The effect of chemical sympathectomy on catecholamine release at birth.

The precise source of circulating catecholamine (CA) at birth and their role in circulatory adaptation is unclear. In order to determine the contribution of increased postganglionic sympathetic nerve activity to the CA surge at birth, we induced complete sympathectomy in near term fetal lambs prior to delivery by giving 6-hydroxydopamine. Chronically catheterized fetal sheep received either 6-hydroxydopamine (n = 5) or control infusion (n = 6).

Autoimmune sympathectomy in fetal rabbits.

An autoimmune model for in utero immunosympathectomy of fetal rabbits was developed. Non-pregnant, female rabbits were injected with purified nerve growth factor and then bred after confirmation of high titers of anti-nerve growth factor antiserum. Fetuses were delivered and sacrificed at 27 and 31 days gestation and tissue norepinephrine concentration was used as an index of sympathetic innervation.

Metabolic clearance and plasma appearance rates of catecholamines in preterm and term fetal sheep.

Plasma catecholamines increase markedly during labor and delivery. Moreover we have noted greater increases at birth in preterm than term lambs. It was unclear whether these differences were due to differences in secretion or clearance.

Effects of amiodarone and desethylamiodarone on rabbit myocardial beta-adrenoceptors and serum thyroid hormones--absence of relationship to serum and myocardial drug concentrations.

The antiadrenergic actions of amiodarone (Am) are well known but its effect and that of its metabolite, desethylamiodarone (DAm), on beta-receptor density (Bmax) and affinity (KD) are poorly defined. Thus, the acute and chronic effects of Am and DAm on myocardial beta-receptors in rabbits were determined relative to changes in thyroid hormones and serum and tissue drug concentrations. Bmax and KD were measured by radio-ligand binding, thyroid hormones by RIA, and drug levels by HPLC.

Involvement of developing sympathetic nervous system in thyroxine-mediated submandibular gland nerve growth factor and epidermal growth factor responses.

Thyroxine (T4) administration in mice during the 2nd wk of postnatal life elicits a precocious increase in submandibular gland-nerve growth factor (SMG-NGF) and epidermal growth factor (SMG-EGF) levels, but the mechanism(s) of T4 action has not been studied. The present report examines the role of the developing sympathetic nervous system (SNS) in the SMG-NGF and EGF responses to T4. For this purpose newborn mice were injected with T4 and/or 6-hydroxydopamine, a toxic congener of norephinephrine which causes selective destruction of sympathetic nerve terminals.

Differential response of ovine placental lactogen levels in maternal and fetal circulations following single umbilical artery ligation in fetal sheep.

We investigated circulating maternal and fetal serum concentrations of ovine placental lactogen (oPL) following single umbilical artery ligation (SUAL) at 108 to 114 days' gestation. Ovine placental lactogen was isolated and purified from placental cotyledons, and a radioimmunoassay developed using previously described methods. Intrauterine growth retardation (IUGR) was manifest as increasing fetal brain-to-liver weight ratio with increasing duration of survival following SUAL.

Effect of thyroid status on lung and heart beta-adrenergic receptors in fetal and newborn sheep.

The effect of altered thyroid status on the development of beta-adrenergic receptor (BAR) density and affinity was investigated in ovine fetal and newborn heart and lung. Fetal (119-121 days gestation) and newborn (2-3 days of age) sheep underwent either thyroidectomy alone, thyroidectomy plus infusion of a large dose of T3 or sham operation. Eight days later BAR were measured in heart and lung using the tritiated radioligand dihydroalprenolol.

Neonatal adaptation: greater sympathoadrenal response in preterm than full-term fetal sheep at birth.

A marked increase in sympathoadrenal activity at birth has been described in animals and humans. Studies to determine whether the magnitude and duration of the catecholamine surge at birth in preterm lambs is similar to full-term lambs were undertaken using an acutely exteriorized fetal lamb. To maintain a physiologically stable preparation, all preterm lambs were given natural sheep surfactant intratracheally before the first breath.

Fetal catecholamine release with preterm delivery.

Neurosympathetic system activity at birth was studied by measuring umbilical arterial plasma catecholamine concentrations in 36 preterm fetuses. Umbilical arterial catecholamine concentrations were correlated with blood gas status, mode of delivery, fetal sex, and fetal heart rate patterns. Significant correlations were observed for plasma norepinephrine and epinephrine versus fetal pH and PO2 and for plasma dopamine versus pH but not PO2.

Thyroid hormones augment catecholamine-stimulated brown adipose tissue thermogenesis in the ovine fetus.

The effects of exogenous changes in thyroid status on in vitro brown adipose tissue (BAT) cellular respiration and thermogenic enzymes (sodium-potassium ATP' ase and alpha-glycerophosphate dehydrogenase) were studied in fetal sheep. Thyroidectomy and insertion of a constant infusion pump followed by 8 days of infusion of either T3 (n = 7) or vehicle (n = 4) were performed in fetal lambs at 119-121 days gestation. The animals were then killed, and perirenal BAT was removed for study.

Adrenal epinephrine and the regulation of pulmonary surfactant release in neonatal rabbits.

Adrenergic mechanisms influence surfactant metabolism; however the nature and importance of catechol-mediated regulation is unclear. We designed experiments to assess the role of endogenous adrenal epinephrine (E) synthesis in neonatal alveolar surfactant release. We administered the experimental adrenal epinephrine synthesis inhibitor SKF 29661 to pregnant rabbits to reduce fetal adrenal E content.

