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Glucose concentration gradients across the uterus and placenta of the pregnant primate
Glucose concentration
gradients across
the uterus and placenta of the pregnant primate CLARK
M.
VINCENT JACK Gainesville,
HINKLEY, G.
N.
M.D.*
STENGER,
BLECHNER,
M.D. M.D.
Florida
Glucose concentrations were measured in the femoral artery and vein of control animals, both pregnant and nonpregnant, to establish normal values in the Macaca speciosa. Uterine arteriovenous differences of total blood glucose concentrations were then determined throughout gestation in anesthetized animals at laparotomy. The changing pattern of glucose gradients across the placenta is described by simultaneous measurements of the glucose levels in the maternal uterine artery, the uterine vein, and the amniotic fluid. The glucose concentrations were also measured in the umbilical vessels at the time of delivery by cesarean section. Maternal arterial glucose levels are similar to those of the unstressed nonpregnant adults. Generally, the arteriovenous blood glucose difierence across the uterus tends to widen as gestation proceeds, showing increasing extraction of glucose from the blood perfusing the uterus. The glucose concentration in the amniotic fluid decreases steadily as pregnancy proceeds. The glucose gradients between the maternal and fetal vascular pools and the amniotic fluid reach a maximum in the last trimester of gestation.
species, also referred to as the stump-tailed macaque, was prompted by a desire to study a primate whose passive disposition makes the establishment of a normal steady state more likely under the conditions of experimentation. The importance of such a steady state has previously been emphasized by Battaglia.2 Review of the literature revealed the absence of established norms for blood glucose in this species and the need for describing the normal range of glucose concentrations before proceeding with further experimentation. For completeness, random determinations of total blood fructose were made in maternal and fetal blood samples; however, in no instance were the concentrations of sufficient magnitude to warrant further investigation.
T H I S R E S E AR C H iS part Of a COntinUing investigation of the placental transfer of essential substrates throughout gestation and concerns the movement of glucose across the placenta of the subhuman primate, Macaca speciosa. A previous study has been reported from this laboratory on the movement of glucose across the human placenta in patients undergoing elective cesarean section at term gestati0n.l In an attempt to understand the transplacental movement of glucose in greater depth, observations were extended to the subhuman primate. Choice of this From the Department Gynecology, University of Medicine.
of Obstretics of Florida
and College
This research was supported in part by United States Public Health Service Grants HD-01542, HD-01683, and HE-06379. *Present address: Department of Obstetrics and Gynecology, University of Alabama Medical Center, Birmingham, Alabama 35233.
Maferial
and
methods
These studies were mate Center of the 893
performed University
at the Priof Florida
894
Hinkley,
July 15, 1969
Stenger, and Blechner
Am. J. Obst. & Gym.
College of Medicine, Gainesville, Florida, using female Macaca speciosae. The monkeys were kept in large runs with free access to food and water. In the series used to establish normal fasting values for total blood glucose, the animals were kept off feed for approximately 12 hours. Each animal was caught by hand and its blood obtained by direct puncture of the femoral vein or artery. No attempt was made to draw simultaneous samples from both vessels. The passive disposition of the females allowed minimal restraint, and only occasionally did the animals appear excited. The duration of gestation in the pregnant animals was estimated from the probable date of conception as previously detailed by Stenger.3 Macaques used for determination of glucose gradients across the placenta at selected gestational ages were fasted for approximately 12 hours and anesthetized with intravenous sodium pento-
Table I. Total femoral animals
blood glucose (mg. s) and vein of nonpregnant
artery
Femoral
artery
Femoral
in
vein
Animal No.
Glucose concentration
Animal No.
