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Fetal oxygen consumption and mechanisms of heart rate response during artificially produced late decelerations of fetal heart rate in sheep
Fetal oxygen consumption and mechanisms of heart rate response during artificially produced late decelerations of fetal heart rate in sheep
Delayed decelerations of fetal heart rate were produced by abruptly decreasing uterine blood flow to zero for 20 seconds in chronically instrumented, normoxic sheep. Fetal 0, consumption, 0, content, and 0, tension in umbilical blood decreased significantly before the decline in heart rate. Fetal arterial blood pressure did not change significantly. Complete vagal blockade abolished the late deceleration and uncovered a late acceleration, which in turn was eliminated by total p-adrenergic blockade. We conclude that these late decelerations in normoxic sheep are vagally mediated and due to chemoreceptor rather than baroreceptor activity. (Au. J. OBSTET. GYNECOL. 136:476, 1960.)
THE E~OLOGV of. late decelerations of fetal heart rate (or Type II dips) has been subject to much speculation. Based on the work of Barcroft and Bauer’ on responses of fetal heart rate of animals to umbilical cord compression with and without an intact vagus nerve, it was initially hypothesized that late decelerations were due IO hypoxia depression, J>resumabl! of’ the myocardium.’ Correiation of heart rate Jlatterns and newborn outcome in the human supported this concept, though the correlation was far from absolute. Two types of late decelerations have been proposed, one a reHex type mediated by the vagus nerve, and the other due to direct hypoxic depression of the myocardium.:’ Attempts ha\-e been made to study late decelerations in experimental animals, but much of the information was obtained during anesthesia, and at times the heart rate patterns have occurred postsurgically without the the Department oj Obstetrics, Gynecology, Rep-odurtt’tlr Sciences und the Cardiovc*cular From
Institute,
I’niwrsity
and Re.Teurch San Fmncuco,
of California,
CaliJomlu. Supported 099RV.
by National
Institutes
of H&h
at the Twenly-jftb Annual .Sorirty fog C~ynecologzc Inzwti(lation, !Marrti I S-18. 1978.
Prusmted
Grant
Meeting Aflnntu,
of’ thp Gcorgi>.
Reprint requests: Dr. J&an 1‘. Parer, Department Obstetkx, Gynecology, and Reprodurtiw Science\. Unizlertrty of California. San Francisco, Califonuu 94143.
478
HD
o/
controlled imposition of asphyxia.‘, ’ We believed that a study of deliberately imposed asphyxia in the unanesthetized animal would be a more valid approach to studying the characteristics of large decelerations. We were unsuccessful in producing late decelerations in the chronically prepared sheep with spontaneous OI induced uterine contractions, even during maternal hypoxia.” Based on the theory that the prime factor in the production of late decelerations is a transient decrease in uterine blood flow below the limit of fetal tolerance,’ a model was developed for producing delayed decelerations of the fetal heart rate by abruptly and transiently decreasing uterine blood flow by distal maternal aortic occlusion in the unanesthetized pregnant sheep. In addition. fetal oxygen consumption was measured durmg this maneuver,x as this was thought to be the ultimate measure of adequacy of fetal oxygenation. The roles of the fetal vagus and P-adrenergic systems were determined by maternal aortic occlusion after complete blockade of each of these branches of the autonomic nervous system.
