Effect of selective occlusion of the umbilical arteries and/or veins on uterine blood flow in sheep

Maternal uterine blood flow was depressed during total umbilical cord occlusion, probably based on an increased fetal cotyledonary tissue pressure (Hasaart and de Haan (1985) Eur. J. Obstet. Gynec. Reprod. Biol., 19, 125-131). This supposed mechanism was further analysed by performing selective occlusions of the umbilical arteries and/or veins (mean occlusion time 35 s). An occluding device which allowed separate occlusion of umbilical veins and arteries was applied to the umbilical cord in 7 chronically prepared fetal lambs between 106 and 135 days gestation. Median uterine artery blood flow (UBF) was measured with an electromagnetic flow meter. During occlusion of both umbilical veins (VV, n = 22) in 6 animals a maximal decrease in UBF to 87.5% of control value (P less than 0.001) was found at the end occlusion, followed by a gradual return to control value in the post occlusion period. Occlusion of both umbilical arteries (AA, n = 29) in 5 animals was accompanied by a slight increase in UBF to 103% of control value (P less than 0.01). Total occlusion of the umbilical arteries and veins simultaneously (n = 17) in 4 animals did not result in any change in UBF. The changes in volume and turgor in the fetal cotyledonary tissue associated with the arterial and venous occlusions should lead to respectively a decrease (AA) and increase (VV) in resistance to maternal flow, causing the changes in uterine blood flow. It is concluded that volume changes in the fetal compartment of the sheep placenta affect maternal uterine blood flow.     

Cardiovascular and metabolic responses to intermittent umbilical cord occlusion in the preterm ovine fetus

OBJECTIVE: To determine the cardiovascular and metabolic responses to umbilical cord occlusion in the preterm ovine fetus and the impact of repetitive intermittent insults over a 4-day period. METHODS: Repetitive umbilical cord occlusions (experimental group, n = 7; control group, n = 7) were performed daily (112-115 days' gestation, term = 147 days). Mean arterial pressure (MAP), fetal heart rate (FHR), and FHR variation were monitored, and arterial blood was sampled at predetermined intervals. RESULTS: During umbilical cord occlusions, arterial oxygen pressure (PaO2) (approximately 17 mmHg) and glucose (approximately 0.3) millimoles per liter (mmol/L) fell and arterial carbon dioxide pressure (approximately 8 mmHg) rose (P < .01) to a similar extent on days 1 and 4. Umbilical cord occlusion produced a rise in lactate over the course of successive umbilical cord occlusions each day, the magnitude of which tended to be reduced by day 4 (0.3 +/- 0.1 versus 0.6 +/- 0.1 mmol/L). Control hour FHR and MAP were unaltered over the 4 days, but the delta (delta) FHR to delta PaO2 ratio during umbilical cord occlusions was less on day 4 than on day 1 (6.0 +/- 0.4 versus 10.9 +/- 1.5 beats per minute/mmHg; P < .01). During occlusion hours, high FHR variation episodes, as a measure of fetal activity, were reduced (14.6 +/- 1.5 versus 4.2 +/- 1.3 min/h; P < .01), whereas the reduction in short-term (7.4 +/- 0.7 to 5.8 +/- 0.6 milliseconds; P < .05) and long-term (34.9 +/- 2.7 to 30.0 +/- 0.6 milliseconds; P < .05) FHR variation reached significance only on day 4. CONCLUSION: The increase in lactate and reduced high-FHR variation episodes over successive umbilical cord occlusions may affect fetal growth and development. Furthermore, repeated umbilical cord occlusions over several days alter the preterm FHR response to subsequent stresses, suggesting an altered chemoreflex response.     

Effect of maternal oxygen administration on fetal oxygenation during graded reduction of umbilical or uterine blood flow in fetal sheep.

