Acute effects of maternal ethanol infusion on fetal cardiac performance

In adult animals and man, both acute and chronic ethanol intake is associated with depression of myocardial performance. Accordingly, the cardiac effects of maternal ethanol infusions, in a manner comparable to common obstetric practice for inhibition of premature labor, were evaluated in six chronically instrumented fetal sheep. Fetal and ewe arterial Po₂, Pco₂, and pH values remained within normal limits with infusion rates of 15 c.c. per kilogram of 10 per cent ethanol over two hours (blood ethanol = 110 mg. per cent) and 15 c.c. per kilogram over one hour (blood ethanol = 210 mg. per cent). Fetal instrument evaluation (for 14 to 30 days after operation) provided data concerning pressures and cardiac dimensions which allowed analysis of left ventricular performance. Ethanol produced a significant depression of the extent (p < 0.01) and velocity (p < 0.001) of left ventricular myocardial fiber shortening as well as in the mean rate of left ventricular circumferential fiber shortening (p < 0.01). These indices of cardiac contractility were depressed in the absence of changes in end diastolic diameter, left atrial pressure, and systemic arterial pressure. Thus, the practice of inhibition of premature labor with ethanol might contribute to depressed myocardial performance in the neonatal period.     

Effect of propranolol infusion on the umbilical and uterine circulations of pregnant sheep.

Propranolol was infused intravenously for 60 minutes to five ewes (4 mug per kilogram per minute) or five fetal sheep (10 mug per kilogram per minute). The umbilical blood flow was significantly decreased by 18 per cent from control at 60 minutes with either maternal or fetal propranolol infusion. Uterine blood flow and maternal and fetal mean arterial pressure did not significantly change. Maternal and fetal heart rates decreased 18 and 9 per cent from control, respectively, during maternal propranolol infusion. With propranolol to the fetus, fetal heart rate decreased 15 per cent and maternal heart rate did not change. During all infusion, maternal and fetal arterial pH, PCO2 and PO2 remained within normal physiologic limits.     

Thromboxane Receptor Blockade Causes Acidemia in the Ovine Fetus

The placenta produces the vasoactive eicosanoids thromboxane and prostacyclin. We hypothesized that fetal administration of SQ 29,548, a thromboxane receptor blocker, would lack direct cardiorespiratory effects in the ovine fetus. Continuous monitoring of maternal and fetal heart rates, blood pressures, and common umbilical artery blood flow was performed in six chronically catheterized pregnant ewes. Serial maternal and fetal arterial blood gases and serum lactates were obtained. After 120 minutes of infusion, a significant decrease in fetal mean arterial pressure and a significant increase in fetal heart rate was observed. A significant decrease in fetal arterial pH (7.41 ± 0.02 to 7.33 ± 0.02), PO₂ (26.8 ± 3.2 to 19.8 ± 3.4), HCO₃^? (27.2 ± 1.5 to 24.9 ± 2.0), and base excess (2.9 ± 1.6 to 0.2 ± 2.3) with a significant elevation in PCO₂ (45.4 ± 2.6 to 50.1 ± 3.3) occurred after 120 minutes of SQ 29,548 infusion. SQ 29,548 infusion caused a significant decrease in common umbilical artery flow, from 249.4 ± 19.4 ml ± min^?1 ·; kg^?1 fetal weight to 178.3 ± 17.9 ml · min^?1 · kg^?1 fetal weight at 120 minutes. Fetal blood lactate levels were significantly elevated from 22.0 ± 3.1 to 54.1 ± 3.8 mg/dL after 120 minutes of SQ 29,548 infusion. Prolonged infusion of SQ 29,548 results in umbilical-placental hypoperfusion and significant alterations in acid-base balance in the ovine fetus.     

