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Biomedical subjects

M G Ross

Publications and source records attributed to M G Ross.

At least 19 recordsLinked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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.

Aging↗

Nitric oxide modulates spontaneous swallowing behavior in near-term ovine fetus.

Human and ovine fetuses demonstrate an enhanced rate of swallowing, an activity critical for amniotic fluid regulation. Fetal swallowing may be modulated by both systemic and central factors. Nitric oxide (NO) is a central neuromodulator that has been localized to brain regions regulating thirst and swallowing. We sought to determine if NO contributes to the regulation of spontaneous ovine fetal swallowing. Six time-dated pregnant ewes with singleton fetuses (129 +/- 1 day) were chronically prepared with fetal vascular and lateral ventricle catheters and electrocorticogram (ECoG) and esophageal electromyogram electrodes. After a 2-h control period, fetuses were given lateral ventricle injection of NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME) and monitored for 2 h. NO precursor L-arginine was then injected into the lateral ventricle, and fetuses were monitored for a final 2 h. All fetuses received an additional control study of fetal swallowing before and after lateral ventricle injection of artificial cerebrospinal fluid (aCSF). Data were analyzed with repeated-measures ANOVA and paired t-test (P < 0.05). Suppression of a central NO with central L-NAME significantly reduced mean (+/-SE) spontaneous fetal swallowing (1.2 +/- 0.1-0.6 +/- 0.1 swallows/min low-voltage ECoG; P < 0.01). Restoration of central NO by L-arginine significantly increased fetal swallowing to pre-L-NAME levels (1.2 +/- 0.1 swallows/min low voltage). There were no changes in fetal swallowing during the control study of aCSF. Fetal ECoG activity and blood pressure did not change during the study or control aCSF injection. We conclude that NO is an important neuromodulator of fetal swallowing activity. Central NO synthase activity may contribute to the heightened level of spontaneous fetal swallowing and thus amniotic fluid regulation.

Animals↗

Fetal diuretic responses to maternal hyponatremia: contribution of placental sodium gradient.

Maternal hyponatremia induces fetal hyponatremia and increased fetal urine flow. We sought to examine the relative contributions of the placental Na(+) gradient vs. the absolute decrease in fetal plasma Na(+) in the fetal diuretic response to hyponatremia. Seven ewes with singleton fetuses (130 +/- 2 days) were prepared. Ewes received intravenous 1-desamino-8-D-arginine vasopressin (20 microg) and warm tap water (2 liters). Maternal plasma Na(+) was decreased to achieve two levels of maternal hyponatremia. Maternal and fetal blood volume were measured with radiolabeled red blood cells. In response to the first decrease in maternal plasma Na(+), fetal plasma Na(+) did not change initially. Subsequently, fetal plasma Na(+) decreased, normalizing the gradient. The second decrease in maternal plasma Na(+) similarly induced a reduced and normalized placental gradient at lower fetal plasma Na(+) values. Fetal urine flow increased in direct proportion to the degree of fetal hyponatremia (13, 38, 63, 100%, respectively). Maternal, although not fetal, blood volume significantly increased in response to hyponatremia. These results suggest that chronic fetal hyponatremia will result in a persistent diuresis, despite placental equilibration.

Animals↗

Regulation of hypothalamic arginine vasopressin messenger ribonucleic acid and pituitary arginine vasopressin content in fetal sheep: effects of acute tonicity alterations and fetal maturation.

