Biomedical subjects

M G Ross

Publications and source records attributed to M G Ross.

At least 19 recordsLinked to original sources

PubMed2006

Placental and membrane aquaporin water channels: correlation with amniotic fluid volume and composition.

OBJECTIVES: To assess the role of aquaporins (AQPs) in the regulation of amniotic fluid (AF) volume, we determined AF volume and composition and placental and fetal membrane AQP expression throughout the second half of murine gestation. METHODS: Pregnant CD1 mice were sacrificed at e10-19 and AF volume and composition determined. Placenta and fetal membranes were screened for AQP gene expression. AQP gene expression was quantified by real-time RT PCR and protein location determined by immunohistochemistry. Changes in AF volume were correlated with AQP expression. RESULTS: Both membranes and placenta demonstrated expression of AQP1, -3, -8 and -9. Advancing gestation was associated with increased AF volume from e10 to e16, with a marked decrease in AF volume from e16 to e19. By immunohistochemistry, AQP1 was localized to placental vessels and AQP3 to trophoblast. AF volume was negatively correlated with fetal membrane AQP1 and placental AQP1 and AQP9 expression, and positively correlated with placental AQP3 expression. CONCLUSION: Changes in AQPs with advancing gestation, and their correlation with AF volume, suggest a role in mediating placental and membrane water flow and ultimately AF volume. AQP1 appears to regulate fetal membrane water flow, and AQP3 is a likely candidate for the regulation of placental water flow.

Amniotic Fluid↗

PubMed2004

In utero development of fetal thirst and appetite: potential for programming.

Thirst and appetite-mediated ingestive behavior develop and are likely programmed in utero, thus preparing for newborn and adult ingestive behavior. Fetal swallowing activity is markedly different from that of the adult, as spontaneous fetal swallowing occurs at a markedly (six-fold) higher rate compared with spontaneous adult drinking activity. This high rate of fetal swallowing is critical for the regulation of amniotic fluid volume and the development of the fetal gastrointestinal tract. Disordered fetal swallowing has been associated with both a decrease (oligohydramnios) and increase (polyhydramnios) in amniotic fluid volume. Both conditions are associated with a significant increase in perinatal morbidity and mortality, and limited treatment modalities are currently available. The mechanisms underlying the high rate of human fetal swallowing are regulated, in part, by tonic activity of central angiotensin II, glutamate N-methyl-D-aspartate receptors, and neuronal nitric oxide synthase. Fetal hypertonicity-mediated dipsogenesis is likely programmed in utero, as offspring of water-restricted ewes demonstrate a programmed syndrome of plasma hypertonicity, with significant hematologic and cardiovascular alterations. Similar to dipsogenic mechanisms, peripheral and central fetal orexic mechanisms also develop in utero, as demonstrated by increased fetal swallowing after both oral sucrose infusion and central injection of neuropeptide Y. The role of leptin in regulating fetal ingestive behavior is interesting because, contrary to actions in adults, leptin does not suppress fetal ingestive behavior. Teleologically, this may be of value during the newborn period, as unopposed appetite stimulatory mechanisms may facilitate rapid fetal and newborn weight gain. An adverse intrauterine environment, with altered fetal orexic factors during the critical developmental period of fetal life, may alter the normal setpoints of appetitive behavior and potentially lead to programming of adulthood hyperphagia and obesity. Further research is needed to delineate the mechanistic relationship between the intrauterine environment and the development of the setpoints of adult appetite and thirst.

Animals↗

PubMed2004

Correlation of maternal plasma volume and composition with amniotic fluid index in normal human pregnancy.