OBJECTIVE: Effects of maternal oxygen administration on fetal blood gases and on oxygen delivery and consumption during reduced uterine and reduced umbilical blood flows were examined. STUDY DESIGN: In eight pregnant sheep (gestational age 133 +/- 4 days) flow transducers were applied to a uterine and the common umbilical artery. Graded reductions in uterine and umbilical blood flows were achieved by a hypogastric artery snare and a balloon cuff encircling the umbilical cord. Fetal femoral arterial and umbilical venous oxygen contents and flows were measured at varying flow reductions with the ewe breathing air or oxygen. RESULTS: During 75% reduction in umbilical blood flow maternal oxygen administration significantly increased fetal oxygen delivery (6.4 +/- 2.5 to 7.7 +/- 2.3 ml/min/kg) and oxygen consumption (4.3 +/- 1.2 to 5.0 +/- 0.8 ml/min/kg). With similar reduction of uterine flow oxygen administration increased oxygen delivery from 8.3 +/- 2.4 to 12.3 +/- 3.6 and oxygen consumption from 3.3 +/- 0.8 to 4.7 +/- 1.6 ml/min/kg. CONCLUSION: Maternal oxygen inhalation improves fetal oxygenation during umbilical but especially during uterine blood flow reduction.     

Fetal infusions of plasma cause an increase in umbilical vascular resistance in sheep

Earlier studies suggested that the fetal placental circulation is relatively inert with fetal placental flow increasing or decreasing with perfusion pressure. Subsequent studies have demonstrated that the placenta may not be an unreactive vascular bed. The present study was undertaken to determine if plasma infusion-induced hypertension increased fetal placental flow in proportion to the driving pressure across the fetal placental circulation. Six fetal sheep were operated on at 118-122 days to place intravascular catheters and a flow sensor on the common umbilical artery. Starting 6 days later, the fetuses were infused with adult sheep plasma. During the 7-day-long infusion period, they received a total of 1515+/-217 (SD) ml of fluid and 93.2+/-12.0 g of protein. Fetal plasma protein concentrations increased from 34.2+/-2.3 to 77.0+/-9.7 g/l (P<0.0001). Fetal arterial blood pressures rose from 42+/-3 to 59+/-4 mmHg (P<0.01) and venous pressures rose from 2.2+/-0.5 to 4.8+/-0.8 mmHg (P<0.01). In spite of the large increase in driving pressure, fetal placental blood flow remained (statistically) constant (627+/-299 ml/min and 552+/-221 ml/min) while fetal umbilical resistance increased from 0.077+/-0.038 to 0.115+/-0.053 mmHg min/ml (P<0.01). On day 7, plasma renin activity had fallen from 6.7+/-4.2 ng/(ml/h) at preinfusion control to 0.6+/-0.6 ng/(ml/h) (P<0.05) and plasma angiotensin-II concentration had fallen from 33.2+/-26.6 to 6.2+/-3.9 pg/ml, although this fall was not statistically significant (P=0.07). Fetal placental flow did not increase with increased driving pressure across the fetal placental circulation. The increase in fetal placental resistance may be a response to the increase in arterial pressure since there was no increase in flow.     

Fetal heart rate overshoot during repeated umbilical cord occlusion in sheep

OBJECTIVE: To assess the clinical utility of overshoot fetal heart rate (FHR) decelerations by examining their occurrence after umbilical cord occlusions of varying frequency and length in near-term fetal sheep. METHODS: Fetuses were allocated to the following three groups: 1-minute umbilical cord occlusion repeated every 5 minutes (1:5 group, n = 8) or every 2.5 minutes (1:2.5 group, n = 8) or 2-minute occlusions repeated every 5 minutes (2:5 group, n = 4). Occlusions were continued for 4 hours or until fetal mean arterial pressure decreased below 20 mmHg during two successive occlusions. RESULTS: In the 1:5 group, fetuses tolerated 4 hours of occlusion without hypotension or clinically significant acidosis and overshoot never occurred. In the 2:5 group, fetuses rapidly became hypotensive and acidotic, and occlusions were terminated at 116.3 +/- 22.9 min (mean +/- standard deviation). Overshoot was seen after every occlusion, starting with the first occlusion. In the 1:2.5 group, fetuses became progressively acidotic and hypotensive and occlusions were stopped at 183.1 +/- 42.8 min. Overshoot occurred after 91.6 +/- 42.5 minutes, at a pH of 7.17 +/- 0.06, base deficit 9.3 +/- 4.5 mmol/L. After the appearance of overshoot there was a more rapid decrease in fetal mean arterial pressure (0.25 [0.21, 0.35, 25-75th percentile] mmHg/minute versus 0.11 [0.03, 0.15] mmHg/minute before overshoot appeared, P <.01). CONCLUSION: These data suggest that overshoot is related to longer (2-minute) occlusions or to developing fetal acidosis and hypotension during 1-minute occlusions. This pattern could have clinical utility, as 1-minute contractions are typical of active labor.     