Human fetal and maternal oxygen tension and acid-base status during delivery at high altitude

The oxygen tension and acid-base status of the mother and fetus have been studied at delivery in 12 subjects from Lima (150 meters above sea level) and Cerro de Pasco (4,200 meters above sea level), Peru. Despite the low Po₂ (60.7 ± 2 mm. Hg, mean ± S.E.) of maternal arterial blood at high altitude, the tension of oxygen measured in microsamples of arterialized capillary blood from the fetal scalp was similar at high altitude (19.0 ± 1.16 mm. Hg) and sea level (21.5 ± 1.12 mm. Hg). The fetus at high altitude is born with a mixed acid-base disturbance that combines a respiratory alkalosis (Pco₂ = 29.8 ± 3.4 mm. Hg) with a metabolic acidosis (base deficit = 7.4 ± 1.6 mEq. per liter and a pH similar to that found at sea level. The low fetal Pco₂ correlates well with the decreased maternal Pco₂ at high altitude, which is due to the additive effect of the hyperventilations of altitude and pregnancy (r = 0.77, p < 0.001.) There is a high degree of correlation between the maternal Pco₂ and the fetal base excess (r = 0.73, p < 0.001). The possible role of these findings on the increased neonatal mortality rate at high altitude is discussed.     

The effect of atropine on heart rate and oxygen consumption of the hypoxic fetus

To determine if vagal blockade during hypoxic bradycardia improves fetal oxygenation, 10 studies were carried out on five chronically instrumented sheep after 0.8 week of gestation. At a mean maternal arterial oxygen tension of 33 ± 4 mm Hg, the fetal heart rate decreased 20% to 137 ± 19 bpm, and fetal oxygen consumption decreased 42% to 4.6 ± 1.5 ml/min/kg of fetus. After 200 μg atropine was infused into a fetal vein, fetal heart rate increased immediately to 249 ± 26 bpm. Fetal oxygen consumption was unchanged. Fetal heart rate increased by 18 bpm after atropine in the normoxic fetus. These studies show that there is a substantial bradycardia due to an increase in vagal activity during hypoxia in the fetus and that blockade of this activity causes a marked tachycardia but no increase in fetal oxygen uptake.     

Alpha and beta adrenergic receptor activity in fetal sheep

Fetal circulatory responses to infusions of isoproterenol and methoxamine were measured in 16 fetal sheep with weights between 138 grams and 4.75 kilograms. During isoproterenol infusion in 9 animals, heart rate increased from a mean of 196 to 247 and mean umbilical blood flow increased from 211 to 269 ml. per kilogram per minute. Cardiac output, measured by radionuclide labeled microspheres, did not change significantly but was redistributed with preferential flow to the placenta and myocardium. During methoxamine infusion in 7 studies, mean arterial pressure increased from a mean value of 46 mm. Hg to 56 mm. Hg and mean unbilical blood flow decreased from 217 to 177 ml. per kilogram per minute. Cardiac output decreased in all animals (mean decrease, 22.5 per cent). Renal blood flow decreased out of proportion to the change in cardiac output; the proportion of cardiac output supplying the lungs increased, and in 6 animals actual flow to the lungs also increased.     

Maternal and fetal effects of exchange transfusion with a red blood cell substitute

Recent reports have demonstrated the efficacy of Fluosol-DA (20%) as a temporary erythrocyte substitute. We investigated two groups of pregnant ewes that underwent exchange transfusion. In group 1, the animals underwent a nearly total isovolemic exchange of Fluosol-DA (20%) for maternal whole blood; in group 2, the red blood cells were removed and the plasma along with Ringer's lactate was replaced isovolumetrically. Although group 1 animals received 100% oxygen and Fluosol-DA (20%), the maternal arterial Po₂ increased to 350 to 400 torr. However, the maternal blood oxygen content decreased during the exchange, with no change in fetal pH, Pco₂, or hematocrit. Maternal blood pressure remained stable and there was a 40% to 50% increase in cardiac output and mean pulmonary arterial pressure. During the exchange, the maternal hematocrit decreased from a mean of 32% to 5.5%; the maternal fluorocrit at the end of the exchange was 9%. Throughout the Fluosol-DA (20%) exchange, the proportion of fetal brain oxyhemoglobin as estimated from infrared transcranial transmittance increased, as did the fetal blood Po₂ and oxygen content. In group 2, the maternal mean blood pressure decreased, and the hematocrit decreased from a mean of 32% to 8%. Despite an increase in the maternal Po₂ to 250 torr, the fetal Po₂ and oxygen content decreased in group 2. This investigation demonstrated that Fluosol-DA (20%) exchange of the mother does not impair delivery of oxygen to the fetus under the conditions of the study.     

Endocrinological and Biophysical Responses to Further Reduction in Oxygenation Following Sustained Hypoxemia in Fetal Goats

Objective: The purpose of this study was to determine fetal endocrinological and biophysical responses to the further reduction in oxygenation following prolonged nonacidemic hypoxemia in fetal goats.

