Biomedical subjects

M G Ross

Publications and source records attributed to M G Ross.

At least 37 records · Page 2Linked to original sources

PubMed2001

Ovine intramembranous pathway permeability: use of solute clearance to determine membrane porosity.

OBJECTIVE: The contribution of the fetal chorioamniotic membranes (i.e. the intramembranous pathway) to the regulation and maintenance of amniotic fluid (AF) volume and composition has yet to be completely understood. Knowledge of membrane permeability properties is vital to understanding how the intramembranous pathway contributes to the overall maintenance of AF homeostasis. Although there are significant data regarding the regulation of intramembranous water flow, there is little understanding of the regulation of intramembranous solute flow. In the present study, we sought to determine the effect of molecular weight or size of non-polar compounds on intramembranous solute movement in the ovine model. METHODS: Five singleton ovine fetuses (117 +/- 3 days) were chronically prepared with bladder, tracheal, amniotic cavity and femoral arterial and venous catheters and an esophageal occluder. The allantoic membranes were excised. After 5 days' recovery, AF volume was calculated by intraamniotic injection of 99Tc-labelled red blood cells (time -6 to 0 h). At time 0, AF exchange routes were limited to the intramembranous pathway by inflation of the esophageal occluder and external drainage of fetal urine and lung fluid. Following intra-amniotic injection of creatinine (Cr, 1 g, MW 11 000 Da, 4 A) and [125I]albumin (RISA, 250 microCi, MW 69 000 Da, 36 A), maternal and fetal plasma and AF samples were collected at timed intervals during the subsequent 5 h. AF solute clearance (Cl(x)) was determined by the changes in AF total solute content. RESULTS: Cr and RISA disappeared from the AF with a corresponding increase in fetal, though not maternal, plasma levels. The mean Cl(Cr) was significantly greater than Cl(RISA) (2.0 +/- 0.3 ml/min vs. 1.0 +/- 0.2 ml/min; p < 0.04). CONCLUSION: Solute clearance from the amniotic cavity is inversely proportional to solute molecular weight/size. Although the membrane comprising the ovine intramembranous pathway is size restrictive, membrane pores allow passage of non-polar solutes up to 36 A. Knowledge of membrane permeability characteristics is essential for the utilization of the intramembranous pathway for fetal therapeutics.

Amniotic Fluid↗

PubMed2001

National Institute of Child Health and Development Conference summary: amniotic fluid biology--basic and clinical aspects.

This report summarizes the National Institute of Child Health and Development sponsored conference on amniotic fluid (AF) biology, held 28-29 September 1999, in Detroit, Michigan. National and international investigators with expertise in AF biology addressed the regulation of AF volume and composition as well as the clinical aspects of interpreting fetal health and well-being from AF indices. A major purpose of the meeting was to consider future directions and opportunities for basic and clinical research which focus on understanding the physiology and pathophysiology and providing therapeutic interventions for abnormalities of AF volume. To achieve this, the workshop participants addressed the current state of knowledge, recent scientific advances and priorities for major questions for which answers must be sought. The fact that it is not known whether AF volume is regulated or what volume-regulatory mechanisms might be involved is a major problem that needs addressing. In the later half of gestation, potential AF volume-regulatory pathways include the two major inflows into the amniotic compartment, i.e. fetal urine and lung liquid, and the two major outflows, i.e. fetal swallowing and intramembranous absorption. If AF volume is regulated, then this must occur through regulation of intramembranous flow, because the other three flows are regulated by the fetus to meet fetal needs. Regulation of AF composition is similarly unknown. In clinical practice, a variety of ultrasonographic indices of AF volume are used, but the relationships of these indices to AF volume have not been determined, nor have their dependency on fetal size, shape or position within the uterus. Further, although aberrations in AF volume both above and below normal are associated with increased fetal and neonatal morbidity and mortality, the predictive utility of the various AF indices remains low and there is little consensus on which is best utilized under conditions of oligohydramnios, normal AF volumes, or polyhydramnios. Further, various clinical AF therapies remain largely experimental and their optimization and utilization need exploration. This report is a condensation of the views presented by the conference participants.

Amniotic Fluid↗

PubMed2001

Ovine fetal swallowing: expression of preterm neurobehavioral rhythms.