OBJECTIVE: Early in human pregnancy, maternal plasma osmolality decreases and plasma volume begins to increase. Continued plasma volume expansion is linked to fetal fluid acquisition, and ultimately normal amniotic fluid volume. Although the mechanisms for these physiological responses are uncertain, we hypothesized that the time course of maternal plasma hypotonicity, plasma volume expansion and amniotic fluid index (AFI) were interrelated. We sought to examine these interrelationships during human pregnancy. METHODS: Normal primiparous pregnant patients had monthly determinations of plasma volume using Evans blue from the second trimester to term, and 8 weeks after delivery. At each visit, fasting, morning blood samples were also drawn to measure hematocrit, osmolality, electrolytes, urea, glucose and creatinine. AFI was determined by ultrasound. RESULTS: Plasma volume, blood volume and AFI demonstrated significant increases with advancing gestational age. There were no significant changes in plasma sodium or osmolality from the second trimester to term. AFI was not associated with either plasma volume or osmolality. CONCLUSION: Although similar factors may therefore be responsible for the initiation of plasma volume expansion and plasma hypotonicity, the magnitude and degree of change of these processes are probably under independent regulation. Individual patient variation in AFI is a result of factors other than maternal blood volume or composition.

Amniotic Fluid↗

PubMed2004

ST-segment analysis of the fetal electrocardiogram improves fetal heart rate tracing interpretation and clinical decision making.

INTRODUCTION: Since its introduction into clinical use, the efficacy of electronic fetal heart rate (FHR) monitoring (EFM) has been questionable. This has been due partly to the marked variation in interpretation of the FHR pattern and subsequent decisions for obstetric intervention, (e.g., the need for prompt delivery). Current application of EFM is limited to the assessment of FHR patterns and uterine contractions. Recent development of higher-order FHR analysis has yielded monitoring systems that can add automated fetal electrocardiographic ST segment analysis to the standard FHR and uterine contraction information. Our goal was to evaluate the effect of adding ST segment analysis to standard FHR information on observer agreement for clinical decision making. METHODS: Seven practitioners who were trained and experienced in combined FHR and ST monitoring reviewed 51 fetal monitor tracings, ranging from 2 to 4 h in length. Reviews were conducted in two sessions and at different times. The first session presented only the FHR and uterine contraction information, following which the participants determined the time at which intervention (decision for operative vaginal or Cesarean section delivery) was indicated. In the second session, the participants were provided with a randomized sequence of the same tracings with the addition of ST segment information, as produced by the STAN monitor system (Neoventa Medical, Gothenburg, Sweden). Observer agreement was based on the proportion of participants who agreed on the need for an intervention, and the per cent agreement on the timing of the intervention within 20 min before or after the median time of intervention. RESULTS: Of the 51 cases included in this study there were ten fetuses with umbilical artery (UA) pH between 7.05 and 7.14, and nine with UA pH of < 7.05. Observer agreement increased significantly for required intervention when the ST segment information was available for tracing analysis as compared with review of the standard tracing alone (0.96 vs. 0.80, p < 0.05) and the timing of intervention (0.92 vs. 0.66, respectively, p < 0.05). Similarly, correct identification for needed interventions on fetuses with abnormal outcomes increased from 86 to 93% while unneeded interventions on normal fetuses decreased from 43 to 6%. CONCLUSION: The addition of ST analysis to standard FHR monitoring improves observer consistency in both the decision for and timing of obstetric interventions. The incorporation of ST segment data with the standard FHR tracing may reduce the number of unneeded obstetric interventions when fetal compromise is absent.

Electrocardiography↗

PubMed2004

Unopposed appetite (orexigenic) mechanisms in the near-term ovine fetus: central leptin does not inhibit sucrose ingestion.

OBJECTIVE: Leptin is produced in adipocytes and is present in the term fetus. In the adult, leptin acts centrally to inhibit neuropeptide Y-induced carbohydrate intake. We sought to examine if central leptin alters fetal ingestion of oral sucrose in the near-term ovine fetus. METHODS: Five pregnant ewes and fetuses were prepared with fetal vascular, sublingual and intracerebroventricular (ICV) catheters and esophageal electromyogram electrodes, and studied at 132 +/- 1 days' gestation (term 145-150 days). Following a 2-h baseline period, 10% sucrose was infused sublingually (0.25 ml/min) for the duration of the study. At time 4 h, leptin (0.075 mg/kg) was administered ICV and fetal swallowing was monitored for an additional 6 h. RESULTS: During the basal period, fetal swallowing averaged 0.7 +/- 0.1 swallows/min. Fetal swallowing increased significantly in response to 10% sucrose (1.2 +/- 0.1 swallows/min; p < 0.05). In response to ICV leptin, fetal swallowing remained significantly elevated at 2, 4 and 6 h (1.3 +/- 0.4, 1.4 +/- 0.3 and 1.5 +/- 0.2 swallows/min, respectively; p < 0.05 vs. control). CONCLUSIONS: These results indicate that central leptin inhibition of sucrose ingestion is not functional in the near-term fetus. We speculate that a leptin-mediated anorexigenic response is not present at birth, such that unopposed appetite stimulatory mechanisms in the newborn may facilitate rapid newborn weight gain despite high body fat levels.

