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FETAL OXYGEN CONSUMPTION, CARBON DIOXIDE PRODUCTION, AND GLUCOSE UPTAKE IN A CHRONIC SHEEP PREPARATION

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(Received February 28; accepted for publication March 28, 1972.)

Supported by U.S. Public Health Service grants HD-00781, HD 01632, and HD 01866. Presented in part to the Society for Pediatric Research, April 1971.

ADDRESS FOR REPRINTS: (F.C.B.) Container 2302, 4200 East Ninth Avenue, Denver, Colorado 80220. PImIArrncs, Vol. 50, No. 3, September 1972 361

FETAL

OXYGEN

CONSUMPTION,

CARBON

DIOXIDE

PRODUCTION,

AND

GLUCOSE

UPTAKE

IN A

CHRONIC

SHEEP PREPARATION

Elizabeth J. James, M.D., John R. Raye, M.D., Edwin L. Gresham, M.D., Edgar L.

Makowski, M.D., Giacomo Meschia, M.D., and Frederick C. Battaglia, M.D.

From the Divi-sion of Perinatal Medicine, Departments of Pediatrics, Physiology, and Obstetrics-Gynecology, University of Colorado Medical Center, Denver, Colorado

ABSTRACT. Metabolic studies were carried out in 22 sheep fetuses free of operative stress. The studies included measurements of umbilical blood flow (175 ± 8 mi/mm/kg), fetal oxygen consumption

(5.99 ± 0.15 mi/mm/kg), carbon dioxide

produc-tion (5.65 ± 0.17 ml/min/kg), glucose uptake

(3.06 ± 0.28 mg/mm/kg), respiratory quotient

(0.94 ± 0.01), and glucose/oxygen

quotientS

(0.41

± 0.03).

The studies demonstrated that fetal

glu-cose uptake could be correlated with the glucose

concentration difference betsveen maternal arterial

and fetal umbilical arterial blood, as well as with

maternal arterial glucose concentration. Umbilical arterial glucose concentration was a function of ma-ternal arterial concentration over the concentration range studied. The study demonstrates that the fetal respiratory quotient is significantly less than one. These data suggest that the accumulation of carbon in the fetus for growth represents approximately 40% of the carbon intake in the growing fetal lamb.

Pediatrics, 50:361, 1972, FETAL OXYGEN

CON5UMP-TION, FETAL RESPIRATORY QUOTIENT, FETAL GLUCOSE

UPTAKE, MATERNAL-FETAL GLUCOSE DIFFERENCES.

IN

the past, physiologic studies of the

fe-tus utilized acute preparations in which surgery and anesthesia may have induced profound metabolic changes. In addition,

each such study had a limited scope, such

as the measurement of fetal oxygen

con-sumption or fetal glucose utilization. Thus, our present knowledge of fetal metabolism is based upon data collected in different and abnormal physiologic states and may

be biased by differences of techniques.

In order to obviate these pitfalls, a new methodology has been developed that

per-mits the simultaneous measurement of the

uptake and excretion of several metabolites

across the placenta of a chronic sheep prep-aration.

The present study was designed to

mea-sure simultaneously 02 consumption, CO2

production, glucose uptake, and urea

excre-tion of fetal lambs between four and nine

days after surgery. A detailed description of

the urea excretion data will be reported in a separate paper.1

MATERIALS AND METHODS

Surgical Preparation

Twenty-two pregnant Dorset and mixed

breed (\Vestern type) ewes

were

studied. The gestational ages of the fetuses on the day of catheter placement ranged from 121 to 140 days as estimated from the breeding records. The ewe was starved for 48 hours

prior to surgery but was allowed water ad

libitum. Surgery was performed with the

ewes under intravenous sodium

pentobar-bital sedation and spinal anesthesia (6 mg tetracaine hydrochloride [Pontocaine]).