Glucose concentration
6E4 6E8 5D3 6F3 6F7 6ElO 6E3 5D2 4L7 4L9 4L2 6E7 5A3 5A6 5A7
68.1 57.2 65.6 61.7 52.6 84.8 70.2 108.3 66.6 77.9 71.5 108.6 60.6 95.6 52.6
6E2 6E4 6E8 5D3 5D4 6El 6F4 6ElO 6E3 5Al 5D2 4L7 4L6 4L1 4L5 6F5 6F6 6FlO 5A3 5A6 5A7 5D5 5Cl
48.8 58.9 58.4 55.9 72.0 69.4 62.5 97.6 57.5 89.4 106.3 63.7 63.8 69.3 69.9 84.1 60.5 61.9 50.1 96.3 48.8 73.3 72.5
Mean 73.4 S.D. t 18.3 S.E.M. i: 4.7
69.1 Mean S.D. + 15.9 + 3.3 S.E.M.
barbital ( 15 to 20 mg. per kilogram). A previous suggestion by Chinnard and associates4 that this drug may cause wide fluctuations of blood glucose concentration was not apparent in our experiments. Using sterile technique at laparotomy, polyvinyl catheters were placed in a femoral artery, a uterine vein, and the amniotic sac. The abdominal incision was then loosely cIosed and the animal allowed to stabilize for approximately one hour before simultaneous samples were obtained from each catheter. When the period of gestation permitted, cesarean section was then performed immediately and samples obtained from the umbilical vessels. Specimens were collected anaerobically in heparinized glass syringes and respiratory gas measurements for other studies, as well as total blood glucose determinations, were made immediately. Glucose concentrations were determined calorimetrically, using the glucose oxidase method described by Huggett and Nixon5 after deproteinization of 0.5 ml. of blood with barium hydroxide and zinc sulfate solutions as described by Somogyi.” Results Total blood glucose values in the femoral artery and vein of nonpregnant animals are presented in Table I. The mean arterial con-
Table II. Total femoral
artery
Femoral
blood glucose (mg. “/o) in and vein of pregnant animals
artery
Femoral
vein
Animal No.
Glucose concentration
Animal No.
Glucose concentration
6E9 6E1 6E6 6F9 6E5 5A4 6E9 6FlO
76.6 43.3 56.9 101.8 54.7 71.4 94.6 109.4
6E9 5A4 5A5 6E5 5A5 6F2 6F9 6E6 6F8 6E4 6F10 6E9
76.2 53.3 58.8 57.4 54.7 54.3 75.6 56.4 62.5 68.4 97.0 44.4
Mean 76.0 SD. 8.5 S.E.M. + If:24.0
Mean 63.2 S.D. + 14.1 S.E.M. + 4.1
Volume Number
104 6
Glucose concenfration gradients
895
A A
A A
A A A A A A
A : A A
I
I
I 40
20
DURATION
Fig. 1. Change in amniotic
fluid glucose
/
I 80
60
1 120
100
OF GESTATION
i DAYS
concentration
during
I
I 140
160
I
gestation in Macaca
speciosa.
Table III. Total blood glucose (mg.aJ,) throughout gestation : Maternal arteriovenous differences and transpIacenta1 gradients Animal No.
Gestational we (days)
6E3 5A4 6F8 6F2 6F8 6F4 5D4 6E4 6El 6E8 6F7 6FlO 6E9 6F9 6E5 5A5 WA, @f-F
35 47 50 62 65 :: 94 97 102 111 132 141 161 162 162 maternal
sradient
femoral
artery;
iq the difference
MA”
MV’”
70.8 60.4 74.7 76.6 66.9 44.0 59.0 49.2 75.4 67.8 94.0 43.1 42.7 53.3 60.8 104.7
68.6 60.1 74.1 66.8 57.6 38.2 57.9 48.2 45.6 61.9 85.8 42.0 28.3 37.6 52.6 97.3
MV, between
maternaf the mean
uterine maternal
MA-MV*
FA*
2.2 0.3 0.6 9.8 9.3 5.8 1.1
55.8 41.1 35.9 48.2 73.3 34.5 16.5 26.8 41.6
5.9 8.2 I.1 14.4 15.7 8.2 7.4
vein;
FA,
fetal
and the mean
FV”
umbiliczd fetal
glucose
artery; values.
