Pediatr. Res. 14: 1047-1052(1980)
arterial oxygen content
choroidal blood flow
fetus
neonate
r e t i n a l b l o o d flow
Retinal and Choroidal Blood Flow in Unstressed
Fetal and Neonatal Lambs
.I he relatiomhip between retinal hlood flow ( R u b ) and choroidal
hlood flow (C'hBE) and the o\>gen content o f arterial hlood wa\
ir~te\tigated i n 12 fetal lanil)\. ? h e p w t n a t a l change4 i n t h e w
flow\ were 4tudied i n twel\e newhorn lanib\. RBI. arid C'hBI. \rere
dcternlined h j mean\ o f radioactite niicro\phere\ 3 to 10 d a j \
arter iniplantation o f the injection and \arnpling catheter\. beta1
hlood flow\ were meawred at different le\cl\ ofo\jgenation. 1 he
po\tnatal flow\ were nlea\ured while the lanlh hreathed roorn air.
'I he fetal data wggest an interse relation\hip between RBI. and
;~rterialo l j g e n content. < oncornitant change\ i n fetal < hHE wcre
unrelated to arterial o\?gen content. B e c a ~ ~ \ocf the i n t e r w
relation4hip between RBI. and arterial o \ j g c n content. the product
of R B Y and arterial o\?gen content wa\ independent o f the \tatc
of fetal 01)genation.
HHE did not change with birth, ~ h e r e a C
\ hBI. increawd. Ihere
ma\ no change i n R B F with po\tnatal age wherea4 C'hBI. decreawd
significantl! with increasing age.
Speculation
A reduced vascular resistance i n the ininlature choroid might he
an important predispo4ing factor i n the detelopnlent o f retrolental
fihroplaoia i n preterni hahies treated with high environniental
ox?gen.
There has been considerable I n t e r c t i n the rcgulat~onof retinal
and choroidal blood Ilow as a result o f the association ol'oxhgen
t o x ~ c i t yand retrolental f i b r o p l a ~ ;(9).
~ I l o l l e r y 1.1 111. ( 6J proposed
a model by which excessive constriction ol' immature retinal
vesaelb might he produced hy an increase i n tissue 1'0:. I n their
study, however, ;I number of assurnpt~unsmade about the retinal
and choroidal circulations were derived from acute experiments
i n anesthetixd animals i n which physiologic reactance ( 18) niight
have altered retinal and choroidal physiology. The goal o f the
present study was to describe the relationships observed under
chronic experimental conditions between the Ikt;il retinal and
clitirt)~J;iIh l t i t ~ fll t > \ s \ ;in<! o\vgcn c.ontcnf\ ci\.c.r ;I ir,idc r:lngc ;ind
changes i n these Ilows w i t h postn;~talage.
Twelve pregnant eNea ol' mised western breed at 130 to 145
days o f gestation and I 2 newborn lambs i n the lirst 5 months alter
b i r t h were studied. Surgery was perfi)rnied under pentobarbital
sedation (5 nig/kg) and. I n the ewes. illso spinal anesthes~a( 8 nig
tetracaine hydrochloride). As described previously for k t a l lambs
(12). polyvinyl chloride catheters (11). 0.9 mni. OD. 1.2 m m ) were
inserted into a transverse .scapular artery, a pedal vein, both pedal
arteries. and the amniotic sac. I n newborn lambs, the catheters
were inserted into a tranbverse scapular artery. the l e f ventricle.
and a femoral artery. The ends o f the catheters i n both k t a l and
newborn lanibs were exter~orl/ed\ l a ;I SC' tunnel and stored ~n a
pouch o n the flank of the ewes and the newborn lambs. respectively.
