Reduction In Uteroplacental Blood Flow Research Articles

The association between persistent maternal hypotension and small for gestational age neonates

The association between maternal hypotension and poor fetal growth has not been well studied. We hypothesized that the presence of persistent maternal hypotension will reflect a chronic reduction of uteroplacental blood flow, leading to placental hypoperfusion and subsequent poor fetal growth. We aimed to evaluate whether persistent hypotension is associated with the risk of having a small for gestational age neonate. A secondary aim was to evaluate whether transient hypotension is associated with the same risk of having a small for gestational age neonate. We performed a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be data, a large prospective cohort study of nulliparous women. The inclusion criteria included delivery of subjects with singleton pregnancies at ≥24 weeks' gestation who had systolic and diastolic blood pressure data at 3 antenatal visits between 6 0/7 and 29 6/7 weeks' gestation. Univariable analyses were performed to evaluate the association among persistent hypotension (systolic blood pressure of <100 mm Hg and or diastolic blood pressure of <60 mm Hg at 3 antenatal visits), transient hypotension (systolic blood pressure <100 mm Hg and diastolic blood pressure <60 mm Hg at any 1 of 3 aforementioned visits but not all 3), maternal characteristics and small for gestational age neonates. Variables found to be significant (P<.05) were included in multivariable logistic regression. Here, 164 of 7233 participants (2.3%) had persistent hypotension. In univariable analyses, subjects with persistent hypotension compared with those without were significantly more likely to have small for gestational age neonates (21.3% vs 11.6%; P<.001). When adjusting for confounders, persistent hypotension remained significantly associated with an increased risk of having a small for gestational age neonate (adjusted odds ratio, 1.65; 95% confidence interval, 1.11-2.44). In multivariable analysis, transient hypotension was not associated with an increased risk of having a small for gestational age neonate. Persistent hypotension was significantly associated with small for gestational age among neonates born to low-risk nulliparous women.

84 The association between persistent hypotension and small for gestational age neonates

We hypothesize that the presence of persistent maternal hypotension will reflect a chronic reduction of uteroplacental blood flow, leading to placental hypoperfusion and subsequent poor fetal growth. We evaluated whether persistent hypotension is associated with the risk of having a small for gestational age (SGA) neonate. We performed a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be data, a large prospective cohort study of low-risk nulliparous women who delivered a singleton pregnancy at >24 weeks, who had systolic (SBP) and diastolic (DBP) blood pressure data over 3 antenatal visits (6+0 to 29+6 weeks gestational age), and complete birthweight data. Persistent hypotension was defined as either SBP <100 millimeters mercury (mmHg) or DBP <60 mmHg present at all 3 visits. SGA was defined as infants born at less than 10th percentile for gestational age and sex. Univariable analyses were performed to evaluate the association between persistent hypotension, maternal characteristics and SGA neonates. Variables found to be significant (p<0.05) were included in the multivariable logistic regression. In this analysis, we included 7,389 participants, of which 289 (3.9%) had persistent hypotension. Subjects with persistent hypotension compared to those without were significantly more likely to have SGA neonates (19.0% v. 11.4%, p<0.001) and to be younger, publicly insured, and have a lower first trimester body mass index (BMI, kg/m2). Additionally, they were less likely to be married and Non-Hispanic white (Table 1). In multivariable analysis, persistent hypotension (aOR 1.46, 95%CI 1.07-2.00), Non-Hispanic black race/ethnicity (aOR 2.10, 95%CI 1.71-2.59), Asian race (aOR 1.64, 95%CI 1.17-2.30), and lower first trimester BMI (aOR 0.97, 95%CI 0.96-0.98) remained significantly associated with an increased risk of having an SGA neonate (Table 2). Persistent hypotension is significantly associated with risk of having a SGA neonate.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Smoking and pregnancy: Epigenetics and developmental origins of the metabolic syndrome.