OBJECTIVE: Fetal swallowing contributes importantly to amniotic fluid volume regulation and fetal gastrointestinal maturation. Near-term ovine fetal swallowing occurs in discrete bouts of activity (at approximately 30-min intervals) in association with fetal electrocortical voltage changes. Thus, swallowing rhythms have been hypothesized to be entrained to fetal neurobehavioral states. In the preterm ovine fetus, electrocortical activity does not demonstrate differentiation into high- and low-voltage periods until 120-130 days' gestation. We sought to quantify patterns of preterm (114 days, 0.75 gestation) ovine fetal swallowing activity and volume, and, in view of the lack of electrocortical pattern changes, to explore whether swallowing activity was regulated by an independent central pacemaker. METHODS: Six singleton ovine pregnancies were chronically prepared with fetal and maternal femoral artery and vein catheters. Biparietal electrocortical electrodes were placed on the fetal skull. Following a minimum 5-day recovery period, fetuses were studied at 114 +/- 1 days. Patterns of fetal swallowing behavior were quantified by computer analysis of laryngeal-esophageal electromyography (EMG) and thoracic esophageal fluid flow during a 12-h period. RESULTS: Esophageal fluid flow was bidirectional, although antegrade flow predominated, leading to an average fluid acquisition rate of 13 +/- 3 ml/h (7.3 +/- 1.8 ml/h per kg) during the 12-h study (302 +/- 87 ml/day). Propagated esophageal EMG activity, representing coordinated 'swallows', averaged 56 +/- 6 swallows/h and correlated well with net esophageal fluid flow. 'Bouts' of swallowing activity (> or = 3 swallows/min) averaged 9 +/- 1 swallows/bout, lasted 1.8 +/- 1.4 min and accounted for 31 +/- 4% of the swallowed volume. Despite the absence of fetal electrocortical high-voltage/low-voltage transitions, there was a 26.1 +/- 3.9-min interval between periods of swallowing bout activity. CONCLUSIONS: Preterm (0.75 gestation) ovine fetal volume swallowed (302 ml/day) and volume swallowed for body weight (175 ml/day per kg) was significantly less than that previously noted at 0.85 gestation (831 ml/day, 274 ml/day per kg, respectively; p < 0.05) although the rates of swallowing activity were similar. The presence of swallowing bout activity at periodic intervals, in the absence of electrocortical differentiation, suggests an intrinsic central pacemaker regulating preterm fetal neurobehavior.

Animals↗

PubMed2001

Twin-twin transfusion syndrome: etiology, severity and rational management.

The twin-twin transfusion syndrome is a serious complication of monochorionic twin pregnancies. Partly as a result of an inadequate understanding of the pathophysiology of the syndrome, there is a lack of consensus in clinical management. We sought to review the available information on the etiology of twin-twin transfusion syndrome, to identify parameters that contribute to the severity of the syndrome, and propose a rational management plan based on pathophysiology, clinical presentation and the efficacy of therapies. We therefore amalgamated recent advances in twin-twin transfusion syndrome computer modelling and clinical studies, particularly on therapeutic outcomes. We found that the oligo-polyhydramnios sequence that defines twin-twin transfusion syndrome prenatally represents a wide continuum of severity in the imbalance between the fetoplacental circulations of both twins. In severe twin-twin transfusion syndrome cases, in which the circulatory imbalance deteriorates beyond fetal control, fetoscopic laser therapy of all anastomoses along the placental vascular equator is predicted to have significantly better survival rates and fewer neurological sequelae than amnioreduction. In contrast, mild twin-twin transfusion syndrome cases have better outcomes after one or at most a few amnioreductions than laser therapy, as a result of significantly fewer procedure-related risks. In conclusion, optimal individual therapy may possibly achieve an 85% survival rate in twin-twin transfusion syndrome, but requires advancement in non-invasive criteria that predict the severity of the syndrome. Identifying such criteria is a future challenge. For the interim, twin-twin transfusion syndrome diagnosed before 26 weeks' gestation has significantly better survival rates and fewer neurological sequelae after laser therapy than amnioreduction. Twin-twin transfusion syndrome diagnosed after 26 weeks can best be treated by amnioreduction, or delivery. Contrary to previous claims, fetoscopic laser therapy has outgrown its experimental status. Although improvements in technique and technology are likely, laser placental ablation has a firm scientific and clinical basis.

Amniotic Fluid↗

PubMed2001

Intact osmoregulatory centers in the preterm ovine fetus: Fos induction after an osmotic challenge.