M-F gradientt
2.7 21.66 912 17.3 7.3 19.0 18.6 42.8 14.5 98.3 2.7 umbilical vein.
63.0 72.0 36.0
FV,
fetal
896
Hinkley,
Stenger,
and
July 15, lY6Y Am. J. Ohst. & Gynec.
Blechner
Table IV. Glucose
concentration differences (mg. @) between maternal and fetal blood and amniotic fluid throughout gestation ~--~__Animal NO. First
AI?’
F-AF
M-AF eradientt
eradientf
trimester
49.6 72.9
5A4 6F8
10.7 1.5 Mean
Second
6.1
trimester
6F2 6F8 5D4 6E4 6El 6E8 6F7
68.8 55.5 37.5
2.9 6.7 20.9 19.9 26.5 33.5 50.0
28.8
34.0 31.3 39.9
._
18.3 12.3 1.9 24.3 32.7 17.9
Third
trimester
6FlO 6E9 6F9 6E5 5A5
24.2 24.0
18.3 11.5 27.8 22.3 24.2
16.9 5.0
17.6
Mean
34.4 76.8
19.9 74.1
35.4
29.0
‘AF, amniotic fluid. tM-AF gradient is the difference between the mean ma:elnal and the amniotic fluid values; F-AF gt-adient is the ditTaence b.+een the mean fetal and the amniotic fluid values.
centration is 73.4 mg. per cent with a standard deviation of 18.3 mg. per cent and a standard error of the mean of 4.7. Mean venous concentration is 69.1 mg. per cent with a standard deviation of 15.9 mg. per cent and a standard error of 3.3. Comparable values for the series of pregnant animals are presented in Table II. The mean arterial concentration is 76.0 mg. per cent and the mean venous concentration 63.2 mg. per cent. Statistically, no significant difference exists between the blood glucose concentrations in the pregnant and nonpregnant female animals. Table III presents the maternal arteriovenous differences and transplacental gradients obtained in the experimental animals thropghout gestation. Because a number of factors may easily and quickly influence total blood glucose concentrations over a .wide range, the importance of maintaining a near-
ly normal steady state during the course of these experiments is recognized. A degree of confidence that the values obtained represent approximately the normal conditions is gained from the average maternal arterial blood glucose concentration of 65.2 mg. per cent in the experimental animals. This value is not significantly different from the mean concentration obtained for glucose in the controls established on unanesthetized prcgnant and nonpregnant animals. In none of the experimental animals is the maternal arterial glucose concentration greater than 105 mg. per cent. ,4 positive maternal artcriovenous difference is observed in each case. Moreover, the mean maternal glucose value is greater than the fetal in all of the 10 allirnals in which it is measured. Table IV outlines the glucose concentration differences between the maternal and fctnl vascular pools and the amniotic fluid, by trimester. throughout gestation. Fig. 1 graphicallv represents the changing amniotic fluid glucose concentration throughout gestation. The decrease in total glucose concentration in the amniotic fluid is not uncxpetted, based on previous rvork clemonstra.tin,y a general tlrcreasc in solute concentration in amniotic fluid as term approaches in the primate.‘, ‘j Comment Despite a certain roughness of the data, caused by the difficulty of stabilizing the concentration of a substance that may be influenced rapidly by both maternal and fetal factors, the arteriovenous difference of glucose across the uterus tends to widen as yestation advances. From Table III the mean arteriovenous difference can be calculated as 4.2 mg. per cent in the first half of pregnancy and 10.2 mg. per cent in the second half. This change results from an increased extraction of glucose from the mater& blood by the uterus and its contents. The corresponding average coefficient of utilization
of glucose
A-V (A
x
100)
per cent for the first half of gestation 15.5 per cent for the second half.
is 6.4 and
Volume 104 Number 6
Glucose concentration gradients
897
A
A
TRIMESTER Fig. 2. The glucose concentration gradient plotted against the trimester of gestation in
OF GESTATION between
maternal
blood
and
amniotic
fluid
is
Macaca speciosa.