Studies were carried out between the third and 10th poatoper;itlLe day. I n eiich ;inirnal. three sets (11' l l t ) ~measurements were
perlijrmed by means of the microsphere technique (3. 11. 14) ;it
dill'ercnt levels o f lktal oxygen;itic)n. Microspheres c)f 15 / ~ n di l ameter ( 3 M ('o.. St. Paul. MN) labeled with e ~ t h c r"C'r. '"C'e. or
-,
Sr were used. ('hanges i n f'etal oxygenation were induced b>
expos~ngthe ewe to ~ a r y i n gconcentr:itionx o f oxygen ( I 0 to
100'; ). The dillkrent gas mixtures werc delivered i n r;indoni order
at high llow rates i n t o a large plastic bag that completely enclowd
the head o f the ewe. T o attain stead.-state cond~tionai n fktal
oxygenation and cardiovascular I'unction at each gas nilsture. ;I
niininium 01'30 nun was allowed li)r cqu~libr;ititrn. Fetal arterial
blood prehsure (1-BP; torr) delined I n this study as the dil'krencc
i n mean pressure between the k t a l abdominal aorta and the
a m n ~ u t i csac, and lktal heart rate ( I ' H K : beats/niin) bere nionitored throughout the c.sperin~ent.Blood Ilow n1e;isuremcnts here
performed when stable I'BP and 1.HR had been recorded for at
least 20 m i n . A t the time ol'each flow nieasurement. blood samples
were collected from each o f t h e arterial catheters Ibr measurements
o f p l l . PC'02. PO2 (;it 3t).50<' by rnciins 01' K;idiorneter HMS3
M K Z ) . 0, content. ( b y means o f the Lex-0,-con). and hernatocr~t
(microcapillary technique). Return to pre-experimentul values 01'
both f'HR and I'BP always occurred af'ter completron of' the
experiments. The ewe was then sacriliced. and the l i t u s was
delivered by cesarlan hection. ('iitheter positions were checked at
autopsy. A l l fetal organs were d~saectedas der,cribed previously
( 14).
The eyes wcre enucleated. and separate samples o f c h o r o i d and
retina werc obtained by n;iy t)fttic diswction procedure described
by A l m and B i l l ( I ) . The tissue samples were dried k>r 24 hr at
80°C'. weighed. and -{-radiation w i t s determined w ~ t ha gamma
counter (Nuclear Chicago three-channel autogamma). I n three
k t a l lambs drq welght/wet weight ratios wcre determined for both
t~h\uc.I.'~>Iboth !i\\uc\ tlic d r y weight/we~
rcli11;il a n d cht\r<~icI:~l
weight ratlo was -0.20. i n agreement w ~ t hobwrvations reported
rn the literature ( I J.
1-or the 110%calcul;itions. i t was assumed (hilt a dry wcight/wet
weight r;itio o f -0.20 applied to r e t ~ n a land chc)roldal t~ssuc
throughout the perinatal period studied.
Blood Ilow to both retina and choroid was calcul;ited according
to the Ibllowing equation:
.
TBI'
=
('PM,. X ts. I ) r W
C'PM,
x
0.20
x I,',,
where T B I : = tissue blood Ilow (ml.rnin ' . I00 g I ) . ('I'M,. =
total cpm I n the tlhsuc sample. ('I'M, = cpm i n the .~rteriul
reference sample. 1s. I ) r W = dry weight ol'the tissue sanlplc. and
F,, = the sampling rate o f t h e withdrawal pump (1.28 rnl.niin ' in
each experiment).
('alculatrons showed that the retinal samples always contained
z2OO microspheres of a part~cularlabel whereas arterial reference
samples and choroidal samples always contained 2 8 0 0 microspheres. T h e relatively large variability ~n retinal blood flow was
due. in part. to the low number of spheres in the retinal tissue
samples (3). T h e injection of a higher total dose of microspheres
would have reduced this variability. at the expense. however. of
more lnterlrence with fetal phystology (2. 19).
u
The newborn lambs were studied between the second and fifth
postoperative days. T h e ~ rpostnatal age at the day ofexperimentation ranged between 2 and 226 days. In most instances. flow
measurements were made with the newborn lamb sittrng quietly
in a large cardboard box breathing room air. To reduce potentially
d~sturbingfactors such as excessive light or noise. the cover of the
box was loosely closed. and the ends of the three catheters were
brought o u t s ~ d ethrough a hole in the top of the box. Blood flow
measurements were perf'c~rniedas descrrhed fix fetal lambs. At the
time of each flow measurement, the arterial blood pressure (torr)
was measured as the dilf'erence in height between the fluid level
in the transverse scapular arterial catheter and the xiphoid process.
After the third microsphere Injection, the newborn lambs were
sacrificed, and tissue was processed as described for the fetal
lambs.