We previously demonstrated a functional systemic dipsogenic response in the near-term fetal sheep (128-130 days; 145 days = full-term) with swallowing activity stimulated in response to central and systemic hypertonic saline. Preterm fetal sheep (110-115 days) do not consistently demonstrate swallowing in response to hypertonic stimuli, and it is unclear whether this is due to immaturity of osmoreceptor mechanisms or neuronal pathways activating swallowing motor neurons. To determine whether osmoreceptive regions in the preterm fetus are activated by changes in plasma tonicity, we examined Fos expression with immunostaining in these neurons in response to an osmotic challenge. Nine preterm fetal sheep [five hypertonic saline-treated fetuses (Hyp) and four isotonic saline-treated fetuses (Iso)] were prepared with vascular and intraperitoneal catheters. Seventy-five minutes before tissue collection, hypertonic (1.5 M) or isotonic saline was infused (12 ml/kg) via an intraperitoneal catheter to fetuses. Brains were examined for patterns of neuronal activation (demonstrated by Fos protein expression). Hyp demonstrated increases in plasma osmolality (~10 mosmol/kg H(2)O) and Na concentrations (5 meq/l). Increased Fos expression was detected in Hyp in the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO), median preoptic nucleus (MnPO), supraoptic (SON), and paraventricular nuclei (PVN) compared with Iso animals. Neuronal activation within the OVLT, SFO, and MnPO indicates intact osmoregulatory mechanisms, whereas activation of the SON and PVN suggests intact fetal neural pathways to arginine vasopressin neurons. These results suggest that preterm fetal swallowing insensitivity to osmotic stimuli may be due to immaturity of integrated motor neuron pathways.

Animals↗

PubMed2001

Amniotic fluid and hemodynamic model in monochorionic twin pregnancies and twin-twin transfusion syndrome.

We developed a mathematical model of monochorionic twin pregnancies and twin-twin transfusion syndrome (TTTS), combining both fetal fluid dynamics and fetoplacental growth and circulation alterations and assuming that transplacental fluid flow from mother to fetus accounts for normal fetal and amniotic fluid volumes. Ten coupled differential equations, describing fetal total body and amniotic fluid volumes, their osmolalities, and fetal blood colloid osmotic pressure, for both donor and recipient twins, were solved numerically. Amniotic flows are controlled by fetal plasma osmolality and hydrostatic and colloid osmotic pressures. We included varying placental anastomoses and placental sharing of the circulations. Consistent with clinical experience, model predictions are: fetofetal transfusion from unidirectional arteriovenous anastomoses cause oligo-polyhydramnios, a normal size recipient but hypovolemic donor; compensating oppositely directed deep and superficial anastomoses moderate discordant development; and anhydramnios results from mild and severe TTTS, where milder forms may even present earlier in gestation than severe TTTS. Unequal placental circulatory sharing may exacerbate discordant development. In conclusion, our model simulates a wide variety of realistic manifestations of amniotic fluid volume and fetal growth in TTTS related to placental angioarchitecture. The model may allow an assessment of the efficacy of current therapeutic interventions for TTTS.

Amniotic Fluid↗

PubMed2001

Central angiotensin induction of fetal brain c-fos expression and swallowing activity.

The present study examined physiological and cellular responses to central application of ANG II in ovine fetuses and determined the fetal central ANG-mediated dipsogenic sites in utero. Chronically prepared near-term ovine fetuses (130 +/- 2 days) received injection of ANG II (1.5 microg/kg icv). Fetuses were monitored for 3.5 h for swallowing activity, after which animals were killed and fetal brains were perfused for subsequent Fos staining. Intracerebroventricular ANG II significantly increased fetal swallowing in near-term ovine fetuses (1.1 +/- 0.2 to 4.5 +/- 1.0 swallows/min). The initiation of stimulated fetal swallowing activity was similar to the latency of thirst responses (drinking behavior) elicited by central ANG II in adult animals. ANG II evoked increased Fos staining in putative dipsogenic centers, including the subfornical organ, organum vasculosum of the lamina terminalis, and median preoptic nucleus. Intracerebroventricular injection of ANG II also caused c-fos expression in the fetal hindbrain. These results indicate that an ANG II-mediated central dipsogenic mechanism is intact before birth, acting at sites consistent with the dipsogenic neural network. Central ANG II mechanisms likely contribute to fetal body fluid and amniotic fluid regulation.

Angiotensin II↗

PubMed2001

Plasma osmolality dipsogenic thresholds and c-fos expression in the near-term ovine fetus.

