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Multiple simultaneous intervillous space pressures recorded in several regions of the hemochorial placenta in relation to functional anatomy of the fetal cotyledon
‘nterviilous
s
mochariai
S.
R.
UWE JOSEF
REYNOLDS,
M.
E.
FREESE,
PH.D.,
M.D.***
CALDEYRQ-BARCIA,
C.
MENDEZ-BAUER,
L.
ESCARCENA, Illinois,
D.Sc.**
M.D.
BIENIARZ:
ROBERTO
Chicago,
nctio
M.D. M.D.
B.S. and .kIontevideo,
Uruguay
Three to four probes were inserted under cine&oroscopy into areas of the IVS of the rhesus monkey placenta. They were seen to lie in or near the central cavities of fetal cotyledons, which are the sites of entry of maternal blood into IVS, or in more peripheral parts of the fetal cotyledon. When possible, samples of blood were withdrawn for oxygen content determinatiom. Pressures were found to be highest in or near the ceniral cavity of a cotyledon, so that the gradient diminished radially from, and above, the cavity toward the subchorial lake. When the uterus contracted, the IVS pressure rose equally near the center and the periphery of the cotyledon. In intermediate positions, pressures rose relatively more and approached the highest central pressure in the cotyledon, and the gradient of pressure toward the periphery increased. In short, uterine contractions force blood from the center of the fetal cotyledon in. the manner that fluid is moved in pistonless pumps. Insofar as limitations of blood sampling techniques permitted, resulting largely from the physiologic factors involved, suggestion of a similar gradient in oxygen content of intervillous space blood was found, decreasing from the center of cotyledons toward their peripheries. These results support the hypothesis of a central entry of maternal arterial blood into the IVS of a cotyledon, fetal uillous structures seem to determine a pressure gradient toward the periphery in the intracotyledonary space, and Braxton Hicks contractions increase the movement of blood from cotyledon centers throughout the IVS.
From the Departments of Anatomy, University of Illinois College of Medicine, Chicago Lying-in Hospital, li’niversity of Chicago, and the Service of Physiological Obstetrics, Faculty of Medicine, Hospital de Clinicas. Supported by United States Public Health Service Grants HD-00975 and HD-00222-05.
“For
footnote
**Commonwealth
see p, 1123. Fund
Fellow.
“““Present address: Department of Obstetrics and Gynecology, Michael Ree.re Hospital, Chicago, Illinois.
Volume Number
102 8
T H I s s T IJ D Y is designed to demonstrate the function,al-anatomic basis of known but unaccounted for variations in IVS” pressures in hemochorial placentas. The study relates pressure gradients between identified morphologic fetal components of the placenta and site of entry of maternal arterial blood with the uterus at rest and contracting (Braxton Hicks contractions). The basis of this report is found in three papers.l+ Procedures Three rhesus monkeys, bred for the purpose, were 128 +_ 1 days, 116 + 1 days, and 106 ri: 1 days pregnant. Valium tranquilizer (10 mg. intravenously repeated as required) and pentobarbitaJ (40 to 50 Gm. intravenously as needed for operative procedures) were used. The femoral artery was catheterized for injection of Valium or pentobarbital, taking samples of maternal blood for 0, and CO, analysis, and making injections of Renografin (70 per cent) for visualization of maternal flow in the IVS. The uterus was partially exposed for lateroventral presentation in a midline incision. The monkeys were very lightly sedated, manually held to lie on their left sides. Injection of opaque medium was by a pressure injector. Visualization of the placenta was by transportable Siemens Monitor with electronic intensifier. The one familiar with this aspect of the work (U. E. F.) punctured the uterus, aiming at the initial and l.argest opaque “puffs” or “smokerings.” Six to 8 such punctures were made. Some were found (Table I) to be in or near the central cavity of a cotyledon; some were in various parts of the IVS (the ICS, SCL, near the ba.sal plate). The probes were 3 cm. lengths of Clay-Adams P-50 polyethylene tubing inside a gauge 18 metal tubing as a