In terms of transplacental gradients, the fluid can be considered a fetal pool in which changes in total glucose concentration may not appear as rapidly as in the fetal bloodstream. When the average glucoseconcentration gradient between maternal blood and amniotic fluid is plotted against the trimester of gestation, a progressive increasein the gradient is apparent (Fig. 2). These gradients, together with the uterine blood flow and the arteriovenous difference amniotic
of glucose across the uterus, describe the manner in which the increasing fetal need for this essentialsubstrate is met throughout the course of pregnancy. The present study shows the increasing gradients and arteriovenous differences found during advancing gestation in a fairly docile primate, Macaca sbeciosa. The glucose concentrations measured during estimations of uterine blood flow in Macaca mulatta will form the basis of a future report.
REFERENCES
1. Stenger, V., Henry, J., Cestaric, E., Eitzman, D., and Prystowsky, H.: AM. J. OBST. & GYNEC. 94: 261, 1966. 2. Battaglia, F. C.: J. Pediat. 62: 926, 1963. 3. Stenger, V. G.: Symp. on the Use of Subhuman Primates in Drug Evaluation, Austin, 1967, University of Texas Press. 4. Chinnard, F. P., Danesino, V., Hartman, W. L., Huggett, A. St. G., Paul, W., and Reynolds, S. R. M.: J. Physiol. 132: 289, 1956.
5. 6.
7.
8.
Huggett, A. St. G., and Nixon, D. A.: Biothem. J. 66: 12P, 1957. Somogyi, M.: J. Biol. Chem. 160: 69, 1945. Battaglia, F. C., Prystowsky, H., Smisson, C., Hellegers, A., and Bruns, P.: Surg. Gynec. & Obst. 109: 509, 1959. Battaglia, F. C., Hellegers, A. E., Haller, C. J., and Behrman, R.: AM. J. OBST. & GYNEC. 88: 32, 1964.
gradients across
the uterus and placenta of the pregnant primate CLARK
M.
VINCENT JACK Gainesville,
HINKLEY, G.
N.
M.D.*
STENGER,
BLECHNER,
M.D. M.D.
Florida
Glucose concentrations were measured in the femoral artery and vein of control animals, both pregnant and nonpregnant, to establish normal values in the Macaca speciosa. Uterine arteriovenous differences of total blood glucose concentrations were then determined throughout gestation in anesthetized animals at laparotomy. The changing pattern of glucose gradients across the placenta is described by simultaneous measurements of the glucose levels in the maternal uterine artery, the uterine vein, and the amniotic fluid. The glucose concentrations were also measured in the umbilical vessels at the time of delivery by cesarean section. Maternal arterial glucose levels are similar to those of the unstressed nonpregnant adults. Generally, the arteriovenous blood glucose difierence across the uterus tends to widen as gestation proceeds, showing increasing extraction of glucose from the blood perfusing the uterus. The glucose concentration in the amniotic fluid decreases steadily as pregnancy proceeds. The glucose gradients between the maternal and fetal vascular pools and the amniotic fluid reach a maximum in the last trimester of gestation.
species, also referred to as the stump-tailed macaque, was prompted by a desire to study a primate whose passive disposition makes the establishment of a normal steady state more likely under the conditions of experimentation. The importance of such a steady state has previously been emphasized by Battaglia.2 Review of the literature revealed the absence of established norms for blood glucose in this species and the need for describing the normal range of glucose concentrations before proceeding with further experimentation. For completeness, random determinations of total blood fructose were made in maternal and fetal blood samples; however, in no instance were the concentrations of sufficient magnitude to warrant further investigation.