In ovine and human pregnancy, fetal swallowing contributes importantly to amniotic fluid homeostasis. Fetal dipsogenic responsiveness to short-term plasma hyperosmolality develops in late gestation, although fetal swallowing is not stimulated in response to long-term plasma osmolality increases (2 to 3%), which typically stimulate adult drinking behavior. To explore the near-term fetal plasma osmolality threshold for swallowing stimulation, we examined the effects of i.v. hypertonic saline-induced subacute increases in plasma hypertonicity on fetal swallowing behavior. Central sites of activation were examined by c-fos expression in putative dipsogenic nuclei. The results demonstrate that subacute 2 to 3% plasma osmolality increases do not stimulate near-term ovine fetal swallowing. However, fetal swallowing activity significantly increased (3 times) after plasma osmolality increased >6% above basal values. Consistent with a specific dipsogenic response, i.v. hypertonic saline induced c-fos expression in the anterior third ventricle region, a putative dipsogenic center, as well as in the fetal hindbrain. The stimulation of fetal swallowing under conditions of higher osmotic stimulation and the correlation with forebrain c-fos expression indicates that near-term fetal osmoregulation mechanisms are functional, although not completely mature. Reduced fetal dipsogenic responsiveness may result from altered osmoreceptor sensitivity, downstream neuronal or synaptic immaturity, or potentially inhibitory actions of stimulated hindbrain nuclei.

Animals↗

PubMed2000

Appearance of central dipsogenic mechanisms induced by dehydration in near-term rat fetus.

Cellular dehydration of central osmoreceptors evokes an integration of behavioral (i.e. drinking) and endocrinologic (i.e. arginine vasopressin secretion) responses to maintain body fluid balance. These osmoregulatory mechanisms have been intensely investigated in adult models. However, there has been limited research of the fetal development of neural mechanisms regulating responses to dehydration. Although behavioral and neuroendocrine responses to dehydration have been demonstrated in utero in precocial species (e.g. ovine), there has been no study to date demonstrating that these responses develop before the neonatal period of altricial species (e.g. rat). This study is the first to use the near-term rat fetus to investigate the effects of maternal subcutaneous hypertonic (2 M NaCl) or isotonic (0.15 M NaCl) saline injection on fetal plasma osmolality and brain FOS-immunoreactivity (FOS-ir). Maternal subcutaneous hypertonic saline significantly increased maternal and fetal plasma osmolality to similar levels (328+/-6 and 326+/-6 mosM/kg, respectively). In response to plasma hypertonicity, maternal and fetal brain FOS-ir increased significantly in the regions including the lamina terminalis, and the supraoptic and paraventricular nuclei (SON and PVN) of the hypothalamus. Together, these data indicate that central mechanisms for dipsogenic and arginine vasopressin secretory responses to hypertonicity are present and responsive in the fetal rat brain at near-term gestation. However, differences between fetal and maternal FOS-ir mapping suggest that fetal osmoreceptor development is not yet completed near term.

Animals↗

PubMed2000

Nitric oxide modulates angiotensin II-induced drinking behavior in the near-term ovine fetus.

OBJECTIVE: Human and ovine fetuses demonstrate an enhanced rate of spontaneous and angiotensin II-stimulated swallowing. Angiotensin II and nitric oxide synthase have been localized to thirst centers in the brain. This study was performed to determine whether central nitric oxide contributes to the regulation of angiotensin II-induced fetal swallowing. STUDY DESIGN: Six pregnant ewes with near-term singleton fetuses were chronically prepared with fetal vascular and lateral ventricle catheters and electrocorticogram and esophageal electromyogram electrodes. After a 2-hour control period, fetuses were administered serial lateral ventricle injections (1 mL) of angiotensin II (3.2 microg; time, 2 hours) and N omega-nitro-L -arginine methyl ester (3 mg; time, 3 hours) and a repeat angiotensin II injection (3.2 microg; time, 5 hours). All fetuses received an additional control study of lateral ventricle injections of artificial cerebrospinal fluid on a previous day. RESULTS: Angiotensin II injection significantly increased mean +/- SEM fetal swallowing (0.9 +/- 0.1 to 2.7 +/- 0.4 swallows/min). N omega-nitro-L -arginine methyl ester significantly decreased fetal swallowing to below the basal rate (0.4 +/- 0.1 swallows/min), and swallowing did not increase with the second angiotensin II dose (in the presence of nitric oxide blockade). CONCLUSIONS: These results demonstrate that inhibition of central nitric oxide suppresses fetal swallowing behavior in response to central angiotensin II. We speculate that tonic nitric oxide facilitates angiotensin II swallowing stimulation by maintenance of glutamate activation of hypothalamic N -methyl-D -aspartate receptors.