*Abbreviations for parts of the placenta that are used in this paper are: 1%: the entire space between the chorio-’ allantoic plate and decidual plate, containing subchorial lake, marginal venous lakes, the fetal cotyledons with their anchored, or stem, villi and free-growing and terminal villi. It is the space that is filled with maternal blood and consists of the following subdivisions; ICS: intracotyledonary spaces of minute and probably variable dimensions among the free villi of fetal cotyledons; ML: marginal venous lake or sinus; CC: central owity of the fetal cotyledons; XL: subchorial lake of the IV!&
IVS pressures
in hemochorial
placenta
1129
shield, pointed like a needle to pierce the uterus. When inserted through the uterus into the placenta, the outer tubing was withdrawn and removed; the distal end of the inside tubing curled open into two or three prongs along previously made slits about 5 mm. in length when not restrained by the outside tube. One or two small ho’les were bored through the probe above the flared ends to reduce the chance of occlusion by fetal villi. Small perforated rubber caps were fitted to the inserted probe and sutured to uterine peritoneum for better fixation. Finally, polyethylene catheters (P-30) were flame-flared so as to fit snugly to the proximal end of the probes. The system was flushed with saline-heparin solution. The initial color of the blood to appear when the probe was inserted was noted (light red; dark blue). To sample blood from the IVS, the probe was disconnected from the pressure recording tube, attached to an oiled tuberculin syringe in an air-tight connection. By measuring the time in minutes from the interruption in the appropriate pressure recordings, an estimate was made of the rapidity or ease of blood flow at the time of sampling. The first blood withdrawn was discarded; the sample for analysis was taken in a fresh syringe. The sampling times required 3 to 11 minutes, as shown in Table I. Hematocrit values., pH, and 0, content were determined when the sample size permitted. Despite difficulties in sampling and analysis well known to students oE the placenta,5 values were obtained for correlation with other data to localize the position of the probes. Only data obtained in duplicate close to or during a recording period were used for correlation with the pressure data. In these experiments, the monkeys were mildly to severely hypotensive, becoming progressively more so as the experiment lasted. This is in agreement with similar studies reported by other authors. Oxygen was given by inhalation from time to time. The fetuses were alive during all recorded observations. Pressures in the IVS were recorded by Sanborn transducers (Model 267B), carrier
1130
Reynolds
et ai.
December I& !9G8 Am. J. Obst. & Gynec.
Volume Number
102 8
IVS pressures
preamplifiers, and recording galvanometers (Sanborn, Model 158-5460-N) . Probes were meticulously balanced for zero pressure, and frequent calibration checks were made. Pressures were readable to 1 mm. Hg and estimated to 0.5 mm. Hg. Uniform sequences of contractions of 9 to 21 contractions were selected for steady state and subjected to statistical analysis. Each contraction with unimpeded recording was analyzed, pressures being read at (a) the start of a contraction, (b) at half ,the time to full contraction, (c) at the peak of contraction, (d) at one-fourth, and (e) at one-half the time for full relaxation (Figs. 1 and 2) . Standard errors of the mean are shown in Figs. 2 and 3. The significance of differences between all computed points in all 3 monkeys was determined and extensive tables prepared, too lengthy to publish here. The key to meaningful appreciation of the
in hemochorial
placenta
significant differences lay in knowing the position of each probe in relation to the maternofetal unit of the hemochorial placenta, the fetal cotyledon. Assessment of the positions was kept by (a) dictated protocol of all experiments, (b) blood gas analyses, (c) the ease with which blood flowed during sampling, and (d) examination of the probe site, fixed in situ. At the end of an experiment, the amniotic fluid was replaced by formalin and the tissues hardened for several months. One of us (U. E. F.) then sectioned the placentas and ascertained the position of each probe. Results Uterus at rest. Fig. 1 shows, on the left, a record of four simultaneous pressure records in Monkey No. 4. Gross differences between the several probes do not appear, but measurement against calibration data shows
Monkey 4 - 128 days First 21 contractions
80
Mean
Maternal
B.!?