OBJECTIVE: Fetal arginine vasopressin contributes to fetal and amniotic fluid homeostasis by increasing water resorption in the kidney and, at higher plasma levels, circulatory homeostasis by vasopressor effects. In utero and neonatal exposure of rat pups to prolonged alterations in plasma osmolality may permanently alter (imprint) pituitary arginine vasopressin content and adult responses to osmotic challenges. Our objective was to investigate fetal developmental changes and the impact of maternal dehydration and maternal hyponatremia on fetal pituitary arginine vasopressin content and hypothalamic arginine vasopressin messenger ribonucleic acid expression. STUDY DESIGN: Ten pregnant ewes with singleton fetuses (135 +/- 1 day) were chronically prepared with maternal vascular catheters. Ewes were assigned to receive water deprivation (n = 4) [desamino, D-Arg8]-arginine vasopressin-induced plasma hyponatremia (n = 3), or 4 days of observation (n = 3). Three additional pregnant ewes with preterm (110 +/- 1 day) singleton fetuses were also included for a study of maturational effects. Daily maternal blood samples were analyzed for determination of plasma arginine vasopressin, electrolytes, and osmolality. After the study protocol, fetuses were operatively delivered, umbilical blood samples obtained, and fetuses put to death for pituitary and hypothalamic tissues. Pituitary arginine vasopressin content was determined by radioimmunoassay, and hypothalamus arginine vasopressin messenger ribonucleic acid expression was detected by Northern blotting. RESULTS: Dehydration significantly (P < .05) increased, and hyponatremia significantly decreased maternal plasma sodium concentration compared with controls. Fetal plasma sodium concentration significantly changed in parallel with maternal values (dehydration: 139 +/- 1 to 150 +/- 1 mEq/L; hyponatremia: 138 +/- 1 to 128 +/- 5 mEq/L). Fetal hypothalamic arginine vasopressin messenger ribonucleic acid expression and pituitary content did not change in relation to these relatively acute alterations in plasma tonicity. However, among all animals, arginine vasopressin messenger ribonucleic acid expression was significantly negatively correlated with pituitary arginine vasopressin content (r2 = 0.563; P = .02). Arginine vasopressin messenger ribonucleic acid expression was significantly lower in both preterm and near-term fetuses (P < .05) than that in the maternal ewe, although pituitary arginine vasopressin content (in micrograms per milligram of protein) was significantly greater in preterm fetuses (P < .01, vs maternal; P < .05, vs near term). CONCLUSIONS: The significant inverse relation between arginine vasopressin content and arginine vasopressin messenger ribonucleic acid suggests a dynamic arginine vasopressin synthesis-content feedback relationship is functional in the near-term fetus. Although relatively acute periods of maternal hypertonicity or hypotonicity do not alter fetal pituitary arginine vasopressin content or hypothalamic arginine vasopressin messenger ribonucleic acid expression, longer-term plasma tonicity alterations may potentially have an impact on the fetal arginine vasopressin hypothalamic-pituitary axis.

Animals↗

Objective definition of shoulder dystocia: a prospective evaluation.

OBJECTIVE: The current study was undertaken to validate the objective definition of shoulder dystocia in a prospectively evaluated group of patients. STUDY DESIGN: Selected vaginal deliveries from January 1995 to December 1996 (N = 722) were evaluated for head-to-body delivery time and use of ancillary obstetric maneuvers. Charts were reviewed for perinatal and outcome data. RESULTS: Ninety-nine deliveries were complicated by shoulder dystocia and 623 deliveries had no shoulder dystocia. The objective definition described infants with lower 1-minute Apgar scores and increased birth weight. All fetal injuries were in the shoulder dystocia group. Duration of the second stage was significantly associated with a diagnosis of shoulder dystocia. The risk of shoulder dystocia was increased with maternal diabetes, but it was not correlated with birth weight in diabetics. CONCLUSIONS: The objective definition of shoulder dystocia identified a group of patients with an increased birth weight and risk of fetal injuries. The use of an objective definition will assist the evaluation of prophylactic and treatment proposals for shoulder dystocia.

Adult↗

Human amniotic fluid mathematical model: determination and effect of intramembranous sodium flux.

OBJECTIVE: A recently described mathematical model of human amniotic fluid dynamics used known and estimated rates of fetal fluid production (lung liquid and urine) and composition (osmolality) to enable calculation of previously unmeasured routes of amniotic fluid resorption, including fetal swallowing and intramembranous (across the amnion) water flow. This "osmolar" model assumed that only free water resorption occurred across the intramembranous route. We hypothesized that intramembranous flow also may include solutes and electrolytes because significant concentration gradients exist between amniotic fluid and fetal plasma. We used mass balance analysis to determine the direction and magnitude of intramembranous sodium flux and to assess the ability of a newly described "sodium" model to predict changes in amniotic fluid volume in response to changes in intramembranous electrolyte flow. Mathematical modeling was used to predict changes in amniotic fluid volume in response to changes in intramembranous electrolyte flow. STUDY DESIGN: Model predictions were calculated using published values for human amniotic fluid and fetal urine composition and volume. Ovine studies were used to derive lung fluid volumes and composition. Fetal swallowing and intramembranous flow were independently determined using net amniotic fluid osmolar (osmolality model) and sodium (sodium model) balance. Differences between osmolality and sodium model predictions were normalized to calculate the net intramembranous sodium flux, assuming a net balance of intramembranous osmotic solute flow. RESULTS: Both sodium and osmolality models predicted swallowed volume to be greater than intramembranous flow until 28 to 32 weeks' gestation, after which the relationship reversed. However, the sodium model predicted greater intramembranous flow and lower swallowing rates compared with the osmolality model at all gestational ages. Osmolar mass balance required daily intramembranous sodium flux into the amniotic fluid, which increased with gestational age. Furthermore, assuming stable swallowing and intramembranous water flow, the model predicts that 5% increases or decreases in amniotic fluid solute concentrations caused by intramembranous flux result in polyhydramnios or oligohydramnios, respectively. CONCLUSION: Sodium and osmolality models demonstrate similarities in determinations of amniotic fluid dynamics. However, mass balance equations demonstrate a net intramembranous flow of sodium into the amniotic fluid under normal conditions. Mathematical modeling suggests that small alterations in daily intramembranous sodium flux may evoke large changes in amniotic fluid volume.