Angiotensin II↗

PubMed2000

Assessment of fetal scalp oxygen saturation determination in the sheep by transmission pulse oximetry.

OBJECTIVE: Electronic fetal heart rate monitoring has an unacceptable false-positive nonreassuring rate, which results in an excess of operative interventions. As a more objective measure of fetal oxygenation, fetal scalp pulse oximetry has been used to assess fetal blood oxygen saturation (SO (2)). The current devices use reflectance oximetry, which has inherent limitations. These include varying depths of signal penetration, variation with position, and potential for optical interference. In this study we evaluated a newly developed transmission pulse oximetry device consisting of transmitter and receiver diodes mounted within the coil of a standard scalp electrode (Spiral O(2)CTG; Respironics Inc, Marietta, Ga). STUDY DESIGN: Six pregnant ewes at 127 to 135 days' gestation (term, 145 days' gestation) were anesthetized, intubated, and prepared with a femoral artery catheter. Fetuses were prepared with brachial artery and jugular vein catheters. Maternal inspired oxygen fraction was titrated from 21% to 3%. Oximetry O(2)CTG devices were positioned on the fetal scalp, and recordings were compared with directly determined fetal arterial pH, PO (2), and SO (2) values. RESULTS: Maternal SaO (2) and PaO (2) ranged from 102% to 16% and 110 to 18 mm Hg, respectively. Fetal SaO (2) and PaO (2) ranged from 76% to 12% and 28 to 8 mm Hg, respectively. There was excellent correlation between direct fetal SaO (2) and scalp SO (2) (r (2) = 0.90; scalp SO (2) = 0.79 SaO (2) + 6.89). With an SaO (2) of <30% as the cutoff point for assessment of fetal compromise, scalp SO (2) measurements had a 94% +/- 10% specificity and a 94% +/- 10% positive predictive value. CONCLUSION: (1) Preliminary studies of the Spiral O(2)CTG sensor demonstrated high correlation of scalp SO (2) with fetal SaO (2). (2) Although potential inaccuracies remain, transmission oximetry may offer potential advantages in consistency, ease of application, and technology with respect to the current reflection oximeter devices.

Animals↗

PubMed2000

A simplified index of the plasma sodium threshold for arginine vasopressin secretion-morning fasting, euhydrated sodium levels.

OBJECTIVE: Human pregnancy results in a reduction in plasma osmolality and thus a reduction in the osmotic threshold for arginine vasopressin secretion. Although the functional characteristics of the osmoregulatory system controlling arginine vasopressin secretion have been carefully defined, determination of the osmotic threshold requires a complex, labor-intensive protocol of an intravenous hypertonic saline infusion. To aid in studies of osmotic threshold resetting in pregnancy, we sought to develop a simplified method for determination of this value. STUDY DESIGN: Ten healthy nonpregnant women between the ages of 18 and 40 years were studied over 2 days. All patients were hospitalized, and morning euhydration was ensured by oral water hydration (5-10 mL/kg) the evening before the study. On the first study day, patients were fed a standard no-salt-added diet; plasma osmolality and sodium values were checked just before and 1 and 2 hours after meals. On the second study day, after fasting blood samples were obtained, patients received an intravenous infusion (0.06 mL. kg(-1). min(-1) for 120 minutes) of hypertonic (5%) saline to gradually increase the plasma sodium level. Blood samples were obtained every 15 minutes for measurement of plasma electrolytes and arginine vasopressin. Plasma arginine vasopressin concentrations were regressed against plasma osmolality and sodium concentration to calculate the osmotic threshold for arginine vasopressin secretion. RESULTS: Hypertonic saline injection significantly increased plasma sodium (from 139 +/- 1 to 149 +/- 1 mEq/L) and osmolality (from 284 +/- 2 to 304 +/- 2 mOsm/kg H(2)O). Plasma arginine vasopressin significantly increased (from 5 +/- 1 to 30 +/- 10 pg/mL). The mean sodium and osmolality thresholds for arginine vasopressin secretion were calculated as 137 +/- 2 mEq/L and 285 +/- 15 mOsm/kg H(2)O. The mean morning fasting sodium level was nearly identical to the calculated sodium threshold, whereas the morning fasting osmolality value was significantly different. CONCLUSIONS: The morning fasting, euhydrated sodium level can be used as a simplified index for the plasma osmotic threshold for arginine vasopressin secretion. This index may provide a useful predictive measure for pregnant women in whom the plasma volume does not expand.