Material and methods The sheep preparation for repetitive measurement of fetal oxygen consumption and sampling of‘ blood supplying and draining the fetal side of the placenta has been described previously.’ In brief, pregnant sheep were prepared with materOOOZ-9378/80/040478+05$00.50/0
0
1980
The C. V. Mosby
Co
Volume Number
136 4
Fetal
nal catheters, an amniotic cavity catheter, a common umbilical artery blood flow transducer, and catheters in the common umbilical vein and fetal distal aorta. The latter yielded blood representative of umbilical arterial blood. An electromagnetic flow transducer was placed on the middle uterine artery draining the pregnant side of the uterus. A Fogarty balloon tip catheter was inserted into a maternal femoral artery, with the tip in the aorta distal to the renal arteries. Sheep were prepared at a mean gestational age of 121 days and studied at least 2 days after surgery (range 2 to 8 days, mean 4.1 days). Blood flows were continuously read out by Statham SP2202 blood flowmeters and recorded on a Beckman R411 Dynograph recorder. Heart rate was determined by cardiotachometer, and blood pressures were measured by Statham strain gauges. Blood gases and pH were measured with Radiometer electrodes at 39” C. Oxygen content was measured by a micromethod with accuracy equal to that of the Van Slyke manometric apparatus.” On inflation of the balloon in the maternal distal aorta, uterine blood flow decreased virtually to zero. Arterial blood pressure distal to the occlusion was greatly decreased. Before, during, and after occlusion blood samples from the umbilical vein and artery were drawn rapidly over an approximately J-second period at intervals no closer than 20 seconds. Occlusion was maintained for 20 seconds. Twenty-nine studies were carried out on six sheep fetuses. In addition, 20 studies were done on five of the fetuses after pretreatment with totally blocking doses of atropine, at least 200 pglkg of fetal weight. In five further studies, aortic occlusion followed completely blocking doses of both atropine and propranolol, with the latter being at least 1 mg/kg of fetal weight. Total blockade was determined by lack of response to acetylcholine and isoproterenol. Composite analyses of hemodynamic and blood gas values were made at intervals of 10 seconds or greater during and after the period of occlusion. Mean values were compared to control values by means of the paired Student’s t test. To eliminate error introduced by doing multiple t tests with a single control, the level of significance was divided by the number of comparisons and, therefore, we rejected the null hypothesis only when p < 0.01.
Results The mean gestational age of the fetuses at the time of the study was 125 days (range 12 1 to 135 days), and the mean fetal weight was 2455 +- 533 gm SD. All fetuses survived the transient decreases in uterine blood flow. Fig. 1 shows a typical example of the procedure. The
oxygen
consumption
and FHR
response
to late decelerations
479
AORTIC OCCLUSION
Ut. BF (ml /min) _I[ 200 MAP (mm lip) 0C 240
r
FHR (bpm)
FAP fmmW
500 &nb.BF
( ml /min 1
Fig. 1. Portion of’ an actual recording of uterine blood flow (Ut. BF), maternal arterial blood pressure (MAP), fetal heart rate (FHR), fetal arterial pressure (FAP) and umbilical blood flow (limb. BF). The 20-second period of aortic occlusion is evident from the decrease of uterine blood flow to zero. period of aortic occlusion is evident from the decrease in uterine blood flow and maternal arterial pressure. There was a delayed decrease in fetal heart rate with no change in umbilical blood flow or fetal arterial pressure. There was a decline in mean fetal oxygen consumption from the control value of 6.8 ml/mm/kg which was evident at the first measurement period after occlusion (Fig. 2). Fetal oxygen consumption reaches its nadir at 20 seconds, and thereafter recovers toward normal with a possible overshoot. However, this does not show a significant statistical difference from the control value. Fetal heart rate, by contrast, is not different from the control values until 30 seconds after commencement of aortic occlusion, that is, 10 seconds after occlusion has ceased. At this time there is significant statistical difference from the control value. In this composite analysis the heart rate is lower than control values even at 100 seconds after commencement of occlusion. N values at control, 10,20,30,40,50, 100, and 130 seconds, and 35 minutes after occlusion are: for
480
Parer,
Krueger,
and Harris Am.
February 15, 1980 J. Obsret. Gynecol.
Time ( set 1
Fig. 4. O2 content of umbilical venous and umbilical arterial blood during and after maternal aortic occlusion (See legend for Fig. 2.)
Fig. 2. Fetal heal-r rate and O2 consumption changes during and after maternal aortic occlusion. The value at time zero is the preocclusion control value in each study. See text for n
values. Asrerisks represent values significantly different from control
i*p
< 0.01:
40 r PO,
:ike;
L
(mmtig)
**p < 0.001). IOC 60
**
****
20
‘lo
i
r
0
I
I
60
80 Time ( sect
Fig.