Administration, Sublingual↗

PubMed2003

Circle of time: errors in the use of the pregnancy wheel.

OBJECTIVE: Despite the accuracy of pregnancy dating by ultrasound, obstetricians commonly use the pregnancy wheel for the assessment of gestational age at each visit. However, there has been limited assessment of the accuracy of the wheel, or variation among wheels. This study sought to determine the accuracy of pregnancy wheels in predicting term gestation, when entering first-trimester ultrasound-determined dating. METHODS: A selection of four pregnancy wheels of varying types were utilized to determine estimated date of delivery (EDD) based upon an ultrasound assessment of 12 0/7 weeks' gestation at random dates throughout each of the 12 months of the year. As a control, EDD was calculated as 196 days from the 12 0/7 week ultrasound assessment by a computerized program using the years 2003-04. The mean difference in days between each wheel and the computer-assessed EDD was determined. Statistical comparison was performed with Kruskal-Wallis one-way analysis of variance with post-hoc Dunnett's test. RESULTS: There were marked differences between the EDD determined by wheels versus the computer. One wheel differed by an average of more than 3 days from computer-assessed EDD, with a range of + 1 to +5 days. The difference between wheels and computer-assessed EDD varied monthly. CONCLUSION: In view of the need for accurate gestational age assessment for clinical interventions (e.g. post-dates testing) clinicians should be aware of the potential inaccuracies of pregnancy wheels.

Data Interpretation, Statistical↗

PubMed2003

Reversal of pregnancy-mediated plasma hypotonicity in the near-term rat.

OBJECTIVE: Maternal plasma hypotonicity occurs early in rat and human pregnancy with resetting of the plasma osmolality threshold for vasopressin secretion and thirst. In humans, amniotic fluid volume reaches maximum levels in the mid-third trimester and decreases thereafter. We hypothesized that a reversal of maternal plasma hypotonicity occurs near term, contributing to reduced fetal and amniotic fluid water content. METHODS: Maternal plasma and amniotic fluid osmolality and sodium levels, including amniotic fluid volume, were measured at 16, 18 and 20 days of rat gestation. Additionally, maternal and fetal brains were analyzed for water and electrolyte content. Non-pregnant adult female rats represented controls. RESULTS: Compared to non-pregnant adults, 16-day and 18-day pregnant rats had significantly lower plasma osmolality (301.0 +/- 2.3 vs. 295.4 +/- 2.8 and 289.7 +/- 3.3 mOsm/kg, respectively) and sodium levels (140.3 +/- 1.0 vs. 135.7 +/- 0.8 and 133.4 +/- 1.4 mEq/l, respectively). Conversely, 20-day pregnant rats showed no significant difference in plasma osmolality (298.4 +/- 3.1 mOsm/kg) or sodium levels (137.6 +/- 1.0 mEq/l) from non-pregnant adults. With advancing gestation, the amniotic fluid volume decreased whereas the osmolality and sodium levels increased significantly. Maternal brain water content was significantly higher in 16-day and 18-day pregnant rats compared to control rats (78.7 +/- 0.1 and 78.1 +/- 0.2 vs. 76.9 +/- 0.2% wet weight) and returned to non-pregnant values in the 20-day pregnant rats (76.6 +/- 0.2%). In association with the maternal changes, fetal brain water and electrolyte content significantly decreased from 16-day to 18-day to 20-day fetuses. CONCLUSION: These findings indicate a reversal of maternal plasma hypotonicity and reduced maternal brain water content in the near-term pregnant rat. We speculate that relative maternal plasma hypertonicity near term may contribute to reduced amniotic fluid volume.