Umbilical flow in the normal and pre-eclamptic placenta. A study in vitro

In order to develop a simple in vitro method for assessing adequacy of placental perfusion, umbilical flow was measured in placentae from 10 normal control women and from 10 women with pre-eclampsia, by infusing through the umbilical arteries a heparinized 0.9% saline solution. The average induced umbilical flow in placentae from uneventful pregnancies was 276 +/- 16 SE ml/min compared with 163 +/- 12 ml/min (p less than 0.001) in the pre-eclamptic group. In angiographic studies, 79 +/- 2 SE% of the cotyledons from the normal series, and only 56 +/- 3% (p less than 0.001) from the pre-eclamptic series were functional. Additionally, gross and histological examination revealed three distinct types of cotyledon. Placental areas that blanched following saline infusion showed no blood in the collapsed villi or in the intervillous space; areas distinguished by a ruddy appearance following perfusion showed blood trapped in the villi and in the intervillous space; in a third area, the findings were mixed. When compared with placental zones identified by perfusion with 5% Hypaque solution, these three anatomical regions corresponded to normal, reduced, or absent flow (blanched, intermediate, or ruddy regions, respectively). We conclude that under the conditions of this in vitro study, pre-eclamptic placentae had a greater proportion of umbilical perfusion deficits than had normal placentae.     

Flow velocity waveforms in uterine and umbilical arteries during submaximal bicycle exercise in normal pregnancy.

Eight healthy women who were not conditioned athletes, at 35-38 weeks' gestation, performed a submaximal bicycle exercise test three times for 4 minutes each with stepwise increases (73 +/- 27, 114 +/- 29, and 161 +/- 16 W) of the work load. The target heart rate at the end of the last load was 170 beats per minute. The systolic-diastolic ratios (S/Ds) of flow velocity waveforms were measured with pulsed color Doppler ultrasound in the uterine and umbilical arteries immediately after each work load and during recovery. The heart rates at the end of each load (133 +/- 3, 156 +/- 3, and 173 +/- 7 beats per minute) corresponded to an average of 70, 83, and 92% of the calculated maximum heart rate. With the subject in the sitting position on the ergometer before exercise, the S/D in the uterine artery was 1.49 +/- 0.09, increasing gradually and significantly during the exercise to the maximum of 2.04 +/- 0.06 at 1 minute of recovery. Heart rate and S/D in the uterine artery correlated significantly (r = 0.58, P less than .01). Although the mean arterial pressure increased significantly during exercise from 92 +/- 6 to 109 +/- 10 mmHg, the significant decrease of the ratio of the mean arterial blood pressure and S/D suggests that the flow in the main uterine artery may decrease during intense exercise. No changes occurred in the S/D of the umbilical artery flow velocity, but the fetal heart rate increased significantly.     