Polyvinyl catheters were placed in a branch

of the fetal umbilical vein and in the mater-nal femoral artery according to techniques

previously descnibed,2 and in the fetal

ped-al artery and vein. Access to the latter two

vessels was gained by incision on the

(2)

>. I-,-, z 4 o6 0 z Q i5 U UA34 CIA 1A 5.50

. . S

5.00 4.50 4.00 #{149} S 3.50 S S E z w I-z 0 U z UI (3 ‘C 0

Fic. 2. The whole blood oxygen contents in the

umbilical artery (a) and umbilical vein (y) of animal UA 34 are plotted against time. Time zero

as in Figure 1.

362

60 70 80 90 100 110 120 130

TIME (n*tutes)

Fic. 1. Whole blood antipyrine concentrations in

the umbilical artery (a) and the umbilical vein

(-‘) of animal UA 34 are plotted against time.

Time zero is the beginning of the antipynine infu-sion in the fetus.

Animal Maintenance

On the first postoperative day, the ewes were brought from the animal quarters to a smaller sampling laboratory where they

were maintained in small individual pens

and allowed food and water ad libitum. All catheters were flushed daily with 1 ml of di-lute heparin solution (1,000 units/mi sa-line) to insure patency. Procaine penicillin

G (600,000 units) and streptomycin (500

mg) were

given intramuscularly to the ewe

on the day of surgery and on the following three days. All fetuses were allowed to

re-10 80 90 1#{212}0 rio

TIME (minutes)

120 130 140

cover from the surgical procedure for at least four days before study. Studies were repeated one to five days after the initial experiment in 16 of the 22 animals. The ewe was then sacrificed and the fetal weight obtained. An estimate of the weight of the fetus on the day of initial study was calculated by extrapolation from the termi-nal fetal weight, using the fetal growth curves.3

Experimental Procedures

In each experiment the fetus received a constant infusion of antipynine through the

pedal vein catheter for the purpose of mea-suning umbilical blood flow by the steady state diffusion technique. The infusion rate averaged 0.1 mi/mm and the concentration of antipyrine in the infusate was between 75 and 150 mg/mi of isotonic saline,

de-pending on the estimated fetal size. Sam-pling of maternal and fetal blood was

be-gun 60 minutes after beginning the antipy-nine infusion. Five to seven sets of blood samples were drawn at approximately 10-minute intervals. Each set consisted of three samples drawn simultaneously from maternal artery, fetal artery, and umbilical vein. The maternal sample was a 2-mi blood sample drawn in a dry plastic syr-inge. This sample was used only for

glu-cose determinations. Each fetal sample

con-sisted of 1 ml of blood drawn in a dry

plas-tic syringe and 0.3 ml of blood drawn an-aerobically in dry, hepaninized glass

capil-laries containing 0.3 mg of NaF. The blood in the plastic syringes was used for glucose

and antipryine analysis, the blood in the capillaries for 02 and CO2 determination. At the beginning and the end of each ex-periment, 1-mi samples of fetal arterial blood were drawn for pH and hematocrit determinations. Total fetal blood loss in each experiment was kept below 20 ml, and there was no change in the hematocnit of

fetal blood.

Analytical Methods

Antipryine concentrations were measured

(3)

auto-TABLE I

FETAL ARTERIAL BLOOD DATA

363

matic chemical analysis

(

AutoAnalyzer ).

The AutoAnalyzer samples were run using a 30/hr 2/ 1 cam with two water blanks

be-tween samples. Oxygen and carbon diox-ide contents were measured on 0.1-mi blood samples by gas chromatography, using a

chromatograph

(

Beckman Model GC-2Af) with parallel columns. Blood glucose was determined by the glucose oxidase method after immediate deprotcinization of 0.1-mi blood samples with zinc sulfate and barium hydroxide. B’ood pH was determined at 39.5#{176}Cby means of a capillary glass elec-trode.