Amniotic Fluid↗

PubMed2003

Ontogeny of cholinergic regulation of fetal upper gastrointestinal motility.

OBJECTIVE: In the fetal rabbit immediately prior to birth (day 30; 0.97 gestation), intragastric atropine suppresses upper gastrointestinal (GI) motility, indicating that cholinergic receptors are expressed and functional at birth. To explore the developmental timing of upper GI cholinergic receptor function, we assessed the effect of intragastric atropine administration in rabbit fetuses during the last 10% of gestation. METHODS: Pregnant rabbits were studied at day 27, day 28 and day 29 of their normal 31-day gestation. In each litter, two fetuses were selected as study fetuses and two as control fetuses. Under ultrasound guidance, fluorescein and either atropine (0.04 microg/g fetal body weight) or normal saline were injected into the fetal stomach. Two hours after injection, fetuses were delivered and the small intestine was harvested. The per cent motility was calculated as the fluorescein travel distance, which was measured by ultraviolet light optical density, divided by the total small intestinal length. RESULTS: Fetal body weight, small intestinal length and per cent motility increased from day 27 to day 29 (p < 0.01). There were no differences in fetal body weight and small intestinal length between atropine and control groups. Atropine significantly decreased per cent motility (versus control values) in fetuses at day 29 and day 28 (56.1 +/- 13.5 vs. 66.1 +/- 11.7% and 59.7 +/- 15.6 vs. 68.3 +/- 11.7%, respectively; p < 0.05), but not at day 27 (52.4 +/- 12.9 vs. 52.8 +/- 11.2%). CONCLUSIONS: These results indicate that upper GI functional cholinergic receptors develop between 0.87 and 0.90 of rabbit gestation. Extrapolation to human development suggests that reduced GI motility in preterm human infants results, in part, from immature GI cholinergic receptors.

Animals↗

PubMed2002

Anticholinergic suppression of fetal rabbit upper gastrointestinal motility.

OBJECTIVE: At birth the newborn digestive tract must assume the responsibility of assimilating nutrients for survival. Immature gastrointestinal motility in the neonate may result in impaired feeding and nutrition. Newborn gastrointestinal motility development requires the expression and functional maturation of gastrointestinal receptors. To explore the timing of fetal responses to gastrointestinal cholinergic motility agents, we assessed the effect of the anticholinergic agent atropine in the late-gestation rabbit fetus. METHODS: Seven pregnant New Zealand White rabbits were studied at day 30 of their normal 31-day gestation. In each litter, two fetuses were selected as study (n = 14) and two as control (n = 14). Under ultrasound guidance, a spinal needle was percutaneously inserted through the maternal uterus into the fetal stomach and 0.5 ml of gastric content was aspirated. Fluorescein, labelled with colored microspheres, and either atropine (0.04 microg/g fetal body weight) or normal saline were injected in a total volume of 0.5 ml. Two hours after injection, fetuses were delivered, the small intestine harvested, and the total small intestinal length and the distance the gastrointestinal fluorescein travelled were measured by ultraviolet light optical density. The fluorescein travelled distance and the per cent motility, defined as the length of fluorescein travelled divided by the total length of the small intestine, were calculated. RESULTS: All fetuses survived the intragastric injection. Mean fetal body weight at delivery was 44.2 +/- 6.7 and 46.8 +/- 7.2 g in atropine and control fetuses, respectively. The fluorescein travelled distance (15.4 +/- 4.2 vs. 19.0 +/- 4.3 cm;. p < 0.01) and per cent motility (51.0 +/- 8.9 vs. 63.8 +/- 11.7%; p < 0.01) of atropine-treated fetuses were significantly lower than those of control fetuses. CONCLUSION: Fetal upper gastrointestinal motility is suppressed in response to intragastric atropine. These results indicate that fetal gastrointestinal cholinergic receptors are expressed and functional in the term (0.97 gestation) rabbit fetus. In utero administration of cholinergic agonists/antagonists may potentially modulate fetal gastrointestinal motility and absorption of amniotic fluid water and solutes.