Methods: Seven further hypoxic experiments were performed after prolonged (24-h) nonacidemic hypoxemia, caused by an infusion of nitrogen into the maternal trachea and by reducing uterine arterial blood flow in four chronically instrumented goat fetuses at 123–131 days' gestation. We measured arginine vasopressin, adrenocorticotropic hormone, cortisol, and cathecolamines as endocrinological parameters. Fetal heart rate, fetal blood pressure, and fetal breathing movement were observed as biophysical parameters.

Results: Fetal arterial pO₂ was significantly decreased from 27.0± 1.2 mmHg (control) to 18.0 ± 0.7 mmHg and 11.3 ± 1.3 mmHg at the end of the prolonged hypoxemia and the further hypoxia, respectively. The further hypoxia induced reductions in fetal heart rate, increases in fetal blood pressure, and a series of gasping. Arginine vasopressin and cathecolamines were elevated significantly by the further hypoxia. Although adrenocorticotropic hormone and cortisol were increasingly elevated, they did not reach a significant level.

Conclusions: Some specific fetal responses—excessive elevations of fetal cathecolamines, arginine vasopressin, accompanied with fetal gasping—were observed during further severe hypoxia.     

Liver Blood Perfusion as a Possible Instrument for Fetal Growth Regulation

Placental and fetal liver blood perfusions are reduced in intrauterine growth-restricted human fetuses. We hypothesized that changes in fetal liver blood supply can alter fetal growth. In nine ewes with twin pregnancies at a gestational age of 119±2 days, a stent (4 mm) was placed into the ductus venosus of one twin (DV_stent group). Alternatively, in 17 near term sheep with twin (n=11) or singleton (n=6) pregnancies, a DV was blocked with an embolization coil (DV_coil group) for about one week. The cell proliferation rate (pKi-67) was determined in the liver, heart, skeletal muscle, kidneys and placenta. The dilatation or occlusion of the DV did not change placental perfusion on the first day or later after surgery. The liver blood supply was decreased in the DV_stent group by more than half from 499±371 to 278±219 ml min⁻¹ (mean±s.d., n=4), and increased two-fold in the DV_coil group (P< 0.05). The percentage of liver/body weight was decreased from 3.9±0.6 per cent in control twin to 3.0±0.2 per cent (n=3) in the DV_stent group. Occlusion of the DV lead to an increase in the percentage of liver/body weight from 3.4±0.8 per cent to 4.3±0.8 per cent (n=11, P< 0.05). Reduced liver blood supply in the DV_stent group was associated with a decrease of cell proliferation in the liver from 12.43±2.31 to 6.5±0.62 (nuclei μm² 10⁻⁴, n=3, P=0.058), in heart from 1.14±0.03 to 0.93±0.02 (nuclei μm² 10⁻⁴, P< 0.05), and in skeletal muscle from 0.82±0.05 to 0.54±0.01 (nuclei μm² 10⁻⁴, P< 0.05). The increased liver blood perfusion following occlusion of the DV increased cell proliferation sixfold in the liver, (n=9, P< 0.005) and twofold in heart muscle, skeletal muscle and the kidneys (P< 0.05), whereas no significant difference was seen in the placenta. The expression of mRNA for IGF-I and IGF-II in the liver was increased in the DV_coil group. In conclusion, these results suggest that liver blood perfusion can regulate fetal growth.     

Hypotension due to spinal anesthesia influences fetal circulation in primary caesarean sections

Purpose

Hypotension due to spinal anesthesia is a well-known side effect in pregnant women receiving caesarean section. Little is known about its impact on fetal blood circulation.

Methods

40 women with uncomplicated singleton term pregnancies prepared for caesarean section were prospectively evaluated by Doppler sonography before and immediately after spinal anesthesia.

Results

In 90% of the women, blood pressure significantly decreased after spinal anesthesia and 42.5% of the patients suffered from severe hypotension. We found a significant negative correlation between maternal blood pressure change and the resistant index (RI) of the umbilical artery (r_s = ? 0.376, p = 0.017) and a significant positive correlation between maternal blood pressure and fetal middle cerebral artery.