Adolescent↗

PubMed2000

Central neuropeptide Y stimulates ingestive behavior and increases urine output in the ovine fetus.

We hypothesized that central neuropeptide Y (NPY) increases swallowing activity and alters renal function in the near-term ovine fetus. Six ewes with singleton fetuses (130 +/- 2 days of gestation; 148 days = term) were chronically prepared with arterial and venous catheters, a fetal lateral cerebroventricular cannula, and fetal bladder and amniotic fluid catheters. For determination of fetal swallowing, electromyogram wires were placed in the fetal thyrohyoid muscle and the upper and lower nuchal esophagus. Electrodes were implanted on the parietal dura for determination of fetal electrocorticogram (ECoG). After 5 days of recovery, fetal swallowing, ECoG, blood pressure, and heart rate were monitored during a 3-h basal period. At t = 3 h, ovine NPY (0.05 mg/kg) was administered into the lateral ventricle, and fetuses were monitored for an additional 8 h. A control study of central administration of artificial cerebral spinal fluid was performed on an alternate day. Central NPY significantly increased swallowing activity during low-voltage ECoG from basal activity (1.26 +/- 0.15 swallows/min) at 4 h (1.93 +/- 0.37 swallows/min), 6 h (1.69 +/- 0.27 swallows/min), and 8 h (2.38 +/- 0.31 swallows/min). NPY significantly increased fetal urine flow (basal: 0.13 +/- 0.02; 4 h: 0.21 +/- 0.04; 6 h: 0. 19 +/- 0.03 ml.kg(-1).min(-1)). These results demonstrate that central NPY stimulates fetal swallowing activity and increases urine output, which may contribute to the in utero development of ingestive behavior.

Animals↗

PubMed2000

Osmotic threshold and sensitivity for vasopressin release and fos expression by hypertonic NaCl in ovine fetus.

In adults, hyperosmolality stimulates central osmoreceptors, resulting in arginine vasopressin (AVP) secretion. Near-term fetal sheep have also developed mechanisms to respond to intravascular hypertonicity with stimulation of in utero AVP release. However, prior studies demonstrating fetal AVP secretion have utilized plasma tonicity changes greater than those required for adult osmotically induced AVP stimulation. We sought to examine near-term fetal plasma osmolality threshold and sensitivity for stimulation of AVP secretion and to correlate plasma hormone levels with central neuronal responsiveness. Chronically instrumented ovine fetuses (130 +/- 2 days) and maternal ewes simultaneously received either isotonic or hypertonic intravascular NaCl infusions. Maternal and fetal plasma AVP and angiotensin II (ANG II) levels were examined at progressively increasing levels of plasma hypertonicity. Intravenous hypertonic NaCl gradually elevated plasma osmolality and sodium levels. Both maternal and fetal plasma AVP increased during hypertonicity, whereas ANG II levels were not changed. Maternal AVP levels significantly increased with a 3% increase in plasma osmolality, whereas fetal plasma AVP significantly increased only at higher plasma osmolality levels (over 6%). Thus the slope of the regression of AVP vs. osmolality was greater for ewes than for fetuses (0.232 vs. 0.064), despite similar maternal and fetal plasma osmolality thresholds for AVP secretion (302 vs. 304 mosmol/kg). Hyperosmolality induced Fos immunoreactivity (FOS-ir) in the circumventricular organs of the fetal brain. FOS-ir was also demonstrated in the fetal supraoptic and paraventricular nuclei (SON and PVN), and double labeling demonstrated that AVP-containing neurons in the SON and PVN expressed Fos in response to intravenous NaCl. These results demonstrate that, in the ovine fetus at 130 days of gestation, neuroendocrine responses to cellular dehydration are functional, although they evidence a relatively reduced sensitivity for AVP secretion compared with the adult.

Age Factors↗

PubMed1999

Influence of fetal to neonatal transition on nitric oxide synthase expression in the nucleus tractus solitarius in sheep.