75 X
r” 1
Placental n Punc.I - . 19 Punc.Z0 20 Punc3x 21 Punc4-A I5
E E
30
-
Rest
--i-l ContractioGl+ 0
h
I
1131
I 4
I 2
Fig. 2. Mean ICS pressures recorded simultaneously in four probes for 15 to 21 contractions recorded in the several channels in Monkey No. 4 (128 day fetus) (Table I). The effect of uterine contraction on simultaneous pressures is shown in Fig. 2. For locations of probes, see insert and Table I.
1132
Weynsids et al.
Monkey
2-
116aoys
Mean
8:
- .
Fig. 3. Simultaneous gestation j.
multiple
pressures
in rhesus
that the pressure in the center of a cotyledon is significantly higher than in the subchorial lake. Probes in the ICS yielded intermediate pressure levels, but nearer the lower rather than the higher value (Fig. 2). ?-Jterus contracted. At the acme of contraction the difference in pressure between the highest and the lowest levels is unchanged; the level of each is raised equally. At the intermediate probes in the ICS, however, the pressures increased relatively more than in either of the other two, and in one more than in the other (Fig. 2). In short, the gradient of pressure differences between maximum (center of cotyledon) and minimum (subchorial lake) levels became steeper as the uterus contracted, showing that the uterine contraction forces bIood from the center of the cotyledon, at its site of entry, throughout the IVS. Fig. 3 shows a similar effect in a different monkey.
monkey
-
Punt.
Maternal
I-
l
B.P
+
Punc2-
0
9
Punc3-
x
17
placenta
(Monkey
No.
2, 116 days’
On occasion, a probe came to rest in the amniotic fluid. Pressures here seldom equaled (in our somewhat hypotensive monkeys) pressures in the IVS except in the SCL. This was true with the uterus at rest or contracted. The maternal blood in or near the center of the fetal cotyledon had 7 to 7.72 ml. 0, per 100 ml. in Probes No. 1 and No. 2 of Monkey No. 4 (Figs. 1 and 2) and the saturation of hemoglobin was 63.8 per cent in Probe No. 2. Values from three ICS points near centers of fetal cotyledons yielded hemoglobin saturations of 65 to 69.5. Ilematocrit values were always lower than in maternal arterial blood. Blood from near the basal plate at the edge of a cotyledon (Monkey I No. 2, Probe No. 2) was completely venous with respect to pH and ~xygen, but the hematocrit value was normal. Other ICS 0, levels in the third monkey were venous, with respect to pH and 0,.
Volume Number
102 8
IVS
Table I. Relative
locations
(punt2
Initial
116
No. Fig.
1 3
116
No. Fig.
2 3
No. Fig.
of multiple
blood color
Red blood
Time
pressures
in hemochorial
placenta
1133
probes in monkey placentas shown in Figs. 2 and 3
for blood sample
Notes mortem
at postfixation in situ
Second sample. Intermediate (5 min.)
Base, center cotyledon
of
Intermediate (5 min.)
Distant from No. 1, base, periphery cotyledon
3 3
Judgment of the location of probe from combined information Tip
in IVS near central part of a cotyledon, located at edge of placenta
Tip
near periphery fetal cotyledon, basal plate
Tip
near edge of a fetal cotyledon, near basal
at of
Base, periphery of a cotyledon
Symbols in Figs. 2 and 3
of near
plate 4
128
No. Fig.
1 2
Clear
No. Fig.
2 2
Dark red blood
Slow
No. Fig.
3 2
Clear red blood
Intermediate (6 min.)
No. Fig.
4 2
red
Clear red blood
Rapid
(3 min.)
(10
Very slow min.)
min.)
(11
Close to center of cotyledon
Tip
is in, or near, center of a fetal cotyledon
Very close to center of cotyledon
Tip
is low in placenta, close to, but not in, center of fetal cotyledon
Above center of cotyledon in intervillous spaces, in upper third of placenta
Tip
in intervillous spaces between central cavity of cotyledon and subchorial
Base and portion
Tip
is near decidual plate over half way to periphery of fetal cotyledon
Tip
was high at first in IVS, above center of fetal cotyledon; then inserted finally to subchorial lake
midof
lake
cotyledon No.