For fetal lambs. the relationship between blood flow and oxygen
content in the ascending aorta ( [02].,:m M ) for both retina and
choroid was analyzed as follows. In general. three blood flow
values were obtained from each animal. A mathematical model
was chosen l i ~ rthe descr~ptionof the flow-oxygen relationships
for the retina and choroid which allowed each animal to have its
own "animal ell'ect" whereas the empirical equation was identical
ti)r each of the twelve animals studied. A major advantage of this
approach over an analysis based on pooled data is that the elftct
of oxygen on organ llow can be a n a l y ~ e d .whereas possible e t k c t s
c>1' dit.1'crcnccs between aninials. part~cularly those due tc) sjbtematic experimental error. are filtered out. T h e flow-oxygen
relation Ibr both the retina and the choroid could be described by
the general equation:
y,, = p + ( I , + /jf(y. x,,) + el,
(2)
where y , , = flow measurement in the j"' experiment on the i"'
a n i m a l r p = a constant, identical Sor all animals: i t , = additive
"animal correction factor" due to the i"' animal. (Correction factor
i t was determined in such a way that the sum o f t h e twelve values
for c t equaled r.ero); /j. y = regression coefficients, assumed to be
the same lijr all animals: x,, = value of [OL],,in the j"' experiment
on the i'" animal: f(y, x,,) = transli~rmof x,, and y (tp.g..ti?. x , , )
= e"'l . etc.): g,, = error term with expectation of zero and standard
deviation proportional to the expectation of y,,.
T h e mathernathical elahc)rat~onassociatcJ with the analysis
descr~bedabove is given in detail in the appendix to this report
and is termed "weighted least-squares method" in the remainder
this publication.
'l'hc flon data and concomitant iirter~alpariirneters in the twelve
fetal lambs used ln this study are I~stedrn Table 1 . For reasons
rnentroned elsewhere ( 13). 0, content rather than 1'0: was used as
index tilr oxygenation in the flow-oxygen relationsh~psstudied.
T h e relationship between R B F and [ a ] , ,is presented in l'igurc I .
Hy the weighted least-squares method, a number of mathematical
I
2
3
4
5
6
o x y g e n c o n t e n t a s c e n d ~ n qa o r t a I mM I
1
heturrn ktal RBI.' and 10.1..I n the ascrnd~ng
1.1p I Krlat~onsh~p
aorta. I'hr !low Jiita c>t' d~l'l'rrrntan~malsare represented b!, 12 d~llrrent
\ynibols. I.rtlr 1s calculated uslng the rrc~procirlfunction f;>r an a n ~ n i a l
with a n ~ n ~eI'
a 1l 'rc.t i t = 0 (see text).
functions were evaluated as to their adequacy to describe the
R B F - [ a ] , , relation. T h e results s u m m a r i ~ e din Table 2 suggest
that some nonlinear functlon describes that relationship best.
However, no clear discrimination could be obtained between the
three nonlinear functions tested. In other fetal neural structures
such as cerebrum, brain stem, and cerebelluni. i t has been denionstrated that the flow-oxygen relation was best described by a
reciprocal function (15). Therelijre. it was assunied that a reciprocal function might best describe the flow-oxygen relation for the
fetal retina. Consequently the following equation was selected:
RBF =
+ / I '/[02Ji, + i t
(3)
By the weighted least-squares method. the parameters in equation 3 were calculated:
RBF
=
-55
+
IYXI/[OJ];, + i t
(4)
In this a n d all subsequent equations. blood llow IS in ml.min ' .
100 g '. The additive animal effect ( I ranged from 0 to +233.
According t o the weighted Icaat-\quare\ rncthcrd. ;~pprt~x~rncltcly
X2'; o f t h e ~ntra-animalvariability in R B F could be explained by
changes in 1 / [ 0 2 ] . , .
Equation 4 can also be expressed as follows:
The equation expresses the relationship between the flow of 0 :
to the fetal retina moles. rnin I . I00 g ' ) and the 10, I.,. We were
not able to demonstrate a significant correlation between the flow
of oxygen to the fetal retina and the level of fetal oxygenation
(sign test. I' > 0 . I ).
The relationsh~pbetween choroidal hlood flow (C'hBF:) in ml.
rnin I . 100 g I ) and [O,],, is presented in Figure 2. Analysis of
this relationship by the weighted least-squares method indicated
that fetal choro~dalhlood flow (C'hBF) and [O,]., were not correlated. C h B F ranged from 900 to 3700 nil.min I . 100 g '. with a
niean lijr all fetal data points combined of I620 ml. rnin ' . 100 g '
( 5 1 2 7 S.E.).
N l W H O K N S'I'1II)Y
The flow data and concomitant arterial parameters ~n the 12
newborn lambs htudied are listed in Table 3. lnasniuch as the level
of oxygenation was not altered in newborn lambs. no mathematic
function could be constructed for the K B F - [ a ] . , relationship. I t is
noteworthy. however. that the neonatal data seem to extend the
trend shown by the k t a l data polnts in the higher [&I., range (Fig.