Electrocardiographic changes following umbilical cord occlusion in the midgestation fetal sheep

BACKGROUND: Clinical studies show that analysis of the fetal electrocardiographic (FECG) ST waveform at term gives important information on the myocardial response to intrapartum asphyxia. However, it is not known whether the preterm fetus responds in a similar fashion. The objective of the present study was to evaluate the FECGST response to umbilical cord occlusion in the preterm fetal sheep. METHODS: Fetal sheep at midgestation were subjected to 25 min umbilical cord occlusion (n = 7) and compared to controls (n = 5). Changes in the FECGST waveform were recorded together with arterial blood pressure, heart rate, and acid base status during the occlusion and for 3 days afterward. RESULTS: Umbilical cord occlusion resulted in immediate bradycardia (control: 187 +/- 7 bpm versus occlusion: 102 +/- 7 bpm), hypertension (control: 43.2 +/- 1.1 mmHg versus occlusion: 59.8 +/- 2.2 mmHg), and an initial increase in the T/QRS ratio (control: 0.10 +/- 0.02 versus occlusion: 0.60 +/- 0.10, P < 0.001), followed by hypotension (21.7 +/- 1.2 mmHg), normalization of the T/QRS ratio, and in some cases the development of negative T waves toward the end of the occlusion. CONCLUSIONS: These studies show that the midgestation fetal sheep has the capacity to react to umbilical cord occlusion with a significant increase in the amplitude of the ST waveform together with an augmentation of blood pressure, which then subsides as the occlusion continues. The appearance of negative ST segment appears to signify significant cardiac dysfunction. The characteristic progression of ST-waveform changes in response to umbilical cord occlusion in midgestation fetal sheep, suggests that monitoring the ST waveform may contribute clinically important information also in the preterm individual.     

Ten-minute umbilical cord occlusion markedly reduces cerebral blood flow and heat production in fetal sheep

OBJECTIVE: The study was undertaken to determine to what extent a 10-minute total umbilical cord occlusion affects autoregulation of cerebral blood flow and cerebral heat production in the fetus. STUDY DESIGN: In seven chronically catheterized late-gestation fetal sheep (127-131 days' gestation), we studied fetal blood gas, hemodynamic, and thermal responses to 10-minute total umbilical cord occlusion. RESULTS: Ten-minute umbilical cord occlusion resulted in marked hypoxia/ischemia, with oxygen content decreasing from 6.5 +/- 0.4 to 0.6 +/- 0.1 vol% and lactate concentration increasing from 1.8 +/- 0.2 to 10.7 +/- 0.7 mmol/L. During this period, the fetuses showed reductions in heart rate from 163.5 +/- 3.4 to 97.1 +/- 5.4 beats/min, mean arterial pressure from 39.4 +/- 2.1 to 21.2 +/- 2.5 mm Hg, cerebral blood flow from 101.3% +/- 8.9% to 49.7% +/- 10.3%, and cerebral heat production from 95.0% +/- 6.3% to 29.6% +/- 4.8%. During cord occlusion, cerebral blood flow was pressure passive from the fourth minute onward. The reduction in cerebral heat production preceded the reduction in perfusion pressure and cerebral blood flow. Recovery of cerebral blood flow and heat production to control values was incomplete for more than 60 minutes after restoration of umbilical flow. CONCLUSION: Ten-minute total umbilical cord occlusion results in major reductions in cerebral blood flow and heat production. Autoregulation of cerebral blood flow was lost within 4 minutes of occlusion, probably as a result of hypoxia, combined with hypotension. The fact that the reduction in cerebral heat production preceded and exceeded the reduction in blood flow may suggest active down-regulation of cerebral metabolism, the mechanism of which is unclear at present.     

Depression of uterine blood flow during total umbilical cord occlusion in sheep

The effect of total umbilical cord occlusion upon maternal blood flow in the internal iliac and median uterine arteries was studied in eight chronically instrumented pregnant sheep. Occlusion of the umbilical cord was performed with an inflatable balloon occluder around the total cord. Blood flow was measured with electromagnetic flow transducers. Total umbilical cord occlusion of short duration (mean 40.1 s) caused a significant decrease in blood flow in the maternal internal iliac and median uterine arteries at the end of the occlusion to respectively 93.9% and 91.7% of the control values.The decrease in internal iliac and median uterine artery blood flow is attributed to an elevated fetal capillary pressure in the placenta, leading to an increased fetal placental tissue pressure which in turn compresses the maternal placental capillaries, resulting in a heightened vascular resistance and a decrease in uterine blood flow.     