Transition from fetal to newborn life is accompanied by a marked rise in circulating norepinephrine (NE) concentrations though arterial blood pressure does not substantively change. Nitric oxide (NO) plays an important role in the central regulation of sympathetic tone in the nucleus tractus solitarius (NTS) and neuronal NO synthase (nNOS) expression is functionally regulated in the brain. The purpose of these studies was to determine the influence of transition at birth on nNOS expression in the brainstem nuclei, particularly in the NTS, associated with changes in arterial pressure and plasma NE concentration. Experiments were performed using time-dated gestational ewes with twin fetuses. Arterial blood pressure was recorded and arterial blood NE concentrations were measured in the term fetus (gestational 147-148 days) and newborn lambs (4 h of postnatal age). The fetal and newborn animals were then perfused with 4% paraformaldehyde. Sections of the medulla were examined by using both immunolabeling with a polyclonal antibody directed against nNOS and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry, a marker for expression of nNOS. Micrographs were quantified using a microscope with reticule grid to measure the number of positive cells containing color staining in the brainstem nuclei. Plasma NE concentration in the newborn was more than two-fold greater compared to fetal values but mean arterial blood pressure was similar between fetus and newborn. The nNOS positive cells and NADPHd positive cells were significantly increased in the medial NTS (mNTS) of the newborn compared to fetus. nNOS immunoreactivity and NADPHd reactivity tended to increase in the rostral ventral medulla (RVM) in newborn, but were not altered in other brainstem nuclei during the transition from fetal to newborn life. The results suggest that nNOS expression in the mNTS is predominately enhanced at 4 h of neonatal age vs. the term fetus. We conclude that elevated circulating NE is associated with up-regulation of nNOS in the mNTS which may serve a protective role in central regulation of neonatal arterial blood pressure.

Animals↗

PubMed1999

Maternal 1-deamino-8-D-arginine-vasopressin-induced sequential decreases in plasma sodium concentration: ovine fetal renal responses.

OBJECTIVE: Acute maternal plasma hypotonicity induces a reduced placental osmotic gradient that contributes to augmented maternal-to-fetal water flow. Subsequently, maternal plasma hyponatremia results in fetal plasma hyponatremia, increased fetal urinary flow, and ultimately increased amniotic fluid volume. We hypothesized that both the degree of reduction in the placental osmotic gradient and the degree of fetal plasma hyponatremia influence fetal urinary diuretic responses. To differentiate the roles of these factors, we determined fetal urinary responses to graded levels of plasma hyponatremia during a constant placental osmotic gradient. Furthermore, we sought to establish the minimum level of plasma hyponatremia necessary to facilitate an increase in fetal urine production. STUDY DESIGN: Seven pregnant ewes (130 +/- 2 days) were prepared with maternal and fetal vascular catheters and a fetal bladder catheter. After 6 days of recovery, fetal urinary flow and urine and plasma compositions were measured during a 2-hour control period. At 2 hours, tap water (2 L, 38 degreesC) with a 20-g bolus of 1-deamino-8-d-arginine-vasopressin was administered to the ewe. Maternal plasma sodium concentration was decreased from control by 5 to 7, 10 to 12, and 15 to 17 mEq/L, and held at each level (levels 1, 2, and 3) for 60 minutes. RESULTS: 1-Deamino-8-d-arginine-vasopressin administration induced sequential decreases in maternal and fetal plasma sodium concentrations (control 146.9 +/- 0.5 mEq/L and 141.0 +/- 0.5 mEq/L, respectively) at level 1 (140.1 +/- 0.6 mEq/L and 136.7 +/- 0.7 mEq/L, respectively), level 2 (132.5 +/- 0.7 mEq/L and 130.6 +/- 1.1 mEq/L, respectively), and level 3 (125.4 +/- 1.2 mEq/L and 123.0 +/- 1.5 mEq/L, respectively). The maternal-fetal placental osmolality and sodium gradients were constant at each hypotonicity level. Fetal urinary flow significantly increased in association with the degree of hyponatremia (from 0.17 +/- 0.03 mL/kg/min to 0. 26 +/- 0.04 mL/kg/min, 0.33 +/- 0.05 mL/kg/min, and 0.38 +/- 00.5 mL/kg/min at levels 1, 2, and 3, respectively). CONCLUSIONS: These results indicate the following: (1) Sequential decreases in maternal plasma tonicity result in parallel decreases in fetal plasma tonicity. (2) The fetal urinary diuretic response is highly correlated with the degree of fetal plasma hypotonicity, despite a constant placental osmotic gradient. A fetal therapeutic response (53% increase in fetal urine production) may be induced by a maternal plasma sodium concentration decrease of only 5 to 7 mEq/L.

