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Biomedical subjects

H L Galan

Publications and source records attributed to H L Galan.

At least 19 recordsLinked to original sources
PubMed2006

Development and mechanisms of fetal hypoxia in severe fetal growth restriction.

Severe fetal growth restriction (FGR) is often associated with hypoxia. We studied FGR hypoxia in an experimental model which is produced by exposing pregnant ewes to a hyperthermic environment. The study utilized simultaneous measurements of several relevant factors, e.g., uterine and umbilical blood flows and O(2) uptakes. Sixteen ewes were divided equally into control (C) and hyperthermic (HT) groups. Hyperthermia (40 degrees C for 12h/35 degrees C for 12h; approximately 35% relative humidity, RH) was maintained for 80 days commencing at approximately 38 days gestational age (dGA term 147+/-3 days). All ewes were then placed in a control environment ( approximately 21 degrees C, 24h; approximately 30% RH) and studied at approximately 134 dGA. Mean HT placental and fetal weights were 39% and 45% of C, respectively (p<0.0001), umbilical O(2) uptake/kg fetus was 76% of C (p<0.01) and umbilical venous PO(2) was reduced (20.2 vs. 29.7 Torr, p<0.001). Contrary to the hypothesis that FGR hypoxia is due to maternal placental hypoperfusion, uterine flow was not reduced in relation to O(2) uptake. The uterine-umbilical venous PO(2) difference was enlarged (38 vs. 23 Torr, p<0.0001). This difference is the expression of a balance between developmental changes in placental structure and oxidative metabolism, which have opposite effects in terms of fetal oxygenation. We postulate that FGR hypoxia results from disproportionate underdevelopment of those changes which allow for a progressive increase in umbilical O(2) uptake.

Animals↗
PubMed2006

Doppler and biophysical assessment in growth restricted fetuses: distribution of test results.

OBJECTIVE: Multi-vessel Doppler ultrasonography and biophysical profile scoring (BPS) are used in the surveillance of growth restricted fetuses (IUGR). The interpretation of both tests performed concurrently may be complex. This study examines the relationship between Doppler ultrasonography and biophysical test results in IUGR fetuses. METHODS: Three hundred and twenty-eight IUGR fetuses (abdominal circumference < 5th percentile, elevated umbilical artery (UA) pulsatility index (PI)) had concurrent surveillance with UA, middle cerebral artery (MCA) and ductus venosus (DV) Doppler ultrasonography and BPS (fetal tone, movement, breathing, maximal amniotic fluid pocket and fetal heart rate). Patients were stratified into three groups according to their Doppler examination: (1) abnormal UA alone; (2) brain sparing (MCA-PI > 2 SD below mean for gestational age); and (3) abnormal DV (PI > 2 SD above the mean for gestational age) and BPS groups: (1) normal (> 6/10); (2) equivocal (6/10); and (3) abnormal (< 6/10). Predictions of short-term perinatal outcomes by both modalities were compared for stratification. The distribution and concordance of Doppler and BPS test results were examined for the whole patient group and based on delivery prior to 32 weeks' gestation. RESULTS: Abnormal UA Doppler results alone were observed in 109 fetuses (33.2%), brain sparing in 87 (26.5%) and an abnormal DV in 132 (40.2%). The BPS was normal in 158 (48.2%), equivocal in 68 (20.7%) and abnormal in 102 (31.1%). Both testing modalities stratified patients into groups with comparable acid-base disturbance and perinatal outcome. Of the nine possible test combinations the largest subgroups were: abnormal UA alone/normal BPS (n = 69; 21%) and abnormal DV Doppler/abnormal BPS (n = 62; 18.9%). Assessment of compromise by both testing modalities was concordant in 146 (44.5%) cases. In 182 fetuses with discordant results the BPS grade was better in 115 (63.2%, P < 0.0001). Marked disagreement of test abnormality was present in 57 (17.4%) fetuses. Of these, abnormal venous Doppler in the presence of a normal BPS constituted the largest group (Chi-square P < 0.002). Stratification was not significantly different in patients delivered prior to 32 weeks' gestation. CONCLUSION: Doppler ultrasonography and BPS effectively stratify IUGR fetuses into risk categories, but Doppler and BPS results do not show a consistent relationship with each other. Since fetal deterioration appears to be independently reflected in these two testing modalities further research is warranted to investigate how they are best combined.