Maternal smoking causes lower birth weight, birth defects, and other adverse pregnancy outcomes. Epidemiological evidence over the past four decades has grown stronger and the adverse outcomes attributed to maternal smoking and secondhand smoke exposure have expanded. This review presents findings of latent and persistent metabolic effects in offspring of smoking mothers like those observed in studies of maternal undernutrition during pregnancy. The phenotype of offspring of smoking mothers is like that associated with maternal undernutrition. Born smaller than offspring of nonsmokers, these children have increased risk of being overweight or obese later. Plausible mechanisms include in utero hypoxia, nicotine-induced reductions in uteroplacental blood flow, placental toxicity, or toxic growth restriction from the many toxicants in tobacco smoke. Studies have reported increased risk of insulin resistance, type 2 diabetes and hypertension although the evidence here is weaker than for overweight/obesity. Altered DNA methylation has been consistently documented in smoking mothers' offspring, and these epigenetic alterations are extensive and postnatally durable. A causal link between altered DNA methylation and the phenotypic changes observed in offspring remains to be firmly established, yet the association is strong, and mediation analyses suggest a causal link. Studies examining expression patterns of affected genes during childhood development and associated health outcomes should be instructive in this regard. The adverse effects of exposure to tobacco smoke during pregnancy now clearly include permanent metabolic derangements in offspring that can adversely affect life-long health.

Preeclampsia: the role of persistent endothelial cells in uteroplacental arteries

We explore the potential role of the endothelial lining of uteroplacental arteries in the pathogenesis of preeclampsia, a severe pregnancy disorder characterized by incomplete invasion of the uterine vasculature by extravillous trophoblast and angiogenic imbalance. In normal pregnancy, the endothelium disappears progressively from the uteroplacental arteries and is replaced by trophoblast and deposition of fibrofibrinoid structure, underpinning the so-called physiological transformation of uterine spiral arteries. We hypothesize that partial persistence of the endothelium, albeit injured, initiates a chain of events leading to the emergence of preeclampsia in 3 sequential stages. The first stage results in retention of the endothelium in uteroplacental arteries secondary to incomplete physiological transformation of the vessels. Consequently, the uteroplacental vessels are reactive to pathological cues, which drives local arteriopathy. The second stage starts with progressive reduction in uteroplacental blood flow, generating oxidative stress in the whole placenta, and heightened maternal inflammation in response to circulating trophoblastic debris. In the third stage, generalized endotheliosis causes systemic angiogenic imbalance, hypertension, and other clinical manifestation of preeclampsia.

INFLUENCE OF BACTERIAL FACTORS ON DETERIORATION OF UTEROPLACENTAL PERFUSION

Objective: to make analysis of isolated deterioration of blood flow in the pool of uterine arteries in low-risk pregnancy after 18-week gestation, to detect connection of blood flow deterioration with infection processes of different location in the organism of pregnant women. Methods. Doppler screening research was made as well as analysis of spectrograms of uteroplacental and fetal blood flow of 357 pregnant women. Results. Low-risk pregnancy was accompanied by high frequency of hyperdynamic deterioration in the system of mother-placenta-fetus (14%), most frequently was detected the reduction of perfusion data of uteroplacental blood flow (67,9%) with almost absolute dominance (prevalence) of one-sided deterioration; high correlation dependence was revealed between reduction of uteroplacental blood flow and existence of extragenital chronic infection foci (71,4%); asymptomatic bacteriuria and infection-and-inflammatory disease of laryngological organs; causal treatment improved hemodynamic rates, with idiopathic forms of uteroplacental perfusion deterioration, pathogenic treatment is recommended, dipyridamol – 75 mg daily (25 mg three times a day) is a chosen medicine. Conclusion. Isolated one-sided deterioration of uteroplacental blood flow during low-risk pregnancy may be considered as the mark of chronic infection foci in the body of a pregnant woman; well-timed diagnostics and causal treatment allow to avoid progressive deterioration of hemodynamic rate.

Placental Aromatase Is Deficient in Placental Ischemia and Preeclampsia.

