Umbilical Vascular Resistance Research Articles

The fetal aortic pressure pulse waveform in normal and compromised pregnancy.

To study the arterial pressure waveform in the descending thoracic aorta during pregnancy in both normal and compromised fetuses. The pressure pulsation waveform propagated along the vascular tree, and acting laterally on the arterial wall, produces a corresponding change in the vessel diameter. The distance between diametrically opposite points of the aortic lumen was followed using a phase locked loop echo tracking system coupled to a B-mode ultrasonic imager (central frequency 3.5 MHz). Tertiary referral unit, teaching hospital. A cross-sectional study of 80 normal fetuses between 20 and 40 weeks yielded normal data. We studied 58 women with evidence of potential fetal compromise (high umbilical artery systolic: diastolic ratio). From the aortic diameter waveform we measured the maximum systolic and minimum diastolic dimension and calculated pulse amplitude. The first derivative of the aortic diameter waveform identified the incisura of aortic and pulmonary valve closure and was used to time the end of ventricular ejection and systole. In normal pregnancy there was an increase in systolic and diastolic diameter and pulse amplitude with advancing gestation. Ventricular ejection time was constant. In the fetal compromised group the absolute systolic and diastolic diameters were within the normal range, but diastolic diameter per unit fetal weight was increased. There was a decrease in pulse amplitude as a percentage of diastolic diameter and an increase in the diastolic systolic diameter ratio. Fetal outcome was examined in relation to the diastolic systolic diameter ratio. Those with a high ratio (above 90th centile of normal group) exhibited significantly more adverse indices of fetal outcome. The fetal aortic pressure pulse waveform was represented by the vessel diameter waveform. In fetal compromise reduced pulse amplitude and increased diastolic to systolic diameter ratio suggest corresponding changes in arterial pressure pulse. We suggest these are the response of the cardiac pump to increased afterload imposed by the high umbilical placental vascular resistance.

Chronic fetal placental embolization and hypoxemia cause hypertension and myocardial hypertrophy in fetal sheep.

To examine the cardiovascular effects on the fetus of an elevated umbilical vascular resistance resulting in fetal hypoxemia, we embolized the fetal side of the placenta in pregnant sheep and measured cardiovascular and hormonal changes and cellular growth in fetal heart. Chronically catheterized fetal sheep were embolized (n = 6) for 21 days between 0.74 and 0.88 of gestation into the descending aorta until arterial oxygen content was decreased by 40-50% of the preembolization value. Control animals (n = 6) received saline only. During embolization, fetuses became chronically hypoxemic (P < 0.001) and hypertensive (P < 0.001), with a progressive increase in umbilical artery resistance index (P < 0.001). There was also an increase in fetal plasma norepinephrine throughout the study period (P < 0.05). On day 21 of embolization, fetuses showed asymmetrical growth restriction, increased heart weight (P < 0.01), and increase in right and left ventricular wall thickness (P < 0.05) compared with control animals. The protein-to-DNA ratio, an index of cell size, increased in the right ventricular myocardium in the embolized group (P < 0.001), suggesting myocardial cell hypertrophy. We conclude that, during chronic placental damage leading to fetal hypoxemia with an increase in umbilical artery resistance index, fetuses developed arterial hypertension and asymmetrical growth restriction and that increases in afterload to the heart and plasma norepinephrine likely caused fetal myocardial hypertrophy.

Elevation of nitrate levels in pregnant ewes and their fetuses

OBJECTIVE: Nitric oxide is a potent vasodilator released by endothelial cells that may play an important role in modulating maternal and fetal vascular tone in normal pregnancy. The current study was designed to evaluate whether plasma or urine nitrite and nitrate (the metabolites of nitric oxide) concentrations are elevated in pregnant compared with those of nonpregnant sheep and whether the nitrate concentrations in the fetal circulation were increased in comparison with the maternal circulation. STUDY DESIGN: Eleven pregnant sheep and seven nonpregnant oophorectomized sheep were instrumented with catheters in the maternal and fetal femoral arteries and veins, uterine and umbilical veins, and amniotic cavity. Blood, urine, and amniotic fluid samples were collected for nitrate determination at least 5 days after surgery. After extraction nitrate was reduced to nitrite and quantitated with the Griess reagent. RESULTS: Arterial plasma nitrate concentrations in the pregnant sheep were significantly elevated compared with those of nonpregnant sheep (5.0 ± 0.9 vs 2.5 ± 0.6 μmol/L, p < 0.05). The urinary nitrate concentrations were also significantly increased in the pregnant sheep compared with those of nonpregnant sheep (89.9 ± 16.3 vs 23.1 ± 4.5 nmol/mg creatinine, p < 0.01). Fetal plasma nitrate concentrations were ninefold higher than the maternal nitrate concentrations (43.9 ± 7 vs 5.0 ± 0.9 μmol/L, p < 0.01), whereas amniotic fluid concentrations were extremely high (133.8 ± 13.8 μmol/L, n = 3). No venous-arterial differences were measurable across either the maternal or fetal sides of the placenta. CONCLUSION: Nitrate concentrations in pregnant sheep and their fetuses are increased. The increased nitrate concentrations in the maternal and fetal circulations may reflect the increased nitric oxide synthesis, which may in part mediate the cardiovascular adaptations to normal pregnancy and the low systemic and umbilical vascular resistance in the fetus. (A M J O BSTET G YNECOL 1996;174:573-7.)