Animals↗

PubMed2002

Correlation between fetal scalp blood samples and intravascular blood pH, pO2 and oxygen saturation measurements.

OBJECTIVE: This study was designed to compare the values of blood gases in local scalp blood, obtained by scalp blood sampling, with direct measurements of fetal preductal arterial blood in fetal sheep. METHODS: Six fetal lambs were catheterized in the brachial artery and vein. Maternal oxygenation was reduced in steps from a fractional inspired oxygen concentration (FiO2) of 20 to 5% by addition of nitrogen to the inhaled gas mixture. Fetal scalp and arterial blood were sampled simultaneously at maternal FiO2 step intervals after maternal FiO2 and oxygen were stable for > 5 min. Blood pH, pO2 and oxygen saturation were measured and linear regression was performed to determine the correlation between these values. RESULTS: Scalp pH correlated well with arterial pH, whereas scalp pO2, pCO2 and oxygen saturation did not. However, when a secondary analysis was performed taking into account the effects of aerobic contamination, scalp pCO2, pO2 and oxygen saturation became highly correlated with arterial values. CONCLUSIONS: Local scalp blood oxygen saturation correlates highly with fetal preductal arterial values, when physiological artifacts are eliminated. The technique of scalp blood sampling introduces error into oxygenation saturation measurements, owing to difficulties in anaerobic sample collection. These results suggest that continuous measurement of fetal scalp oxygenation by noninvasive oximetry may be superior to direct sampling of scalp blood.

Animals↗

PubMed2001

Intracerebroventricular carbachol induces FOS immunoreactivity in lamina terminalis neurons projecting to the supraoptic nucleus.

Central application of the non-selective cholinergic receptor agonist, carbachol, induces water intake, vasopressin (VP) release and an acute increase in arterial blood pressure. Forebrain sites, particularly those located along the lamina terminalis (LT) (i.e. the subfornical organ (SFO), organum vasculosum (OV) and the median preoptic nucleus (MePO)) and in the hypothalamus, have been proposed as the major targets for producing the effects induced by intracerebroventricular (i.c.v.) carbachol injections. However, the functional and neuroanatomical relationship among carbachol-activated cells along the LT and hypothalamic areas such as the supraoptic nuclei (SON), is unclear. The present study investigated the i.c.v. carbachol-induced activity of the soma of LT projections which descend from the SFO, OV and MePO and terminate in the region of the SON. Cells along the LT were retrogradely labeled from SON-targeted injections of fluoro-gold, and FOS-immunoreactivity (FOS-ir) was used to assess activation. A significant number of cells in the SFO, OV and MePO were double-labeled for both FOS-ir and fluoro-gold. The FOS labeling in the cells of the LT-associated structures was significantly reduced by pretreatment with the i.c.v. muscarinic antagonist, atropine. Taken together, the results indicate that neurons located in structures located along the LT and projecting to the region of the SON are activated by i.c.v. carbachol and that these receptors are likely to be muscarinic.

Animals↗

PubMed2001

Effect of hypoxia on fetal rabbit gastrointestinal motility.