Amniotic Fluid↗

Fos response of fetal sheep anterior circumventricular organs to osmotic challenge in late gestation.

We hypothesized that the anterior circumventricular organs (ACVO) and the supraoptic (SON) and hypothalamic paraventricular nuclei (PVN), among other structures that play a role in sensing extracellular body fluid volume and composition in postnatal animals (as demonstrated by Fos protein production by the immediate-early gene c-fos), would show similar activation in fetal sheep during an osmotic challenge. The brains of 10 fetal sheep [6 treated, 4 controls; 129-131 days of gestational age (dGA) = 0.87 gestation] were immunostained for Fos. Seventy-five minutes before tissue collection the dams were given intravenous 20% mannitol (1 ml . min-1 . kg-1 for 10 min). Subsequently, the ACVO, SON, and PVN were scored for the amount of neuronal Fos immunostaining. The subfornical organ (SFO; 24.5 +/- 9.0 vs. 1.7 +/- 1.2), the organum vasculosum of the lamina terminalis (OVLT; 26.8 +/- 5.6 vs. 7.0 +/- 2.0), the SON (39.8 +/- 3.0 vs. 0.15 +/- 0.1), and the PVN (59.8 +/- 7.9 vs. 0.7 +/- 0.7) had increases (P < 0.05) in the average number of Fos-positive cells per field compared with controls, whereas the median preoptic nucleus did not. Double immunostaining for Fos and arginine vasopressin (AVP) or oxytocin (OT) indicated that AVP- but not OT-immunopositive neurons in SON and PVN respond to osmotic challenge. These results demonstrate that the SFO, OVLT, SON, and PVN are activated by osmotic challenge in fetal sheep at 130 dGA.

Animals↗

Development of ingestive behavior.

Swallowing represents a primary physiological function that provides for the ingestion of food and fluid. In precocial species, swallowing activity likely develops in utero to provide for a functional system during the neonatal period. The chronically instrumented ovine fetal preparation has provided the opportunity for recent advances in understanding the regulation of in utero swallowing activity. The near-term ovine fetus swallows fluid volumes (100-300 ml/kg) that are markedly greater, per body weight, than that of the adult (40-60 ml/kg). Spontaneous in utero swallowing and ingestive behavior contribute importantly to the regulation of amniotic fluid volume and composition, the acquisition and potential recirculation of solutes from the fetal environment, and the maturation of the fetal gastrointestinal tract. Fetal swallowing activity is influenced by fetal maturation, neurobehavioral state alterations, and the volume of amniotic fluid. Furthermore, intact dipsogenic mechanisms (osmolality, angiotensin II) have been demonstrated in the near-term ovine fetus. It remains unknown to what degree, if any, fetal swallowing may be influenced by nutrient appetite, salt appetite, or taste. Nevertheless, the development of dipsogenic and additional regulatory mechanisms for ingestive behavior occurs during fetal life and may be susceptible to changes in the pregnancy environment. This review describes what is currently known regarding the in utero development of ingestive behavior and the importance of this activity for fetal and perhaps ultimately adult fluid homeostasis.

Aging↗

Anticholinergic suppression of ovine fetal swallowing activity.

OBJECTIVE: Fetal swallowing contributes importantly to amniotic fluid volume regulation as the primary route of fluid resorption, reaching 500 to 1000 ml/day near term. Near-term ovine fetal swallowing activity occurs predominantly during low-voltage electrocortical activity. In view of the potential to pharmacologically alter electrocortical activity, we hypothesized that fetal administration of a centrally acting cholinergic antagonist may be used to modulate fetal swallowing activity. To explore cholinergic modulation of swallowing activity, we examined fetal swallowing and electrocortical activity in response to central and peripheral cholinergic suppression by atropine sulfate. STUDY DESIGN: Singleton ovine fetuses (n = 6) were chronically prepared with vascular catheters and thyrohyoid, nuchal, and thoracic esophageal electromyogram and biparietal electrocortical electrodes. Swallowing and electrocortical activity were monitored for 2 hours before and after intravenous injection (1 ml of 0.15 mol/L sodium chloride) of atropine sulfate (1 mg/kg). On a subsequent day an identical study was performed with use off atropine methyl nitrate (3 mg/kg), an atropine analog that does not cross the blood-brain barrier. RESULTS: Atropine sulfate decreased low-voltage electrocortical activity (56% +/- 5% to 14% +/- 4%), increased high-voltage electrocortical activity (40% +/- 5% to 81% +/- 5%), and did not change intermediate electrocortical activity (4% +/- 1% to 5% +/- 1%). Fetal swallowing activity decreased from 46 +/- 12 to 12 +/- 2 swallows per hour after atropine sulfate administration. Atropine methyl nitrate had no discernible effect on either fetal electrocortical or swallowing activity. Fetal arterial pressure, plasma osmolality, pH, PCO2, and PO2 did not change. CONCLUSIONS: Central cholinergic antagonism suppresses low-voltage fetal electrocortical and swallowing activity in the ovine fetus. Studies exploring spontaneous or induced fetal swallowing should consider the behavioral state of the fetus when conclusions are drawn about changes in the swallowing activity.