6
Dark
blood
Slow ( 10 min.), one fast second time (4 min.)
Hematocrit levels were always low. In one monkey, oxygen given to the mother caused complete hemoglobin saturation in blood near the center of a fetal cotyledon. Comment
IVS pressures recorded simultaneously are not equal, as others have noted in singlepoint recording. However, when the differences are correlated with the morphology of the fetal cotyledon and the entry of maternal blood. in its central cavity, correlation is found with higher pressures and 0, levels
Center of cotyledon; however, amniotic fluid seen at start of second sample
there. Similarly, in the SCL or in the ICS distant from the central cavity and especially near the basal plate pressures are lower and the bIood is fully venous with respect to 0,. Finally, the effect of uterine contraction is to raise equally the level of pressure in the center of the cotyledon and the SCL as intrauterine pressure is transmitted directly to these points. At intermediate points, however, pressures increase reIatively more, so suggesting that the intrauterine pressure forces blood from the high-pressure areas into the lower, irrigating the IVS with blood
1134
Reynolds
December Am. J. Obst.
et al.
2, 1968 & Gynec.
from the center of the cotyledon. The question rightly arises why the increased blood pressure about the villous elements does not obliterate the fetal villous capillaries. Observations on the fetus in utero show that, following Pascal’s law, the increase in intrauterine pressure is transmitted fully and directly to the fetal cardiovascular system. Fetal blood pressure rises along with the intrauterine pressure.‘j Since the IYS does
electrodes, may reveal the qua&y of blood in the several regions of the IVS on a continuous time axis. The positions of the probes must be established and anything less than this will be quite meaningless,It suffices to say that the experimental design of this study, on one hand, and a concept of the maternal-fetal vascular relationships, on the other, provide a fresh and understandable basis on which to construct other studies in
not respond
the future
in the same manner
it is clear
that it must be regarded as a separate compartment and, in a morphologic sense, as part of the uterine wall. The difficulties in obtaining meaningful analyses of IVS blood described by Fuchs, Spa&man, and Assalij are confirmed by us. Our data agree with theirs and those of other investigators. However, since we now know that uterine contractions causevariable irrigation of maternal blood throughout the XVS: and unevenly at that,2 it is clear that in blood samplesthat require 3 to 10 minutes to collect except in the center of a cotyledon or the SCL, conditions va-ry during the sampling. For this reason, paired samples from a single site may vary appreciably. A different experimental design, preferably one employing continuous inlying p0, and pC0,
and so lead
to a cIearer
view
of
the conditions of the two-way exchange that occurs between the maternal and the fetal vascular compartments, at least so far as water
and blood
gases are concerned.
Acknowledgment is made to the entire Servicio de Fisiologia Obstetrica and Departamiento de Radiodiagnostico, Hospital de Clinicas, Montevideo, Uruguay. A group of highly trained technicians and the staff dedicated more than one full month to the preparation for, and prosecution of, the experiments on which this paper is based. Grateful acknowledgment is made to the following people who comprised our working team, and without whose able participation these experiments could not have been done: N. Azambujo, M.D., S. V. Pose, M.D., J. J. Poseiro, M,D., F. Alvarez, M.D., V. Saguier, M.D., and L. Gulin, M.D.
REFERENCES
1. Preese, u. E.: AM. J. 0~s~. & GYNEC. 94: 354, 1966. 2. Freese, U. E.: AM. J. OBST. & GYNEC. 94: 361, 1966. 3. Reynolds, S. R. M.: AM. J. QBST. & GYNEC. 94: 425, 1966.
4. Reynolds,S. R. M.: Anat. Rec. 157: 43, 1967.
5. Fuchs, F., Spackman, T., and Assali, N. S.: AM. J. OBST. & GYNEC. 86: 226, 1963. 6: Reynolds, S. R. M.: Paul, W. M., and Huggett, A. St. G.: Bull. Johns Hopkins Hosp. 95: 256, 1954. See also Reynolds, S. R. M.: Obst. & Gynec. 32: 134; 1968.
s
mochariai
S.