3). ChBI.' was slightly higher ~n newborn lambs than in fetuses.
T h e values for C'hBF ranged from 1550 to 3966 ml. rnin '. I00 g '
w ~ t ha mean ol.2700 rnl. min I . 100 ' ( kI60 S.E.).Coniparison of
the mean ('hBF before and after birth indicated that this value
KL.1 INAL ANI)
(
IIOKOII) \ I
I040
131 0 0 1 ) I 1.OW
I':tble I . Rerrtlnl cinrl c~horoidulh1ood.flow.c. ~ i r hrhe cot~c~ot~~irrin/
v ~ l l t rf o. ~r FHP, as ,cell us PO?. PCO., pH. and /OL]:, in the uscending
uorra oj'rhe /-7/i~rullutnhs
Lxperlnient
no.
Identlf-ing
sqmbol
KBF
(ml. min
'
lw&' )
C'hRl:
(ml. min
'
I N &I )
I.BP
(torr)
I
-
7
I XO
137
117
I 15
141
I00
I I6
161
I 50
64
89
62
258
374
334
174
234
148
X5
96
179
64
64
233
62
73
Ih2
78
141
1312
1042
2930
2249
1495
1551
2036
3676
2204
1550
I897
1354
93 I
927
1330
141 1
1596
1338
1649
1721
1797
1725
2215
I065
9 19
l 666
1215
1049
1173
1244
14 18
3
760
1725
7
X0
3
303
7141
255 1
1
( )
3
I
2
3
I
(J
.7.
3
I
V
2
3
I
-
n
7
3
I
A
7
3
I
-
A
7
3
I
2
3
I
2
3
I
+
*
..
0
7
3
I
rn
37
45
I
1.1
46
4X
47
37
36
3X
45
49
47
35
42
34
29
78
32
2X
30
41
36
36
42
40
43
5I
50
52
70
[C):It4
.
(mM)
~-
4.06
5.58
4.02
2.50
3.30
3.08
1.61
1.07
3.21
3.61
1.75
3 08
3.17
2.1 I
3 21
2.77
2. I4
2.10
2.98
I .26
2.56
4. I9
4 24
1 73
5.03
4.59
1.45
4.60
3.80
1.41
4.64
PO,
(torr)
I'C'O.
(torr)
23
36
23
IX
21
71
IX
14
26
23
I6
3X
44
39
47
47
48
42
40
43
42
35
38
44
42
46
47
44
41
4X
39
47
45
~~
@!L
I XO
25
2I
29
21
17
IX
22
I6
20
27
2X
I6
2X
27
IX
75
27
I5
75
14
41
3X
30
26
49
46
41
54
4X
7.44
7.38
7.44
7.36
7.37
7.36
7.34
7.24
7.30
7.37
7.33
7.38
7.38
7.36
7.37
7.35
7.32
7.37
7.34
7.21
7.34
7.36
7.3 1
7.33
7.45
7.46
7.73
7.38
7.35
7 35
7.32
7 32
I .7 I
6 62
5.84
1.34
I2
30
75
13
3X
47
42
35
7.26
7.27
7.42
7.25
--
73
50
i t ~ ~ ~ ~ i o t ~ .rhc~ir
~
(irk'qti(~(:),
it1
T a b l e 7. M a r h c ~ t ~ t i ~ r i c ~ u l ~ / ic~r~ciltirrrc~d,Ji)r
dcscrihitlg rhr R BF o \-,,Ken relariot1
Mathenii~t~cal
funct~on
Lniplrlc
eguatic~n
ti\) = I [ +/I.\
I-lnear l u n c t ~ o n
I ( \ ) = 11 + / I . ' / \
K c c ~ p r ~ ~ l.i~nctlc~ri
cal
I.ognr~tlinilct.ilnct~on t i \ ) = !I + /].In x
L:.cponent~al I ' u n c t ~ ~ ~ nI ( \ ) = + /i.e '
Lstlrnate I;lr
percentage
e r r( )
2 I ,I)
I9 0
IS 3
18.0
-
-
--
1)egrers
of
freedom
-17
-77
-17-
71
w a s significantly h i g h e r In n e w b o r n l a m b s ( S t u d e n t r test: P <
). .1'11c f ~ c ~ h t r ~ ; t l .tt l~ c r ~
111dl?l<)<~d
Il~>tv1,) ~ I > I I rclirl:~
I
i ~ n dcl>,>rt~id
. I
( F i g . 4 ) w a s e v a l u a t e d a s l i ~ l l o w s .T h e m e a n v a l u e f o r R B F a n d
4
5
6
1
2
3
o x y g e n content d s c e n d n q a o r t a I TIM
C'hHf- w a s c a l c u l a t e d f o r e a c h n e w b o r n l a m b . T h e S p e a r m a n
('orrelation coelficient ( 10) d e t e r m i n e d f o r t h e r e l a t i o n s h l p beI : I ~ 2. Kelarl~~nslilp
hetween ('IiRI- itnd (O.I.,In the itscend~ngaorta.