Data Analysis

Umbilical blood flow (f) was calculated according to the following equation:

RI-RM-RL

f = 0.98 [Ala

-

[A} [i]

where R1 represents the rate of antipyrine

infusion, R1 the rate of antipyrine

metab-olized by the fetus, and R1, is the rate of ac-cumulation of antipynine in the fetal body

water. The [Ala

-

[A],. difference is the concentration difference of antipyrine in the fetal arterial and umbilical venous plasma, respectively. The 0.98 coefficient represents the conversion factor from plasma to blood

concentration for antipyrine. The RM was

calculated as in the original paper.4 The RL

factor was calculated as the product of fetal body weight times the slope of the line re-sulting from a plot of concentration of anti-pyrine in the fetal artery against time as

determined by the method of least squares. This procedure is well suited to the steady state of a chronic preparation in which the rate of accumulation of antipyrine in fetal body fluids is a linear function of time (Fig. 1). The combined rates of fetal antipyrine accumulation and metabolism were a small

fraction of the infusion rate in all animals

(mean, 8.3%; range, 5.2% to 12.2%). Similarly, during each study period at least five paired arterial-venous samples were obtained for measurement of oxygen, CO2 and glucose content. Figure 2 shows the values for

oxy-.

llematocrit pH mM/i02 CO2

mM/i

mean 34.5 7.384 3J27 24.O

S.D. 4.7 0.034 0.65 1.76

SEM 0.8 0.006 0.11 0.9

gen content in the umbilical vein and fetal artery during the same study period as in Figure 1. Since the variability of arterio-venous differences shown in Figure 2 is probably in large part a reflection of sam-pling and analytical errors, no attempt was made to compute multiple 02 consumptions from such data. The average variance (2) of

the arteriovenous differences of oxygen in mM/i within a study period was 0.05. Mean arterio-venous differences of 02,

CO2

and glucose were calculated from all the data of one experiment and used to compute

mean fetal oxygen consumptions, carbon di-oxide productions, and glucose uptakes ac-cording to the Fick principle:

fetal 02 consumption = umbilical

venous-arterial concentration difference of

02 X umbilical blood flow

fetal CO2 production = umbilical arterio-venous concentration difference of

CO2

X umbilical blood flow

fetal glucose uptake = umbilical venous-arterial concentration difference of glu-cose X umbilical blood flow.

Fetal arterial blood pH was determined using a pH meter (Radiometert Model 4) during each study period; acidosis did not occur in any of the animals studied (range,

7.300 to 7.465).

In 11 of the animals used in this study, fetal urea production was estimated also. The method used to measure urea produc-tion will be presented in a separate paper.1

o Technicon Instruments Corp., Tarrytown, New York.

fBeckman.

(4)

