile rats inhibits growth of arterial diameter. Am J Physiol 1985;248(Heart Circ Physiol 17):H540-6. Heath D, Wood EH, DuShane JW, Edwards JE. The structure of the pulmonary trunk at different ages and in cases of pulmonary hypertension and pulmonary stenosis. J Pathol Bacteriol 1959;77:443-56. Reed KL, Meijboom EJ, Sahn DJ, Scagnelli SA, Valdes-Cruz LM, Shenker L. Cardiac Doppler flow velocities in human fetuses. Circulation 1986;73:41-6. Light LH, Cross G. Convenient monitoring of cardiac output and global left ventricular function by transcutaneous aortovelography--an effective alteration to cardiac output measurements. In: Spencer MP, ed. Cardio Doppler diagnosis, Vol 1. The Hague: Martinus Niihoff Publishers, 1984:69-80. McDonald DA. Blood flow in arteries, 2nd ed. London: Edward Arnold, 1974:351-88.
During the course of this study Dr Machii was a Research Fellow from the Kitasato University, Faculty of Medicine, Kanagawa, Japan. We thank Marsha I. Schenker for excellent secretarial assistance.
5. 6.
7. 8.
9. 10.
11. 12.
References 1. Clarkson PM, Brandt PWT. Aortic diameters in infants and young children: normative angiographic data. Pediatr Cardiol 1985;6:3-6. 2. Van Meurs-Van Woezik H, Klein HW, Markus-Silvis L, Krediet P. Comparison of the growth of the tunica media of the ascending aorta, aortic isthmus and descending aorta in infants and children. J Anat 1983;136:273-81. 3. Becker AE. Segmental aortic hypoplasia or how to interpret the flow concept. Int J Cardiol 1988;20:247-55. 4. Lacour-Gayet F, Bruniaux J, Serraf A, et al. Hypoplastic
13. 14.
15.
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Background. The aorta in n e w b o r n s rapidly adapts by growth to postnatal circulatory conditions. The question arises what structural features are associated with growth and whether differences occur b e t w e e n the various segments. Methods. N i n e t e e n specimens have b e e n studied: seven from babies less than I month, seven from I m o n t h to 1 year, and five from 1 to 4 years. In each b a b y the diameter of the aortic segments and its branches were measured. Histologically the n u m b e r of elastin lamellae was counted, and furthermore, collagen density was quantified at several m e a s u r e m e n t sites. Results. The diameter of each segment increases rapidly after birth and more so than that of the descending
aorta, except for the brachiocephalic artery a n d its branches and the left c o m m o n carotid artery, albeit not at the same rate. The ascending aorta is the only segment that shows a decrease in the ratio of elastin lamellae to diameter. Collagen density was always highest in the d e s c e n d i n g aorta. Conclusions. These observations show that postnatal growth of the thoracic aorta is associated with distinct structural r e m o d e l i n g soon after birth; these observations are of clinical relevance in case of aortic arch abnormalities.
he aorta in n e w b o r n babies rapidly adapts to postnatal circulatory conditions, which shows angiographically as an increase in diameter of the distal part of the transverse arch a n d in w i d e n i n g of the isthmus [1]. It has b e e n claimed that an increase in internal diameter of the ascending aorta is paralleled by an increase in the socalled packing density of the elastin lamellae [2]. This raises the question as to what are the basic structural features present at the time of adaptive vascular growth (ie, in the perinatal period a n d early infancy). U n d e r standing these aspects is relevant, as an a b n o r m a l aortic wall structure has b e e n d o c u m e n t e d in patients with hypoplastic transverse arch [3] a n d growth after end-toe n d repair for obstructive arch anomalies r e m a i n s controversial [4-6]. This study was u n d e r t a k e n to clarify the relationship b e t w e e n the diameter a n d the length of the various segments of the thoracic aorta a n d the microscopic features pertinent to growth.
ties. The specimens were g r o u p e d together according to age. Seven were obtained from babies less than 1 m o n t h of age (male/1 day, n = 2; female/1 day, n = 3; male/5 days, n = 1; female/25 days, n = 1), seven from 1 m o n t h to 1 year (male/1 month, n = 1; male/3 months, n = 3; male/4 months, n = 1; male/5 months, n = 1; female/8 months, n = 1), a n d five from I to 4 years (male/1 year, n = 3; male/2 years, n = 1; female/4 years, n = 1). All specimens were obtained from the Cardiovascular Registry a n d all had b e e n fixed in 4% formalin for a considerable length of time.