Adolescent↗
PubMed2002

Temporal sequence of abnormal Doppler changes in the peripheral and central circulatory systems of the severely growth-restricted fetus.

OBJECTIVE: To identify the temporal sequence of abnormal Doppler changes in the fetal circulation in a subset of early and severely growth-restricted fetuses. METHODS: This was a prospective observational study in a tertiary care/teaching hospital. Twenty-six women who were diagnosed with growth-restricted fetuses by local standards before 32 weeks' gestation and who had abnormal uterine and umbilical artery Doppler velocimetry were enrolled onto the study. To compare Doppler changes as a function of time, pulsed-wave Doppler ultrasound was performed on five vessels in the fetal peripheral and central circulations. Doppler examinations were performed twice-weekly and on the day of delivery if the fetal heart rate tracing became abnormal. Doppler indices were scored as abnormal when their values were outside the local reference limits on two or more consecutive measurements. Biometry for assessment of fetal growth was performed every 2 weeks. Computerized fetal heart rates were obtained daily. Delivery was based on a non-reactive fetal heart rate tracing and not on Doppler information. Patients with a severely growth-restricted fetus who were delivered for maternal indications such as pre-eclampsia were excluded. Perinatal outcome endpoints included: intrauterine death, gestational age at delivery, newborn weight, central nervous system damage of grade 2 or greater, intraventricular hemorrhage and neonatal mortality. RESULTS: Mean gestational age and newborn weight at delivery were 29 (standard deviation (SD), 2) weeks and 818 (SD, 150) g, respectively. The sequence of Doppler velocimetric changes was described by onset time cumulative curves that showed two time-related events. First, for each vessel there was a progressive increase in the percent of fetuses developing a Doppler abnormality. Second, severely growth-restricted fetuses followed a progressive sequence of acquiring Doppler abnormalities which were categorized into 'early' and 'late' Doppler changes. Early changes occurred in peripheral vessels (umbilical and middle cerebral arteries; 50% of patients affected 15-16 days prior to delivery). Late changes included umbilical artery reverse flow, and abnormal changes in the ductus venosus, aortic and pulmonary outflow tracts (50% of patients affected 4-5 days prior to delivery). The time interval between the occurrence of early and late changes was significantly different (P < 0.0001) and late changes were significantly associated with perinatal death (P < 0.01). CONCLUSIONS: Doppler velocimetry abnormalities develop in different vessels of the severely growth-restricted fetus in a sequential fashion. Late changes in vascular adaptation by the severely growth-restricted fetus are the best predictor of perinatal death.

Blood Circulation↗
PubMed2002

Placental development in normal and compromised pregnancies-- a review.

Intrauterine growth restriction (IUGR) is a significant cause of infant mortality and morbidity. It is now clear that IUGR infants exhibit higher rates of coronary heart disease, type 2-diabetes, hypertension and stroke as adults. Therefore, fetal growth not only impacts the outcome of the perinatal period, but also impacts adult well-being. The etiologies of IUGR are numerous, but are often associated with abnormalities in placental structure and function. The process of implantation and placentation requires the production of a plethora of growth factors, cell-adhesion molecules, extracellular matrix proteins, hormones and transcription factors. Many of these exhibit altered expression within the placenta of IUGR pregnancies. However, it has been difficult to fully assess their role during the development of placental insufficiency (PI) in the human, underscoring the need for animal models. Using an ovine model of PI-IUGR we have observed changes in the expression of vascular endothelial growth factor, placental growth factor, their common receptors, as well as angiopoietin 2 and its receptor, Tie 2. We found that changes in these growth factors can be associated with both acute and chronic changes in placental vascular structure and function. These studies and others are providing needed insight into the developmental chronology of placental insufficiency.

