Effects of increased core temperature on breathing movements and electrocortical activity in fetal sheep

Core temperature of fetal sheep was raised by perfusing warm water through a loop implanted into the abdomen, or into the stomach via the oesophagus. Raising fetal temperature by 0.8-2 degrees C was associated with an increase in amplitude and incidence of breathing movements, and an increase in the proportion of breathing movements that occurred during high voltage electrocortical (ECoG) activity. Fetal hyperthermia was maintained for 8 h, but the augmentation of breathing movements did not last for more than 2-3 h. The results indicate that changes of maternal temperature caused by hot weather, exercise, fever, and possibly diurnal changes of body temperature could alter the amplitude and pattern of fetal breathing movements.     

The adenosine A(1)-receptor antagonist 8-CPT reverses ethanol-induced inhibition of fetal breathing movements.

Administration of either ethanol or adenosine inhibits fetal breathing movements (FBM), eye movements, and low-voltage electrocortical activity (LV ECoG). The concentration of adenosine in ovine fetal cerebral extracellular fluid increases during ethanol-induced inhibition of FBM. The purpose of this study was to determine the effect of a selective adenosine A(1)-receptor antagonist, 8-cyclopentyltheophylline (8-CPT) on the incidence of FBM during ethanol exposure. After a 2-h control period, seven pregnant ewes received a 1-h intravenous infusion of ethanol (1 g/kg maternal body wt), followed 1 h later by a 2-h fetal intravenous infusion of either 8-CPT (3.78 +/- 0.08 microg. kg(-1). min(-1)) or vehicle. Ethanol reduced the incidence of FBM from 44.0 +/- 10.4 to 2.7 +/- 1.3% (P < 0.05) and 51.2 +/- 7.6 to 11.9 +/- 5.0% (P < 0.05) in fetuses destined to receive 8-CPT or vehicle, respectively. In the vehicle group, FBM remained suppressed for 7 h. In contrast, during the first hour of 8-CPT infusion, FBM returned to baseline (31 +/- 11%) and was not different from control throughout the rest of the experiment. Ethanol also decreased the incidence of both low-voltage electrocortical activity and eye movements, but there were no differences in the incidences of these behavioral parameters between the 8-CPT and vehicle groups throughout the experiment. These data are consistent with the hypothesis that adenosine, acting via A(1) receptors, may play a role in the mechanism of ethanol-induced inhibition of FBM.     

Indomethacin antagonizes the ethanol-induced suppression of breathing activity but not the suppression of brain activity in the near-term fetal sheep

The effect of indomethacin on the ethanol-induced suppression of fetal breathing movements, low-voltage electrocortical (ECoG) activity, and electro-ocular (EOG) activity was studied in the near-term fetal sheep. Ten conscious instrumented pregnant ewes (between 129 and 131 days of gestation; term, 147 days) received 1-h maternal intravenous infusion of 1 g ethanol/kg total body weight and simultaneous fetal treatment with either indomethacin (2 mg/kg fetal body weight/h) (n = 5) or an equivalent volume of phosphate buffer (n = 5) intravenously for 9 h. Fetal ECoG activity, EOG activity, and fetal breathing movements were monitored continuously over the experimental periods. In animals treated with ethanol and buffer (n = 5), fetal breathing movements were suppressed for 8 h and low-voltage ECoG and EOG activity was suppressed for 2 h below preinfusion levels. In animals treated with ethanol and indomethacin (n = 5), fetal breathing movements were elevated for 13 h but low-voltage ECoG and EOG activity remained suppressed for 3 h below preinfusion levels. The data suggests that indomethacin can antagonize the ethanol-induced suppression of fetal breathing movements, but does not alter the ethanol-induced suppression of ECoG or EOG activity.     

Fetal breathing is not initiated after cord occlusion in the unanaesthetized fetal lamb in utero.