t w e e n t h e s e m e a n v a l u e s f o r K B t ; a n d C'hBF. w i t h a g e . w e r e
1 . 1 0 ~ data Iron1 d~l'l'erentk t u w s were ~ d e n t ~ l i eh)
d ublng the same I?
0.17 ( d f = 9: P > 0. I ) a n d -0.62 (dl'= 10: P C 0.05).respectively.
hqrnbc~lsas In I.lgure I .
i n d i c a t i n g n o r e l a t i o n s h t p b e t w e e n K B F a n d a g e , a n d a signtlic a n t l y d e c r e a s i n g C'hBf: w i t h p o s t n a t a l a g e .
0.01
+
T h e c u r v i l i n e a r r e l a t i o n s h i p b e t w e e n k r a l K B F a n d [O;],,
s e e m e d 10 b e d e s c r i b e d hest by a rcciproc;~l f u n c t i o n . S u c h a
r e l a t i o n s h l p w o u l d n o t b e s u r p r i s i n g b e c a u s e in t h e s a m e g r o u p of
animalh. t h e r e l a t i o n s h i p b e t w e e n flow a n d o x y g e n in v a r i o u s
o t h e r c e n t r a l n e r b o u s s y s t e m tissues w a s a l s o best d e s c r i b e d b y
s u c h s lilnction ( IS). T h i s similarity in l l o w r e s p o n s e t o c h a n g i n g
levels o f [ 0 2 ] . , in b o t h fetal retina a n d c e n t r a l n e r v o u s s y s t e m
suggests t h a t it s i m i l a r mec.hanisni regulates llow t o b o t h tissues
w h e n t h e [O,],, 1s altered. I n t h e present s t u d y . X2"; o f t h e intra; i n i n ~ ; ~variability
l
in R B F c o u l d b e e x p l a i n e d b y 1/[0.].,. T h e
Table 3. Rrrinul u r ~ dchoroidul hlood.florc,.s )c,irh rhc c~onc~onlirut~t
i~ulue.s/oraxe, st~.crc~t,~ic,
BP. PO,. PC'O., pll, atul /0./.,it, rile m,sc.c~t~dirlg
rt~
onrru of rhr 12 t ~ e ~ , h o1unlh.s
An~nial
Postnatal
age
(dayh)
Exper~nientno.
I
7
1
7
5
5
I
1
IY
I
I
7
5
65
65
I(H)
5
1(WJ
7
5
I(M)
3
h
h
h
7
7
7
X
X
Y
Y
148
148
148
75
75
75
149
149
149
226
ZZh
10
13
I0
II
13
4
4
II
12
4
5
7
3
4
4
X
II
Mean
>ystem~c
I
I
-7
3
I
7
3
I
7
3
1
3
2
3
I
7
3
I
(rill
KBI
nlln ' lo() g
C'hHl:
HI'
'
(torr)
1'0,
lJ( '0:
(ntM)
(torr)
(rorr)
296 l
4 24
71
43
7 74
Xh
YO
3966
3Y2Y
5.18
4.5'
h i
63
37
36
7 42
7 41
YX
53
hY
S3
104
89
2613
2x39
2033
28x4
2303
2930
5.27
h 52
6.65
6.34
hh
6.70
70
6')
67
hi
62
68
37
3h
36
35
35
35
7.41
7 40
7.4 l
7 47
7.44
7.43
75
40
57
hl
52
77
5X
62
YO
45
71
IY2 0
1985
1550
3247
295 I
2x67
2733
247
2h5X
2195
2619
6.42
h 70
6.88
8.04
7 h3
7 XI
6.99
6.XO
6.6 l
h 63
h 33
72
73
73
64
65
hY
73
74
74
71
7X
37
3X
37
34
35
34
33
31
33
35
29
7.40
7 39
7 39
7 37
7.4 1
7 47
7 30
7 41
7 40
7 42
7 40
49
32
3h
40
3151
249s
1130
383'4
75
XI)
h 67
0.7 I
hl
hh
7 12
6.99
hS
67
4I
37
40
37
7.40
7 39
7 34
7 33
4I
SO
3924
2634
6.72
h 74
h7
h i
37
42
7 34
7.30
')
( m l , min
I(NI g ' 1
1 0 2 1
\OX
Y9
lo4
YO
85
X5
101
X5
,
(14
-!p!