Animals↗

Three-dimensional method for determination of amniotic fluid volume in intrauterine pockets.

BACKGROUND: Although current ultrasound techniques provide a linear (amniotic fluid index; AFI) or two-dimensional area index of amniotic fluid (AF), these indices have limited correlation with actual AF volume. We sought to quantify the three-dimensional volume of ultrasound-identified AF pockets, as assessed by the AFI and two-dimensional area methods. The BVI 2500 (Bladder Volume Instrument 2500; Diagnostic Ultrasound Corp., Redmond, WA) has been used to quantify the volume of residual urine in the bladder. INSTRUMENT AND METHOD: The BVI 2500 (Diagnostic Ultrasound Corp.) ultrasound uses a rotating 2-MHz transducer, computer-defined fluid interface, and computer integration of 12 cross-sectional images to calculate three-dimensional fluid volume. After providing written informed consent, 14 term pregnant patients (36-42 weeks) were evaluated using the BVI 2500 and an Ultramark 8 sector scan (Advanced Technology Laboratory, Bothell, WA). The largest vertical fluid pocket in each quadrant of the abdomen was identified with the sector scan, and vertical and horizontal measurements for AFI and two-dimensional area were recorded. Simultaneous AF volume measurements of each pocket were performed three times with the bladder volume instrument, and maximum values were used. Three-dimensional volume, two-dimensional area, and AFI values were compared by correlation analysis, with P < or = .05 considered statistically significant. EXPERIENCE: Among all patients, the average (+/- standard deviation) AFI was 7.6 +/- 4.1 (range 1.5-16.4) cm, and the average two-dimensional area was 30.9 +/- 21.1 (range 4.3-81.3) cm2. This corresponded to an average three-dimensional volume of 215 +/- 134 (range 23-497) cm3. Three-dimensional volume correlated highly with both AFI (r = 0.9; P < .001) and two-dimensional area (r = 0.86; P < .001). One AFI centimeter was equivalent to a volume of 30 cm3. CONCLUSION: There are highly significant linear correlations of three-dimensional amniotic fluid volumes with AFI and two-dimensional area. The four pockets used in AFI determination account for only 50% of total AF volume. Three-dimensional determinations may aid in clinical assessments of AF volume.

Adult↗

Ovine fetal laryngeal chemoreflex thresholds and respiratory effects.

In newborn infants, laryngeal contact with solutions of low chloride concentration or pH evokes swallowing, laryngeal adduction, and respiratory inhibition (laryngeal chemoreflex). To determine whether the laryngeal chemoreflex is present during fetal life and its effect on fetal respiratory activity, eight time-bred ewes (128 +/- 2 days) were prepared with fetal electrocortical diaphragm and esophageal electrodes and a nasopharyngeal catheter. After a 60-minute control period, increasing volumes (0.1 to 1.0 ml/kg) of 0.15 mol/L NaCl or distilled water (0.05 to 1.0 ml/kg) and decreasing concentrations of NaCl (0.15 to 0.02 mol/L) at a fixed volume (0.3 ml/kg) were sequentially administered through the nasopharyngeal catheter (38 degrees C). The minimum water volume that stimulated swallowing was significantly less than the minimum 0.15 mol/L NaCl volume (0.10 +/- 0.02 vs. 0.70 +/- 0.05 ml/kg). The maximum NaCl concentration that stimulated swallowing was 0.04 +/- 0.01 mol/L During the control period, respiratory activity averaged 14.6 +/- 0.7 breaths/minute and did not change during absent swallow responses or isotonic saline-induced swallows. However, respiratory activity significantly decreased during water (4.7 +/- 0.6 breaths/minute) and hypotonic saline-induced swallow responses (3.7 +/- 0.7 breaths/minute). Fetal electrocortical activity did not change during absent or stimulated swallows. We conclude that laryngeal water or hypotonic saline solution may stimulate fetal swallowing and suppress fetal respiratory activity, similar to the newborn laryngeal chemoreflex. We speculate that an exaggeration of the laryngeal chemoreflex apnea response in the newborn may predispose to sudden infant death syndrome.

Animals↗