UA4 4 139 3.76 31 5.70 5.36 0.94

6 141 4.04 Q7 5.59 5.00 0.89 2.97 0.42

UA9 4 144 3.54 264 6.27 6.70 1.07 1.53 0.19

6 146 3.80 220 5.77 4.95 0.86 2.95 0.40

UA28 4 129 3.20 147 5.18 4.81 0.93 2.16 0.33

6 131 3.44 137 5.31 4.69 0.88 4.78 0.70

UA34 4 130 2.74 198 7.82 7.89 1.01 3.75 0.38

7 133 3.04 198 7.82 7.08 0.91 5.54 0.55

UA36 4 140 3.52 128 5.43 4.94 0.91 1.80 0.26

UA37 7 145 3.69 190 7.29 5.82 0.80

9 147 3.96 179 5.38 5.13 0.95

UAS8 4 134 3.35 211 7.16 7.10 0.99

6 136 3.60 128 4.53 4.50 0.99

UA39 4 127 2.00 172 7.09 6.91 0.97

6 129 2.15 156 5.73 5.29 0.92

UA4O 5 138 3.12 189 7.44 7.07 0.95 3.03 0.32

6 139 3.23 203 6.42 .5.55 0.86 2.17 0.26

UA4I 5 132 2.66 131 7.06 7.20 1.02 6.09 0.68

6 133 2.76 124 6.84 6.50 0.95 4.96 0.57

TWIN PREGNANCIES

UA 1 7 133 3.68 169 5.29 3.07 0.48

UAS 6 127 2.19 272 5.84 5.20 0.89

9 130 2.44 203 5.59 5.42 0.97 2.74 0.38

UA 10 4 127 3.51 172 6.05 5.48 0.90 3.78 0.49

7 130 3.90 UI 5.97 5.87 0.98 5.88 0.78

UA11 4 127 2.94 164 6.56 6.23 0.95 1.67 0.20

9 132 3.52 172 6.17 6.34 1.03 1.18 0.15

UA12 4 141 4.40 116 4.90 4.61 0.94 3.02 0.48

UAIS 4

5 141

142 3.81

3.94

170

149

5.23

5.24

5.72

4.02

1.10

0.77

3.37

2.56

0.51

0.39

UA17 5 189 4.05 228 5.56 4.98 0.90 1.64 0.23

UA19 4 131 2.43 194 6.05 5.31 0.88 3.31 0.43

UA 0 (growth. 6 133 1.87 174 4.81 4.46 0.93 1.74 0.28

retarded fetus) 8 135 2.00 133 4.41 4.40 1 .00 1 .59 0.28

TABLE II

SUMMARY OF DATA

Days Gestational Fe/al Umbilical 0 CO2 Fetal Gluco8e

Fetal Glucose/02 Animal No. Post- Age Wcigh Blood Flow Consumption Production RQ Uptake

Quotient

op. (days) (kg) (mi/mm/kg) (ml/min/kg) (mi/mm/kg) (mg/mm/kg)

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TABLE II (Continued) Animal No Days Post-op. Gestation Age (days) a! Fetal Weight (kg) Umbilical

Blood

.

Flow

(ml/mnzn/kg) 02 Consumption . (mi/mm/kg) CO2 Production

.

(mi/mm/kg) F eta RQ Fetal Glucose Uptake

.

(mg/nun/kg)

Glucose, ‘0

Quotient

GT413 8 141 ‘2.68 144 5.94 5.79 0.98

UA26 (ill ewe) 4 5 125 126 2.50 2.59 186 203 4.80 4.88 5.21 4.56 1.08 0.94 1.00 2.51 0.16 0.40 UA27 4 6 128 130 2.66 2.85 185 129 6.20 6.09 5.90 5.88 0.95 0.96 2.05 3.37 0.26 0.43 RESULTS

The concentrations of 02

and

C02,

the

pH and hematocnit in the blood drawn via the fetal pedal artery are summarized in Table I. Table II presents the mean data obtained on umbilical uptakes in all experi-ments. For comparative purposes, the data are expressed per kilogram of fetal weight.

The single and twin pregnancies are grouped separately.

Fetal Oxygen Consumption

The fetal 02 consumption for all animals

was 5.99 ± 0.15 mI/mm/kg. The means for the single and twin pregnancies were 6.31 ±

0.23 and 5.56 ± 0.14, respectively, differ-ences which were of borderline significance

(P < 0.02). Figure 3 presents the fetal 02

consumption as a function of fetal weight. The relationship was best expressed by a second order regression, suggesting that fetal 02 consumption tends to plateau at the end of pregnancy. There are two animals

(UA 20 and UA 26) whose data are plotted but not included in the calculation of re-gression lines in Figure 3 and all subsequent figures. The reasons for their exclusion are as follows: tile fetus of animal UA 20 was markedly growth retarded, being the smaller of discordant twins (2.0 versus 3.87 kg), and animal UA 26 was ill with chronic diarrhea and hypoglycemia at the time of study. Figure 3 shows that tile lowest fetal 02

consumption was found in the intra-utenine growth-retarded fetus on two occasions.

Figure 4 presents the fetal 02

consump-tion expressed per kilogram of fetal weight. The 02 consumption decreases as fetal

weight increases, indicating that the smaller fetuses consume more oxygen on a weight basis. The lower 02 consumptions found in animals UA 20 and UA 26 compared with

the rest of the group are evident.

Respiratory Quotient

The mean carbon dioxide production for all animals was 5.65 ± 0.17 nil/mm/kg. The carbon dioxide production showed the same relationships as did oxygen

consunip-tion to fetal weight and gestational age. These data are presented in Table II. The mean respiratory quotient was 0.94 with 99% confidence limits 0.92 to 0.96 as ob-tained by Fieller’s theorem. No relation-ship was seen between RQ and fetal weight or gestational age over the time period studied.