During fetal hypoxic stress, blood flow is shunted from nonvital to life-preserving organs, including the heart and brain. Reduced oxygen to the small intestine (SI) induces mucosal injury and may contribute to neonatal necrotizing enterocolitis (NEC). As little is known about the relationship between fetal hypoxia and GI motility, we assessed potential effects in a rabbit model. Twenty-one pregnant rabbits were randomized into two groups, hypoxia (Hyp) and control (Cont). Seven litters were studied at Gestational Days 24, 27, and 30 of their normal 31-day gestation. Under ultrasound guidance each fetal stomach was percutaneously accessed. Fluorescein, labeled with color-coded microspheres for precise fetal identification, was injected. Hyp rabbits breathed 11% oxygen for 1 h after recovery from anesthesia; Cont rabbits breathed room air. Two hours after injection, fetuses were delivered and weighed. The SI was harvested, the length recorded, and the distance fluorescein traveled measured by UV light optical density. Results were analyzed by the unpaired Student test. All injected fetuses (N = 167) survived. The length fluorescein traveled was shorter in Hyp than Cont at all gestational days studied (P < 0.01): Day 24, Hyp = 6.7 +/- 2.0 vs Cont = 8.4 +/- 2.1 cm; Day 27, Hyp = 10.1 +/- 2.9 vs Cont = 19.1 +/- 4.4 cm; and Day 30, Hyp = 16.8 +/- 3.5 vs Cont = 23.1 +/- 5.2 cm. The percentage motility, defined as the length of fluorescein travel divided by total SI length, was also significantly less at all gestational days. Fetal rabbit GI motility was significantly decreased by maternal hypoxia during the last third of gestation. Hypoxia-induced reduction in GI motility may contribute to neonatal NEC.

Animals↗

PubMed2001

Ontogeny of fetal rabbit upper gastrointestinal motility.

BACKGROUND: The gastrointestinal (GI) tract performs the digestion, propulsion, and absorption of nutrients both pre- and postnatally, although little is known about the development of fetal motility. We evaluated the development of GI motility using a novel fetal rabbit model. METHODS: Nine pregnant rabbits were obtained and three litters were studied at day 24 (n = 24), 27 (n = 29), and 30 (n = 24) of their 31-day gestation. Under ultrasound guidance fetal position was identified, a spinal needle was percutaneously inserted into each fetal stomach, and fluorescein, labeled with color-coded microspheres, was injected. Two hours later, fetuses were delivered and weighed, and the small intestine was harvested. The absolute length of fluorescein traveled was measured by ultraviolet light optical density and the percentage motility was calculated by dividing the absolute length of fluorescein traveled by the total small intestinal length. RESULTS: All injected fetuses survived. The length of fluorescein traveled significantly increased from day 24 (8.1 +/- 2.1 cm) to day 27 (18.8 +/- 4.6 cm) and 30 (22.6 +/- 5.2 cm). The length of fluorescein traveled significantly correlated with body weight on day 27 and 30. Calculated percentage motility significantly increased from day 24 to 30. However, percentage motility showed no correlation with fetal weight. CONCLUSIONS: This study describes a novel rabbit model for the assessment of in vivo fetal GI motility. Motility matured during the last third of gestation when assessed by the absolute length of fluorescein travel and the percentage motility. These results confirm that late-gestation fetuses have developed sufficient motility to propel potential nutrients, drugs, or gene therapy vectors to the small intestinal absorptive surface area.

Animals↗

PubMed2001

Clavicle fracture in labor: risk factors and associated morbidities.

OBJECTIVE: Neonatal clavicle fracture has been previously reported to occur in association with shoulder dystocia, suggesting liability on behalf of the obstetrician. However, clavicle fracture is often inconsistently diagnosed, and shoulder dystocia commonly subjectively defined. Using a formal pediatric diagnosis protocol and an objective definition of shoulder dystocia, we sought to determine the incidence, antecedents, and associated morbidities of clavicle fracture and the potential association with shoulder dystocia. STUDY DESIGN: All deliveries at Harbor-UCLA Medical Center complicated by clavicle fracture from January 1996 to March 1999 were studied. Deliveries with clavicle fracture were compared to all vaginal deliveries during this period. RESULTS: Among 4297 deliveries, twenty-six were complicated by clavicle fracture (0.5%). Clavicle fracture was significantly associated with increased maternal age and birth weight greater than 4 kg, though not associated with shoulder dystocia or operative vaginal delivery. Clavicle fracture was associated with meconium passage and with neonatal orthopedic abnormalities. CONCLUSION: Neonatal clavicle fracture is associated with infant birth weight greater than 4 kg, but not with the occurrence of objectively defined shoulder dystocia. However, infants with clavicle fracture may be at increased risk for additional complications.

Birth Injuries↗

PubMed2001

Central leptin stimulates ingestive behavior and urine flow in the near term ovine fetus.