Adult↗
PubMed2001

Reduction of subcutaneous mass, but not lean mass, in normal fetuses in Denver, Colorado.

OBJECTIVE: To test the hypothesis that reduced birth weight in normal fetuses born at moderately high altitude (Denver), compared with the birth weight in normal fetuses born at sea level (Milan), is caused by a reduction in both lean mass and subcutaneous fat mass. STUDY DESIGN: Ninety-four normal singleton pregnancies (46 in Denver, 48 in Milan) had serial ultrasonographic axial images obtained to assess subcutaneous tissues of fetuses as a measure of body fat. The abdominal wall thickness and mid upper arm and mid thigh were examined. The equation was: Subcutaneous tissue equals total cross-sectional area minus bone and muscle area. Lean mass included the area of muscle and bone, head circumference, and femur length. RESULTS: Gestational age at delivery was similar between groups. Birth weight was less at Denver's altitude (2991 +/- 79 g versus 3247 +/- 96 g; P =.04). Abdominal wall thickness, mid upper arm, and mid thigh subcutaneous tissues measurements were significantly reduced at Denver's altitude and increased further in significance with advancing gestational age. Lean mass measurements were similar between groups. CONCLUSIONS: The reduced birth weight of the newborns in Denver was the result of a reduction in fetal subcutaneous fat tissue and not lean mass. Ultrasonography can be used to follow subcutaneous measurements longitudinally and to detect differences, and potentially disease processes, in study populations.

Adipose Tissue↗
PubMed2001

Early and persistent reduction in umbilical vein blood flow in the growth-restricted fetus: a longitudinal study.

OBJECTIVE: We have previously shown, in a cross-sectional study, that the reduction in umbilical vein blood flow in intrauterine growth-restricted fetuses is due to reduced umbilical vein velocity. The purpose of this longitudinal study in intrauterine growth-restricted fetuses was to determine whether the umbilical vein velocity reduction, which, in turn, reduces blood flow, persists throughout gestation or represents a late event that precedes indicated delivery. STUDY DESIGN: Twenty-one intrauterine growth-restricted fetuses with an abnormal umbilical artery velocimetry underwent serial sonographic and Doppler examinations from 23 to 36 weeks of gestation. Umbilical vein diameter and velocity were measured, and umbilical vein absolute (milliliters per minute) and weight-specific blood flow (milliliters per minute per kilogram) were calculated. Umbilical vein diameter, velocity, and blood flow were expressed per abdominal circumference. Intrauterine growth-restricted findings were compared to local reference data. RESULTS: Intrauterine growth-restricted fetuses showed persistent reductions in umbilical vein blood flow per abdominal circumference and weight-specific blood flow (milliliters per minute per kilogram) from the time of diagnosis of intrauterine growth-restriction. Umbilical vein velocity was reduced in the intrauterine growth-restricted fetuses, although umbilical vein diameter did not change. CONCLUSION: Reduction of umbilical vein blood flow is an early finding in intrauterine growth-restricted fetuses, and it can persist for several weeks until delivery. This reduction in blood flow is due to reduced umbilical vein velocity.

Adult↗
PubMed2001

Cotyledon and binucleate cell nitric oxide synthase expression in an ovine model of fetal growth restriction.