T
Material and Methods
Heart Specimens The study is based on 19 heart specimens, together with the thoracic aorta, of mature n e w b o r n babies, infants, a n d children. There were no cardiovascular a b n o r m a l i Accepted for publicationFeb 8, 1997. Address reprint requests to Dr Machii, Divisionof CardiovascularSurgery, Ebina General Hospital CardiovascularCenter, 1519Kawaraguchi, Ebina, Kanagawa24304,Japan. © 1997 by The Society of Thoracic Surgeons Published by Elsevier Science Inc
(Ann Thorac Surg 1997;64:511-5) © 1997 by The Society of Thoracic Surgeons
Morphometry The external diameters of the various segments of the thoracic aorta were m e a s u r e d as displayed in Figure 1. The d e s c e n d i n g aorta was m e a s u r e d at 2.5 cm distal to the insertion of the arterial duct or its ligament. The external diameters of the brachiocephalic artery, the right subclavian artery, the right a n d the left c o m m o n carotid artery, a n d the left subclavian artery were m e a s u r e d at 5 m m from their origin. To compensate for age, the diameter of each s e g m e n t was divided by that of the descending aorta a n d expressed as a ratio. The length of the proximal a n d distal transverse arch a n d that of the aortic isthmus were taken as shown in Figure 1.
Histology Transverse sections were taken at the measurements had been performed. The finely processed, e m b e d d e d in paraffin, thickness. The histologic sections were
sites where the blocks were rouand cut at 5-/~m stained with he-
0003-4975/97/$17.00 PII S0003-4975(97)00445-1
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Ann Thorac Surg 1997;64:511-5
sites. T h e a v e r a g e of t h e t w o c o u n t s w a s t h e n c a l c u l a t e d . To c o m p e n s a t e for a g e t h e n u m b e r of elastic l a m e l l a e w a s d i v i d e d b y t h a t of t h e d e s c e n d i n g a o r t a a n d exp r e s s e d as a ratio. B e c a u s e t h e n u m b e r of e l a s t i n l a r n e l l a e is c o n s i d e r e d to b e d i r e c t l y r e l a t e d to t h e d i a m e t e r [7], w e h a v e also c a l c u l a t e d t h e ratio n u m b e r of e l a s t i n l a m e l l a e to d i a m e t e r .
o r o x . TA
TA
~dist.
Collagen Density ii
T h e total a m o u n t of c o l l a g e n w a s q u a n t i f i e d w i t h t h e u s e of a m i c r o d e n s i t o p h o t o m e t e r , u s i n g s e c t i o n s s t a i n e d w i t h p i c r o s i r i u s r e d F3BA [8]. T h e m e a s u r e m e n t s w e r e p e r f o r m e d o n a V i c k e r s M85 s c a n n i n g a n d i n t e g r a t i n g m i c r o d e n s i t o m e t e r . In e a c h s e c t i o n 20 r a n d o m l y s e l e c t e d f r a m e s , w i t h i n t h e m i d d l e p a r t of t h e m e d i a , w e r e s c r e e n e d . T h e v a l u e s o b t a i n e d w e r e c o r r e c t e d for v a r i a t i o n s in t h i c k n e s s of t h e s e c t i o n s a n d s t a i n i n g c o n c e n t r a tions, u s i n g a r e f e r e n c e s e c t i o n . T h e a v e r a g e w a s calcul a t e d a n d e x p r e s s e d as a p e r c e n t a g e o f total c o l l a g e n in r e l a t i o n to total p r o t e i n .
s/
i,'
ist
Statistical Analysis Statistical a n a l y s i s w a s p e r f o r m e d as a m e a n + t h e s t a n d a r d d e v i a t i o n . D a t a w e r e a n a l y z e d b y a n a l y s i s of variance. Post-hoc intergroup comparisons were perf o r m e d u s i n g F i s c h e r ' s p r o t e c t e d l e a s t s i g n i f i c a n t differe n c e test. A p r i o r i l e v e l of s i g n i f i c a n c e w a s s e t at a p v a l u e of less t h a n 0.05.