Conclusion

Healthy fetuses seem to compensate well in situations with decreased uteroplacental blood flow due to maternal hypotension measured by means of RI changes in the fetal umbilical and middle cerebral artery. This raises the question if growth-restricted and/or preterm fetuses are able to compensate similarly or if general anesthesia would be a method of choice.

     

The effect of epidural analgesia upon fetal and neonatal status

The effect of epidural analgesia on the fetal and neonatal status was studied in 72 patients who received a standard epidural block during labor. Recordings were made of maternal blood pressure, fetal heart rate, and uterine contractions. Observations on the neonates continued to the day of discharge from the hospital. A control group of 100 patients who received either no analgesia during labor or a form of pain relief other than epidural block was also studied. The control patients were monitored for obstetric indications and therefore are not strictly comparable to the study group. The study group of patients was subdivided into 4 groups (SG1 to SG4). Twenty-four patients in SG2 received oxytocin and did not develop hypotension; 7 patients in SG3 did not receive oxytocin and developed hypotension; 20 patients in SG4 neither received oxytocin nor developed hypotension. Significant fetal heart rate (FHR) decelerations were seen in 55 per cent of the study patients; these occurred most frequently in those patients who developed hypotension (71 per cent) but also developed in 40 per cent of those patients whose blood pressure remained stable. The most common significant FHR pattern was that of late deceleration, occurring in 33.3 per cent of the study group of patients. Of the neonates from the study group of mothers, 9.7 per cent had low Apgar scores compared to 17 per cent of the control neonates. The majority recovered shortly after the 5 minute Apgar observation and continued normally until the day of discharge.     

Alterations in maternal corticosteroid levels influence fetal urine and lung liquid production

OBJECTIVE: This study was designed to test the hypotheses that disruption of maternal adrenal secretion in late pregnancy requires fetal adaptations in order to maintain fetal blood volume and fetal viability. METHODS: Pregnant ewes were adrenalectomized at approximately 112 days, and cortisol and aldosterone were replaced to either normal pregnant levels (with 1 mg/kg per day of cortisol and 3 microg/kg per day of aldosterone) or normal nonpregnant levels of aldosterone or cortisol (0.5 mg/kg per day of cortisol or 1.5 microg/kg per day of aldosterone). RESULTS: Fetal blood volume, blood pressure, lung liquid production, urine production, free water clearance, and glomerular filtration rate were measured at 130 days. In a separate group, fetal organ blood flow was measured. Fetal blood volume was not significantly decreased by disruption of maternal corticosteroid secretion. However fetal urine production and free water clearance were reduced in fetuses of low cortisol or low aldosterone ewes. Fetal lung liquid secretion was also significantly reduced in the low aldosterone group. The glomerular filtration rate was reduced in fetuses of all adrenalectomized ewes, regardless of replacement dose. Fetal blood pressure was significantly reduced in the fetuses of low aldosterone ewes; blood flow to several fetal organs was increased in this group, indicating that decreased vascular resistance may contribute to the relative hypotension. CONCLUSION: Alterations in maternal adrenal corticosteroid levels resulted in fetal adaptation to maintain fetal blood volume despite relative maternal hypovolemia. These adaptations occurred at the expense of fetal urine and lung liquid production.     

Relationship of fetal oxygen consumption and acid-base balance to fetal hematocrit

We evaluated the effects of alterations in fetal hematocrit on fetal oxygenation in 10 chronically catheterized fetal lambs. Hematocrit was varied from 10% to 55% by slow isovolemic exchange transfusions with plasma or packed red blood cells obtained freshly from donor fetuses. At each hematocrit studied, we measured umbilical blood flow (Q̇_umb) and the oxygen concentrations in umbilical venous blood (Cuv_O2) and arterial blood (Ca_O2) and calculated fetal oxygen delivery (Q̇_umb · Cuv_O2), oxygen extraction [(Cuv_O2 − Ca_O2], and oxygen consumption [Q̇_umb (Cuv_O2 − Ca_O2)]. Fetal oxygen delivery was maximal at a fetal hematocrit of 33% (mean oxygen delivery = 23 ml of oxygen per minute per kilogram of fetus) and decreased as hematocrit was raised or lowered from that value. Despite these reductions in oxygen delivery, fetal oxygen consumption was relatively stable (at about 7 ml of oxygen per minute per kilogram) at hematocrits ranging from about 16% to 48% because of compensatory increases in fetal oxygen extraction. Regardless of whether oxygen delivery decreased because of anemia or polycythemia, fetal oxygen consumption was maintained as long as oxygen delivery was greater than about 14 ml of oxygen per minute per kilogram of fetus. When oxygen delivery was <14 ml of oxygen per minute per kilogram, fetal oxygen consumption fell while arterial blood base deficit increased, indicating that oxygen supply was inadequate for fetal oxygen demands. These results indicate that fetal aerobic metabolism can be sustained over a wide range of fetal hematocrits. Furthermore, our data support the concept that the level of fetal oxygen delivery is an important determinant of the adequacy of fetal oxygenation.     