- -
Fig. 3 Kelatlonsh~pof
the ascend~ngaorta
k t a )l . (
and neonatal
(
)
KHI- w~th10!1,, ~n
close relationship between K B f ' and l/[O,j],,indicate!, that the
maintenance of oxygen delivery to the retlna by way o f t h e retinal
vessels is carefully controlled over a wide range of oxygenation.
However. it should be e m p h a s i ~ e dthat the microsphere technique
as used in this study did not permit assessment of regional tlows
and oxygen delivery to various areas o f t h e retina. Rather. to have
sufficient tissue (and therefore adequate numbers of mrcrospheres)
for quantitation. the ret~nalflow as a whole was studied. I t 13
possible that the reciprocal relationsh~pbetween KBF and 0:
content described for the retina as a whole. may not he true fix a
selected area (1.e.. the periphery).
To our knowledge. R B F In the fetus has not previously been
measured. In adults. it is generally accepted that the arterial PO:
is an rmportant flow-regulating factor in the retina ( 6 8 ) .However.
i t is still obscure whether R B F correlates better with 02-content
or with PO2 in the .supplying artery. In the present btudy. both
[OJ].,and Pa@ were altered simultaneously. Thus. i t was Impossible to determine if one of the two ~ndices for oxygenation
correlated with fetal R B F better than the other. Jones cr al. ( 10)
lound that cerebral blood flow in the fetal lamb correlated better
b
'"
2
,
2')
JC,
q'
;
(.I
sost natat age
3.7il
ai',
1.1g 4. Keldt~~in\li~p
o f ( hHI ( I .ind K H I
u ~ t hpo\tnatdl age 1-he
decredzed \~gn~licantl)
u11h po\rna~~11
age
C'hBI
with [O.]., than w ~ t hP a 0 2 . [ 0 , ] . , is of fundamental Importance to
the organism. ('ain ( 4 ) found that under circumstances of extreme
oxygen deprivation ln the adult, whole-body 0, uptake was
determined by [021.,
rather than P a 0 2 . Although there is no such
inli)rn~ationiivallable for the retina. it is pos.sible that RBI-'
Further ~nvest~gations
arc
responds directly t i ) changes In [02].,.
required.
The range of (O.]., and PaO, in the newborn lambs was too
zniall to pernut conclusions about the f l o w - a relatton\h~psin the
retinal circulation of the newborn. In the case of both [ O , ] , ;ind
I'a02. however. the neonatal d a t ; ~points appear to Ibllow the
trend established by the fetal Ilow-0. relationships in the higher
ranges 01' [O,],, and PaO. ( F ~ g b 3. and 5 ) . Further enperrrnents
covering a wider range of [O,], levels in the neonate are needed
2 I)
.2#7
P
,
di
h(
rrmd nq dart a
8
HO
tnrr r
to determine whether the flow-0, relatlonshlp is the same durlng
the fetal and newborn periods.
I t has been demonstrated that blood How In the adult retina
changes markedly with variations in arterial f'<'O: (Pa('*) ( I .
17). In the present study. the range of PaC'O., In both lkti11 and
neonatal I a m b was too small to permil ;I conclusion about the
presence of this relationship in these lilk phases.
Although Ictal C'hBI: was not correlated wrth (031.,.
home
interesting phenomena were observed in the pcrinatal period.