Heat exposure early in ovine pregnancy results in placental insufficiency and intrauterine growth restriction (PI-IUGR). We hypothesized that heat exposure in this model disrupts placental structure and reduces placental endothelial nitric oxide synthase (eNOS) protein expression. We measured eNOS protein content and performed immunohistochemistry for eNOS in placentas from thermoneutral (TN) and hyperthermic (HT) animals killed at midgestation (90 days). Placental histomorphometry was compared between groups. Compared with the TN controls, the HT group showed reduced delivery weights (457 +/- 49 vs. 631 +/- 21 g; P < 0.05) and a trend for reduced placentome weights (288 +/- 61 vs. 554 +/- 122 g; P = 0.09). Cotyledon eNOS protein content was reduced by 50% in the HT group (P < 0.03). eNOS localized similarly to the vascular endothelium and binucleated cells (BNCs) within the trophoblast of both experimental groups. HT cotyledons showed a reduction in the ratio of fetal to maternal stromal tissue (1.36 +/- 0.36 vs. 3.59 +/- 1.2; P< or = 0.03). We conclude that eNOS protein expression is reduced in this model of PI-IUGR and that eNOS localizes to both vascular endothelium and the BNC. We speculate that disruption of normal vascular development and BNC eNOS production and function leads to abnormal placental vascular tone and blood flow in this model of PI-IUGR.

Animals↗
PubMed2001

DeLee suction. Does it have clinical significance?

OBJECTIVE: To evaluate the null hypothesis that there would be no difference in neonatal outcome in infants who underwent DeLee suction vs. those who underwent bulb suction when thick meconium was present. This difference was defined as a one-day difference in length of stay, two-point difference in the five-minute Apgar score or significant difference in blood gases. STUDY DESIGN: A power calculation based on a one-day length of stay found that 115 patients would be needed in each arm. A cohort of 115 consecutive deliveries with the presence of thick meconium was reviewed during each time period when DeLee suction was utilized and then matched with deliveries that used bulb suction. RESULTS: Two hundred thirty charts were reviewed. Length of stay, one-minute Apgar score, five-minute Apgar score, blood gases, gestational age and incidence of amnioinfusion were compared. There was no significant difference in any variable. Meconium aspiration syndrome in the period studied remained stable at < 1%. CONCLUSION: There was no significant clinical change in neonatal outcome with the abandonment of nasopharyngeal DeLee suction on the perineum when meconium was present. We recommend the use of bulb suction as routine obstetric practice even in the presence of thick meconium.

Apgar Score↗
PubMed2000

Comparison of low- and high-altitude Doppler velocimetry in the peripheral and central circulations of normal fetuses.

OBJECTIVE: Our aim was to test the hypothesis that Doppler velocimetry of the peripheral and central circulations in normal fetuses is not affected by moderately high altitude (Denver, Colo-1609 m) compared with sea level (Milan, Italy-40 m). STUDY DESIGN: One hundred nineteen patients with singleton pregnancies underwent Doppler waveform analysis of the following: umbilical artery, uterine artery, middle cerebral artery, ductus venosus, and the tricuspid and mitral valves. RESULTS: Birth weights were reduced at Denver's altitude (P<.001). The early/late diastolic inflow ratios of the atrioventricular valves increased with gestational age (P<.01), whereas systolic/diastolic ratios of the uterine and umbilical arteries decreased with gestational age (P<.01). There were no Doppler velocimetry differences in any vessel between Denver's and Milan's altitudes. CONCLUSIONS: Gestational age has the same effect on Doppler index at both high and low altitudes. Moderately high altitude does not affect uteroplacental or fetal vascular Doppler index and may reflect normal acclimatization in the smaller Denver fetuses.

Adult↗
PubMed2000

Estradiol improves pulmonary hemodynamics and vascular remodeling in perinatal pulmonary hypertension.