3. L~mhilical
blood
flow
and
umbilical
venous-umbilical
Fig. 5. Umbilical venous and arterial oxygen and carbon dioxide tension during and afrer maternal aortic occlusion. (See legend for Fig. 2.)
arterial oxygen content differences during and after maternal aortic
occlusion.
iSee legend
for
Fig. 2.)
f&Ii heart rate 29. 3, 2 1. 5, l?, 9. 17, 8, il!ld 99: for fetal 0, consumption, the values arc 15, 2, 12. 3. 9, 3. 1 1, 3, and 12. In subsequent figures. cardiovascular measurements have the former n values and respirator! gas measun-ements the latter II values. The components for calculation of‘ the fetal oxygen consumption are shown in Fig. 3. There are only minor changes in umbilical blood flow, and no value is significantl) different from control. The fetal umbilical venous-umbilical arterial oxygen content difference decreases markedly with aortic occlusion and closeI> parallels the changes in fetal oxygen consumption. The oxygen content of umbilical venous and umbilical arterial blood are illustrated in Fig. 4. Several of the changes are significantly different from control, but the changes occur more dramatically in the umbilical vein. Similar changes are seen in the oxygen tension values in umbilical venous and umbilical arterial blood
(Fig. 5); the decrease in umbilical vein O2 tension is much more marked than that in the umbilical artery, although there is also a significant decline in the values in the umbilical artery. Changes in umbilical blood carbon dioxide tension were modest (Fig. 5). The changes in pH and base excess of umbilical arterial and venous blood are also yuantitatively small (Fig. 6). The changes in fetal arterial, umbilical venous, and amniotic fluid pressures during the aortic occlusion are illustrated in Fig. 7. There is no significant change in any of these values. Following pretreatment with totally blocking doses of atropine, the delayed deceleration is completely- abolished and replaced with a delayed acceleration (Fig. 8). Minor, though significant, increases in umbilical blood flow and arterial blood pressure following vagal blockade were probably a result of the increased heart rate. In five further studies, the late acceleration was shown to be due to P-adrenergic activity, as it was completely abolished with totally blocking doses of propranolol.
Volume Number
136 4
Fetal oxygen
consumption
(mmHq)
PH
and FHR
response
to late decelerations
481
4ok Umb.v.
Umb. a
Am.f/
7.3oL---J---j + 8 OCCLUSION
P
Time (set)
r
Fig. 7. Umbilical arterial and venous mean blood pressures and amniotic cavity pressure during and after aortic occlusion. (See legends for Fig. 2.) Time ( set )
Fig. 6. Umbilical venous pH and base excess during and after maternal aortic occlusion. (See legend for Fig. 2.)
FHR ( bpd
Comment The decline in uterine blood flow below the limits of fetal tolerance to hypoxia during uterine contractions is thought to be the primary feature in the production of late decelerations, and this is the basis for our model. The nadir of the fetal heart rate occurs 30 seconds after the beginning of aortic occlusion; the nadir of fetal O2 consumption, tension, and content occurs 20 seconds after the occlusion. Pretreatment of the fetus with totally blocking doses of atropine completely abolishes the late deceleration. This suggests that the decelerations in the previously normoxic fetuses are entirely vagally mediated. This study shows that there is no change in mean fetal arterial blood pressure, but there’is a substantial decline in umbilical venous oxygen tension during aortic occlusion. This blood is largely transported across the foramen ovaleg, to and distributed from the left ventricle to the vessels supplied by the proximal aorta. These late decelerations are most likely chemoreceptor mediated. The umbilical venous blood was sampled just distal to the ductus venous, and the discrepancy in the nadir of the O2 and fetal heart rate values may be explained by circulation time from sampling site to sensor (either peripheral or central). A recent preliminary report by Martin and coworkers’] described a transient fetal hypertension accompanying late decelerations produced by a similar model in sheep. Examination of our records showed that in nine studies there was no change in fetal arterial blood pressure; in 15 there was an increase; and in five, there was a decrease following aortic occlusion. The mean value in fetal arterial blood pressure actually showed a slight, though nonsignificant, decline with aortic occlusion. During spontaneous fetal hypoxemia, it is more likely for substantial transient hypertension to occur (unpublished data).