First. the hlood flow to the chorold was xignilicantly higher alier
birth. Inasmuch as the blood pressure is higher in the newborn
( 5 ) . this might rellect a lack of autoregulat~on in this tissue
structure. as has been reported fi)r the adult a n ~ r n a lby Alm and
Bill ( I ) . Second. in the first 5 months after h ~ r t h C'hBF
.
tends to
decrease with age whereas syhteniic blood pressure has been
reported to increase (5. 20). This suggests a delayed development
( \ I < 1 I \ l l O V 0 1 1 1 1 1 1'1 K( k \ I l l I I K K O K 1 \ 1 1 [ I l l
of' the ulttrnate "mature" vascular reststance in the choroidal
\ < , I 0 1 I N l K \ \ h l b l \ I \ \ K l \ I l O h I \!'I
\ I N 1 1 ) I{\ \
vascular bed. O n e might speculate that. in con~pariaonwith the ( , [ 1'1\ I KcN II NI O1 W
r 0 \ \ ( ~ l N b l 0 I ) l 1 \N \ I k f l 1) N l T l f TI11 N'l l ~ ~ l l I )l l
mature newborn state. the vascular resistance in the premature
I I \ \ I \Ql \ K t \ M I I I I O I )
choroid is even lower and consequently blood flow is h ~ g h e rat
(stochastic
variables
are underlined)
a n y given perfusion pressure. Such a high flow rate. together with
the absence of a n 0.-related Ilow regulating nicchanism. would
, l = ~ + t ~ , + / t ' ( y x , l +( ,i =l 1. . . . . N : j = I. .... N , )
greatly favor the development of' high local tissue oxygen tensions
in premature babies treated with high environmental oxygen.
where N = number of' animals: N , = number of experiments in
C'learly, further studies are needed both in terms of delining the i'" animal.
regional changes in R B F and <'hBF at various levels of oxygenation and also by alteration In O 2 capacity. niore sharply delineating the role of Pa@ vcrr.scts0 2 content in the regulation of RBI:.
where y,, = blood flow measurement In the j'" experiment ol'the
i'" aninial; p = a constant equal for all animals: 11, = additive etlrct
due to the i"' animal: /I, y = regression coeffic~ents;~ssuniedto be
I r n . .\. .ind HIII. :\ 711e ~ r \ \ g c r\uppl\
~
1,) ~ l l cret1n.i I I 1 l l c c ~ \t t 1 I i ~ g l11it1.1~
<Icul:~rprc\\urc .lnd (11 111crc:iwd:irtcr1'11 ~~1rha111
d10\1de ter1\1011,111u\e:~l.i~id the same ti,r each animal: x,, = value t,r [O-I,,in the j'l' experiment
re111iaI h l ~ ~ c11<1u
d 111 '.it\ ,\ct:~l'li!\~ol Sc,lnd , ,SJ 3111> I ILl7?j
of the i"' animal:
x , , ) = I'unction of' x,, and y ( c . ~ .f (. y . x,,) =
IiiII. :\ 0 c u l . i r illid I I ~ ~ nI eL r \ c h l c ~ ~Ilou
d .!I rn,rr~~:il
: I I I ~~~icre:~\cJ
.\111i. .\ .
I / x , , , o r f ( y , x , , ) = e . x , , . ~ r f ( y . x , ~(In
) = x,, + - ( ) / x , , J : e , , = e r r o r
~ ~ i ~ r . i - ~ ~prc\\ilrc\
~ u I , ~ r I I I ~ ~ ~ ( > n h( c~ \~\ i : i c . il ~
r u.\~) \ t ~ l c I \ u1t11 r . ~ d ~ < ~ . i c t ~ \ c l !
ldhcllcd r ~ ~ ~ ~ r o \ p hI cI Ir Ce ~\ L I ~ I 11<1u
I I ~ d c t c r ~ i ~ ~ ~ i .111
it~
hr.1111
o ~ ~c\ ~ r \<>111c
~ d
c>~ticr term w ~ t hexpectation Lero and standard deviation proportional
li\\ue\ I \ p I.\e K c \ . 15 15 ( 1 9 7 1 )
t o the expectation ~ t ' y , ~ .
Bi~ckherg,( i I ) . L U L L , J ( , IJ:i!nc. 0 l i . IIOIIIII.III. J I I . ~ l r c l ~ J~ c1'.. :IIIC!
T h e observed value f\)r v,, and not the expected term 01' v,, 15
I , \ t ~ ~ , I ,) I
S<>,,,C
<,I <.,,,>r I t 1 ,,,,..,\,,r,,,)7
r~).l<~,,,,l
l>l<>,>,l
1 1 , ~u,1t1
~
s u l > ~ ~ ~ t i lii t) rc J~ h crl-<)Ic
tcrm I., in the n1tIdc.l :~h<)ve
r : i ~ l ~ c ~ . i ~r ~
. ~~~~\cer < > \ p I i Jc r e.\ppl
\
I ' h \ r l c ~ l . 1 1 i c / X I 1'17 1 I
In this model, estimates i~,
ti,. /i. and of, respectively. 1,. o,./ I .