Leptin inhibits ingestive behavior and induces diuresis and natriuresis. To examine whether leptin influences fetal physiologic functions, we investigated the effect of central leptin on ovine fetal swallowing activity and urine flow. Six pregnant ewes with singleton fetuses (130 +/- 2 d gestation) were prepared with maternal and fetal arterial and venous catheters, fetal lateral intra-ventricle cannula, fetal bladder and amniotic fluid catheters. Electromyogram wires were placed in the fetal thyrohyoid muscle and upper and lower nuchal esophagus and electrodes were implanted on the parietal dura. Five days after surgery, recombinant human leptin was infused into the lateral ventricle and the fetus monitored for 8 h. Central leptin increased fetal swallowing activity during low-voltage electrocortical activity from basal values (0.96 +/- 0.08 swallows/min) at 2 h (1.41 +/- 0.24 swallows/min), 4 h (2.81 +/- 0.57 swallows/min), 6 h (2.53 +/- 0.59 swallows/min) and 8 h (2.08 +/- 0.39 swallows/min, p < 0.05). In comparison to basal values, low voltage electrocortical activity decreased (57 +/- 5% to 42 +/- 4%) and high voltage electrocortical increased (43 +/- 5% to 61 +/- 4%). In response to leptin, fetal urine flow initially decreased from basal values at 2 h (0.12 +/- 0.03 to 0.08 +/- 0.02 ml/kg/min, p < 0.05) then subsequently increased at 4 h and 6 h (0.20 +/- 0.04; 0.21 +/- 0.04 ml/kg/min, respectively, p < 0.05). Central leptin significantly increases near term ovine fetal swallowing activity and urine output, suggesting that leptin contributes to in utero development of ingestive behavior.

Animals↗

PubMed2001

Effects of central angiotensin II receptor antagonism on fetal swallowing and cardiovascular activity.

OBJECTIVE: Fetal plasma angiotensin II levels are 10 times the levels found in adults. Despite these high levels, central injection of angiotensin II may stimulate fetal swallowing and increase fetal arterial blood pressure. We postulated that the high rate of spontaneous fetal swallowing and normal fetal pressor regulation may be dependent, in part, on central angiotensin II. In view of the potential dipsogenic role of both type 1 and type 2 angiotensin II receptors, we examined the central effect of the nonselective angiotensin II receptor antagonist saralasin on fetal swallowing and cardiovascular responses. STUDY DESIGN: Six time-dated pregnant ewes and fetuses were chronically prepared with fetal vascular and intracerebroventricular catheters, electrocorticograms, and esophageal electromyogram electrodes and studied at 130 +/- 1 days' gestation. After an initial 2-hour baseline period (0 to 2 hours), saralasin (1 mL, 64 microg) was injected intracerebroventricularly (2 to 4 hours). After 4 hours the dose of saralasin was repeated together with angiotensin II (1 mL, 6.4 microg), and the fetuses were monitored for a final 2 hours. Four fetuses also underwent an identical control study (on an alternate day) in which saralasin was replaced with artificial cerebrospinal fluid. RESULTS: Blockade of central angiotensin II receptors by intracerebroventricular saralasin significantly reduced mean (+/- SEM) spontaneous fetal swallowing (1.3 +/- 0.1 to 0.4 +/- 0.1 swallows per minute; P <.001) but did not alter fetal mean blood pressure (50 +/- 5 versus 56 +/- 5 mm Hg). Intracerebroventricular angiotensin II, in the presence of saralasin, did not affect swallowing (0.6 +/- 0.1 swallows per minute) or fetal blood pressure. In the control study, intracerebroventricular artificial cerebrospinal fluid did not change fetal swallowing (0.9 +/- 0.1 versus 1.0 +/- 0.1 swallows per minute), whereas intracerebroventricular angiotensin II significantly increased swallowing activity (1.0 +/- 0.1 versus 2.0 +/- 0.1 swallows per minute; P <.001) and fetal blood pressure (51 +/- 2 to 59 +/- 3 mm Hg; P =.003). CONCLUSIONS: Tonic activity of central angiotensin II receptor stimulation contributed to the high rate of basal ovine fetal swallowing but not fetal basal blood pressure. Angiotensin II-mediated fetal dipsogenic and pressor responses are a result of specific angiotensin II receptor binding in central brain regions. These results indicate that fetal exposure to angiotensin II antagonists or angiotensin-converting enzyme inhibitors may have adverse effects on fetal and amniotic fluid homeostasis.