240
Urdf3.F (ml/min/kgl
*
2oo
+,;-:-.-.-.~.-. -I--.
, 6. I40
t
‘-IF11
FAP ( m m Hg)
J-q+ c
0
20
’ ’ ’ ’ 40
60
TIME
(secl
Fig. 8. Fetal heart rate, umbilical blood flow and fetal arterial blood pressure at control (C), immediately after intravenous atropine 600 pg to the fetus (O), and at intervals during and after maternal aortic occlusion. There were 20 studies on five sheep. (See legend for Fig. 2.)
In similar studies with the mother breathing hypoxic gas mixtures, we have produced late decelerations which cannot be abolished by pretreatment with atropine. We assume that these latter decelerations are caused not by reflex chemoreceptor stimulation but by hypoxic myocardial depression (Harris and associates, unpublished studies). Studies done on monkeys using electromagnetic flowmeters show an abrupt decrease in uterine blood flow with uterine contractions.’ The same result probably occurs during uterine contractions in the human,’ although the techniques used in these tests are open to criticism. The prolonged, low intensity, diffuse contraction seen in the sheep probably is accompanied by a less striking, though more prolonged decline, in uterine blood flow.’ This may explain why we were unable to produce late decelerations of fetal heart rate in fetal sheep with maternal contractions despite imposed maternal hypoxia and the use of oxytocin.6
482
Parer.
Krueger,
and Harris
1t‘e conclude that ours is an adequate model with which to study the characteristics of’ late decelerations of fetal heart rate, and that in the normoxic sheep these
REFERENCES
Barcroft, J.: Researches on prenatal life, Oxford, 1946, Blackwell Scientific Publications. Hon, E. H.: An atlas of fetal heart rate patterns, New Haven, Connecticut, 1968, Harty Press, Inc. Martin, C. B.. Ir.: Rermlation of the fetal heart rate and genesis of FHR patte&s. Semin. Perinatol. 2:131, 1978. Myers, R. E., Mueller-Heubach, E., and Adamsons, K.: Predictability of the state of fetal oxygenation from a quantitative analysis of the components of late deceleration. AM. J. OBSTET. GYNECOL. 115:1083, 1973. 4. James, L. S., Morishima, H. O., Daniel, S. S., Bowe, E. T., Cohen, H., and Neimann, W. H.: Mechanism of late deceleration of the fetal heart rate. AM. J. OBSTET. GYNECOL. 115:578, 1972. 6. Parer, J. T.: The effect of contractions and hypoxia on fetal oxygen consumption in the chronically instrumented sheep. VIII Worid Congress of Gynecology and Obstetrics, Mexico City, 1976.
February 15, 1980 Am. J. Obstet. Gynecol.
decelerations are chemoreceptor, ceptor. mediated.
7.
8.
9. 10.
11.
rather
than barore-
Greiss, F. C.: Concepts of uterine blood flow, in Wynn, R. M., editor: Obstetrics and Gynecology Annual, kew York, 1973, Appleton Century Crofts, pp. 55-83. Parer, J. T.: Oxygen consumption of the fetal sheep in utero. Biol. Neonate. 33:167. 1978. Dawes, G. S.: Changes in the circulation at birth. Br. Med. Bull. 17:148, 1961. Heymann, M. A., Creasy, R. K., and Rudolph, A. M.: Quantitation of blood flow patterns in the foetal lamb in utero, in Foetal and Neonatal Physiology, Proceedings of the Sir Joseph Barcroft Centenary Symposium, Cambridge, England, 1973, Cambridge University Press, pp. 129-135. Martin, C. B., de Haan, J., Wildt, B. v. d., Jongsma, H. W., Dieleman, A., and Arts, T. H. M.: Mechanisms of late FHR decelerations: Studies with autonomic blocking agents in fetal lambs. Abstracts of Scientific Papers. 26th Annual Meeting, Sot. Gynecol. Invest., San Diego, California, 1979, p. 59.