Fig 1. Diagram of the thoracic aorta showing the various segments and the sites of measurements. (dist. TA = distal transverse arch; ist. = isthmus; prox. TA = proximal transverse arch.)
Results
Morphometry m a t o x y l i n a n d e o s i n , a n elastic t i s s u e stain, a n d t h e p i c r o s i r i u s r e d F3BA stain. In e a c h c a s e t h e n u m b e r of m e d i a l e l a s t i n l a m e l l a e w a s c o u n t e d at t w o o p p o s i n g
T h e v a l u e s o b t a i n e d are s h o w n in T a b l e 1. T h e a v e r a g e a b s o l u t e d i a m e t e r of e a c h s e g m e n t i n c r e a s e d signific a n t l y w i t h age. O n c e d i a m e t e r s w e r e e x p r e s s e d as a ratio
Table 1. Morphometry of Different Segments of the Thoracic Aorta and its Branches a Age
I Measurement External diameter Ascending aorta Brachiocephalic artery Right subclavian artery Right common carotid artery Proximal transverse arch Left common carotid artery Distal transverse arch Left subclavian artery Aortic isthmus Descending aorta Length Proximal transverse arch Distal transverse arch Aortic isthmus
(<1 mo)
7.1 4.6 3.6 3.5
+ 0.5 + 0.6 + 0.6 -+ 0.7
6.5 + 0.5 3.4 + 0.7 5.9 3.4 5.1 6.7
-+ 0.5 -+ 0.3 -+ 0.7 + 0.8
1.1 + 0.3 1.8 - 0.8 3.1 -+ 0.6
II (1 mo to <1 y)
10.6 5.9 4.8 4.8
--- 1.4 -+ 0.8 -+ 0.4 -+ 0.5
10.4 -+ 1.5 4.9 -+ 0.3 8.5 4.7 7.8 8.1
-+ 1.2 -+ 0.7 + 1.5 + 1.4
0.7 + 0.5 3.4 + 2.0 3.1 --+ 1.2
II1 (>1 y)
p Values I vs II
II vs III
I vs III
-+ 2.0 -~ 0.8 ~ 0.4 -+ 0.6
0.0001 0.0034 0.0006 0.0010
0.0026 0.0005 <0.0001 0.0010
<0.0001 <0.0001 <0.0001 <0.0001
13.0 -~ 1.3 5.9 -+ 0.5
<0.0001 0.0001
0.0015 0.0107
<0.0001 <0.0001
~ 1.1 -+ 0.6 -+ 0.9 -~ 0.7
0.0001 0.0005 0.0004 0.0214
0.0020 0.0003 0.0048 0.0220
<0.0001 <0.0001 <0.0001 0.0002
0.8 -~ 0.8 3.6 + 1.6 5.0 + 1.6
0.2468 0.0728 1.000
0.7956 0.7899 0.0109
0.4166 0.0600 0.0109
13.4 7.8 6.4 6.2
10.6 6.2 9.9 9.7
a The mean -+ standard deviation of the absolute figures in millimeters are shown for each of the three age groups, together with the p values.
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Table 2. Ratio of the Different Segments of the Thoracic Aorta and its Branches a I (<1 mo)
Segment Ascending aorta Brachiocephalic artery Right subclavian artery Right common carotid artery Proximal transverse arch Left common carotid artery Distal transverse arch Left subclavian artery Aortic isthmus
1.08 0.68 0.54 0.52 0.98 0.50 0.88 0.52 0.78
Age II (1 mo to <1 y)
± 0.15 ± 0.08 ± 0.07 ± 0.10 _+ 0.12 ± 0.09 ± 0.11 ± 0.06 ± 0.15
1.33 0.72 0.60 0.60 1.29 0.62 1.06 0.58 0.96
_+ 0.17 _+ 0.09 -+ 0.09 ± 0.08 _+ 0.18 _+ 0.08 ± 0.13 ± 0.05 ± 0.13
III (>1 y) 1.38 0.81 0.66 0.64 1.34 0.61 1.09 0.64 1.02
± 0.12 ± 0.10 ± 0.06 ± 0.05 _+ 0.05 _+ 0.07 ± 0.05 ± 0.03 + 0.03
I vs II
p Values II vs III
I vs III
0.0067 0.2668 0.1894 0.1050 0.0005 0.0160 0.0066 0.0220 0.0107
0.5735 0.1864 0.1899 0.3734 0.5528 0.9013 0.5942 0.0722 0.4187
0.0035 0.0271 0.0186 0.0244 0.0003 0.0331 0.0037 0.0006 0.0032
a The ratio was obtained by dividing the diameter of each segment by the diameter of the descending aorta and expressed as a mean +- standard deviation, together with the p values.