Borderline hypotension: how does it influence cerebral regional tissue oxygenation in preterm infants?

Aim: To monitor cerebral regional tissue oxygenation (crSO₂) of preterm infants continuously and to analyze the influence of arterial hypotension on crSO_2.

Methods: In this prospective, observational study crSO₂, peripheral oxygen saturation (SpO₂), heart rate (HR) and mean arterial blood pressure (MABP) were monitored continuously for 24?h, starting within the first 6?h after birth. Furthermore, cerebral fractional tissue oxygen extraction (cFTOE) was calculated. Preterm neonates with and without arterial hypotension (MABP below the gestational age in weeks) were compared to each other.

Results: Forty-six preterm infants could be analyzed, 17 with (33.4?±?1.9 weeks, 2016.5?±?548.5?g) and 29 without arterial hypotension (33.3?±?1.3 weeks, 1924.7?±?451.9?g). Altogether, we detected 30 episodes of hypotension, with a mean duration of 1.6?±?1.2?h per infant and a mean decrease in MABP of 2.2?±?0.9?mmHg. During hypotension mean crSO₂ was 7 5?±?11%, 2?h prior to that 76?±?10% and 2?h after the hypotension 7 7?±?10%, therefore no significant alterations could be observed. Moreover, there was no significant difference in mean 24-h crSO₂, SpO₂ and cFTOE between the two groups.

Conclusion: Mild short-term hypotensive episodes in preterm infants did not affect crSO₂. This suggests that cerebral autoregulation is maintained in case of borderline-hypotension and may protect infants from cerebral injury.     

Immunosuppression during pregnancy: transmission of azathioprine and its metabolites from the mother to the fetus

After oral administration of ³⁵S-azathioprine (³⁵S-AT) to 3 women during the ninth, fourteenth, and fifteenth weeks of pregnancy, the radioactivity in fetal blood was 64 to 93 per cent of that in maternal blood at abortion 150 to 360 minutes later. In chromatography, most of the label (48 to 63 per cent) in fetal blood moved like the uric acid reference, representing thiouric acid, a metabolite of AT. In maternal blood, three major components were found: thiouric acid (27 to 41 per cent), 6-mercaptopurine (6-MP) (14 to 27 per cent), and AT (21 to 28 per cent). The placenta and amniotic fluid contained mostly thiouric acid (41 to 49 per cent), but 6-MP (5 to 13 per cent) and AT (9 to 25 per cent) were also present. Both transplacental and transamniotic transmission of AT and its metabolites from the mother to the fetus seem possible.     

The effect of acute maternal hypoxia on fetal oxygenation and the umbilical circulation in the sheep

The mean oxygen consumption was 8.4 ± 1.9 ml/min/kg in the near-term fetal sheep. In response to acute maternal hypoxia fetal O₂ consumption decreased to lower than 50% of the control values. The decrease was rapidly instituted, proportional to the degree of hypoxia, sustained for up to 47 min and stable over this period. With increasing duration of hypoxia, a progressive metabolic acidosis developed. Recovery of oxygen consumption occurred rapidly after hypoxia ceased, though the acidosis was not resolved until 2 h later. Umbilical blood flow was maintained during maternal hypoxia and umbilical arterial and venous pressures increased. A fetal bradycardia invariably accompanied the hypoxia.     