Delayed decelerations of fetal heart rate were produced by abruptly decreasing uterine blood flow to zero for 20 seconds in chronically instrumented, normoxic sheep. Fetal 0, consumption, 0, content, and 0, tension in umbilical blood decreased significantly before the decline in heart rate. Fetal arterial blood pressure did not change significantly. Complete vagal blockade abolished the late deceleration and uncovered a late acceleration, which in turn was eliminated by total p-adrenergic blockade. We conclude that these late decelerations in normoxic sheep are vagally mediated and due to chemoreceptor rather than baroreceptor activity. (Au. J. OBSTET. GYNECOL. 136:476, 1960.)
THE E~OLOGV of. late decelerations of fetal heart rate (or Type II dips) has been subject to much speculation. Based on the work of Barcroft and Bauer’ on responses of fetal heart rate of animals to umbilical cord compression with and without an intact vagus nerve, it was initially hypothesized that late decelerations were due IO hypoxia depression, J>resumabl! of’ the myocardium.’ Correiation of heart rate Jlatterns and newborn outcome in the human supported this concept, though the correlation was far from absolute. Two types of late decelerations have been proposed, one a reHex type mediated by the vagus nerve, and the other due to direct hypoxic depression of the myocardium.:’ Attempts ha\-e been made to study late decelerations in experimental animals, but much of the information was obtained during anesthesia, and at times the heart rate patterns have occurred postsurgically without the the Department oj Obstetrics, Gynecology, Rep-odurtt’tlr Sciences und the Cardiovc*cular From
Institute,
I’niwrsity
and Re.Teurch San Fmncuco,
of California,
CaliJomlu. Supported 099RV.
by National
Institutes
of H&h
at the Twenly-jftb Annual .Sorirty fog C~ynecologzc Inzwti(lation, !Marrti I S-18. 1978.
Prusmted
Grant
Meeting Aflnntu,
of’ thp Gcorgi>.
Reprint requests: Dr. J&an 1‘. Parer, Department Obstetkx, Gynecology, and Reprodurtiw Science\. Unizlertrty of California. San Francisco, Califonuu 94143.
478
HD
o/
controlled imposition of asphyxia.‘, ’ We believed that a study of deliberately imposed asphyxia in the unanesthetized animal would be a more valid approach to studying the characteristics of large decelerations. We were unsuccessful in producing late decelerations in the chronically prepared sheep with spontaneous OI induced uterine contractions, even during maternal hypoxia.” Based on the theory that the prime factor in the production of late decelerations is a transient decrease in uterine blood flow below the limit of fetal tolerance,’ a model was developed for producing delayed decelerations of the fetal heart rate by abruptly and transiently decreasing uterine blood flow by distal maternal aortic occlusion in the unanesthetized pregnant sheep. In addition. fetal oxygen consumption was measured durmg this maneuver,x as this was thought to be the ultimate measure of adequacy of fetal oxygenation. The roles of the fetal vagus and P-adrenergic systems were determined by maternal aortic occlusion after complete blockade of each of these branches of the autonomic nervous system.