( d i a m e t e r d i v i d e d b y t h e d i a m e t e r of t h e d e s c e n d i n g a o r t a ) a d i f f e r e n t p a t t e r n w a s o b s e r v e d ( T a b l e 2). A significant increase was observed in the two youngest age groups (<1 month and between 1 month and I year) w i t h r e s p e c t to t h e a s c e n d i n g a o r t a , t h e p r o x i m a l a n d d i s t a l t r a n s v e r s e a r c h , t h e a o r t i c i s t h m u s , t h e left c o m m o n c a r o t i d a r t e r y , a n d t h e left s u b c l a v i a n a r t e r y . I n t h e b r a c h i o c e p h a l i c a r t e r y a n d its b r a n c h e s , t h e r a t i o d i d n o t i n c r e a s e s i g n i f i c a n t l y i n t h i s p e r i o d . T h e d i a m e t e r of t h e a s c e n d i n g a o r t a w a s l a r g e r t h a n t h a t of t h e d e s c e n d i n g a o r t a a t all a g e s (ratio <1). In t h e p r o x i m a l a n d d i s t a l transverse arch, the ratio became larger than I only after 1 m o n t h of a g e a n d t h e a o r t i c i s t h m u s r a t i o r e a c h e d t h a t n u m b e r o n l y a f t e r I y e a r of a g e ( T a b l e 2). W i t h r e s p e c t to l e n g t h d i f f e r e n t r e s u l t s w e r e o b t a i n e d ( T a b l e 1). T h e l e n g t h of t h e a o r t i c i s t h m u s i n s p e c i m e n s m o r e t h a n I y e a r of a g e w a s s i g n i f i c a n t l y l o n g e r t h a n t h a t in s p e c i m e n s of y o u n g e r ages; b e t w e e n t h e t w o y o u n g e r age groups no significant increase in length was found. In c o n t r a s t , t h e d i s t a l t r a n s v e r s e a r c h b e c a m e l o n g e r at a n e a r l i e r stage, t h a t is a f t e r 1 m o n t h of age. T h e r e w a s n o
c h a n g e i n t h e l e n g t h of t h e p r o x i m a l t r a n s v e r s e a r c h at a n y age.
Histology T h e n u m b e r of e l a s t i n l a m e l l a e i n e a c h s e g m e n t is s h o w n i n T a b l e 3. I n all s e g m e n t s of a o r t a , e x c e p t t h e r i g h t s u b c l a v i a n a r t e r y , t h e n u m b e r of e l a s t i n l a m e l l a e w a s s i g n i f i c a n t l y h i g h e r i n t h e c a s e s of I m o n t h a n d b e y o n d , compared with the youngest specimens. Once expressed as a r a t i o ( n u m b e r of e l a s t i n l a m e l l a e d i v i d e d b y t h a t of the descending aorta) only the ascending aorta showed a s i g n i f i c a n t l y h i g h e r n u m b e r a n d o n l y i n s p e c i m e n s of less t h a n 1 m o n t h ( T a b l e 3). T h e r a t i o s o b t a i n e d b y d i v i d i n g t h e n u m b e r of e l a s t i n l a m e l l a e b y t h e d i a m e t e r a r e s h o w n i n T a b l e 4. T h e r a t i o o b t a i n e d for t h e a s c e n d i n g a o r t a i n b a b i e s less t h a n 1 m o n t h of a g e w a s s i g n i f i c a n t l y h i g h e r t h a n t h a t i n t h e descending aorta, thus indicating a relatively high numb e r of e l a s t i n l a m e l l a e . T h i s r a t i o d e c r e a s e d s i g n i f i c a n t l y i n t h e a s c e n d i n g a o r t a i n t h e e a r l y p e r i o d . T h e r a t i o s of o t h e r s e g m e n t s k e p t c o n s t a n t or d e c r e a s e d g r a d u a l l y
Table 3. Absolute Number of Elastin Lamellae +_ Standard Deviation ,for Each Age Group, Together With p Values and the Ratio a Age I