R.
UWE JOSEF
REYNOLDS,
M.
E.
FREESE,
PH.D.,
M.D.***
CALDEYRQ-BARCIA,
C.
MENDEZ-BAUER,
L.
ESCARCENA, Illinois,
D.Sc.**
M.D.
BIENIARZ:
ROBERTO
Chicago,
nctio
M.D. M.D.
B.S. and .kIontevideo,
Uruguay
Three to four probes were inserted under cine&oroscopy into areas of the IVS of the rhesus monkey placenta. They were seen to lie in or near the central cavities of fetal cotyledons, which are the sites of entry of maternal blood into IVS, or in more peripheral parts of the fetal cotyledon. When possible, samples of blood were withdrawn for oxygen content determinatiom. Pressures were found to be highest in or near the ceniral cavity of a cotyledon, so that the gradient diminished radially from, and above, the cavity toward the subchorial lake. When the uterus contracted, the IVS pressure rose equally near the center and the periphery of the cotyledon. In intermediate positions, pressures rose relatively more and approached the highest central pressure in the cotyledon, and the gradient of pressure toward the periphery increased. In short, uterine contractions force blood from the center of the fetal cotyledon in. the manner that fluid is moved in pistonless pumps. Insofar as limitations of blood sampling techniques permitted, resulting largely from the physiologic factors involved, suggestion of a similar gradient in oxygen content of intervillous space blood was found, decreasing from the center of cotyledons toward their peripheries. These results support the hypothesis of a central entry of maternal arterial blood into the IVS of a cotyledon, fetal uillous structures seem to determine a pressure gradient toward the periphery in the intracotyledonary space, and Braxton Hicks contractions increase the movement of blood from cotyledon centers throughout the IVS.
From the Departments of Anatomy, University of Illinois College of Medicine, Chicago Lying-in Hospital, li’niversity of Chicago, and the Service of Physiological Obstetrics, Faculty of Medicine, Hospital de Clinicas. Supported by United States Public Health Service Grants HD-00975 and HD-00222-05.
“For
footnote
**Commonwealth
see p, 1123. Fund
Fellow.
“““Present address: Department of Obstetrics and Gynecology, Michael Ree.re Hospital, Chicago, Illinois.
Volume Number
102 8
T H I s s T IJ D Y is designed to demonstrate the function,al-anatomic basis of known but unaccounted for variations in IVS” pressures in hemochorial placentas. The study relates pressure gradients between identified morphologic fetal components of the placenta and site of entry of maternal arterial blood with the uterus at rest and contracting (Braxton Hicks contractions). The basis of this report is found in three papers.l+ Procedures Three rhesus monkeys, bred for the purpose, were 128 +_ 1 days, 116 + 1 days, and 106 ri: 1 days pregnant. Valium tranquilizer (10 mg. intravenously repeated as required) and pentobarbitaJ (40 to 50 Gm. intravenously as needed for operative procedures) were used. The femoral artery was catheterized for injection of Valium or pentobarbital, taking samples of maternal blood for 0, and CO, analysis, and making injections of Renografin (70 per cent) for visualization of maternal flow in the IVS. The uterus was partially exposed for lateroventral presentation in a midline incision. The monkeys were very lightly sedated, manually held to lie on their left sides. Injection of opaque medium was by a pressure injector. Visualization of the placenta was by transportable Siemens Monitor with electronic intensifier. The one familiar with this aspect of the work (U. E. F.) punctured the uterus, aiming at the initial and l.argest opaque “puffs” or “smokerings.” Six to 8 such punctures were made. Some were found (Table I) to be in or near the central cavity of a cotyledon; some were in various parts of the IVS (the ICS, SCL, near the ba.sal plate). The probes were 3 cm. lengths of Clay-Adams P-50 polyethylene tubing inside a gauge 18 metal tubing as a
*Abbreviations for parts of the placenta that are used in this paper are: 1%: the entire space between the chorio-’ allantoic plate and decidual plate, containing subchorial lake, marginal venous lakes, the fetal cotyledons with their anchored, or stem, villi and free-growing and terminal villi. It is the space that is filled with maternal blood and consists of the following subdivisions; ICS: intracotyledonary spaces of minute and probably variable dimensions among the free villi of fetal cotyledons; ML: marginal venous lake or sinus; CC: central owity of the fetal cotyledons; XL: subchorial lake of the IV!&