T H I S R E S E AR C H iS part Of a COntinUing investigation of the placental transfer of essential substrates throughout gestation and concerns the movement of glucose across the placenta of the subhuman primate, Macaca speciosa. A previous study has been reported from this laboratory on the movement of glucose across the human placenta in patients undergoing elective cesarean section at term gestati0n.l In an attempt to understand the transplacental movement of glucose in greater depth, observations were extended to the subhuman primate. Choice of this From the Department Gynecology, University of Medicine.
of Obstretics of Florida
and College
This research was supported in part by United States Public Health Service Grants HD-01542, HD-01683, and HE-06379. *Present address: Department of Obstetrics and Gynecology, University of Alabama Medical Center, Birmingham, Alabama 35233.
Maferial
and
methods
These studies were mate Center of the 893
performed University
at the Priof Florida
894
Hinkley,
July 15, 1969
Stenger, and Blechner
Am. J. Obst. & Gym.
College of Medicine, Gainesville, Florida, using female Macaca speciosae. The monkeys were kept in large runs with free access to food and water. In the series used to establish normal fasting values for total blood glucose, the animals were kept off feed for approximately 12 hours. Each animal was caught by hand and its blood obtained by direct puncture of the femoral vein or artery. No attempt was made to draw simultaneous samples from both vessels. The passive disposition of the females allowed minimal restraint, and only occasionally did the animals appear excited. The duration of gestation in the pregnant animals was estimated from the probable date of conception as previously detailed by Stenger.3 Macaques used for determination of glucose gradients across the placenta at selected gestational ages were fasted for approximately 12 hours and anesthetized with intravenous sodium pento-
Table I. Total femoral animals
blood glucose (mg. s) and vein of nonpregnant
artery
Femoral
artery
Femoral
in
vein
Animal No.
Glucose concentration
Animal No.
Glucose concentration
6E4 6E8 5D3 6F3 6F7 6ElO 6E3 5D2 4L7 4L9 4L2 6E7 5A3 5A6 5A7
68.1 57.2 65.6 61.7 52.6 84.8 70.2 108.3 66.6 77.9 71.5 108.6 60.6 95.6 52.6
6E2 6E4 6E8 5D3 5D4 6El 6F4 6ElO 6E3 5Al 5D2 4L7 4L6 4L1 4L5 6F5 6F6 6FlO 5A3 5A6 5A7 5D5 5Cl
48.8 58.9 58.4 55.9 72.0 69.4 62.5 97.6 57.5 89.4 106.3 63.7 63.8 69.3 69.9 84.1 60.5 61.9 50.1 96.3 48.8 73.3 72.5
Mean 73.4 S.D. t 18.3 S.E.M. i: 4.7
69.1 Mean S.D. + 15.9 + 3.3 S.E.M.
barbital ( 15 to 20 mg. per kilogram). A previous suggestion by Chinnard and associates4 that this drug may cause wide fluctuations of blood glucose concentration was not apparent in our experiments. Using sterile technique at laparotomy, polyvinyl catheters were placed in a femoral artery, a uterine vein, and the amniotic sac. The abdominal incision was then loosely cIosed and the animal allowed to stabilize for approximately one hour before simultaneous samples were obtained from each catheter. When the period of gestation permitted, cesarean section was then performed immediately and samples obtained from the umbilical vessels. Specimens were collected anaerobically in heparinized glass syringes and respiratory gas measurements for other studies, as well as total blood glucose determinations, were made immediately. Glucose concentrations were determined calorimetrically, using the glucose oxidase method described by Huggett and Nixon5 after deproteinization of 0.5 ml. of blood with barium hydroxide and zinc sulfate solutions as described by Somogyi.” Results Total blood glucose values in the femoral artery and vein of nonpregnant animals are presented in Table I. The mean arterial con-
Table II. Total femoral
artery
Femoral
blood glucose (mg. “/o) in and vein of pregnant animals
artery
Femoral
vein
Animal No.
Glucose concentration
Animal No.