Sonographic, stereological and Doppler flow velocimetric assessments of placental maturity

To determine whether sonographic assessments of increasing placental maturity are associated with changes in the theoretical diffusing capacity of the organ and with changes in vascular resistance. Placental maturity was assessed sonographically in 10 organs: five were classified as completely immature and five as completely mature. Doppler flow velocimetric recordings were obtained shortly before delivery performed by elective caesarean section. Placental biopsies taken immediately after delivery were analysed stereologically. No differences were observed in either placental weight or volume, but the morphometric diffusing capacity of the villous membrane was 40% higher in the mature than in the immature placentas. Doppler indices did not alter with increasing placental maturity. Normal term placentas differ significantly in their diffusion characteristics, even when organ weight and volume remain constant. Umbilical vascular resistance may be heavily influenced by the number of parallel circulatory units offered by the placental lobules.

Comparison of ANG II in fetal and pregnant sheep: metabolic clearance and vascular sensitivity

Fetal sheep appear less responsive to infused angiotensin II (ANG II) than pregnant ewes. This may reflect a greater fetal metabolic clearance rate (MCRANGII) and thus lower plasma ANG II levels. We therefore determined fetal MCRANGII, half-life (T1/2), and placental removal of ANG II. Fetal sheep (n = 13; 113-139 days of gestation) received 0.573-5.73 micrograms ANG II/min iv for 30 min while arterial pressure and heart rate were monitored. Serial blood samples were obtained before and during a 30-min infusion to measure ANG II and calculate MCRANGII and after stopping the infusion to determine T1/2. MCRANGII was similar across gestation and at doses < or = 2.29 micrograms/min (683 +/- 49 vs. 74 +/- 5 ml.min-1.kg-1 for adults) but was 30-40% lower with 5.73 micrograms ANG II/min (494 +/- 57 ml.min-1.kg-1, P < 0.05). T1/2 was 15-21 s. Fetal placental ANG II removal averaged 87 +/- 3 vs. 20 +/- 6% for uteroplacental removal; this was unaffected by dose and was linear with plasma ANG II levels, and saturation was not evident. Plasma ANG II levels rose proportionally with infusion rate and did not change significantly over time; thus fetal plasma ANG II concentrations can be predicted from MCRANGII. Measured and predicted ANG II levels at each infusion rate and time point were similar: r = 0.87, slope = 0.87 (P < 0.001). At equivalent predicted plasma ANG II levels fetal and maternal pressor responses were similar (P > 0.1); however, increases in umbilical vascular resistance exceeded those in uteroplacental vascular resistance (P < 0.03). Fetal MCRANGII is approximately 10-fold greater than maternal, partially reflecting the extensive capacity of ANG II removal by the placental circulation. Contrary to previous conclusions, fetal-maternal pressor sensitivity to ANG II does not differ, whereas the placental vasculature is more sensitive to ANG II than the uteroplacental circulation.

The effects of maternal vascular pressure on the dimensions of the placental capillaries.