('.II~, S M
O \ \ g u i d e l ~ \ r r \,tncI trp~:thr~n dog' durlrig . I I I ~ ~ I I.rnd
C
JI?I>O\IC
t i \ p < ~ \ ~J . Appl
~
I ' h \ \ i c ~ l . 4.' ? ? h ( 1 ' / 7 7 )
and y were deterrn~nedin such a way that
K l l I KI N( I S \NI) N O I I S
I
?
3
\6>,,,L<.\
4
5
t~g~
01 M ~ ~ I LI 1Ai rIh l ~ ~ I i c r ~ .
l ) . i ~ c \ .( i S I e1.11 :trid Ncc,r~:t~:tll ' J i \ \ ~ ~ ~ l~Ye.irht>ok
< tllcdg,>,I ' I O S ~
I . lJ~1lp111,
(
J , L ~ Ks)Iincr,
~ ~ d 1 bl O\\gcri \uppl) 1,) llic rclirlai
111c rct111:iI J I I ~c l i ~ ~ r ~c ~ r~c~u l .~~ il ~l &it
~ i 11<~rri1.11
~i\
. I I I ~i r ~ c r c ~ ~ \cirtcr~.~l
cd
,~\~gcri
I L V I \ I G > I I \ I I I \ ~ , I Opti~t~.~l~~i,~l.
,S i x x I l C l f + l ~
was
t ,~rtcrl.iI1 ' 0 C I I I rel,111\c
7 t.pcroli. ( ; . J o h l i \ o n . M . :1ri4 Nohlc. J K 1 . 1 1 ~c l l c ~ ,)I
retlnal h l t ~ o dIliw 111 nh,nhc\\ In\e\l Oph~h.iln~i,l.
l J 142 ( I U 7 i l
X I l ~ c h l i ~ i nJr . 1 3 . .ind I r.i!\cr. K S111dic\ $11 rc11ri.il L I I ~ I I ~ . I ~ I O 111
I I 111:111 Oh\cr\.i.
II,>II\
,111\e\\cl d ~ . ~ n i c t c,irterlo\c~icn~\
r,
1ix>ge11~ l ~ l l c r cJ ~I iI ~~I cI I ~ C L~I ~~ r ~ l ~ I : i t i o ~ i
0 l)<!llcr>,(
Irc>111
1111ic(
~rclll.il~~,n.
.'1
Ill? ( Ic~1,01
I : I I I I ~ ~ ; I I ~J . T l11\1or\ 01 o\\ge11 tIicrakp\ . I I I ~ rctr~ilc~it:~l T h e
1ihr~1pI.1~1.1
l'ed~.~lr~c\.
i- i c l l I l'I7hl
I 0 Jc~nr,.M I ) . J r . Sheldun. K I . I'eetcr\. I I . bl.ihou\h~, I I . ,111d h1c~cli1.1.
(; K e g ~ ~ l ~ i(11t ~eerchr.11
o~i
h l c ~ ~11<1u
d 111 llic c > \ i ~ ilctu\
c
\ I I I I I ' I I > \ I < ~ I. - ' i T
I 1 162 ( ICJ7Xl
'I
minimdl
J ; i ~ ~ i c I\ . S . .i~id
percentile error w a determined as li~llows:
where p =
N + I. ~ncaae ol'one regreasron coeflicient ( P )
... .. . N
I N + 2. ~n case of two rcgreasion coeflicienth (I<.
/'
Y
-
-().
If
11 could be aaaurned
( t h u / j = 0). estimate5
that blood Ilou wa5 independent o f [O:].,
i~,
for /I + ( I , could be determined in such
a way that
thus
I
li,= N,
l' ( 1 /y,l
I
,. ,.
- N
I
1
N
,
I
[
yll
-
(11
!)I
+ (I,}
I/>,,
I
)?
I
I'
wa5 minimal.
Let: 11, = 11 + ( I , . then the t'unction:
Remark 0 5 S,,,,,,5 S
:\ n1ea5ure 01' the expla~ncdvarlatlon ~n blood flow balue5 b! a
gl\en (low-oxygen I'unctiun was ohta~nedh!
would be rnin~nialwhen the part~aldcrr\ati\es,
= 0 li)r r = 1.
oi~,
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