Partial ligation of the ductus arteriosus (DA) in the fetal lamb causes sustained elevation of pulmonary vascular resistance (PVR) and hypertensive structural changes in small pulmonary arteries, providing an animal model for persistent pulmonary hypertension of the newborn. Based on its vasodilator and antimitogenic properties in other experimental studies, we hypothesized that estradiol (E(2)) would attenuate the pulmonary vascular structural and hemodynamic changes caused by pulmonary hypertension in utero. To test our hypothesis, we treated chronically instrumented fetal lambs (128 days, term = 147 days) with daily infusions of E(2) (10 microg; E(2) group, n = 6) or saline (control group, n = 5) after partial ligation of the DA. We measured intrauterine pulmonary and systemic artery pressures in both groups throughout the study period. After 8 days, we delivered the study animals by cesarean section to measure their hemodynamic responses to birth-related stimuli. Although pulmonary and systemic arterial pressures were not different in utero, fetal PVR immediately before ventilation was reduced in the E(2)-treated group (2.43 +/- 0.79 vs. 1.48 +/- 0.26 mmHg. ml(-1). min, control vs. E(2), P < 0.05). During the subsequent delivery study, PVR was lower in the E(2)-treated group in response to ventilation with hypoxic gas but was not different between groups with ventilation with 100% O(2). During mechanical ventilation after delivery, arterial partial O(2) pressure was higher in E(2) animals than controls (41 +/- 11 vs. 80 +/- 35 Torr, control vs. E(2), P < 0. 05). Morphometric studies of hypertensive vascular changes revealed that E(2) treatment decreased wall thickness of small pulmonary arteries (59 +/- 1 vs. 48 +/- 1%, control vs. E(2), P < 0.01). We conclude that chronic E(2) treatment in utero attenuates the pulmonary hemodynamic and histological changes caused by DA ligation in fetal lambs.

Animals↗
PubMed2000

Prolonged infusions of estradiol dilate the ovine fetal pulmonary circulation.

Factors mediating both the rapid and sustained fall in pulmonary vascular resistance (PVR) at birth are incompletely understood. Acute or prolonged estrogen treatment causes vasodilation of several vascular beds in adults. Although fetal estrogen levels rise in late gestation, their effects in the fetal pulmonary circulation have not been studied. To determine whether estrogens can cause pulmonary vasodilation in the fetus, we infused 17beta-estradiol (E2) into the left pulmonary artery (LPA) of chronically catheterized fetal lambs, measured pulmonary artery pressure and LPA blood flow, and calculated PVR. Brief E2 administration (1-, 10-, and 100-microg doses) did not change baseline pulmonary hemodynamics and failed to enhance endothelium-dependent vasodilation as assessed by the dilator response to acetylcholine. However, prolonged E2 infusion (2- 8 d) caused a 2.6-fold increase in pulmonary blood flow (73+/-6 versus 188+/-44 mL/min, baseline versus E2 treatment, p<0.05), and the response was sustained for at least several hours. Treatment with the nitric oxide synthase inhibitor nitro-L-arginine (L-NA) reversed the E2-induced fall in PVR (0.15+/-0.05 versus 0.51+/-0.15 mm Hg/mL/min; before versus after L-NA, p<0.05). Endothelial nitric oxide synthase expression and endothelin-1 content were not different in E2-responders and controls, suggesting that altered expression of these mediators did not account for the increased flow. We conclude that prolonged E2 infusion causes an unusual pattern of vasodilation in the ovine fetal lung. On the basis of these observations of exogenous E2 treatment, we speculate that endogenous E2 enhances pulmonary vasodilation at birth.

Animals↗
PubMed1999

Umbilical vein blood flow determination in the ovine fetus: comparison of Doppler ultrasonographic and steady-state diffusion techniques.

OBJECTIVE: This study was undertaken to assess the accuracy of triplex ultrasonographic measurement of venous umbilical blood flow in comparison with the steady-state diffusion technique and to determine the impact of cotyledon weight and number on umbilical blood flow. STUDY DESIGN: Six late-gestation ewes with long-term catheter placement were studied for venous umbilical blood flow with the ethanol steady-state diffusion technique and with triplex-mode ultrasonography (color Doppler, pulsed-wave Doppler, and real-time ultrasonography). At necropsy the number and weight of the cotyledons serving each umbilical vein were recorded. RESULTS: Umbilical blood flow determined by triplex-mode ultrasonography (207. 5 +/- 8.6 mL. kg(-1) fetus. min(-1)) was virtually identical to that determined with the steady-state diffusion technique (208.1 +/- 7.3 mL. kg(-1) fetus. min(-1); P =.9). When values were normalized for the weight or number of cotyledons serving each vein, there was no difference in umbilical blood flow between small and large umbilical veins in all the sheep. CONCLUSIONS: Our study validates the accuracy of the triplex ultrasonographic method and provides justification for its use in future human investigations. In absolute terms umbilical blood flow frequently differs between the 2 veins. When expressed per number or mass of cotyledons, however, the umbilical blood flows are similar.