Fetal Glucose Uptake

Figure 5 demonstrates that fetal glucose uptake was directly related to the glucose concentration difference between maternal arterial blood and fetal umbilical arterial blood (A-a). Over the concentration range

studied (maximum A-a difference = 40 mg

I 100 ml) there was no evidence of a maxi-mum fetal glucose uptake having been reached. The differences in glucose uptake versus A-a for the intra-uterine growth-re-tarded fetus, UA 20, and the ill ewe, UA 26,

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glu-25

20

15

10

x

‘C

#{149}Twin

U ISjflgI#{233}

#{149}GR sIE

1.5 2.0 2.5 3.0 3.5 4.0 4.5

FETAL WEIGHT (Ka)

Fxo. 3. Total umbilical oxygen uptake (o2) for all animals is plotted against fetal weight (W). The curve drawn through the points was computed by second order

regression analysis. In this, and all subsequent figures, the data from the ill ewe UA 26 (IE) and the intra-uterine growth-retarded fetus UA 20 (GR) were not

included in the calculation of regression equations.

C

I

Ui

0. z Ui

Ui LI.

cose concentration and fetal glucose uptake, as shown in Figure 6. Umbilical arterial glucose concentration also was a function of maternal arterial glucose concentration, as shown in Figure 7. Since fetal glucose up-take was a function of maternal arterial glu-cose concentration, there was a range of fe-tal glucose uptakes in the animals studied from 1.00 to 6.09 mg/min/kg, with a mean of 3.06 ± 0.28 mg/mm/kg. The glucose! oxygen quotient, representing the fraction

of the total fetal oxygen consumption re-quired to completely metabolize aerobically

the glucose acquired by the fetus via the umbilical circulation, was calculated for

each fetus. A mean glucose/oxygen quotient of 0.41 was found, indicating that a maxi-mum of 41% of the oxygen consumption could be accounted for by glucose metabo-lism. The glucose/oxygen quotient was a function of the maternal-fetal arterial con-centration difference of glucose.

DISCUSSION

Data from previous studies in sheep on fetal oxygen consumption are summarized

in Table

III.

The range of oxygen consump-tions reported from different laboratories is from approximately 4 to 8 ml/kg/min, a range which is comparable to the

animal-to-animal variation observed within the present study.

The present study demonstrates that the fetal respiratory quotient is significantly

less than 1.00. Early indirect estimates of

fetal RQ included measurement of the ma-ternal

RQ

before and after occlusion of the placental circulation,6 with the conclusion that the fetal RQ was one. In vitro esti-mates of the fetal RQ as being equal to one have also been reported. These findings have been interpreted as supporting the concept that carbohydrate is the most

im-portant fetal metabolic substrate. However, it must be kept in mind that even if the fe-tal RQ were equal to one, the conclusion from such data that the fetus is obtaining his major support from the metabolism of

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negligi-.

C

Ui

a

I

FETAL WEIGHT (Ka)

3.5 4.0 4.5

FIG. 4. Umbilical oxygen uptake in mi/mm/kg fetal weight. Symbols as in Fig. 3. Regression equation for data:

Qo0/kg 7.939-0.574W.

6

5

4

3

2

I

*

a

10 20 30 40 50 60

A-a GLUCOSE CONCENTRATION DIFFERENCE (mg%) C

Lu

FIG. 5. Umbilical glucose uptake in mg/mm/kg (1/kg) for all animals vs the glu-cose concentration difference between the maternal arterial blood (A) and the umbilical arterial blood (a). Symbols as in Fig. 3. Regression equation for data:

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6

I

Lu

4

Lu

U)

0

‘4

a

10 20 30 40 50 60

Lu

(I) 0

1

MATERNAL ARTERIAL GLUCOSE (mg%)

data:

a = 0.461 + 0.356A.

MATERNAL ARTERIAL GLUCOSE (mg%)

FIG. 6. Umbilical glucose uptake for all animals (/kg) vs maternal arterial glucose concentration (A). Symbols as in Fig. 3.Regression equation for data:

Qg/kg -0.0394+0. 087A.