IntroductionPreeclampsia is a maternal hypertensive disorder with uncertain etiology and a leading cause of maternal and fetal mortality worldwide, causing nearly 40% of premature births delivered before 35 weeks of gestation. The first stage of preeclampsia is characterized by reduction of utero-placental blood flow which is reflected in high blood pressure and proteinuria during the second half of pregnancy. In human placenta androgens derived from the maternal and fetal adrenal glands are converted into estrogens by the enzymatic action of placental aromatase. This implies that alterations in placental steroidogenesis and, subsequently, in the functionality or bioavailability of placental aromatase may be mechanistically involved in the pathophysiology of PE.MethodsSerum samples were collected at 32–36 weeks of gestation and placenta biopsies were collected at time of delivery from PE patients (n = 16) and pregnant controls (n = 32). The effect of oxygen tension on placental cells was assessed by incubation JEG–3 cells under 1% and 8% O2 for different time periods, Timed-mated, pregnant New Zealand white rabbits (n = 6) were used to establish an in vivo model of placental ischemia (achieved by ligature of uteroplacental vessels). Aromatase content and estrogens and androgens concentrations were measured.ResultsThe protein and mRNA content of placental aromatase significantly diminished in placentae obtained from preeclamptic patients compared to controls. Similarly, the circulating concentrations of 17-β-estradiol/testosterone and estrone/androstenedione were reduced in preeclamptic patients vs. controls. These data are consistent with a concomitant decrease in aromatase activity. Aromatase content was reduced in response to low oxygen tension in the choriocarcinoma JEG–3 cell line and in rabbit placentae in response to partial ligation of uterine spiral arteries, suggesting that reduced placental aromatase activity in preeclamptic patients may be associated with chronic placental ischemia and hypoxia later in gestation.ConclusionsPlacental aromatase expression and functionality are diminished in pregnancies complicated by preeclampsia in comparison with healthy pregnant controls.

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Objectives Blood pressure (BP) elevation after experimental reduction in uteroplacental blood flow in primates is associated with proteinuria and has been a surrogate for studying placental dysfunction manifesting as preeclampsia in humans. Controlling BP is the mainstay of treatment but the effect of antihypertensive treatment on the acute BP response is poorly understood in this animal model. We examined the effect of three oral antihypertensive agents in the treatment of BP in an experimental setting to determine the BP response. Methods Papio hamadryas (baboon) BP was recorded continuously via intra-arterial telemetry in late pregnancy after induction of placental ischaemia by surgical ligation of a uterine branch artery. Proteinuria, haematology, biochemistry and fetal growth were assessed. Antihypertensives hydralazine 15 mg bid, methyldopa 10 mg/kg bid and labetalol 40 mg bid were administered orally for four days followed by a three-day washout phase. The average BP change for each drug from day 1 and 2 of treatment compared to day 3 and day 4 of treatment was evaluated. Results The antihypertensives resulted in a reduction in BP (average 1.4 mmHg, n = 2). Hydralazine and methyldopa showed a 0.4 mmHg and 2.4 mmHg reduction in systolic BP respectively, whereas labetalol showed no decrease; hydralazine and methyldopa showed a 0.5 mmHg and 1.8 mmHg reduction in diastolic BP respectively, and labetalol showed a 0.6 mmHg decrease in diastolic BP. Conclusions Preliminary data shows that hydralazine and methyldopa cause an acute decrease in systolic BP and diastolic BP in an experimental model of preeclampsia in non-human primates. The lack of BP reduction with labetalol may reflect altered drug efficacy or metabolism in this species or inadequate dosing. Disclosures S.J. Pears: None. A. Hennessy: None. S. Lim: None. K. Chau: None. K. Yeung: None. S. Heffernan: None. A. Makris: None.

Metabolic Pathways Involved in 2-Methoxyestradiol Synthesis and Their Role in Preeclampsia

Preeclampsia (PE) remains a major cause of maternal/fetal morbidity-mortality worldwide. The first stage of PE is characterized by placental hypoxia due to a relative reduction in uteroplacental blood flow, resulting from restricted trophoblast invasion. However, hypoxia is also an essential element for the success of invasion. Under hypoxic conditions, 2-methoxyestradiol (2-ME) could induce the differentiation of cytotrophoblast cells into an invasive phenotype in culture. 2-Methoxyestradiol is generated by catechol-O-methyltransferase, an enzyme involved in the metabolic pathway of estrogens. During pregnancy, circulating 2-ME levels increase significantly when compared to the menstrual cycle. Interestingly, plasma levels of 2-ME are lower in women with PE than in controls, and these differences are apparent weeks or even months before the clinical manifestations of the disease. This article reviews the metabolic pathways involved in 2-ME synthesis and discusses the roles of these pathways in normal and abnormal pregnancies, with particular emphasis on PE.