Effect of Oxymorphone Hydrochloride on Ovine Fetal Heart Rate Variability

In order to determine the effect of the narcotic analgesic oxymorphone hydrochloride (Numorphan, DuPont) on fetal heart rate (FHR) variability, mathematical indices of short-term and long-term FHR variability were determined continuously from R–R intervals of the electrocardiogram in eight chronically instrumented ovine fetuses for 60 min before and after a maternal intravenous bolus of 0.04 mg/kg oxymorphone. The index of short-term variability decreased from 12.7 ± 2.0 during control to 9.7 ± 1.7 during the period from 10 to 30 min after oxymorphone administration during periods of low-voltage, high-frequency electrocortical activity (LVHF ECoG) (P < 0.05). Mean FHR was decreased from 169 ± 8 beats per minute (bpm) during control to 155 ± 7 bpm 30 to 50 min after oxymorphone (P < 0.05). Fetal electrocortical activity was also determined and the decrease in FHR short-term variability occurred despite an increase in the percent time spent in LVHF electrocortical activity from 53 ± 4% during the control period to 74 ± 5% after the oxymorphone injection (P < 0.05). Long-term FHR variability was unaffected by the oxymorphone administration. This study indicates that maternal administration of oxymorphone hydrochloride causes decreased short-term fetal heart rate variability in sheep.     

Sulfate Transfer in the Dually Perfused Human Placenta

Sulfate is utilized by fetus and placenta in a variety of biosynthetic reactions essential to normal growth and development. At birth, cord blood sulfate concentrations are higher than in the maternal circulation, suggesting a concentrative mechanism across the maternal/fetal interface. To examine the role of the placenta in this transport, we perfused human placentas within an hour of delivery and measured fluxes of an amino acid marker, L-leucine, and radiolabeled (³⁵SO₄) sulfate anion between maternal (open) and fetal (closed) circuits. Under these conditions, leucine rapidly accumulated in the closed fetal compartment, reaching a maximal fetal/matemal ratio of 1.88 ± 0.23 (mean ± SE). In contrast, net accumulation of ³⁵SO₄ was not observed, although net SO₄ efflux from the maternal circuit was modestly higher than that from the fetal compartment. The fetal/maternal ³⁵SO₄ ratio varied between 0.97 ± 0.04 (n = 10) at the lowest and 1.03 ± 0.06 at the highest in samples taken every 20 min over more than 2 h of perfusion.

In six of seven preparations, ³⁵SO₄ was modestly but significantly concentrated in the perfused placental tissue [a tissue-to-medium ratio of 1.22 ± 0.10 (n = 7, P < 0.05)]. Approximately 15% of the tissue label was acid-precipitable, indicating that accumulation of label was the result of incorporation into macromolecules. We conclude that maternal-to-fetal sulfate transport is not concentrative in the perfused placenta under conditions that support accumulation of leucine and sulfoesterification of macromolecules. Other mechanisms must be considered to account for the sulfate gradient across the human placenta at term.     

Cardiovascular Responses to Neuromuscular Blockade in the Anemic Ovine Fetus

Currently little is known about the cardiovascular responses of the anemic fetus to neuromuscular blockade. We hypothesized that, despite marked anemia with potentially decreased cardiac reserve, the fetal responses to Pancuronium neuromuscular blockade would differ significantly when compared with neuromuscular blockade with Atracurium (a cardiovascular sparing agent). Ten fetal sheep (137 ± 1 (SE) days gestation) were divided into three groups (21 experiments): Pancuronium (n = 7), Atracurium (n = 6), and Control (n = 8). Fetal anemia (Hct = 21.8 ± 0.7%) was produced by serial hemorrhage over 3 days. Fetal arterial (FAP) and venous (FVP) pressures, heart rate (FHR), and arterial pH, pO₂, and pCO₂ were measured at ?20, 0, 10, 20, 30, 60, and 90 minutes relative to neuromuscular blockade. Data were analyzed by three-way ANOVA for repeated measures. Pancuronium neuromuscular blockade increased FHR (15–20 bpm, P <. 0001) and decreased FVP (-0.8 mm Hg, P <. 0001). Atracurium had no effect on FHR, FAP, or FVP. Fetal pH (0.024, P <. 0001) and pO₂ (1-2 mm Hg, P =. 0001) increased in both neuromuscular-blocked groups. Fetal pCO₂ decreased in the Pancuronium-blocked animals (P =. 02). We conclude that, in anemic fetuses, neuromuscular blockade with Atracurium produced minimal cardiovascular effects when compared to neuromuscular blockade with Pancuronium. Both agents produced small improvements in fetal pH and blood gases.     

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 μg/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.