Efficacy of carotid collateral perfusion in anaesthetized sheep fetuses

The purpose of this study was to learn to what extent carotid collateral circulation is efficient in maintaining cephalic blood flow in the sheep fetus. Under halothane anaesthesia six fetal sheep at 124-135 days of gestation were instrumented with inflatable occluders around both common carotid arteries, an inductive flow probe around one external carotid artery, and arterial catheters to measure carotid sinus and aortic pressure. In acute experiments, the occluders were inflated on one side, or the other, or both sides simultaneously, while carotid blood flow, driving pressures and fetal heart rate were determined. Ipsi- and bilateral occlusion reduced carotid blood flow from about 42 ml/min to 10-0 ml/min and decreased sinus pressure from 39 mmHg to 29.1+/-2.9 (mean+/-s.d.) and 16.7+/-3.7 mmHg, respectively. Occlusion of the contralateral carotid artery increased ipsilateral carotid blood flow from 45+/-10 ml/min to 64+/-14 ml/min within 0.2 sec. Heart rate and aortic and sinus pressures did not change appreciably. Analysis of an analogue resistance network demonstrated that the observed carotid flow increases (less than twice normal) do not require changes of vascular resistances.It is concluded that the fetal sheep, as in the adult of many species, possesses an efficient carotid collateral system.     

Tei index for prenatal diagnosis of acute fetal hypoxia due to intermittent umbilical cord occlusion in an animal model

OBJECTIVE: To study the effectiveness of the pulsatility index for veins of ductus venosus (DV-PIV) and the Tei index in a prospective assessment of fetal hypoxic-ischemic brain damage in a near-term ovine fetus model with intermittent umbilical cord occlusion (UCO). METHODS: Twelve fetal sheep were studied with umbilical cord occlusion performed in the experimental group animals by complete inflation of an occluder cuff for 90 s, every 30 min for approximately 2.5 h. Fetal arterial blood was sampled at 5 min before the first umbilical cord occlusions, approximately 60 s of the first umbilical cord occlusions, and 3 min after each occlusion for blood gas, pH, neuron-specific enolase (NSE) and S100B. Doppler measurements and Doppler echocardiographic examinations were performed 5 min before the first umbilical cord occlusions and 3 min after each successive occlusion. RESULTS: In experimental group animals, UCO caused a large decline in arterial PaO(2) (to approximately 7.70 mmHg, p < 0.01), a modest decline in pH (to approximately 7.24, p < 0.01), and a modest rise in PaCO(2) (to approximately 53.31 mmHg, p < 0.01), with a return more or less to baseline after occluder release. and there was significant change as compared with the control animals (all p < 0.01) with cumulative changes in responses to repetitive cord occlusions. The DV-PIV waveforms, right ventricle (RV) and LV Tei indices, the serum levels of NSE and S100B increased with cord occlusions (all p < 0.05), and were significantly higher than the control animals (all p < 0.05) with a cumulative changes in responses to repetitive cord occlusions. RV and LV Tei indices were significantly correlated with PaO(2) (r = - 0.684, p < 0.01 and r = - 0.725, p < 0.01), PaCO(2) (r = 0.682, p < 0.01 and r = 0.780, p < 0.01), pH (r = - 0.538, p < 0.01 and r = - 0.681, p < 0.01), NSE (r = 0.653, p < 0.01 and r = 0.687, p < 0.01), and S100B (r = 0.606, p < 0.01 and r = 0.640, p < 0.01). Significant but weaker correlations were also present between DV-PIV and the parameters considered. CONCLUSION: Umbilical cord occlusion during the latter part of the pregnancy, enough to cause significant hypoxemia and acidosis, results in a significant increase of DV-PIV, RV and LV Tei indices, and the serum levels of NSE and S100B. There was a strong correlation between the RV and LV Tei indices and blood gas, pH, and NSE, S100B with hypoxia. Therefore, the Tei index might be an easy and useful quantitative parameter for assessing fetal hypoxic ischemia.     