The effect of different phenylephrine infusion rates on uteroplacental blood flow during cesarean delivery under spinal anesthesia

Introduction Hypotension associated with spinal anesthesia is more common and profound in the pregnant population, resulting in adverse effects to both the mother and the fetus. It is now widely accepted that the vasopressor of choice during cesarean delivery is phenylephrine. However, an overdose of phenylephrine may cause reflex bradycardia and decreased maternal and fetal cardiac output. In contrast, lower phenylephrine doses may not be adequate to avoid or control hypotension. The optimal phenylephrine dose and its direct effect on uteroplacental blood flow are yet to be determined. Aim of the work This study aimed to examine the direct effect of different phenylephrine infusion rates on uterine blood flow during cesarean delivery spinal anesthesia. Assessment of uteroplacental blood flow was performed using Doppler ultrasound of the uterine artery from which uterine blood flow indices were obtained, namely, peak systolic velocity (PSV) and pulsatility index (PI). Materials and methods This is a prospective, randomized double-blind study. We included 90 age-matched American Society of Anesthesiologists (ASA) I or II parturients with term singleton pregnancies admitted for elective cesarean delivery under spinal anesthesia. We excluded candidates with hypertension, cardiovascular or cerebrovascular disease, type 1 diabetes mellitus, allergy or hypersenstivity to phenylephrine, known fetal abnormalities, intrauterine growth retardation, and any contraindication to spinal anesthesia. The patients were distributed randomly into three equal groups (n = 30 each). Groups 25, 50, and 75 received 25, 50, and 75 μg/min phenylephrine infusion, respectively, after spinal anesthesia was administered. The maternal uterine artery was identified by colored Doppler ultrasound and pulsed-wave Doppler was used to measure PSV and calculate PI before spinal anesthesia and at 5 and 15 min after the block was performed. Maternal hemodynamics and measures of fetal well-being (Apgar score and umbilical venous pH) were also recorded. Results PI at 15 min after spinal anesthesia was significantly higher in group 75 in comparison with the baseline value (P < 0.05) and also in comparison with groups 50 and 25 (P < 0.05). Furthermore, the percentage of decrease in PSV, compared with the baseline, was also significantly higher in group 75 compared with the other two groups at both 5 and 15 min (P < 0.05). Group 75 also showed a significantly higher incidence of hypertension and bradycardia in comparison with both the other groups. However, the number of hypotensive episodes as well as nausea and vomiting was significantly higher in group 25 compared with the other two groups (P < 0.05). There was no significant difference in fetal outcome among the different groups. Conclusion and recommendationsAt a dose of 75 μg/min, phenylephrine induced a significant reduction in uteroplacental blood flow as evidenced by decreased PSV compared with baseline values and an increase in PI compared with the other two groups. This decrease in uteroplacental blood flow was not associated, however, with poor fetal outcome. Further studies are needed to address the correlation between uteroplacental blood flow and fetal outcome with different phenylephrine doses in patients with uteroplacental insufficiency.

Preeclampsia 2012.

Preeclampsia is a common complication of pregnancy associated with high maternal morbidity and mortality and intrauterine fetal growth restriction. There is extensive evidence that the reduction of uteroplacental blood flow in this syndrome results from the toxic combination of hypoxia, imbalance of angiogenic and antiangiogenic factors, inflammation, and deranged immunity. Women treated for preeclampsia also have an increased risk for cardiovascular and renal disease. At present it is unclear if the increased cardiovascular and renal disease risks are due to residual and or progressive effects of endothelial damage from the preeclampsia or from shared risk factors between preeclampsia and cardiac disease. Moreover, it appears that endothelin-1 signaling may play a central role in the hypertension associated with preeclampsia. In this paper, we discuss emerging data on the pathogenesis of preeclampsia and review therapeutic options.