Material and methods The sheep preparation for repetitive measurement of fetal oxygen consumption and sampling of‘ blood supplying and draining the fetal side of the placenta has been described previously.’ In brief, pregnant sheep were prepared with materOOOZ-9378/80/040478+05$00.50/0
0
1980
The C. V. Mosby
Co
Volume Number
136 4
Fetal
nal catheters, an amniotic cavity catheter, a common umbilical artery blood flow transducer, and catheters in the common umbilical vein and fetal distal aorta. The latter yielded blood representative of umbilical arterial blood. An electromagnetic flow transducer was placed on the middle uterine artery draining the pregnant side of the uterus. A Fogarty balloon tip catheter was inserted into a maternal femoral artery, with the tip in the aorta distal to the renal arteries. Sheep were prepared at a mean gestational age of 121 days and studied at least 2 days after surgery (range 2 to 8 days, mean 4.1 days). Blood flows were continuously read out by Statham SP2202 blood flowmeters and recorded on a Beckman R411 Dynograph recorder. Heart rate was determined by cardiotachometer, and blood pressures were measured by Statham strain gauges. Blood gases and pH were measured with Radiometer electrodes at 39” C. Oxygen content was measured by a micromethod with accuracy equal to that of the Van Slyke manometric apparatus.” On inflation of the balloon in the maternal distal aorta, uterine blood flow decreased virtually to zero. Arterial blood pressure distal to the occlusion was greatly decreased. Before, during, and after occlusion blood samples from the umbilical vein and artery were drawn rapidly over an approximately J-second period at intervals no closer than 20 seconds. Occlusion was maintained for 20 seconds. Twenty-nine studies were carried out on six sheep fetuses. In addition, 20 studies were done on five of the fetuses after pretreatment with totally blocking doses of atropine, at least 200 pglkg of fetal weight. In five further studies, aortic occlusion followed completely blocking doses of both atropine and propranolol, with the latter being at least 1 mg/kg of fetal weight. Total blockade was determined by lack of response to acetylcholine and isoproterenol. Composite analyses of hemodynamic and blood gas values were made at intervals of 10 seconds or greater during and after the period of occlusion. Mean values were compared to control values by means of the paired Student’s t test. To eliminate error introduced by doing multiple t tests with a single control, the level of significance was divided by the number of comparisons and, therefore, we rejected the null hypothesis only when p < 0.01.
Results The mean gestational age of the fetuses at the time of the study was 125 days (range 12 1 to 135 days), and the mean fetal weight was 2455 +- 533 gm SD. All fetuses survived the transient decreases in uterine blood flow. Fig. 1 shows a typical example of the procedure. The
oxygen
consumption
and FHR
response
to late decelerations
479
AORTIC OCCLUSION
Ut. BF (ml /min) _I[ 200 MAP (mm lip) 0C 240
r
FHR (bpm)
FAP fmmW
500 &nb.BF
( ml /min 1
Fig. 1. Portion of’ an actual recording of uterine blood flow (Ut. BF), maternal arterial blood pressure (MAP), fetal heart rate (FHR), fetal arterial pressure (FAP) and umbilical blood flow (limb. BF). The 20-second period of aortic occlusion is evident from the decrease of uterine blood flow to zero. period of aortic occlusion is evident from the decrease in uterine blood flow and maternal arterial pressure. There was a delayed decrease in fetal heart rate with no change in umbilical blood flow or fetal arterial pressure. There was a decline in mean fetal oxygen consumption from the control value of 6.8 ml/mm/kg which was evident at the first measurement period after occlusion (Fig. 2). Fetal oxygen consumption reaches its nadir at 20 seconds, and thereafter recovers toward normal with a possible overshoot. However, this does not show a significant statistical difference from the control value. Fetal heart rate, by contrast, is not different from the control values until 30 seconds after commencement of aortic occlusion, that is, 10 seconds after occlusion has ceased. At this time there is significant statistical difference from the control value. In this composite analysis the heart rate is lower than control values even at 100 seconds after commencement of occlusion. N values at control, 10,20,30,40,50, 100, and 130 seconds, and 35 minutes after occlusion are: for
480
Parer,
Krueger,
and Harris Am.
February 15, 1980 J. Obsret. Gynecol.
Time ( set 1
Fig. 4. O2 content of umbilical venous and umbilical arterial blood during and after maternal aortic occlusion (See legend for Fig. 2.)
Fig. 2. Fetal heal-r rate and O2 consumption changes during and after maternal aortic occlusion. The value at time zero is the preocclusion control value in each study. See text for n
values. Asrerisks represent values significantly different from control
i*p
< 0.01:
40 r PO,
:ike;
L
(mmtig)
**p < 0.001). IOC 60
**
****
20
‘lo
i
r
0
I
I
60
80 Time ( sect
Fig.