Animals↗
PubMed1999

Relationship of umbilical vein blood flow to growth parameters in the human fetus.

OBJECTIVE: Our purposes were to determine the relationship of the growth of umbilical blood flow to growth in body measurements of human fetuses in uncomplicated pregnancies. The study also aimed to assess the relative contributions of growth in umbilical vein diameter and of increased velocity to the increase in umbilical blood flow. STUDY DESIGN: An animal study was conducted to assess the accuracy of umbilical vein blood flow measurements obtained by triplex mode ultrasonography. Seven pregnant ewes underwent triplex mode umbilical vein flow determination. These results were compared with historical flow data obtained by a steady-state diffusion technique in 34 ewes matched for gestational age and weight. In a separate study performed on human beings, reproducibility and precision of triplex mode flow determination were assessed, as were the relationships between umbilical vein flow and gestational age and head and abdominal circumferences. This cross-sectional study was performed with 70 healthy fetuses ranging from 20 weeks' gestation to term. Best-fit interpolating equations and confidence limits were calculated for blood flow measurements versus gestational age and head and abdominal circumferences. RESULTS: In the validation study performed on sheep there were no significant differences between triplex mode and steady-state measurement groups with respect to gestational age or weight. The umbilical vein flows were similar between triplex mode and steady-state measurement groups (P =.881). In the human study the intraobserver and interobserver coefficients of variation for the vein diameter, mean velocity, and absolute umbilical vein blood flow varied from 2.9% to 12.7%. The mean duration of examination was 3 +/- 1 minutes. The umbilical vein diameter and mean velocity increased throughout pregnancy. The absolute umbilical vein flow increased exponentially from 97.3 mL/min at midgestation to 529.1 mL/min at 38 weeks' gestation, whereas umbilical vein flow per kilogram of fetal weight did not change significantly with gestational age. There was a strong correlation between absolute umbilical vein flow and the fetal head and abdominal circumferences. CONCLUSIONS: The triplex mode ultrasonographic technique can play an innovative role in obtaining quick and reproducible measurements of umbilical vein blood flow. The approach was validated with a sheep model. Umbilical vein blood normalized for fetal weight (milliliters per minute per kilogram of fetal weight) and absolute flow (in milliliters per minute) are consistent with previous human studies. We have established new reference values of umbilical vein blood flow relative to head and abdominal circumferences. The growth of umbilical venous diameter accounted for most of the growth in umbilical vein flow.

Animals↗
PubMed1999

Relationship of fetal growth to duration of heat stress in an ovine model of placental insufficiency.