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TABLE III

COMPARISON OF MEAN (± SEM) OXYGEN CossuIPTIoNs AND UMBILICAL BLOOD Fwws

Reference Animal

.

Number

of

Cases

FetalAge

( s)

Uminlical

Blood Flow

(mi/mm/kg)

Fetal 02

.

Consumption

(mi/mm/kg)

.

Type of Preparation

12 Sheep 10 135-146 104 4.2 ± 0.2 Acute, fetus exteriorized

13 Sheep 22

10

87- 95 137-141

217 ± 12 170 ± 14

5.4 ± 0.5 4.6 ± 0.3

Acute, fetus exteriorized Acute, fetus exteriorized

14 Sheep 24 81-136 199 ± 16 6.9±0.4 Acute, fetus in utero

Sheep and Goats 16 102-139 233 ± 19 7.1 ±0.4 Acute, fetus in utero

Sheep and Goats 17

9

6

83-147 93-130

100-146

231 ±25 245 ±43

302 ±30

8.4±0.5 8.4±0.5

8.5 ± 0.3

Acute, fetus in utero Acute, fetus in ulero

Chronic, fetus in utero

Present Investigation Sheep 20 121-140 175 ± 8 6.0 ± 0.‘2 Chronic, fetus in utero

ble with respect to excretion. It can be shown that the carbon accumulated during growth is not a negligible fraction of car-bon excretion. Using our data on fetal

growth, glucose uptake, carbon dioxide pro-duction, and urea excretion in the sheep fe-tus, it is possible to estimate the amount of carbon transfer across the placenta in the unstressed fetus. The sheep fetus increases his weight by approximately 35 gm/kg!

day.3 Analysis of a homogenate of the whole fetus in seven of the fetuses studied

showed that the mean carbon content is 9% of fetal wet weight. The mean carbon accumulation of the fetus per day is, there-fore, equal to 0.09 X 35 gm/kg or 3.15 gm carbon/kg. The carbon gained by the fetus in the form of glucose can be estimated from the fetal glucose uptake:

3.06 mg glucose/mm/kg X 72 mg carbon /180 mg glucose X 1,440 mm/day =

1,763 mg carbon/kg/day

Carbon excreted as carbon dioxide is equal

to

5.65 ml C02/min/kg X 0.539 mg C/ml

CO2

X 1440 mm/day = 4,382 mg car-bon/kg/day

Huffman Laboratories, Inc., Wheatridge, Colo-rado.

and carbon excreted as urea is equal to4

0.54 mg urea/mm/kg X 0.2 mg C/mg urea X 1,440 mm/day 156 mg

car-bon/kg/day.

Total carbon excretion in the form of car-bon dioxide and urea is, therefore, equal to 4.38 + 0.156 gm, or 4.54 gm/kg/day. Since 4.54 gill/kg/day excreted must first cross the placenta from mother to fetus and 3.15 gm/kg/day crosses and is kept in the form

of weight gain, then a total of 7.69 gm/kg /day crosses from mother to fetus. Thus, on the assumption that CO2 and urea represent the only two major excretory products, the accumulation of carbon represents 40% of the carbon intake of a growing fetal lamb.

This study establishes for the first time

that there is a definite correlation between fetal glucose uptake and both maternal blood glucose concentration and the

mater-nal-fetal glucose concentration difference. Over the concentration range studied, there was no evidence of fetal glucose uptake

plateauing at a maximum value; i.e., no evi-dence of saturation of a carrier system over the concentration range which we have ob-served. Our findings are at variance with

those of Crenshaw,8 who reported that fetal glucose uptake varied from day to day and

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mater-nal glucose concentrations. The reasons for this disagreement are not readily apparent, since he also studied animals free of surgi-cal or anesthetic stress. Not surprisingly, a wide range of fetal glucose uptakes has been reported in animals studied under surgical

stress. Alexander, et a!. reported values of 5 mg/mm/kg in exteriorized fetuses, and others of 9 to 10.7 mg/mmn/kg/1O Figure 5 in the present report brings out clearly the

correlation between fetal glucose uptake and the concentration difference of glucose

between the two arterial streams. A very low fetal glucose uptake was found in the ill ewe (UA 26) and in the intra-uterine

growth-retarded fetus (UA 20), although

for entirely different reasons. In the ill ewe, maternal hypoglycemia developed, estab-lishing a low A-a glucose difference and, thus, a low glucose uptake. In the intra-uterine growth-retarded fetus, glucose up-take was low despite a large A-a concentra-tion difference, strongly suggesting a marked inefficiency in placental exchange.