Activation of the hypothalamic-pituitary-adrenal axis with repetitive umbilical cord occlusion in the preterm ovine fetus

OBJECTIVE:To determine whether repeated hypoxic insults with umbilical cord occlusion over 4 days will lead to activation of the hypothalamic-pituitary-adrenal (HPA) axis altered adrenocortical responsiveness in the preterm ovine fetus. METHODS: Umbilical cord occlusions of 90 seconds duration were performed every 30 minutes for 3 to 5 hours each day (experimental group n = 7, control group n = 7; at 112-116 days' gestation, term = 147 days). Arterial blood was sampled at predetermined times for blood gases and pH, plasma ACTH, and cortisol. Pituitary proopiomelanocortin (POMC) and glucocorticoid receptor (GR) mRNA also were localized and quantified by in situ hybridization. RESULTS: During umbilical cord occlusions fetal arterial oxygen pressure (approximately 17 mmHg) and pH (approximately 0.05) decreased, and carbon dioxide pressure increased (approximately 8 mmHg) as measured on days 1 and 4, but with no cumulative blood gas or pH change over successive occlusions for any of the 4 study days. Plasma ACTH increased, as measured after cord occlusion and over the course of successive cord occlusions on days 1 and 4, and returned to control values by the next day. The cumulative increase in ACTH was much less on day 4 than day 1 (15 +/- 3 compared with 101 +/- 25 pg/mL, P <.05). Plasma cortisol increased, as measured after cord occlusion and over the course of successive cord occlusions on day 4 only (2.7 +/- 0.4 to 4. 7 +/- 0.3 ng/mL, P <.05). POMC mRNA increased 2.5-fold in the pars distalis of the pituitaries from cord occlusion compared to control fetuses, but was unchanged in the pars intermedia. GR mRNA, which was detected in the pars distalis only, was unaltered. CONCLUSION: Repetitive umbilical cord occlusion in the preterm ovine fetus resulted in the activation of the HPA axis, with increased adrenocortical responsiveness over time, and involved differential regulation of POMC mRNA expression in the pars distalis and pars intermedia of the pituitary, but with no change in GR.     

Umbilical artery pulsatility index and placental vascular resistance during acute hypoxemia in fetal lambs

The effect of hypoxemia on the pulsatility index (PI) of the umbilical artery flow velocity waveform and placental vascular resistance was studied. Fetal hypoxemia was induced by maternal breathing of a low-oxygen gas mixture. Umbilical venous blood flow was measured with an electromagnetic flowmeter. Placental vascular resistance (PVR) was defined as the ratio perfusion pressure (mean arterial pressure minus umbilical venous pressure) and umbilical blood flow. Umbilical artery velocity waveforms were obtained by a 5-MHz pulsed Doppler device around one umbilical artery in 4 lambs and by a transcutaneous 4-MHz continuous wave Doppler transducer in 3 lambs. Fetal arterial oxygen content was lowered from 2.28 +/- 0.18 to 0.93 +/- 0.15 mM (p less than 0.05), while pCO2 and pH remained unchanged. Control values of the hemodynamic variables were compared with values during deepest hypoxemia. Fetal heart rate, mean arterial and umbilical venous pressure, PVR and the umbilical artery PI did not significantly change, whereas umbilical blood flow increased from 436 +/- 64.7 to 491 +/- 65.9 ml/min (p less than 0.05) during deepest hypoxemia. Individual regression analysis, however, showed a significant inverse correlation of umbilical venous pressure whereas PVR had a positive correlation with actual oxygen content. It is concluded that acute fetal hypoxemia slightly decreases PVR, but does not affect the umbilical artery PI in sheep. Decreasing fetal oxygenation is associated with an increase in pressure in the umbilical vein.     

Effect of the supine position on uterine and umbilical blood flow during the third trimester of uncomplicated pregnancies in multiparous patients.