The study sought stereological evidence for the sluice flow phenomenon in the human term placenta. Two series of experiments were conducted on caesarean delivered placentae. In both, two fetal arteries were cannulated and perfused. In the first series, five placentae were perfusion-fixed under arterial pressures of 40 mmHg and 60 mmHg, and an external pressure of 10 mmHg in the intervillous space. In the second series, five placentae were perfusion-fixed at arterial pressures of 70 mmHg and 90 mmHg with an external pressure of 30 mmHg. Stereological estimates relating to the size of the capillaries and the thickness of the villous membrane were then made. In each series, as the arterial pressure rose, there was an increase in the volume fraction and surface area of the fetal capillaries, and a concomitant decrease in the mean thickness of the villous membrane. These changes were negated as the external pressure rose, indicating the importance of the pressure differential between the capillary lumen and the intervillous space in determining the dimensions of the fetal capillaries. The study demonstrated that placental capillaries are elastic and hence deformable. If a sufficiently high pressure is generated in the intervillous space, they may therefore be compressed. This may explain the increase in umbilical vascular resistance demonstrated by doppler studies in pregnant women scanned in the supine position. In this situation the venous drainage from the intervillous space is believed to be impeded by the gravid uterus compressing the inferior vena cava.

Fetal hemodynamic response to maternal intravenous nicotine administration

OBJECTIVES: Our study was designed to test the hypothesis that maternally administered nicotine has significant effects on fetal hemodynamics and umbilical systolic/diastolic ratios.STUDY DESIGN: Nine pregnant ewes received maternal intravenous infusions of 10, 20, and 30 µg/kg/min of nicotine. Maternal and fetal blood pressure, heart rate, and uterine and umbilical blood flow were recorded.RESULTS: Maternal intravenous administration of nicotine (10, 20, and 30 µg/kg/min of maternal body weight) produced significant (p < 0.05) increases in fetal blood pressure (2%, 11%, and 25%, respectively), decreases in fetal heart rate (0%, 8%, and 12%), and decreases in umbilical blood flow (0%, 0%, and 19%). Umbilical systolic/diastolic ratios increased slightly at the 30 µg/kg/min dose of nicotine, but these changes did not reach significance. Maternal blood pressure increased (10%, 25%, and 53%), and uterine vascular resistance increased (5%, 64%, and 344%) significantly (p < 0.05); uterine blood flow increased at the 10 µg/kg/min dose ( + 5%) and decreased by 23% and 42% at the highest two doses of nicotine.CONCLUSION: Maternal nicotine administration in late-term pregnant sheep produced significant increases in fetal arterial blood pressure and umbilical vascular resistance, decreased fetal heart rate, and umbilical blood flow but did not significantly alter systolic/diastolic ratios. (AM J OBSTET GYNECOL 1992;167:1624-31.)

Doppler velocimetry of the umbilical artery in pregnancies complicated by insulin-dependent diabetes mellitus

The purpose of this study was to investigate vascular resistance by Doppler ultrasound in the umbilical artery of insulin-dependent diabetics longitudinally over the course of pregnancy. Special interest was put on the effects of glycemic control and maternal vascular disease on the flow velocity waveform (FVW) and the predictive value of Doppler flow measurements with regard to perinatal morbidity. Using a duplex-pulsed wave scanner, the resistance-index (PR index) in the umbilical artery was calculated. The mean value of a 24-h blood glucose profile and the concentration of glycosylated hemoglobin (HBA 1C) were used as parameters of metabolic control. 53 pregnant diabetic women were examined longitudinally during the course of pregnancy on average on three occasions (range: 1–7) between 17 weeks of gestation and delivery at 37.7 ± 1.3 (mean ± SD) weeks. To test the predictive value of Doppler flow velocimetry with regard to perinatal morbidity the results were compared to the FVWs measured in the umbilical arteries of 30 non-diabetic women with normal fetal outcome. Vascular resistance in the umbilical artery of the diabetics declined significantly during the course of pregnancy, with a mean PR index of 0.729 (SD 0.051) at 17 weeks and 0.603 (SD 0.083) at the end of pregnancy ( P < 0.002). The majority of PR indices were within the range reported for normal pregnancy and measured in the non-diabetic women. Regression analysis showed no significant correlation between vascular resistance and mean blood glucose level ( r = 0.1325) or concentration of HBA 1C ( r = −0.0519). Maternal vascular disease had no effect on umbilical FVWs. Umbilical vascular resistance was slightly higher in small fetuses and fetuses with perinatal distress but could not predict macrosomia or other specific diabetic morbidity.

Doppler assessment of the normal early fetal circulation.

Combined transvaginal and transabdominal Doppler ultrasound allows recording of fetal intra- and extracardiac flow velocity waveforms in late first- and early second- trimester pregnancies. At 10-12 weeks, end-diastolic flow velocities were always absent in the fetal descending aorta and umbilical artery, but were present in over half of the intracerebral artery waveforms. The pulsatility index in the three vessels decreased significantly with advancing gestational age, suggesting a reduction in fetal and umbilical placental vascular resistance. Peak velocities during atrial contraction (A-wave) were nearly twice as high as those during early diastolic filling (E-wave), reflecting low ventricular compliance. Continuous forward flow in the umbilical vein was associated with a pulsatile systolic and diastolic forward flow in the ductus venosus. Retrograde flow was only present in the inferior vena cava.