Finally, the mean glucose/oxygen quo-tient of 0.41 in the present study confirn#{238}s

our earlier observations in which we re-ported a mean quotient of 0.48 for fetuses of fed ewes,1’ supporting the concept that the fetus does indeed use substrates other than glucose for aerobic metabolism.

SUMMARY

Umbilical blood flow, oxygen consump-tion, carbon dioxide production, glucose up-take, respiratory quotients, and glucose! oxygen quotients have been determined in 22 sheep fetuses during the last third of pregnancy. Urea production rates were de-termined on the same fetuses and will be reported separately. Mean values ± SEM are as follows: umbilical blood flow, 175 ±

8 mI/mm/kg; oxygen consumption, 5.99 ±

0.15 ml/min/kg; carbon dioxide production, 5.65 ± 0.17 ml/min/kg; glucose uptake, 3.06 ± 0.28 mg/mm/kg; RQ, 0.94 ± 0.01; glucose/oxygen quotient, 0.41 ± 0.03. Fetal glucose uptake was shown to correlate both

with

the

glucose

concentration difference between maternal arterial and fetal

umbili-cal arterial blood and with maternal arterial glucose concentration. Umbilical arterial glucose concentrations were a function of maternal arterial concentrations.

IMPLICATIONS

The sheep fetus in the last part of

preg-nancy needs approximately 7.7 gm of car-bon/day/kg in order to meet the demands of growth (3.2 gm/kg/day) and excretion (4.5 gm/kg/day). It would appear from our measurements that only 22% of this

carbon crosses the placenta in the form of glucose. This estimate is important because it shows that the carbon accumulated dur-ing growth is a large portion of the total

carbon crossing the placenta.

REFERENCES

1. Gresham, E. L., James, E. J., Raye, j. R., Bat-taglia, F. C., Makowski, E. L., and Meschia, G.: Production and excretion of urea by the fetal lamb. PimIATlucs, 50:372, 1972. 2. Meschia, C., Makowski, E. L., and Battaglia,

F. C.: The use of indwelling catheters in the

uterine and umbilical veins of sheep for a

description of fetal acid-base balance and oxygenation. Yale J. Biol. Med., 42:154, 1970.

3. Gresham, E. L., Rankin, J. H. C., Makowski, E. L., Meschia, C., and Battaglia, F. C.: An evaluation of fetal renal function in a chronic sheep preparation. J. Clin. Invest., 51:149, 1972.

4. Meschia, C., Cotter, J. R., Makovski, E. L., and Barron, D. H.: Simultaneous measure-ment of uterine and umbilical blood flows and oxygen uptakes. Quart. J. Exper. Phys-iol., 52:1, 1966.

5. Fieller, E. C.: A fundamental formula in the statistics of biological assay, and some appli-cations. J. Pharm. Pharmacol., 17:117, 1944.

6. Needham, J.: Chemical Embryology. New

York: The Macmillan Company, pp. 728-729, 1931.

7. Dickens, F., and Simer, F.: The metabolism of normal and tumor tissue. Biochem. J., 24:

1301, 1930.

8. Crenshaw, C., Jr.: Fetal glucose metabolism. Clin. Obstet. Cynec., 13:579, 1970. 9. Alexander, D. P., Britton, H. G., and Nixon,

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10. Mann, L. I., Prichard, J. W., and Symmes, D.: The effect of glucose loading on the fetal re-sponse to hypoxia. Amer. J. Obstet. Gynec.,

107:610, 1970.