We established the effects of the supine position on umbilical blood flow when measured during the third trimester in 30 multiparous, normotensive patients. Blood flow in the umbilical and uterine arteries and blood pressure in the brachial and popliteal arteries were blindly taken by two different observers: first in the lateral and 5 min later in the supine position. There was a significant difference in mean blood pressure between the two postures. However, there was no statistical difference in the pulse pressure or in systolic/diastolic ratio in the umbilical and uterine arteries between the two positions. Postural changes in normotensive multiparous patients do not affect uterine and umbilical blood flow during the third trimester of uncomplicated pregnancies.     

Qualitative assessment of maternal uterine and fetal umbilical artery blood flow and resistance in laboring patients by Doppler velocimetry

The purpose of this study is to evaluate the effect of uterine contractions during labor on both the uterine and the umbilical circulations. Twenty-seven patients in active labor were studied by continuous-wave Doppler velocimetry. Umbilical, left uterine, and right uterine arterial waveforms were obtained before, during, and after peak uterine contractions, and the ratio of maximum systolic and minimum diastolic velocities was calculated. Fifteen patients showed absent flow in end diastole on the uterine artery waveform and had significantly higher intra-amniotic pressures (64.5 +/- 3.5 mm Hg) during the peak amplitude of the uterine contraction compared with the 12 patients with maintained end diastolic flow (46.5 +/- 2.6 mm Hg; p less than 0.05). During the peak amplitude of the uterine contractions the 12 patients maintaining end-diastolic flow had significantly higher systolic/diastolic ratios in the uterine artery (6.5 +/- 1.5) compared with either before or after a contraction (2.1 +/- 0.15 and 2.0 +/- 0.2, respectively; p less than 0.05). Also, these 12 patients showed a linear relationship between the systolic/diastolic ratio and the intrauterine pressure. However, no differences were observed in the umbilical artery systolic/diastolic ratios before, during, or after a contraction in the intensity range studied. On the contrary, during contractions an increase in uterine artery resistance occurs with decreased or absent end-diastolic flow, which bears an inverse linear relationship to the intensity of the contraction. This suggests that during uterine contractions the human fetus continues to have uninterrupted fetoplacental blood flow, whereas the degree of interruption or reduction in uteroplacental blood flow is dependent on the intensity of uterine contraction.     

Fetal cardiorespiratory changes during spontaneous prelabor uterine contractions in sheep

Fetal cardiorespiratory changes during spontaneous prelabor uterine contractions (called contractures) were studied in 12 chronically catheterized fetal sheep at 120 to 143 days' gestation. During contractures the carcass blood flow increased significantly from 27 +/- 2 (SEM) to 32 +/- 3 ml/min/100 gm. There were no significant changes in combined ventricular output or in blood flow to the umbilical circulation, brain, heart, adrenal glands, gut, kidney, and lung. Fetal arterial blood pressure increased from 57 +/- 2 to 62 +/- 1 mm Hg (p less than 0.001) during contractions. There were no significant changes in fetal heart rate. In the fetal femoral artery during contractures the oxygen content decreased from 6.1 +/- 0.2 to 5.4 +/- 0.2 ml/dl of blood (p less than 0.001), and carbon dioxide tension increased significantly from 44 +/- 0.4 to 45 +/- 0.4 mm Hg (p less than 0.001). The pH did not change. The increase in carcass blood flow during contractures suggests that there was an increase in fetal skeletal muscular activity or tone. An increase in fetal skeletal muscle activity, together with a decrease in uterine blood flow could explain the small decrease in fetal oxygen content that occurs with each contracture. Fetal compression and/or changes from rapid eye movement to synchronized sleep or arousal observed during contractures are possible stimuli causing increased fetal skeletal muscle tone or activity. Since contractures periodically result in neuromuscular activity in the fetus in its protected fluid-filled environment, they may play a key role in fetal neuromuscular development by stimulating "exercising" in the fetus in utero.     