Hypertension Induced by Episodic Reductions in Uteroplacental Blood Flow in Gravid Rat

Background. The etiology of preeclampsia remains unclear. Animal modeling of preeclampsia has been useful; however, no model to date represents episodic changes in uteroplacental blood flow that may occur in preeclampsia. Objective. To develop a gravid rat model characterized by episodic reductions in uteroplacental blood flow. Method. Pregnant Sprague Dawley rats were used and subjected to SHAM, reduced uterine perfusion pressure (RUPP), or aortic occlusion on gestational Day 14. Aortic occlusion surgery consisted of implantation of a silastic vascular occluder around the abdominal aorta and silver clips around the uterine–ovarian arteries. Aortic occlusion animals were subjected to five consecutive days of occlusion (40% reduction) each session lasting 1 h. On Day 21, maternal mean arterial pressure (MAP) and fetal morphology were assessed. For isolated blood vessels, resistance-sized mesenteric arteries were harvested and mounted on a pressure arteriograph. Result. Occluder animals experienced a 10 mmHg rise in MAP as compared to SHAM (p < 0.05), and RUPP MAP was significantly increased as compared to control subjects (p < 0.05). Pups from Occluder animals exhibited a decrease in fetal weight as compared to SHAM (p < 0.05), but an increase in fetal weight as compared to RUPP (p < 0.05). Myogenic reactivity of second-order mesenteric arteries increased in Occluder animals as compared to SHAM (p < 0.05), but were similar to that of RUPP. Conclusion. Episodic reductions in uteroplacental blood flow play a crucial role in the altered vascular reactivity seen in Occluder animals and may represent a new model to investigate the mechanisms associated with episodic reductions in uteroplacental blood flow in pathological pregnancies.

Increased Myogenic Reactivity of Resistance‐sized Mesenteric Arteries from Pregnant Rats with Episodic Reductions in Uteroplacental Perfusion

Pregnancy is associated with increased placental blood flow (BF) to the developing fetus. A central component of preeclampsia is thought to be a reduction in placental BF leading to altered vascular reactivity. It is suggested that short term elevations in blood pressure may lead to periodic reductions in uteroplacental blood flow (UBF) and this may play a role in preeclampsia. The purpose of this study was to develop a gravid rat model characterized by episodic reductions in UBF to elucidate the role of periodic decreases in UBF on vascular reactivity. We used pregnant Sprague Dawley rats and subjected them to Sham or aortic occlusion surgery on Day 14 of gestation. Aortic occlusion surgery consisted of implantation of a silastic vascular occluder around the abdominal aorta along with silver clips (0.106mm ID) around the uterine‐ovarian arteries. Aortic occlusion animals were subjected to 5 days of reduced UBF (40% reduction) for 1 hour each session. On Day 21, second order mesenteric arteries were mounted on a pressurized arteriograph. Myogenic reactivity of small mesenteric arteries was increased in Occluder animals compared to Sham (p&lt;0.05). This data suggest that episodic reductions in UBF may mimic some of the characteristics of preeclampsia including altered vascular reactivity toward a constrictive phenotype. Aortic occlusion may be a new model for investigating mechanisms associated with reduced UBF.

Hypotonieprophylaxe und -therapie bei Regionalanästhesien zur Sectio caesarea

Regional anesthesia for Caesarean delivery is often accompanied by a reduction in maternal blood pressure. Maternal hypotension may lead to a reduction in uteroplacental blood flow with consecutive fetal acidosis. In order to avoid reductions in uteroplacental blood flow, tremendous research has been performed, showing that the avoidance of aortocaval compression, compression of the lower extremities, and prehydration with colloids are effective in reducing maternal hypotension. Further means include the recent introduction of low dose spinal anesthesia with a combination of small amounts of local anesthetics and opioids. Nevertheless, maternal hypotension is not always preventable and the use of vasopressors is still frequently required. Although ephedrine has been considered the vasopressor of choice over the last decades, current studies show that fetal acidosis is less frequently encountered with the use of phenylephrine, which should thus be considered as a first-line agent.