Segment Ascending aorta Right subclavian artery Distal transverse arch Left subclavian artery Descending aorta
(<1 mo) 58.7 (1.46 24.3 (0.61 41.7 (1.04 17.4 (0.43 40.4
+ 6.3 ± 0.17) ± 3.1 -+ 0.10) ± 8.3 ± 0.21) ± 1.6 ± 0.04) + 3.2
II (1 mo to <1 y) 69.3 (1.24 29.0 (0.52 52.9 (0.95 23.6 (0.43 55.4
± 7.0 ± 0.12) ± 4.8 _+ 0.07) ± 9.4 ± 0.15) ± 5.5 ± 0.09) ± 4.2
III (>1 y) 76.4 (1.24 39.2 (0.63 60.4 (0.98 26.4 (0.42 62.6
± 4.6 + 0.15) ± 6.1 ± 0.12) ± 4.0 +- 0.12) ± 4.9 ± 0.07) + 8.8
p Values I vs II
II vs III
I vs III
0.0058 (0.0211) 0.0739 (0.348) 0.0184 (0.3707) 0.0139 (0.9697) <0.0001
0.0683 (0.8526) 0.0016 (0.985) 0.1244 (0.8204) 0.2735 (0.9668) 0.0390
0.0002 (0.0226) <0.0001 (0.392) 0.0010 (0.5505) 0.0021 (0.9391) <0.0001
a These values were obtained by dividing the number of elastin lamellae of each case with that of the descending aorta, expressed as the mean -+ standard deviation.
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Table 4. Ratio Obtained by Dividing the Number of Elastin Lamellae by Diameter Expressed as a Mean +_ Standard Deviation for Each Age Group, Together With p Values
Segment Ascending aorta Right subclavian artery Distal transverse arch Left subclavian artery Descending aorta
I (<1 mo) 8.24 ± 6.63 ± 7.19 ± 5.44 ± 6.01 ±
0.90a 1.73 1.73b 1.34 0.72
Age II (1 mo to <1 y)
III (>1 y)
I vs II
p Values II vs III
I vs III
6.55 _+0.67 6.06 ± 0.84 6.27 _+ 1.18 4.81 _+ 1.14c 6.94 ± 0.96
5.83 + 1.10 6.13 ÷ 0.89 5.77 _+0.86 4.31 ÷ 1.00~ 6.51 _+ 1.19
0.0025 0.4104 0.2236 0.3371 0.1109
0.1779 0.9328 0.5308 0.4828 0.4467
0.0003 0.5026 0.0913 0.1244 0.4580
a Significant (p < 0.05) compared with all segments except distal transverse arch. c Significant (p < 0.05) compared with all segments.
with age, although they did not reach levels of statistical significance. C o m p a r i n g these ratios in each age group, the ratios in the a s c e n d in g aorta w e r e significantly greater than those in other s e g m e n t s except the distal transverse arch in the y o u n g e s t age group, and this t e n d e n c y d i m i n i s h e d in the two older age groups. Moreover, the right subclavian artery h a d a significantly smaller ratio c o m p a r e d with other s e g m e n t s in these periods (Table 4).
Collagen Density The collagen density is shown in Table 5. The values obtained for the d e s c e n d i n g aorta w e r e significantly higher than those for the ascending aorta and the distal transverse arch at all ages. The collagen density in each s e g m e n t kept constant with aging (Table 5). Comment This study shows that neonatal growth of the thoracic aorta is not uniformly distributed over the different segments. Two observations are outstanding. First, it appears that the diameters of the ascending aorta, the proximal and distal aortic arches, the aortic isthmus, left c o m m o n carotid artery, and the left subclavian artery show a significant increase c o m p a r e d with the growth in d i a m e t e r of the d e s c e n d i n g aorta. Second, the absolute n u m b e r of elastin lamellae in the ascending aorta already reaches adult levels before 1 year of age. The n u m b e r is also relatively high at birth, c o m p a r e d with its diameter. H o w e v e r , very soon a relative decrease occurs so that the
b Significant (p < 0.05) compared with left subclavian artery.