We investigated the role of cord occlusion in the initiation of breathing at birth using an extracorporeal membrane oxygenator system to control fetal blood gases independently of the placenta in 12 chronically instrumented fetal lambs. In group IA (n = 9; exp = 12) PaCO2 was kept constant (5.62 +/- 0.21 to 5.70 +/- 0.23 kPa) during cord occlusion. Group IB (n = 7; exp = 8) were cord occlusion experiments from group IA in which no fetal breathing movements had occurred; CO2 flow to the membrane was increased and fetal PaCO2 rose significantly (5.45 +/- 0.24 to 8.27 +/- 0.56 kPa). In group II (n = 7; exp = 12) PaCO2 was allowed to increase from 5.98 +/- 0.24 kPa to 8.09 +/- 0.48 kPa after cord occlusion. Within 5 min of cord occlusion, FBM did not occur in 11 out of 12 experiments in group IA or in 11 out of 12 experiments in group II. In contrast in group IB breathing did occur in 5 out of 8 experiments. When they occurred, fetal breathing movements were always associated with low voltage electrocortical activity. Our results do not support the hypothesis that the initiation of breathing within 5 minutes of birth is dependent on an inhibitory factor of placental origin. Furthermore these data suggest an association between the presence of breathing and a substantial rise in PaCO2.     

Effects on fetal and maternal body temperatures of exposure of pregnant ewes to heat, cold, and exercise.

We exposed Dorper-cross ewes at approximately 120-135 days of gestation to a hot (40 degrees C, 60% relative humidity) and a cold (4 degrees C, 90% relative humidity) environment and to treadmill exercise (2.1 km/h, 5 degrees gradient) and measured fetal lamb and ewe body temperatures using previously implanted abdominal radiotelemeters. When ewes were exposed to 2 h of heat or 30 min of exercise, body temperature rose less in the fetus than in the mother, such that the difference between fetal and maternal body temperature, on average 0.6 degrees C before the thermal stress, fell significantly by 0.54 +/- 0.06 degrees C (SE, n = 8) during heat exposure and by 0.21 +/- 0.08 degrees C (n = 7) during exercise. During 6 h of maternal exposure to cold, temperature fell significantly less in the fetus than in the ewe, and the difference between fetal and maternal body temperature rose to 1.16 +/- 0.26 degrees C (n = 9). Thermoregulatory strategies used by the pregnant ewe for thermoregulation during heat or cold exposure appear to protect the fetus from changes in its thermal environment.     

Effect of hyperoxia (PaO2 50-90 mmHg) on fetal breathing movements in the unanaesthetized fetal sheep

Hypoxia inhibits fetal breathing movements but after birth it stimulates breathing. These differences have long been thought to involve central nervous inhibitory mechanisms. Such mechanisms might exert a tonic inhibition of fetal breathing movements at normal fetal PaO2 and the rise in PaO2 at birth might lift this inhibitory effect. To test this hypothesis 7 fetal sheep were chronically instrumented at 125-130 days for recording electrocortical activity (ECoG), and the electromyograph (EMG) activity of the diaphragm and neck muscles. Catheters were placed in a fetal carotid and a brachial artery and in the fetal trachea. For an extracorporeal membrane oxygenation system a 12 F gauge silastic catheter was placed in the right atrium for draining fetal blood and a 9.6 F gauge catheter was placed in a carotid artery to return oxygenated blood. Three days after operation the fetuses were connected to the extracorporeal membrane oxygenation system and fetal PaO2 was raised to 65.2 +/- 4.4 mmHg (SEM) for 6 to 19 h without changing pH or PaCO2. Neither the incidence of high voltage ECoG (48.5 +/- SEM 2.0% vs 52.8 +/- 3.3%) nor of fetal breathing movements (37.3 +/- 2.6% vs 23.8 +/- 5.9%) changed during the periods of hyperoxia. Since fetal breathing movements did not become continuous, we conclude that the lower PaO2 in the fetus compared to the neonate does not exert a tonic inhibitory influence on fetal breathing movements.     