3. L~mhilical
blood
flow
and
umbilical
venous-umbilical
Fig. 5. Umbilical venous and arterial oxygen and carbon dioxide tension during and afrer maternal aortic occlusion. (See legend for Fig. 2.)
arterial oxygen content differences during and after maternal aortic
occlusion.
iSee legend
for
Fig. 2.)
f&Ii heart rate 29. 3, 2 1. 5, l?, 9. 17, 8, il!ld 99: for fetal 0, consumption, the values arc 15, 2, 12. 3. 9, 3. 1 1, 3, and 12. In subsequent figures. cardiovascular measurements have the former n values and respirator! gas measun-ements the latter II values. The components for calculation of‘ the fetal oxygen consumption are shown in Fig. 3. There are only minor changes in umbilical blood flow, and no value is significantl) different from control. The fetal umbilical venous-umbilical arterial oxygen content difference decreases markedly with aortic occlusion and closeI> parallels the changes in fetal oxygen consumption. The oxygen content of umbilical venous and umbilical arterial blood are illustrated in Fig. 4. Several of the changes are significantly different from control, but the changes occur more dramatically in the umbilical vein. Similar changes are seen in the oxygen tension values in umbilical venous and umbilical arterial blood
(Fig. 5); the decrease in umbilical vein O2 tension is much more marked than that in the umbilical artery, although there is also a significant decline in the values in the umbilical artery. Changes in umbilical blood carbon dioxide tension were modest (Fig. 5). The changes in pH and base excess of umbilical arterial and venous blood are also yuantitatively small (Fig. 6). The changes in fetal arterial, umbilical venous, and amniotic fluid pressures during the aortic occlusion are illustrated in Fig. 7. There is no significant change in any of these values. Following pretreatment with totally blocking doses of atropine, the delayed deceleration is completely- abolished and replaced with a delayed acceleration (Fig. 8). Minor, though significant, increases in umbilical blood flow and arterial blood pressure following vagal blockade were probably a result of the increased heart rate. In five further studies, the late acceleration was shown to be due to P-adrenergic activity, as it was completely abolished with totally blocking doses of propranolol.
Volume Number
136 4
Fetal oxygen
consumption
(mmHq)
PH
and FHR
response
to late decelerations
481
4ok Umb.v.
Umb. a
Am.f/
7.3oL---J---j + 8 OCCLUSION
P
Time (set)
r
Fig. 7. Umbilical arterial and venous mean blood pressures and amniotic cavity pressure during and after aortic occlusion. (See legends for Fig. 2.) Time ( set )
Fig. 6. Umbilical venous pH and base excess during and after maternal aortic occlusion. (See legend for Fig. 2.)
FHR ( bpd
Comment The decline in uterine blood flow below the limits of fetal tolerance to hypoxia during uterine contractions is thought to be the primary feature in the production of late decelerations, and this is the basis for our model. The nadir of the fetal heart rate occurs 30 seconds after the beginning of aortic occlusion; the nadir of fetal O2 consumption, tension, and content occurs 20 seconds after the occlusion. Pretreatment of the fetus with totally blocking doses of atropine completely abolishes the late deceleration. This suggests that the decelerations in the previously normoxic fetuses are entirely vagally mediated. This study shows that there is no change in mean fetal arterial blood pressure, but there’is a substantial decline in umbilical venous oxygen tension during aortic occlusion. This blood is largely transported across the foramen ovaleg, to and distributed from the left ventricle to the vessels supplied by the proximal aorta. These late decelerations are most likely chemoreceptor mediated. The umbilical venous blood was sampled just distal to the ductus venous, and the discrepancy in the nadir of the O2 and fetal heart rate values may be explained by circulation time from sampling site to sensor (either peripheral or central). A recent preliminary report by Martin and coworkers’] described a transient fetal hypertension accompanying late decelerations produced by a similar model in sheep. Examination of our records showed that in nine studies there was no change in fetal arterial blood pressure; in 15 there was an increase; and in five, there was a decrease following aortic occlusion. The mean value in fetal arterial blood pressure actually showed a slight, though nonsignificant, decline with aortic occlusion. During spontaneous fetal hypoxemia, it is more likely for substantial transient hypertension to occur (unpublished data).