Animals↗

PubMed1999

Prediction by maternal risk factors of neonatal intensive care admissions: evaluation of >59,000 women in national managed care programs.

OBJECTIVE: Managed care plans have adopted risk assessment tools as part of pregnancy disease state management strategies to assist in reducing poor pregnancy outcomes and related costs. We evaluated the relationships of maternal risk factors to determine which pregnancy risk factors were associated with neonatal intensive care unit (levels II and III) admission. STUDY DESIGN: Risk assessments were performed through perinatal telephone interviews of nurses with 59, 861 pregnant women during 1996 and 1997 calendar years as part of managed care maternity risk screening and education programs. A series of 3 interviews was conducted, at 17 weeks and 28 weeks average gestational age and at 2 weeks post partum. Univariate chi(2) analysis was performed on >50 historical and pregnancy risk factors to determine the associations with neonatal intensive care unit admission. Significant factors were included in a stepwise logistic regression model. Receiver operating curves were generated for the use of significant factors in a risk scoring system in the prediction of neonatal intensive care unit admission, and the percentages of neonatal intensive care unit days attributable to significant risk factors were calculated. RESULTS: Among the participants most women (90%) had their prenatal visit during the first trimester. The mean maternal age was 30.2 +/- 5.2 years, with 74% of women reportedly of white ethnicity, 86% married, and 44.3% primigravid. The mean gestational age at birth decreased with increasing number of fetuses from singletons to quadruplets. The chi(2) analysis identified 26 significant risk factors associated with neonatal intensive care unit admission. Of these, 14 remained significant by logistic regression. Multiple gestation, preterm premature rupture of membranes, diabetes, abruptio placentae, pregnancy-induced hypertension, and preterm labor were independently associated with at least a 3-fold risk of neonatal intensive care unit admission. A modeled risk scoring system that used these and other significant factors was poorly predictive of neonatal intensive care unit admission. However, an analysis of neonatal intensive care unit length of stay attributable to significant risk factors concluded that 19% of all neonatal intensive care unit days in this population were associated with multiple gestations. Furthermore, 85% of neonatal intensive care unit days were the result of infant lengths of stay >/=1 week. CONCLUSION: This analysis of a managed care population showed similar risk factors to those traditionally associated with neonatal intensive care unit admission. Although many of these risk factors are not preventable, identification of neonatal intensive care unit admission risks with a screening program may be of use for focusing interventions, and earlier identification of these factors may allow maximum impact of interventions. Importantly, a reduction in the incidence of higher-order multiple gestations might help to reduce neonatal intensive care unit admissions and costs.

Adult↗

PubMed1999

Central Fos expression in fetal and adult sheep after intraperitoneal hypertonic saline.

We hypothesized that neural structures, involved in sensing extracellular body fluid composition in adult animals during an osmotic challenge, would show similar patterns of activation in fetal sheep. Eight adult sheep [4 hypertonic saline-treated adults (HYP-A), 4 isotonic saline-treated adults] and six near-term fetal sheep [3 hypertonic saline-treated fetuses (HYP-F), 3 isotonic saline-treated fetuses; 130 days gestation] were prepared with vascular and intraperitoneal catheters. Seventy-five minutes before tissue collection, hypertonic (1.5 M) or isotonic saline was infused via an intraperitoneal catheter to adult (18 ml/kg) or fetal sheep (6 ml/kg). Brains were examined for patterns of neuronal activation (demonstrated by Fos protein expression). HYP-A and HYP-F demonstrated similar acute increases in plasma osmolality ( approximately 10 mosmol/kgH2O) and comparable patterns of Fos expression within the organum vasculosum of the lamina terminalis (HYP-A, 67 +/- 2 vs. HYP-F, 63 +/- 6; means +/- SE) and hypothalamic supraoptic (SON; HYP-A, 107 +/- 8 vs. HYP-F, 102 +/- 7) and paraventricular nuclei (PVN; HYP-A, 71 +/- 18 vs. HYP-F, 124 +/- 19). Fewer activated neurons were detected in HYP-A vs. HYP-F within the subfornical organ (HYP-A, 33 +/- 8 vs. HYP-F, 91 +/- 17) and median preoptic nucleus (HYP-A, 33 +/- 5 vs. HYP-F, 70 +/- 6). In adults and fetuses, counterstaining for arginine vasopressin revealed that neurons within the SON and PVN respond to osmotic challenge. These findings demonstrate that central osmoregulatory centers in adult and near-term fetal sheep are similarly activated by osmotic challenge.

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