IVS pressures
in hemochorial
placenta
1129
shield, pointed like a needle to pierce the uterus. When inserted through the uterus into the placenta, the outer tubing was withdrawn and removed; the distal end of the inside tubing curled open into two or three prongs along previously made slits about 5 mm. in length when not restrained by the outside tube. One or two small ho’les were bored through the probe above the flared ends to reduce the chance of occlusion by fetal villi. Small perforated rubber caps were fitted to the inserted probe and sutured to uterine peritoneum for better fixation. Finally, polyethylene catheters (P-30) were flame-flared so as to fit snugly to the proximal end of the probes. The system was flushed with saline-heparin solution. The initial color of the blood to appear when the probe was inserted was noted (light red; dark blue). To sample blood from the IVS, the probe was disconnected from the pressure recording tube, attached to an oiled tuberculin syringe in an air-tight connection. By measuring the time in minutes from the interruption in the appropriate pressure recordings, an estimate was made of the rapidity or ease of blood flow at the time of sampling. The first blood withdrawn was discarded; the sample for analysis was taken in a fresh syringe. The sampling times required 3 to 11 minutes, as shown in Table I. Hematocrit values., pH, and 0, content were determined when the sample size permitted. Despite difficulties in sampling and analysis well known to students oE the placenta,5 values were obtained for correlation with other data to localize the position of the probes. Only data obtained in duplicate close to or during a recording period were used for correlation with the pressure data. In these experiments, the monkeys were mildly to severely hypotensive, becoming progressively more so as the experiment lasted. This is in agreement with similar studies reported by other authors. Oxygen was given by inhalation from time to time. The fetuses were alive during all recorded observations. Pressures in the IVS were recorded by Sanborn transducers (Model 267B), carrier
1130
Reynolds
et ai.
December I& !9G8 Am. J. Obst. & Gynec.
Volume Number
102 8
IVS pressures
preamplifiers, and recording galvanometers (Sanborn, Model 158-5460-N) . Probes were meticulously balanced for zero pressure, and frequent calibration checks were made. Pressures were readable to 1 mm. Hg and estimated to 0.5 mm. Hg. Uniform sequences of contractions of 9 to 21 contractions were selected for steady state and subjected to statistical analysis. Each contraction with unimpeded recording was analyzed, pressures being read at (a) the start of a contraction, (b) at half ,the time to full contraction, (c) at the peak of contraction, (d) at one-fourth, and (e) at one-half the time for full relaxation (Figs. 1 and 2) . Standard errors of the mean are shown in Figs. 2 and 3. The significance of differences between all computed points in all 3 monkeys was determined and extensive tables prepared, too lengthy to publish here. The key to meaningful appreciation of the
in hemochorial
placenta
significant differences lay in knowing the position of each probe in relation to the maternofetal unit of the hemochorial placenta, the fetal cotyledon. Assessment of the positions was kept by (a) dictated protocol of all experiments, (b) blood gas analyses, (c) the ease with which blood flowed during sampling, and (d) examination of the probe site, fixed in situ. At the end of an experiment, the amniotic fluid was replaced by formalin and the tissues hardened for several months. One of us (U. E. F.) then sectioned the placentas and ascertained the position of each probe. Results Uterus at rest. Fig. 1 shows, on the left, a record of four simultaneous pressure records in Monkey No. 4. Gross differences between the several probes do not appear, but measurement against calibration data shows
Monkey 4 - 128 days First 21 contractions
80
Mean
Maternal
B.!?