Antepartum fetal surveillance tests during sickle cell crisis

A study was conducted to evaluate the characteristics of antepartum fetal assessment tests for women with sickle cell disease during crisis. A total of 24 women with 39 episodes of crisis after 34 weeks of pregnancy were studied. All subjects were evaluated with nonstress tests, biophysical profile score, and uterine and umbilical artery systolic/diastolic ratios during and after sickle cell crisis. Results revealed that the incidence of nonreactive nonstress tests was significantly higher during crisis compared with the period after crisis (58.9% vs 10.3%, p \\lt 0.05). The frequency of biophysical profile score \\lt8 was significantly higher during crisis compared with after crisis (33.3% vs 7.7%, p \\lt 0.05). All subjects had an increase in uterine systolic/diastolic ratio during crisis. The average uterine systolic/diastolic ratio was 3.92 (range, 2.16 to 4.24) during crisis and 2.54 (range, 1.98 to 3.23) after crisis (p \\lt 0.05). In contrast, there was no significant change in the mean umbilical systolic/diastolic ratios during and after crisis (2.58 and 2.62, respectively). We conclude that, although sickle cell disease crisis is associated with a higher incidence of abnormal biophysical test results, in most patients these results will revert to normal after crisis. The increase in uterine vascular resistance without a concordant increase in umbilical vascular resistance suggests that the transient effects of sickling during crisis may not compromise umbilical blood flow.

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 tocolytic agents on fetal umbilical velocimetry

In this prospective study, we sought to examine the changes in umbilical vascular resistance induced by tocolytic therapy. Umbilical artery velocimetry was performed in 46 patients with preterm labor before tocolysis and at 1 hour and 24 hours after tocolysis was initiated. Raw systolic/diastolic ratios were corrected for concomitant changes in fetal heart rate. Thirty patients received subcutaneous terbutaline and 16 were treated with intravenous magnesium. Systolic/diastolic ratios decreased in patients treated with terbutaline. This decline persisted after correction for increases in fetal heart rate. No significant changes in systolic/diastolic ratios were seen in patients treated with magnesium. We conclude that terbutaline may affect umbilical vascular resistance. Possible clinical implications of these findings are discussed.

Angiotensin II and alpha-agonist. I. Responses of ovine fetoplacental vasculature

During ovine pregnancy the uteroplacental vasculature is less responsive to angiotensin II (ANG II)-induced vasoconstriction than the systemic vasculature, whereas responses to alpha-agonists are just the opposite. Comparisons of fetal systemic and placental vascular responses to these agents are not well described, nor have they been compared with maternal responses. We determined steady-state responses to fetal infusions (5-7 min) of ANG II (0.023-5.73 micrograms/min) and phenylephrine (PHEN, 0.031-7.64 micrograms/min), continuously monitoring mean arterial pressure (MAP), heart rate (HR), and umbilical blood flow (UmBF). Although both vasoconstrictors caused dose-dependent increases in MAP and umbilical vascular resistance (UmVR), responsiveness (delta MAP and delta UmVR) to ANG II (mol/min) was 35- to 60-fold greater than to PHEN. ANG II caused dose-dependent decreases in UmBF (2-48%); PHEN had minimal effects except at the highest dose, UmBF decreasing only 18%. Although patterns of fetal responses of MAP, UmBF, and UmVR to ANG II resembled maternal responses of MAP and uterine blood flow and uterine vascular resistance, the former were greatly attenuated. Similar observations were made with PHEN for UmBF and UmVR but not MAP. ANG II is a more potent fetal systemic and placental vasoconstrictor than PHEN; however, compared with those of the mother the responses are attenuated. Moreover, the fetoplacental vascular bed appears unresponsive to alpha-adrenergic stimulation, possibly reflecting a mechanism for maintaining UmBF when plasma catecholamines are elevated.