240
Urdf3.F (ml/min/kgl
*
2oo
+,;-:-.-.-.~.-. -I--.
, 6. I40
t
‘-IF11
FAP ( m m Hg)
J-q+ c
0
20
’ ’ ’ ’ 40
60
TIME
(secl
Fig. 8. Fetal heart rate, umbilical blood flow and fetal arterial blood pressure at control (C), immediately after intravenous atropine 600 pg to the fetus (O), and at intervals during and after maternal aortic occlusion. There were 20 studies on five sheep. (See legend for Fig. 2.)
In similar studies with the mother breathing hypoxic gas mixtures, we have produced late decelerations which cannot be abolished by pretreatment with atropine. We assume that these latter decelerations are caused not by reflex chemoreceptor stimulation but by hypoxic myocardial depression (Harris and associates, unpublished studies). Studies done on monkeys using electromagnetic flowmeters show an abrupt decrease in uterine blood flow with uterine contractions.’ The same result probably occurs during uterine contractions in the human,’ although the techniques used in these tests are open to criticism. The prolonged, low intensity, diffuse contraction seen in the sheep probably is accompanied by a less striking, though more prolonged decline, in uterine blood flow.’ This may explain why we were unable to produce late decelerations of fetal heart rate in fetal sheep with maternal contractions despite imposed maternal hypoxia and the use of oxytocin.6
482
Parer.
Krueger,
and Harris
1t‘e conclude that ours is an adequate model with which to study the characteristics of’ late decelerations of fetal heart rate, and that in the normoxic sheep these
REFERENCES
Barcroft, J.: Researches on prenatal life, Oxford, 1946, Blackwell Scientific Publications. Hon, E. H.: An atlas of fetal heart rate patterns, New Haven, Connecticut, 1968, Harty Press, Inc. Martin, C. B.. Ir.: Rermlation of the fetal heart rate and genesis of FHR patte&s. Semin. Perinatol. 2:131, 1978. Myers, R. E., Mueller-Heubach, E., and Adamsons, K.: Predictability of the state of fetal oxygenation from a quantitative analysis of the components of late deceleration. AM. J. OBSTET. GYNECOL. 115:1083, 1973. 4. James, L. S., Morishima, H. O., Daniel, S. S., Bowe, E. T., Cohen, H., and Neimann, W. H.: Mechanism of late deceleration of the fetal heart rate. AM. J. OBSTET. GYNECOL. 115:578, 1972. 6. Parer, J. T.: The effect of contractions and hypoxia on fetal oxygen consumption in the chronically instrumented sheep. VIII Worid Congress of Gynecology and Obstetrics, Mexico City, 1976.
February 15, 1980 Am. J. Obstet. Gynecol.
decelerations are chemoreceptor, ceptor. mediated.
7.
8.
9. 10.
11.
rather
than barore-
Greiss, F. C.: Concepts of uterine blood flow, in Wynn, R. M., editor: Obstetrics and Gynecology Annual, kew York, 1973, Appleton Century Crofts, pp. 55-83. Parer, J. T.: Oxygen consumption of the fetal sheep in utero. Biol. Neonate. 33:167. 1978. Dawes, G. S.: Changes in the circulation at birth. Br. Med. Bull. 17:148, 1961. Heymann, M. A., Creasy, R. K., and Rudolph, A. M.: Quantitation of blood flow patterns in the foetal lamb in utero, in Foetal and Neonatal Physiology, Proceedings of the Sir Joseph Barcroft Centenary Symposium, Cambridge, England, 1973, Cambridge University Press, pp. 129-135. Martin, C. B., de Haan, J., Wildt, B. v. d., Jongsma, H. W., Dieleman, A., and Arts, T. H. M.: Mechanisms of late FHR decelerations: Studies with autonomic blocking agents in fetal lambs. Abstracts of Scientific Papers. 26th Annual Meeting, Sot. Gynecol. Invest., San Diego, California, 1979, p. 59.