Glucose concentration
6E9 6E1 6E6 6F9 6E5 5A4 6E9 6FlO
76.6 43.3 56.9 101.8 54.7 71.4 94.6 109.4
6E9 5A4 5A5 6E5 5A5 6F2 6F9 6E6 6F8 6E4 6F10 6E9
76.2 53.3 58.8 57.4 54.7 54.3 75.6 56.4 62.5 68.4 97.0 44.4
Mean 76.0 SD. 8.5 S.E.M. + If:24.0
Mean 63.2 S.D. + 14.1 S.E.M. + 4.1
Volume Number
104 6
Glucose concenfration gradients
895
A A
A A
A A A A A A
A : A A
I
I
I 40
20
DURATION
Fig. 1. Change in amniotic
fluid glucose
/
I 80
60
1 120
100
OF GESTATION
i DAYS
concentration
during
I
I 140
160
I
gestation in Macaca
speciosa.
Table III. Total blood glucose (mg.aJ,) throughout gestation : Maternal arteriovenous differences and transpIacenta1 gradients Animal No.
Gestational we (days)
6E3 5A4 6F8 6F2 6F8 6F4 5D4 6E4 6El 6E8 6F7 6FlO 6E9 6F9 6E5 5A5 WA, @f-F
35 47 50 62 65 :: 94 97 102 111 132 141 161 162 162 maternal
sradient
femoral
artery;
iq the difference
MA”
MV’”
70.8 60.4 74.7 76.6 66.9 44.0 59.0 49.2 75.4 67.8 94.0 43.1 42.7 53.3 60.8 104.7
68.6 60.1 74.1 66.8 57.6 38.2 57.9 48.2 45.6 61.9 85.8 42.0 28.3 37.6 52.6 97.3
MV, between
maternaf the mean
uterine maternal
MA-MV*
FA*
2.2 0.3 0.6 9.8 9.3 5.8 1.1
55.8 41.1 35.9 48.2 73.3 34.5 16.5 26.8 41.6
5.9 8.2 I.1 14.4 15.7 8.2 7.4
vein;
FA,
fetal
and the mean
FV”
umbiliczd fetal
glucose
artery; values.
M-F gradientt
2.7 21.66 912 17.3 7.3 19.0 18.6 42.8 14.5 98.3 2.7 umbilical vein.
63.0 72.0 36.0
FV,
fetal
896
Hinkley,
Stenger,
and
July 15, lY6Y Am. J. Ohst. & Gynec.
Blechner
Table IV. Glucose
concentration differences (mg. @) between maternal and fetal blood and amniotic fluid throughout gestation ~--~__Animal NO. First
AI?’
F-AF
M-AF eradientt
eradientf
trimester
49.6 72.9
5A4 6F8
10.7 1.5 Mean
Second
6.1
trimester
6F2 6F8 5D4 6E4 6El 6E8 6F7
68.8 55.5 37.5
2.9 6.7 20.9 19.9 26.5 33.5 50.0
28.8
34.0 31.3 39.9
._
18.3 12.3 1.9 24.3 32.7 17.9
Third
trimester
6FlO 6E9 6F9 6E5 5A5
24.2 24.0
18.3 11.5 27.8 22.3 24.2
16.9 5.0
17.6
Mean
34.4 76.8
19.9 74.1
35.4
29.0
‘AF, amniotic fluid. tM-AF gradient is the difference between the mean ma:elnal and the amniotic fluid values; F-AF gt-adient is the ditTaence b.+een the mean fetal and the amniotic fluid values.