Effects of uteroplacental restriction on the relaxin-family receptors, Lgr7 and Lgr8, in the uterus of late pregnant rats

The peptide hormone relaxin stimulates uterine growth and endometrial angiogenesis and inhibits myometrial contractions in a variety of species. The receptor for relaxin is a leucine-rich repeat containing G-protein-coupled receptor Lgr7 (RXFP1) that is highly expressed in the myometrium of late pregnant mice, with a significant decrease in receptor density observed at term. The present study first compared the expression of Lgr7 with another relaxin-family receptor Lgr8 (RXFP2) in the uterus and placenta of late pregnant rats. The uterus was separated into endometrial and myometrial components, and the myometrium into fetal and non-fetal sites, for further analysis. We then assessed the response of these receptors to uteroplacental restriction (UPR). Expression of the Lgr7 gene was significantly higher in the uterus compared with the placenta. Within the uterus, on Day 20 of gestation, there was equivalent expression of Lgr7 in fetal and non-fetal sites of the myometrium, as well as in the endometrium v. myometrium. The second receptor investigated, Lgr8, was also expressed in the endometrium and myometrium, but at significantly lower levels than Lgr7. Bilateral ligation of the maternal uterine blood vessels on Day 18 of gestation resulted in uteroplacental restriction, a decrease in fetal weight and litter size, and a significant upregulation in uterine, but not placental, Lgr7 and Lgr8 gene expression in UPR animals compared with controls. These data suggest that both relaxin family receptors are upregulated in response to a reduction in uteroplacental blood flow in rats.

Effect of chronic nicotine treatment on a1‐adrenoceptor‐mediated contraction and eNOS protein levels in pregnant uterine artery

Cigarette smoking during pregnancy has been associated with high rate of spontaneous abortion, underweight newborns, and sudden infant death syndrome. One of the potential effects of smoking is that nicotine may act on the maternal-fetal unit, including episodic hypoxia-ischemia, and affect the uteroplacental circulation. Uterine artery (UA) is the only source to deliver oxygen and nutrition that ensures normal fetal development. However, little is known about the effect of nicotine on the UA contractility. The present study was designed to test the hypothesis that nicotine enhances α1-adrenoceptor-mediated contraction and decreases in eNOS protein levels of the pregnant UA. UAs were isolated from pregnant ewes (~140 days gestation). Tissues were subjected to nicotine treatment for 48 hrs. After treatment, endothelium cells from the UAs were isolated and eNOS protein levels were determined by Western blot. Phenylepherine (PE) -mediated contractions were measured in tissue bath. PE produced dose-dependent contraction of pregnant UAs. Chronic nicotine treatment significantly potentiated PE-induced contractions. Chronic nicotine treatment also significantly decreased eNOS protein levels compared to control. The results suggest that nicotine has chronic effect on UA contractility through the mechanisms underlying enhancing its contractile sensitivity to α1-adrenoceptor agonist and inhibiting eNOS protein expression. The enhanced UA contractility may cause a reduction in utero-placental blood flow and consequent fetal growth retardation.

Assessment of volume preload on uteroplacental blood flow during epidural anaesthesia for Caesarean section

Epidural and spinal anaesthesia are the preferred mode of anaesthesia for Caesarean section. Volume preloading is recommended to prevent maternal hypotension and a reduction in uteroplacental blood flow, although positive effects of volume preloading on maternal cardiac output and arterial pressure are debatable. Doppler measurements of the umbilical artery beyond deriving pulsatility indices are not routinely performed. After Institutional Review Board approval and written informed consent, 14 consecutiVe women with epidural anaesthesia for Caesarean section received either hydroxyethyl starch 500 mL or gelatine 500 mL. Haemodynamic variables monitored were maternal arterial pressure, maximal blood flow velocity and pulsatility indices of the uterine artery derived from Doppler measurements. Maternal arterial pressure and pulsatility indices in both groups did not change from baseline after intravenous colloid infusion. However, uterine blood flow increased significantly in both groups. The effectiveness of volume preloading may therefore be better described by changes in maximum uterine blood flow velocity than by pulsatility indices or maternal arterial pressure.

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. (Am J Obstet Gynecol 2002;187:178-86.)

Effects of chronic reduction in uterine blood flow on fetal and placental growth in the sheep.