Uterine and fetal umbilical artery flow velocity waveforms in normal first trimester pregnancies

In 85 normal singleton pregnancies between 8 and 13 weeks gestation, Doppler flow velocity waveform recordings were attempted from the left and right uterine artery and fetal umbilical artery. Acceptable waveforms were obtained from the uterine arteries in 83 and from the fetal umbilical artery in 61 of the 85 pregnancies. There was virtually no difference between the left and right uterine artery on average. The marked decrease in pulsatility (PI) and resistance (RI) indices from both uterine arteries reflects the ongoing process of secondary trophoblast invasion into the muscular part of the spiral arteries. Absent end-diastolic velocities were observed in 59 of 61 fetal umbilical artery flow velocity waveform recordings. PI values from the fetal umbilical artery suggest unaltered umbilical placental vascular resistance during the first trimester of pregnancy.

Relationship between the ovine fetal umbilical artery blood flow waveform and umbilical vascular resistance

Ultrasonic umbilical artery blood flow velocity waveform indexes decrease throughout gestation as umbilical blood flow increases. However, it is not known whether the decrease in indexes such as systolic/diastolic ratio is a direct result of a change in umbilical vascular resistance. Umbilical artery blood flow was measured as vasoactive agents angiotensin II, arginine vasopressin, norepinephrine, serotonin, and the thromboxane A2 sympathomimetic agent U-46619 were infused into the inferior vena cava of chronically instrumented ovine fetuses. Angiotensin II, arginine vasopressin, norepinephrine, serotonin, and U-46619 all significantly increased fetal arterial pressure levels. Angiotensin II, arginine vasopressin, and U-46619 significantly reduced umbilical blood flow and fetal heart rate. All five pressor agents increased umbilical vascular resistance. Systolic/diastolic ratios were obtained from pulsatile umbilical blood flow tracings. Systolic/diastolic ratios before infusions were significantly correlated with baseline values of umbilical blood flow (r = -0.55) and umbilical vascular resistance (r = 0.52). Systolic/diastolic ratios decreased with increasing infusion rates of angiotensin II, arginine vasopressin, norepinephrine, and serotonin, and increased with infusion of U-46619. There was no significant correlation between systolic/diastolic ratio and either umbilical blood flow or umbilical vascular resistance during infusion of angiotensin II, arginine vasopressin, or serotonin. Systolic/diastolic ratio decreased with increasing umbilical vascular resistance during norepinephrine infusion (r = -0.44). Systolic/diastolic ratio changed in the predicted direction only when umbilical vascular resistance was increased by infusion of U-46619 (r = 0.80). We conclude that umbilical artery waveform analysis is not an adequate predictor of acute changes in umbilical blood flow or vascular resistance.

Differential responses of uterine and umbilical vasculatures to angiotensin II and norepinephrine

Although the uterine vascular responses to endogenous vasoactive substances have been extensively investigated in pregnant sheep, the fetal umbilical responses to angiotensin II (ANG II) and norepinephrine (NE) have not been well characterized. Twenty-five pregnant ewes between 105 and 115 days of gestation were anesthetized and instrumented for hemodynamic measurements, systemic fetal and maternal intravenous infusions, and local maternal uterine arterial infusions of ANG II and NE. Fetal and maternal arterial pressure and heart rate, maternal uterine blood flow (total of left and right middle uterine arteries), and fetoplacental blood flow (common umbilical artery) were measured during continuous infusions of ANG II or NE. Fetal infusions of ANG II (0.03-1.0 micrograms.min-1.kg estimated fetal body wt-1) increased fetal arterial blood pressure by as much as 44% over base-line values, decreased umbilical blood flow by as much as 63%, and increased umbilical vascular resistance by up to 345%. Fetal infusions of NE (0.1-3 micrograms.min-1.kg-1) increased fetal arterial pressure 42% and increased umbilical vascular resistance by up to 38% but did not significantly alter fetoplacental blood flow. No significant maternal changes were observed during fetal infusions. Maternal infusion of ANG II increased maternal arterial pressure by as much as 59% and significantly increased uterine vascular resistance at the two highest doses but significantly decreased uterine blood flow only at the highest dose (17%; P less than 0.05). Maternal infusions of NE increased arterial pressure by as much as 113%, decreased uterine blood flow by as much as 76%, and increased uterine vascular resistance 3- to 10-fold over the base-line value.(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal hemodynamic and fetoplacental vascular response to exogenous arginine vasopressin