75 X
r” 1
Placental n Punc.I - . 19 Punc.Z0 20 Punc3x 21 Punc4-A I5
E E
30
-
Rest
--i-l ContractioGl+ 0
h
I
1131
I 4
I 2
Fig. 2. Mean ICS pressures recorded simultaneously in four probes for 15 to 21 contractions recorded in the several channels in Monkey No. 4 (128 day fetus) (Table I). The effect of uterine contraction on simultaneous pressures is shown in Fig. 2. For locations of probes, see insert and Table I.
1132
Weynsids et al.
Monkey
2-
116aoys
Mean
8:
- .
Fig. 3. Simultaneous gestation j.
multiple
pressures
in rhesus
that the pressure in the center of a cotyledon is significantly higher than in the subchorial lake. Probes in the ICS yielded intermediate pressure levels, but nearer the lower rather than the higher value (Fig. 2). ?-Jterus contracted. At the acme of contraction the difference in pressure between the highest and the lowest levels is unchanged; the level of each is raised equally. At the intermediate probes in the ICS, however, the pressures increased relatively more than in either of the other two, and in one more than in the other (Fig. 2). In short, the gradient of pressure differences between maximum (center of cotyledon) and minimum (subchorial lake) levels became steeper as the uterus contracted, showing that the uterine contraction forces bIood from the center of the cotyledon, at its site of entry, throughout the IVS. Fig. 3 shows a similar effect in a different monkey.
monkey
-
Punt.
Maternal
I-
l
B.P
+
Punc2-
0
9
Punc3-
x
17
placenta
(Monkey
No.
2, 116 days’
On occasion, a probe came to rest in the amniotic fluid. Pressures here seldom equaled (in our somewhat hypotensive monkeys) pressures in the IVS except in the SCL. This was true with the uterus at rest or contracted. The maternal blood in or near the center of the fetal cotyledon had 7 to 7.72 ml. 0, per 100 ml. in Probes No. 1 and No. 2 of Monkey No. 4 (Figs. 1 and 2) and the saturation of hemoglobin was 63.8 per cent in Probe No. 2. Values from three ICS points near centers of fetal cotyledons yielded hemoglobin saturations of 65 to 69.5. Ilematocrit values were always lower than in maternal arterial blood. Blood from near the basal plate at the edge of a cotyledon (Monkey I No. 2, Probe No. 2) was completely venous with respect to pH and ~xygen, but the hematocrit value was normal. Other ICS 0, levels in the third monkey were venous, with respect to pH and 0,.
Volume Number
102 8
IVS
Table I. Relative
locations
(punt2
Initial
116
No. Fig.
1 3
116
No. Fig.
2 3
No. Fig.
of multiple
blood color
Red blood
Time
pressures
in hemochorial
placenta
1133
probes in monkey placentas shown in Figs. 2 and 3
for blood sample
Notes mortem
at postfixation in situ
Second sample. Intermediate (5 min.)
Base, center cotyledon
of
Intermediate (5 min.)
Distant from No. 1, base, periphery cotyledon
3 3
Judgment of the location of probe from combined information Tip
in IVS near central part of a cotyledon, located at edge of placenta
Tip
near periphery fetal cotyledon, basal plate
Tip
near edge of a fetal cotyledon, near basal
at of
Base, periphery of a cotyledon
Symbols in Figs. 2 and 3
of near
plate 4
128
No. Fig.
1 2
Clear
No. Fig.
2 2
Dark red blood
Slow
No. Fig.
3 2
Clear red blood
Intermediate (6 min.)
No. Fig.
4 2
red
Clear red blood
Rapid
(3 min.)
(10
Very slow min.)
min.)
(11
Close to center of cotyledon
Tip
is in, or near, center of a fetal cotyledon
Very close to center of cotyledon
Tip
is low in placenta, close to, but not in, center of fetal cotyledon
Above center of cotyledon in intervillous spaces, in upper third of placenta
Tip
in intervillous spaces between central cavity of cotyledon and subchorial
Base and portion
Tip
is near decidual plate over half way to periphery of fetal cotyledon
Tip
was high at first in IVS, above center of fetal cotyledon; then inserted finally to subchorial lake
midof
lake
cotyledon No.