Pregnancy is associated with a significant increase in uteroplacental blood flow (UBF), which is responsible for delivering adequate nutrients and oxygen for fetal and placental growth. The present study was designed to determine the effects of vascular insufficiency on fetal and placental growth. Thirty-nine late-term pregnant ewes were instrumented to investigate the effects of chronic UBF reduction. Animals were split into three groups based on uterine blood flow, and all animals were killed on gestational day 138. UBF, which began at 851 +/- 74 ml/min (n = 39), increased in controls (C) to 1,409 +/- 98 ml/min (day 138 of gestation) and in the moderately restricted (R(M)) group to 986 +/- 69 ml/min. In the severely restricted (R(S)) group, UBF was only 779 +/- 79 ml/min on gestational day 138. This reduction in UBF significantly affected fetal body weight with R(M) fetuses weighing 3,685 +/- 178 g and R(S) fetuses weighing 2,920 +/- 164 g compared with C fetal weights of 4,318 +/- 208 g. Fetal brain weight was not affected, whereas ponderal index was significantly reduced in R(M) (2.94 +/- 0.09) and R(S) fetuses (2.49 +/- 0.08) compared with the value of the C fetuses (3.31 +/- 0.08). Placental weight was also significantly reduced in the R(M) group, being 302 +/- 24 g, whereas the R(S) group placenta weighed 274 +/- 61 g compared with the C values of 414 +/- 57 g. Fetal heart, liver, lung, and thymus were all significantly smaller in the R(S) group. Thus the present study shows a clear relationship between the level of UBF and both fetal and placental size. Furthermore, the observation that fetal brain weight was not affected, whereas fetal body weight was significantly reduced suggests that this experimental preparation may provide a useful model in which to study asymmetric fetal growth restriction.

Uteroplacental circulatory disturbance mediated by prostaglandin F 2α in rats exposed to microwaves☆

To clarify the effects of microwaves on pregnancy, uterine or uteroplacental blood flow and endocrine and biochemical mediators, including corticosterone, estradiol, prostaglandin E 2 (PGE 2), and prostaglandin F 2α (PGF 2α), were measured in rats exposed to continuous-wave (CW) microwave at 2 mW/cm 2 incident power density at 2450 MHz for 90 min. Colonic temperature in virgin and pregnant rats was not significantly altered by microwave treatment. Microwaves decreased uteroplacental blood flow and increased progesterone and PGF 2α in pregnant, but not in virgin rats. Intraperitoneal (i.p.) administration of angiotensin II, a uteroplacental vasodilator, before microwave exposure prevented the reduction in uteroplacental blood flow and the increased progesterone and PGF 2α in pregnant rats. Increased corticosterone and decreased estradiol during microwave exposure were observed independent of pregnancy and pretreatment with angiotensin II. These results suggest that microwaves (CW, 2 mW/cm 2, 2450 MHz) produce uteroplacental circulatory disturbances and ovarian and placental dysfunction during pregnancy, probably through nonthermal actions. The uteroplacental disturbances appear to be due to actions of PGF 2α and may pose some risk for pregnancy.

The effects of long-term infusions of angiotensin II into the pregnant ewe on uterine blood flow and on the fetus.

The effects of intravenous (i.v.) infusions of 62.5 microg/h of angiotensin II (Ang II) on maternal arterial pressure (MMAP), cardiac output (CO), and uteroplacental blood flow (UPF) were studied in 11 chronically catheterized pregnant ewes and their fetuses. Over the first 4 h of infusion, MMAP (p < 0.01) increased and CO decreased (p < 0.05). UPF and fetal PO2, PCO2, and pH were unchanged. After 16-24 h, MMAP increased further (p < 0.05-p < 0.005); UPF decreased (p < 0.05), and vascular resistance increased (p < 0.05). Fetal arterial PO2 decreased and PCO2 increased (p < 0.001; p < 0.05). There were correlations between fetal arterial PO2 and UPF (r = 0.6; p < 0.00005; n = 81), pH and UPF (r = 0.39; p < 0.0003; n = 81) and a negative correlation between PCO2 and UPF (r = -0.5; p < 0.00005; n = 81). Infusions of 33 microg/h of noradrenaline initially caused a decrease in UPF. In the longer term, UPF was unchanged, as was UVR. There were no changes in fetal blood gases or pH, but there was a correlation between fetal arterial PO2 and UPF (r = 0.48; p < 0.01; n = 27). The short-term effects of Ang II and noradrenaline on UPF and UVR are similar to effects reported previously. The finding that long-term infusions of Ang II caused a reduction in UPF and compromised fetal gas exchange was unexpected. Thus the protective effect of reduced vascular reactivity of the uteroplacental circulation to Ang II is only a transient phenomenon.