11. Tsoulos, N. G., Colwill, J. R., Battaglia, F. C., Makowski, E. L., and Meschia, C.: Compar-ison of glucose, fructose and 02 uptakes by

fetuses of fed and starved ewes. Amer. J.

Physiol., 221:234, 1971.

12. Dawes, C. S., and Mott, J. C.: The increase in oxygen consumption of the lamb after birth. J. Physiol., 146:295, 1959.

13. Dawes, C. S., and Mott, J. C.: Changes in 02

distribution and consumption in foetal lambs with variations in umbilical blood flow. J.

Physiol. 170:524, 1964.

14. Meschia, G., Cotter, J. R., Breathnach, C. S., and Barron, D. H.: The diffusibility of oxy-gen across the sheep placenta. Quart. J. Exp.

Physiol., 50:466, 1965.

15. Crenshaw, C., Huckabee, W. E., Curet, L. B.,

Mann, L., and Barron, D. H.: A method for the estimation of the umbilical blood flow in unstressed sheep and goats with some re-sults of its application. Quart. J. Exp. Phys-iol., 53:65, 1968.

RULES FOR PLAYING WITH THE BABY-AS RECOMMENDED IN 1914

In the first edition (1914) of Infant Care,

United States Children’s Bureau Publication

No. 8 (Washington, D.C.), parents were

warned about playing with their baby as noted

below:

The rule that parents should not play with the baby may seem hard, but it is w’ithout doubt a safe one. A young, delicate, or nervous baby especially needs rest and quiet, and however robust the child much of the play that is indulged in is more or less harmful. It is a great pleasure to hear the baby laugh and crow in apparent delight, but often the means used to produce the laughter, such as tick-ling, punching, or tossing makes him irritable and restless. It is a regrettable fact that the few minutes of play that the father has when he gets home at night, which is often almost the only time he has with the child, may result in nervous disturbance of the baby and upset his regular habits.

The mother should not kiss the baby directly on

the mouth, nor permit others to do so, as infections of various kinds are spread in this way. She needs also to be cautioned about rocking the baby,

jump-ing him up and down on her knee, tossing him,

shaking his bed or carriage, and, in general, keeping him in constant motion. All these things disturb the

baby’s nerves and make him more and more

de-pendent upon these attentions. But this is not to say that the baby should be left alone too completely. All babies need “mothering,” and should have

plenty of it. When the young baby is awake he

should frequently be taken up and held quietly in the mother’s arms, in a variety of positions, so that no one set of muscles may beconie overtired.

An older child should be taught to sit on the floor or in his pen or crib during part of his waking hours,

or he will be very likely to make too great demands

upon the mother’s strength. No one who has not

tried it realizes how much nervous energy can be consumed in “minding” a baby who can creep or walk about, and who must be continually watched and diverted, and the mother who is taking the baby through this period of his life will need to conserve all her strength, and not waste it in useless forms of

activity.’

NOTED BY T. E. C., Jn., M.D.

REFERENCE

1. West, M.: Infant Care (U.S. Children’s Bureau,

(12)

1972;50;361

Pediatrics

Meschia and Frederick C. Battaglia

Elizabeth J. James, John R. Raye, Edwin L. Gresham, Edgar L. Makowski, Giacomo

GLUCOSE UPTAKE IN A CHRONIC SHEEP PREPARATION

FETAL OXYGEN CONSUMPTION, CARBON DIOXIDE PRODUCTION, AND

Services

Updated Information &

http://pediatrics.aappublications.org/content/50/3/361

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(13)

1972;50;361

Pediatrics

Meschia and Frederick C. Battaglia

Elizabeth J. James, John R. Raye, Edwin L. Gresham, Edgar L. Makowski, Giacomo

GLUCOSE UPTAKE IN A CHRONIC SHEEP PREPARATION

FETAL OXYGEN CONSUMPTION, CARBON DIOXIDE PRODUCTION, AND

http://pediatrics.aappublications.org/content/50/3/361

the World Wide Web at:

The online version of this article, along with updated information and services, is located on

American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

References

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