Analysis of Variance↗

PubMed2001

Expression of aquaporin-8 in human placenta and chorioamniotic membranes: evidence of molecular mechanism for intramembranous amniotic fluid resorption.

OBJECTIVE: The intramembranous pathway of amniotic fluid absorption has recently been recognized as a critical regulatory path for amniotic fluid resorption, which contributes importantly to amniotic fluid volume homeostasis. Yet, the underlying molecular and cellular mechanisms for water absorption across the amniotic membranes remain unknown. We hypothesize that amniotic fluid water is absorbed across aquaporin water channels in the chorioamniotic membranes. Recently the water channel aquaporin-8 complementary DNAs for mice, rats, and humans have been cloned; and aquaporin-8 has been found to be expressed in the placenta and in other organs. The objective of the present study was to determine whether aquaporin-8 is expressed in human chorioamniotic membranes. STUDY DESIGN: Freshly frozen human amnion, chorion, placenta, and umbilical cord of a normal term pregnancy were used in this study. Reverse transcriptase-polymerase chain reaction was used to determine the aquaporin-8 gene expression. In situ hybridization with biotin-labeled aquaporin-8 riboprobe was undertaken to localize the cellular expression of aquaporin-8 gene in these human fetal membranes. RESULTS: Using reverse transcriptase-polymerase chain reaction, we have demonstrated that aquaporin-8 is expressed in human amnion, chorion, and placenta. Further studies of in situ hybridization of aquaporin-8 identified aquaporin-8 gene expression in epithelial cells of chorion and amnion and of the syncytiotrophoblasts and outer layer trophoblasts of placenta. CONCLUSION: This is the first study that demonstrates the expression of aquaporin-8 water channel in human chorioamniotic membranes. These results suggest that aquaporin-8 may be a water channel that mediates amniotic fluid resorption by way of the intramembranous pathway.

Amnion↗

PubMed2001

Fetal urine and amniotic fluid in monochorionic twins with twin-twin transfusion syndrome: simulations of therapy.

OBJECTIVE: Therapy for twin-twin transfusion syndrome includes amnioreduction, septostomy, and laser ablation, but there is no accepted standard of care. Mechanisms for the reported improvement in survival are incompletely understood. We sought to model the mechanisms and predict the response of varying severities of twin-twin transfusion syndrome and placental angioarchitectures to current therapies to determine optimal clinical interventions. STUDY DESIGN: We used our mathematic model of twin-twin transfusion syndrome that predicts fetal and amniotic fluid abnormalities that are related to the placental angioarchitecture. Amnioreduction was modeled as reduction in amniotic fluid volume; septostomy was modeled as the merging of donor and recipient amniotic fluid, and laser ablation was modeled as the cessation of all placental anastomotic blood flows. RESULTS: Amnioreduction reduces amniotic fluid pressure, which improves transplacental fluid flow from mother to fetus and increases both donor and recipient blood volume. However, net arteriovenous transfusion increases, because of increased donor arterial pressure, which negates, in part, the benefit of amnioreduction. Septostomy allows amniotic fluid to be swallowed by the donor, with minimal effects on donor growth and blood volume. Laser ablation eliminates anastomotic exchange of blood and reduces discordant fetal growth. CONCLUSION: Amnioreduction may be effective in milder twin-twin transfusion syndrome pregnancies but ineffective in severe cases. Septostomy is unlikely to offer significant therapeutic efficacy. Laser ablation is equally effective in mild and severe twin-twin transfusion syndrome but has a higher spontaneous abortion rate than amnioreduction. The model indicates improved outcomes with the use of amnioreduction in mild twin-twin transfusion syndrome cases and with laser ablation in severe cases.

Amniocentesis↗