6
Dark
blood
Slow ( 10 min.), one fast second time (4 min.)
Hematocrit levels were always low. In one monkey, oxygen given to the mother caused complete hemoglobin saturation in blood near the center of a fetal cotyledon. Comment
IVS pressures recorded simultaneously are not equal, as others have noted in singlepoint recording. However, when the differences are correlated with the morphology of the fetal cotyledon and the entry of maternal blood. in its central cavity, correlation is found with higher pressures and 0, levels
Center of cotyledon; however, amniotic fluid seen at start of second sample
there. Similarly, in the SCL or in the ICS distant from the central cavity and especially near the basal plate pressures are lower and the bIood is fully venous with respect to 0,. Finally, the effect of uterine contraction is to raise equally the level of pressure in the center of the cotyledon and the SCL as intrauterine pressure is transmitted directly to these points. At intermediate points, however, pressures increase reIatively more, so suggesting that the intrauterine pressure forces blood from the high-pressure areas into the lower, irrigating the IVS with blood
1134
Reynolds
December Am. J. Obst.
et al.
2, 1968 & Gynec.
from the center of the cotyledon. The question rightly arises why the increased blood pressure about the villous elements does not obliterate the fetal villous capillaries. Observations on the fetus in utero show that, following Pascal’s law, the increase in intrauterine pressure is transmitted fully and directly to the fetal cardiovascular system. Fetal blood pressure rises along with the intrauterine pressure.‘j Since the IYS does
electrodes, may reveal the qua&y of blood in the several regions of the IVS on a continuous time axis. The positions of the probes must be established and anything less than this will be quite meaningless,It suffices to say that the experimental design of this study, on one hand, and a concept of the maternal-fetal vascular relationships, on the other, provide a fresh and understandable basis on which to construct other studies in
not respond
the future
in the same manner
it is clear
that it must be regarded as a separate compartment and, in a morphologic sense, as part of the uterine wall. The difficulties in obtaining meaningful analyses of IVS blood described by Fuchs, Spa&man, and Assalij are confirmed by us. Our data agree with theirs and those of other investigators. However, since we now know that uterine contractions causevariable irrigation of maternal blood throughout the XVS: and unevenly at that,2 it is clear that in blood samplesthat require 3 to 10 minutes to collect except in the center of a cotyledon or the SCL, conditions va-ry during the sampling. For this reason, paired samples from a single site may vary appreciably. A different experimental design, preferably one employing continuous inlying p0, and pC0,
and so lead
to a cIearer
view
of
the conditions of the two-way exchange that occurs between the maternal and the fetal vascular compartments, at least so far as water
and blood
gases are concerned.
Acknowledgment is made to the entire Servicio de Fisiologia Obstetrica and Departamiento de Radiodiagnostico, Hospital de Clinicas, Montevideo, Uruguay. A group of highly trained technicians and the staff dedicated more than one full month to the preparation for, and prosecution of, the experiments on which this paper is based. Grateful acknowledgment is made to the following people who comprised our working team, and without whose able participation these experiments could not have been done: N. Azambujo, M.D., S. V. Pose, M.D., J. J. Poseiro, M,D., F. Alvarez, M.D., V. Saguier, M.D., and L. Gulin, M.D.
REFERENCES
1. Preese, u. E.: AM. J. 0~s~. & GYNEC. 94: 354, 1966. 2. Freese, U. E.: AM. J. OBST. & GYNEC. 94: 361, 1966. 3. Reynolds, S. R. M.: AM. J. QBST. & GYNEC. 94: 425, 1966.
4. Reynolds,S. R. M.: Anat. Rec. 157: 43, 1967.
5. Fuchs, F., Spackman, T., and Assali, N. S.: AM. J. OBST. & GYNEC. 86: 226, 1963. 6: Reynolds, S. R. M.: Paul, W. M., and Huggett, A. St. G.: Bull. Johns Hopkins Hosp. 95: 256, 1954. See also Reynolds, S. R. M.: Obst. & Gynec. 32: 134; 1968.