Effect of changes in thyroid status on tissue respiration in fetal and newborn sheep.

The effect of both exogenous and endogenous changes in thyroid status on in vitro tissue respiration and thermogenic enzymes (sodium-potassium-adenosine triphosphatase and alpha-glycerophosphate dehydrogenase) was studied in fetal and newborn sheep. Oxygen consumption of liver and brain increased from 25 +/- 4.1 and 58.

Identification and partial purification of phenylethanolamine N-methyl transferase in the developing ovine lung.

Phenylethanolamine N-methyl transferase (PNMT), the terminal enzyme in epinephrine biosynthesis, was identified in fetal and newborn ovine lung. The ovine lung PNMT demonstrated the appropriate substrate specificity and affinity (Km, 9 x 10(-6) M). Although some homology between adrenal and lung PNMT was observed on polyacrylamide gel electrophoresis, the lung PNMT differed in its migration on ion exchange chromatography and was not inhibited by pharmacologic inhibitors active against the adrenal enzyme.

Saturated phosphatidylcholine secretion and the effect of natural surfactant on premature and term lambs ventilated for 2 days.

Lambs prematurely delivered by cesarean section and term lambs were supported on ventilators and studied over a period of 2 days. Sequential measurements of ventilatory requirements, lung compliance, and arterial pH, pO2, and pCO2 values documented the course of the lung disease. In five premature lambs the pCO2 increased to 77 +/- 5 mm Hg (mean +/- SE) by 40.

Development of brown adipose tissue thermogenesis in the ovine fetus and newborn.

Despite the importance of brown adipose tissue (BAT) in the regulation of thermogenesis and energy expenditure in both newborn and adult mammals, the functional ontogenesis of this tissue is largely unknown. In the present study, we describe the maturation of several aspects of BAT thermogenesis in fetal and newborn sheep. Cell respiration of brown adipocytes isolated from perirenal BAT was measured using a Gilson differential respirometer.

Ontogenesis and sex differences in rabbit fetal adrenal phenylethanolamine N-methyltransferase.

The development of the sympatho-adrenal system is important for neonatal adaptation to extrauterine life. On the basis of previous studies suggesting relatively accelerated adrenal maturation in the female rabbit fetus, we conducted an ontogenetic study of male-female differences in adrenal levels of phenylethanolamine N-methyltransferase (PNMT), the terminal enzyme in epinephrine biosynthesis. Geometric mean adrenal PNMT activities increased significantly from 5.

Fetal catecholamine release in response to labor and delivery.

Umbilical arterial plasma norepinephrine and epinephrine were measured using a sensitive, specific radioenzymatic assay. Plasma catecholamines were correlated with umbilical arterial blood gases, durations of the first and second stages of labor, duration of rupture of the membranes, fetal heart rate tracings, and fetal sex. Significant correlations were observed for plasma norepinephrine versus fetal pH and PO2 and plasma epinephrine versus pH but not PO2.

Neonatal adaptation: sympatho-adrenal response to umbilical cord cutting.

The present studies were designed to assess the individual effects of delivery and umbilical cord cutting on the stimulation of the sympatho-adrenal system during parturition. Pregnant ewes with time-dated singleton pregnancies were used in an acutely exteriorized fetal lamb model with an intact umbilical circulation. We observed a minimal, transient elevation in plasma catecholamines (CAT) coincident with the operative procedures and delivery.

Ontogenesis of tissue catecholamines in fetal and neonatal rabbits.

The ontogenesis of tissue catecholamine concentrations in heart, lung, brown adipose tissue, adrenal and para-aortic chromaffin tissue was assessed in fetal and newborn rabbits using a radioenzymatic assay adapted to perchloric extracts of tissue. Measurements were conducted at 20, 24, 27 and 31 days gestation and at 3 and 7 days of age. Myocardial norepinephrine was detectable at 20 days gestation, the earliest age studied.

Sex differences in lung and adrenal neurosympathetic development in rabbits.

To assess the possible mechanism for the increased incidence and severity of the respiratory distress syndrome (RDS) in male versus female infants, we studied neurosympathetic development in the lung and adrenal glands in male and female fetal and newborn rabbits. Tissue levels of catecholamines, norepinephrine (NE), epinephrine (E), and dopamine (DA) were measured using a sensitive radioenzymatic assay. Beta adrenergic receptor development in the lung was studied using the tritiated radioligand dihydroalprenolol.

Ontogenesis of beta-adrenergic receptors in the ovine placenta.

Radioligands with high specific activity and high affinity have recently become available to study the beta-adrenergic receptor (BAR). BAR may be important in the placenta for mediating a variety of metabolic and hemodynamic effects of catecholamines including placental hormone synthesis and secretion, placental glycogenolysis, and placental blood flow. Little is known regarding the development of the BAR.

Duration and characteristics of treatment of premature lambs with natural surfactant.

Premature lambs were treated with 50 mg/kg of natural surfactant lipid by tracheal instillation either at birth or shortly thereafter when respiratory failure was documented. All lambs were delivered by cesarean section and supported on infant ventilators with 100% oxygen under conditions to mimic the care of human infants with the respiratory distress syndrome. The natural surfactant used for therapy was recovered by lavage from sheep lung.