OBJECTIVE: Intrauterine growth restriction in an ovine model occurs after exposure to environmental heat stress for 80 days beginning at 35 days' gestation. Our objective was to determine whether intrauterine growth restriction is reversible on removal of the heat stress after only 55 days of exposure; that is, does a brief exposure at a critical point of development suffice? STUDY DESIGN: Five pregnant ewes were exposed to heat stress beginning at 35 days' gestation and were removed after 55 days of exposure. Five ewes in a control group were studied as contemporaneous controls and added to data from 37 ewes in a control group previously studied. Serial fetal biometric ultrasonographic measurements (biparietal diameter, abdominal circumference, femur length, and tibia length) were obtained beginning at 50 days' gestation. Growth curves were calculated for each parameter, and comparisons were made between fetuses in the group exposed to heat stress for 55 days and 42 fetuses in the control group and 4 fetuses from a previous study that were exposed to heat for 80 days. Regression lines, 95% confidence intervals, and slopes were determined for each study group. RESULTS: Both the 55-day and the 80-day heat exposure groups showed a significant reduction in fetal and placental weights compared with the control group. Animals in the 80-day group had significantly lower fetal and placental weights than the animals in the 55-day group (P <.05). Indexes of somatic growth (abdominal circumference, femur length, and tibia length) for the control group were significantly greater than those of either the 55-day group or the 80-day group (P <.001). Asymmetric growth restriction was evident in both heat groups by a biparietal diameter/abdominal circumference ratio that was significantly higher than in the control group (P <.004 for the 55-day group and P <.001 for the 80-day group). The slopes for somatic parameters (abdominal circumference, femur length, and tibia length) versus time became significantly different between the control and 55-day groups at 77, 101, and 80 days' gestation, respectively. The 55-day group had abdominal circumference and femur length measurements that were significantly greater than those in the 80-day group. CONCLUSION: The fetuses in the 55-day and 80-day groups reflect a pattern of asymmetric intrauterine growth restriction. Our findings suggest that the initial insult affecting fetal and placental growth occurs early in gestation, but removal of fetuses after only 55 days of exposure significantly reduces the degree of fetal growth restriction compared with that found in those fetuses exposed for 80 days.

Abdomen↗
PubMed1998

Doppler velocimetry of growth-restricted fetuses in an ovine model of placental insufficiency.

OBJECTIVE: With an ovine model in which growth restriction was induced by exposure to heat stress, our aims were as follows: (1) to describe the normal gestational age-related changes in Doppler velocimetry in the ovine fetal aorta and umbilical artery and (2) to compare Doppler velocimetry between heat-stressed and non-heat-stressed fetuses. STUDY DESIGN: Five ewes were exposed to heat stress for 55 days beginning at 35 days' gestation. Five ewes were not exposed and served as controls. Aortic and umbilical artery pulsed Doppler velocimetry was obtained, including the systolic/diastolic ratio, pulsatility index, and resistance index. Data were obtained between 50 and 120 days' gestation. Linear regression analysis was used to analyze gestational age-related changes in velocimetry. Comparison of mean index values between heat-stressed and non-heat-stressed fetuses were made with analysis of variance. RESULTS: Heat-stressed fetuses demonstrated significantly higher systolic/diastolic ratios and pulsatility index values for both umbilical artery (p < 0.025; p < 0.033) and aorta (p < 0.017; p < 0.022) compared with controls. The umbilical artery and aortic resistance index values were not different between groups (p < 0.079; p < 0.28). The slopes for each of the Doppler index values were negative in both normal and heat-stressed fetuses. Umbilical artery and aortic end-diastolic flows remained absent through the first 70 days of gestation in both groups. CONCLUSION: Doppler velocimetry index values decrease with increasing gestational age, reflecting decreased placental bed vascular resistance. The higher Doppler index values seen in the heat-stressed group are consistent with increased placental vascular resistance. The normal absence of diastolic flow until 70 days' gestation is similar to the pattern described in humans.

Animals↗
PubMed1997

Prolonged endothelin A receptor blockade attenuates chronic pulmonary hypertension in the ovine fetus.