centration is 73.4 mg. per cent with a standard deviation of 18.3 mg. per cent and a standard error of the mean of 4.7. Mean venous concentration is 69.1 mg. per cent with a standard deviation of 15.9 mg. per cent and a standard error of 3.3. Comparable values for the series of pregnant animals are presented in Table II. The mean arterial concentration is 76.0 mg. per cent and the mean venous concentration 63.2 mg. per cent. Statistically, no significant difference exists between the blood glucose concentrations in the pregnant and nonpregnant female animals. Table III presents the maternal arteriovenous differences and transplacental gradients obtained in the experimental animals thropghout gestation. Because a number of factors may easily and quickly influence total blood glucose concentrations over a .wide range, the importance of maintaining a near-
ly normal steady state during the course of these experiments is recognized. A degree of confidence that the values obtained represent approximately the normal conditions is gained from the average maternal arterial blood glucose concentration of 65.2 mg. per cent in the experimental animals. This value is not significantly different from the mean concentration obtained for glucose in the controls established on unanesthetized prcgnant and nonpregnant animals. In none of the experimental animals is the maternal arterial glucose concentration greater than 105 mg. per cent. ,4 positive maternal artcriovenous difference is observed in each case. Moreover, the mean maternal glucose value is greater than the fetal in all of the 10 allirnals in which it is measured. Table IV outlines the glucose concentration differences between the maternal and fctnl vascular pools and the amniotic fluid, by trimester. throughout gestation. Fig. 1 graphicallv represents the changing amniotic fluid glucose concentration throughout gestation. The decrease in total glucose concentration in the amniotic fluid is not uncxpetted, based on previous rvork clemonstra.tin,y a general tlrcreasc in solute concentration in amniotic fluid as term approaches in the primate.‘, ‘j Comment Despite a certain roughness of the data, caused by the difficulty of stabilizing the concentration of a substance that may be influenced rapidly by both maternal and fetal factors, the arteriovenous difference of glucose across the uterus tends to widen as yestation advances. From Table III the mean arteriovenous difference can be calculated as 4.2 mg. per cent in the first half of pregnancy and 10.2 mg. per cent in the second half. This change results from an increased extraction of glucose from the mater& blood by the uterus and its contents. The corresponding average coefficient of utilization
of glucose
A-V (A
x
100)
per cent for the first half of gestation 15.5 per cent for the second half.
is 6.4 and
Volume 104 Number 6
Glucose concentration gradients
897
A
A
TRIMESTER Fig. 2. The glucose concentration gradient plotted against the trimester of gestation in
OF GESTATION between
maternal
blood
and
amniotic
fluid
is
Macaca speciosa.
In terms of transplacental gradients, the fluid can be considered a fetal pool in which changes in total glucose concentration may not appear as rapidly as in the fetal bloodstream. When the average glucoseconcentration gradient between maternal blood and amniotic fluid is plotted against the trimester of gestation, a progressive increasein the gradient is apparent (Fig. 2). These gradients, together with the uterine blood flow and the arteriovenous difference amniotic
of glucose across the uterus, describe the manner in which the increasing fetal need for this essentialsubstrate is met throughout the course of pregnancy. The present study shows the increasing gradients and arteriovenous differences found during advancing gestation in a fairly docile primate, Macaca sbeciosa. The glucose concentrations measured during estimations of uterine blood flow in Macaca mulatta will form the basis of a future report.
REFERENCES
1. Stenger, V., Henry, J., Cestaric, E., Eitzman, D., and Prystowsky, H.: AM. J. OBST. & GYNEC. 94: 261, 1966. 2. Battaglia, F. C.: J. Pediat. 62: 926, 1963. 3. Stenger, V. G.: Symp. on the Use of Subhuman Primates in Drug Evaluation, Austin, 1967, University of Texas Press. 4. Chinnard, F. P., Danesino, V., Hartman, W. L., Huggett, A. St. G., Paul, W., and Reynolds, S. R. M.: J. Physiol. 132: 289, 1956.
5. 6.
7.
8.
Huggett, A. St. G., and Nixon, D. A.: Biothem. J. 66: 12P, 1957. Somogyi, M.: J. Biol. Chem. 160: 69, 1945. Battaglia, F. C., Prystowsky, H., Smisson, C., Hellegers, A., and Bruns, P.: Surg. Gynec. & Obst. 109: 509, 1959. Battaglia, F. C., Hellegers, A. E., Haller, C. J., and Behrman, R.: AM. J. OBST. & GYNEC. 88: 32, 1964.