ascending aorta w i d e n s out of proportion with its n u m ber of elastin lamellae. W h a t could be the explanation for these p h e n o m e n a ? O n e could hypothesize that the increased v o l u m e of blood to be c o n v e y e d by the ascending aorta and aortic arch after birth causes the increase in diameter. The significant increase in d i a m e t e r of the left subclavian artery also suggests redistribution of blood toward this vessel. Indeed, it is generally accepted that arterial growth (ie, diameter) relates to b l o o d flow [9-11]. This is nicely illustrated also by c o m p a r i n g the ascen d ing aorta and the p u l m o n a r y trunk. During the gestational perio d - i n general t e r m s - - l e f t ventricular output is less than that of the right ventricle, but these differences gradually increase an d at the time of birth both ascen d i n g aorta a nd p u l m o n a r y trunk have almost similar d i am et ers a nd a similar configuration of elastin lamellae [12, 13]. However, the p r e s e n t study also shows that the n u m b er of elastin lamellae is not d e t e r m i n e d on the basis of flow only, as the d e s c e n d i n g aorta has significantly less elastin lamellae than the ascen d i n g aorta despite an almost eq u al d i a m e t e r at birth. Moreover, as p o i nt e d out before, after birth the ascen d i n g aorta shows a rapid relative decrease in the n u m b e r of elastin lamellae, which surely cannot be attributed to a decrease in flow. It is tempting, therefore, to consider other rheologic factors as well. For instance, after birth the p e a k blood velocity in the ascending aorta changes from approximately 90 cm/s in fetuses to approximately 140 cm/s at 6 m o n t h s of age [13, 14]. At the same time the absolute output from the left ventricle increases with b o d y growth. However,
Table 5. The Mean Values +_ Standard Deviation of the Collagen Density Using the Picrosirius Red Stain, Quantified Densitophotometn'cally and Expressed as a Percentage of Total Protein for Each Group, Together With the p Values Age Segment Ascending aorta Distal transverse arch Descending aorta
p Values
I (<1 mo)
II (1 mo to <1 y)
III (>1 y)
I vs II
II vs III
I vs III
26.9 ± 2.0 25.3 ± 2.0 42.1 +_ 7.4a
24.8 ± 2.3 24.8 ± 3.4 36.3 ± 5.0~
25.0 +- 2.2 26.1 _+ 3.5 36.8 ± 4.8a
0.0805 0.7228 0.0878
0.8824 0.4662 0.9056
0.1400 0.6822 0.1432
a Significant (p < 0.05) compared with ascending aorta and distal transverse arch in each age group.
Ann Thorac Surg 1997;64:511-5
MACHII AND BECKER MORPHOLOGY OF NORMAL AORTIC ARCH GROWTH
w i t h i n t h e aorta flow v e l o c i t y a n d oscillation d e c r e a s e with increasing distance from the pumping chamber, w h e r e a s t h e p r e s s u r e p u l s e i n c r e a s e s [15]. H e n c e , o n e m a y s p e c u l a t e that t h e s e factors c o n t r i b u t e to the g e n e s i s of elastin l a m e l l a e , b u t b e c a u s e of the differences b e t w e e n the a s c e n d i n g a n d d e s c e n d i n g aorta, t h e s e factors also c a u s e a r e l a t i v e d e c r e a s e in the n u m b e r of elastin l a m e l l a e in the a s c e n d i n g aorta c o m p a r e d w i t h that in t h e d e s c e n d i n g aorta. O u r o b s e r v a t i o n s of n o r m a l g r o w t h characteristics rev e a l distinct r e m o d e l i n g of t h e a s c e n d i n g aorta a n d t h e aortic arch s o o n after birth, that is b e f o r e I m o n t h of age. In this p a r t i c u l a r p e r i o d the p o t e n t i a l for g r o w t h and, m o s t likely, a d a p t a t i o n to s e c o n d a r y c h a n g e s , s u c h as t h o s e i n d u c e d b y c o n g e n i t a l h e a r t defects, is high. T h e s e o b s e r v a t i o n s , t h e r e f o r e , m a y s e r v e as r e f e r e n c e o n c e c o n f r o n t e d w i t h a b n o r m a l i t i e s of the aortic arch.
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During the course of this study Dr Machii was a Research Fellow from the Kitasato University, Faculty of Medicine, Kanagawa, Japan. We thank Marsha I. Schenker for excellent secretarial assistance.
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