Based on past studies of an experimental model of severe intrauterine pulmonary hypertension, we hypothesized that endothelin-1 (ET-1) contributes to high pulmonary vascular resistance (PVR), hypertensive lung structural changes, and right ventricular hypertrophy (RVH) caused by prolonged closure of the ductus arteriosus. To test this hypothesis, we studied the effects of BQ 123, a selective ET(A) receptor antagonist, after ligation of the ductus arteriosus in utero. In 19 late gestation fetal lambs (126+/-3 d; 147 d, term) we ligated the ductus arteriosus at surgery, and treated animals with either BQ 123 (1 mg/d) or vehicle (0.1% DMSO, HTN) in the pulmonary artery for 8 d. Chronic BQ 123 treatment attenuated the rise in mean pulmonary artery pressure (PAP) 8 d after ductus arteriosus ligation (78+/-2, HTN vs. 70+/-4 mmHg, BQ 123, P < 0.05). To study the effects of ET(A) blockade at birth, 15 animals were delivered by cesarean section and ventilated with 10% oxygen (O2), 100% O2 and inhaled nitric oxide (NO). Lambs treated with BQ 123 had lower PVR after delivery during ventilation with 10% O2, 100% O2, and inhaled NO (HTN vs. BQ 123, P < 0.05 for each intervention). Acute BQ 123 treatment (2 mg/30 min) lowered PVR in three HTN animals ventilated with 100% O2 and inhaled NO (P < 0.05). Chronic BQ 123 treatment prevented the development of RVH as determined by the ratio of the right ventricle/left ventricle + septum (0.79+/-0.03, HTN vs. 0.57+/-0.06, BQ 123, P < 0.05) and attenuated the increase in wall thickness of small pulmonary arteries (61+/-2, HTN vs. 50+/-2%, BQ 123, P < 0.05). In summary, chronic intrauterine ET(A) receptor blockade decreased PAP in utero, decreased RVH and distal muscularization of small pulmonary arteries, and increased the fall in PVR at delivery. We conclude that ET(A) receptor stimulation contributes to the pathogenesis and pathophysiology of experimental perinatal pulmonary hypertension.

Administration, Inhalation↗
PubMed1997

Paralysis of the preterm rabbit fetus inhibits the pulmonary uptake of intraamniotic iron dextran.

OBJECTIVE: Whether fetal breathing movements or gasping result in the movement of amniotic fluid substances into the distal airways remains controversial. We evaluated the effect of paralysis of the preterm rabbit fetus on the pulmonary distribution of iron dextran. STUDY DESIGN: Laparotomy was performed on 10 New Zealand White rabbits of 25 days' gestation (term 31 days) under general anesthesia. Fetuses in one uterine horn were given an intramuscular injection of pancuronium (1.5 mg/kg) and fetuses in the other horn were given an equal volume of normal saline solution as controls. A 1 ml volume of iron dextran (100 mg/ml) was injected into the amniotic sac of all fetuses. The laparotomy was closed, and 20 to 24 hours later the fetuses were removed by hysterotomy and assessed for paralysis. Necropsy was performed. Lungs were stained with prussian blue and evaluated histologically for the presence of iron. RESULTS: A total of 92 pups were delivered (49 given pancuronium, 43 given normal saline solution), of which 64 were born alive. There were no differences between groups for live births (31 pancuronium, 33 normal saline solution), pup body weight, or lung weight. Pups given normal saline solution demonstrated more breathing motions, spontaneous movement, and brown (color of iron dextran) stomach contents than did the pups given pancuronium (p < 0.001). At necropsy a greater number of control pups (31/33) had brown lungs grossly compared with pups given pancuronium (2/31, p < 0.001). Lung histologic examination showed that more control pups (29/29) had iron in the trachea and main bronchi compared with pancuronium pups (0/27, p < 0.001), and more control pups (29/29) had iron in the distal lung airways compared with pancuronium pups (0/27, p < 0.001). With use of the Optimas Image Analysis System, iron in the lungs of control pups was found to be equally distributed between right versus left lungs, upper half versus lower half lungs, and anterior versus posterior lung sections. More iron was identified in the central airways than in the periphery (p < 0.001). CONCLUSION: We conclude that paralysis prevents the uptake of iron dextran into the main and distal airways of the rabbit fetus. Although lung fluid production results in a net efflux of fluid, we speculate that fetal breathing movements can result in the movement of fluid into distal airways and potentially provide fetal therapy.

Amniotic Fluid↗