Fetal umbilical vascular response to chronic reductions in uteroplacental blood flow in late-term sheep

OBJECTIVE: The present study was designed to determine the effects of chronic reduction in uterine blood flow (UBF) on umbilical blood flow (UmbBF) and fetal cardiovascular hemodynamics and oxygenation. STUDY DESIGN: Sixteen sheep with singleton pregnancies were instrumented on gestational day (GD) 110; an externally adjustable vascular occluder was placed on the common internal iliac artery. UBF in control animals rose from 867 +/- 61 mL/min on GD 115 to 1520 +/- 158 mL/min (n = 8) on GD 138, whereas UBF in restricted animals was maintained at 750 +/- 50 mL/min (n = 8). RESULTS: UmbBF in control animals increased from 472 +/- 25 mL/min to 744 +/- 58 mL/min over the study period from GD 115 to GD 138. This was associated with normal gestational increases in fetal arterial pressure and significant reductions in calculated umbilical vascular resistance. Although restricted animals initially had a similar UmbBF on GD 115, UmbBF rose only to 545 +/- 43 mL/min over the study period (control vs restricted, P <.008). Although fetal arterial pressure showed normal gestational changes, umbilical vascular resistance failed to decrease over gestation in restricted animals as it did in control animals. Fetal heart rate and oxygenation showed normal changes in both groups. CONCLUSION: Chronic reduction in UBF prevents umbilical vascular resistance from undergoing normal gestational decreases, leading to significantly lower UmbBF. This altered umbilical perfusion pattern would be expected to significantly affect fetal delivery of oxygen and nutrients and ultimately fetal growth.     

The preejection period of the fetal cardiac cycle. I. Umbilical cord occlusions

The preejection period (PEP) of the fetal cardiac cycle was studied in the chronically instrumented fetal lamb. A specially constructed device permitted the occlusion of either both umbilical veins, or of both umbilical arteries, or of the total umbilical cord. A prolongation of the PEP together with an increase in blood pressure was a consistent finding during any type of cord occlusion. In poorly oxygenated fetal lambs a two-step increase in the duration of the PEP was observed during the occlusion. It was accompanied by a simultaneous two-step increase in fetal arterial blood pressure. A correlation was found between the steady-state fetal pO2 before the occlusion and the increase in fetal arterial diastolic blood pressure during the blockade of the umbilical circulation. During occlusion the main determining factors of the PEP prolongation appear to be the increase in afterload and the decrease in preload of the fetal heart. The second step in the prolongation of the PEP during the occlusions in poorly oxygenated fetal lambs is attributed to a chemoreceptor-induced reflex, resulting in a redistribution of cardiac output in the fetal lamb.     

Fetal responses to maternal infusions of angiotensin II

It is unclear whether the fetus is affected by maternal infusions of angiotensin II; therefore we studied maternal and fetal responses (n = 9) to angiotensin II (1.15, 2.29, 11.5 micrograms/min) infused 5 minutes into the vena cava of chronically instrumented sheep (129 to 137 days of gestation) while monitoring PO2, PCO2, pH, heart rate, uterine blood flow, and arterial and umbilical venous pressures. Pregnant sheep demonstrated expected dose-related increases in mean arterial pressure and decreases in uterine blood flow (p less than 0.05). Increases in fetal mean arterial pressure also correlated with the maternal dose of angiotensin II (r = 0.77, p less than 0.001). Fetal heart rate appeared to increase with 2.29 micrograms/min; however, bradycardia was observed with 11.5 micrograms/min (p less than 0.05) and was associated with decreased PaO2, 19.0 +/- 1.0 to 14.3 +/- 1.4 mm Hg (p less than 0.05), increased PaO2 (p less than 0.05), and decreased umbilical venous PO2, 31.4 +/- 2.3 to 27.0 +/- 1.9 mm Hg. The decreases in PO2 correlated with decreases in uterine blood flow (r = 0.60, p less than 0.002, and r = 0.75, p less than 0.005, respectively). Nevertheless, changes in fetal mean arterial pressure also occurred in the absence of altered fetal oxygenation; thus decreased uterine blood flow and fetal oxygenation alone cannot explain the fetal cardiovascular responses. It is suggested that angiotensin II or an active metabolite may cross the ovine placenta.