Fetal hemodynamics and fetoplacental blood flow were measured in chronically instrumented ovine fetuses during intravenous infusion of arginine vasopressin. Vasopressin was infused at rates ranging from 1 to 300 ng/min/kg estimated fetal mass. This range of infusion rates produces plasma arginine vasopressin levels observed throughout a wide range of fetal stress. No maternal effects were observed at any infusion rates used in this investigation. Fetal heart rate declined linearly with the log of the infusion rate. Mean fetal arterial pressure showed a sigmoidal response to log arginine vasopressin infusion rate, reaching a plateau at 30 ng/min/kg. Umbilical vascular resistance increased throughout the entire range of infusion rates. Fetoplacental blood flow decreased with increasing infusion rate but decreased only 4% to 13% throughout the range of infusion rates that produce plasma arginine vasopressin levels commonly observed during fetal stress. Because umbilical vascular resistance continued to rise after arterial pressure reached a plateau, fetoplacental blood flow decreased 31% at the highest infusion rate. However, the plasma vasopressin level associated with this infusion rate is probably in excess of that associated with severe fetal distress. The fetoplacental vascular bed is, therefore, either relatively insensitive to arginine vasopressin, or is capable of autoregulation in the face of high circulating levels of arginine vasopressin.

Direct determination of the ovine fetal umbilical artery blood flow waveform

Ultrasonographic umbilical artery blood flow velocity waveform analysis has been proposed as a means of noninvasive assessment of fetal well-being. We computed waveform indices from directly measured umbilical artery blood flow in chronically instrumented ovine fetuses from 109 to 138 days of gestation (term, 145 days). The three waveform indices (systolic/diastolic ratio, pulsatility index, and resistance index) correlated significantly with each other (r = 0.90 to 0.98). These indices progressively decreased with gestation and were significantly correlated with calculated umbilical vascular resistance (r = 0.68 to 0.70, p less than 0.01) and with umbilical blood flow (r = -0.71, p less than 0.01). During the final week of pregnancy, systolic/diastolic ratio could be predicted by the combination of placental size (total cotyledonary mass), fetal size (ponderal index), and either umbilical blood flow or umbilical vascular resistance (multiple linear regression, r2 = 0.94). Fetal heart rate declined from day 109 of gestation to 138 days. Fetal heart rate was significantly correlated with waveform indices only when values exceeded 170 beats/min (r = -0.37 to -0.51). Ovine fetal umbilical artery waveform indices changed at approximately the same rate as those reported for human fetuses in late gestation on the basis of external Doppler ultrasonographic velocity measurements. These results suggest that the sheep is a suitable model for investigations of umbilical artery waveform analysis.

Ovine placental perfusion balance: Effect of marijuana smoke

This study was designed to test the hypothesis that maternal marijuana smoking impairs placental oxygen transfer in late ovine pregnancy by disrupting perfusion balance between the maternal and fetal placental circulations. Placental hemodynamics were assessed in nine chronically prepared ewes 1 hour after exposure to smoke from either a marijuana (n = 5) or a placebo (n = 4) cigarette. When compared with placebo smoke, maternal marijuana smoke exposure resulted in a fall in both uterine and umbilical placental vascular resistance and a 30% improvement in placental perfusion balance at a cotyledonary level. We conclude that maternal marijuana smoking in late ovine pregnancy has a direct relaxant effect on both maternal and fetal placental vascular smooth muscles that decreases the normal heterogeneity of flow and improves macroscopic placental perfusion balance. However, the observed concurrent 6 torr decrease in fetal oxygen tension suggests that perfusion balance is actually disrupted at a microcirculatory level.

The Effects of Bupivacaine on the Umbilical Circulation and Placental Gas Exchange in the Fetal Lamb

Seven chronically catheterized fetal sheep at 125-140 days gestation were studied in 12 experiments to determine the direct effects of the local anesthetic bupivacaine (infused intravenously to the fetus) on the umbilical circulation and placental gas exchange. Electrocortical activity, umbilical blood flow, heart rate, and umbilical arterial and venous pressures were continuously monitored in experiments comprising a baseline period, a drug infusion period and a recovery period, each of 2 hr duration. Samples of umbilical arterial and venous blood were taken for blood gas analysis, and for bupivacaine assay using high pressure liquid chromatography technique. Fetal plasma bupivacaine levels were 1.3 +/- 0.3 microgram/ml (mean +/- SEM) between 60-120 min of infusion. Heart rate and umbilical blood flow decreased significantly to 89 and 94% of control, respectively, (P less than 0.05) during the infusion and returned to control levels by 2 hr afterwards. Mean umbilical arterial and venous pressures were not significantly altered, and no significant rise in umbilical vascular resistance occurred. No changes occurred in umbilical arterial or venous pH, PO2, or PCO2. In summary, bupivacaine reversibly depressed fetal heart rate and umbilical blood flow without detrimental changes in fetal blood gas or acid-base status.