Development of tolerance to ethanol-induced suppression of breathing movements and brain activity in the near-term fetal sheep during short-term maternal administration of ethanol

The effect of short-term maternal ethanol administration on the ethanol-induced suppression of fetal breathing movements, electrocortical (ECoG) activity, and electroocular (EOG) activity was determined in the near-term fetal sheep. Twelve conscious instrumented pregnant ewes (between 125 and 139 days of gestation; term, 147 days) received 1-h intravenous infusion of 1 g ethanol/kg total body weight daily for six days (n = 6) or an equivalent volume of normal saline daily for six days (n = 6). On the seventh day, the ethanol- and saline-pretreated animals were administered 1 g ethanol/kg total body weight. A further six ewes received 1-h intravenous infusion of 1 g ethanol/kg total body weight (n = 3) or an equivalent volume of normal saline (n = 3) daily for thirteen days with both groups receiving 1 g ethanol/kg total body weight on day fourteen. Fetal ECoG and EOG activities, and fetal breathing movements were monitored continuously over the post- operative and experimental periods. Saline infusion had no significant effect on the parameters studied. Fetal breathing movements were suppressed for 8 h after the first ethanol dose, and were not significantly suppressed after fourteen days of once-daily, maternal ethanol administration. Low-voltage ECoG and EOG activities were suppressed for 3 h after the first ethanol dose, and were not significantly suppressed after seven days of repeated ethanol administration. Maternal and fetal blood gases and acid-base balance were not significantly affected by maternal ethanol administration. These data demonstrate that short-term maternal administration of ethanol results in the development of tolerance to ethanol in the mature fetus.     

Effect of increased arterial CO2 on fetal breathing and behavior in sheep

We studied breathing and behavioral response to increased arterial CO2 (PaCO2) in 12 fetal sheep between 130 and 145 days of gestation. Of these 12 fetuses, 10 had an increase in PaCO2 through maternal rebreathing of CO2; in the other 2 fetuses CO2 was increased via an endotracheal tube and application of continuous distending airway pressure. We used our window technique to observe and videotape fetal behavior. The experiments consisted of recording breathing activity and behavior during resting conditions (1 low- and high-voltage ECoG cycle) and during administration of CO2. We measured electrocortical activity (ECoG), eye movements (EOG), electromyography of the diaphragm (EMGdi) and neck muscles, tracheal (Ptr), amniotic, and carotid arterial pressures. Administration of CO2 by the rebreathing technique produced an increase in the amplitude of breathing activity as reflected by an increase in Ptr from 5.0 +/- 0.6 to 12 +/- 1.9 mmHg (P less than 0.01) and an increase in SEMGdi from 32 +/- 4 to 77 +/- 8% max (P less than 0.001). Frequency increased due to a decrease in inspiratory (TI) and expiratory duration. Ptr/TI increased from 11.0 +/- 2.0 to 37.4 +/- 9.0 mmHg/s (P less than 0.05) and SEMGdi/TI increased from 67 +/- 7 to 221 +/- 28% max/s (P less than 0.001). Although the response was at times prolonged into the transitional high-voltage zone, it did not persist during established high-voltage ECoG.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fetal breathing adaptation to prolonged hypoxaemia in sheep

Prolonged (6 days) fetal hypoxaemia was produced by placing pregnant ewes in an environmental chamber. A constant flow of N2 into the chamber reduced the fraction of inspired oxygen (Fi02) to 0.139 +/- 0.001, simulating an altitude of 4270 m. This reduced maternal PaO2 by about 39 mmHg and PaCO2 by nearly 5 mmHg, which produced a hypocapnic (delta PaCO2 = -5 mmHg) hypoxaemia (delta PaO2 = -8 mmHg) in the fetus. An analysis of the first 4 h of breathing recorded each day (1800-2200 h; start of hypoxaemia: 1200 h) showed that the incidence (12 +/- 2.0 min/day) during the first day of hypoxaemia was significantly less (P less than 0.05) than that (24 +/- 3.1 min/h) during the same time of the control day. By the second day, breathing had returned to normal. Further analysis indicated that a normal incidence of breathing may have occurred as early as 14 h after starting hypoxaemia. These results suggest that fetal breathing movements adapt rather quickly to this degree of hypocapnic hypoxaemia.     

Effects of naloxone on the breathing, electrocortical, heart rate, glucose and cortisol responses to hypoxia in the sheep fetus

Continuous infusions of naloxone HC1 (0.5 mg/kg or 3.8 mg/kg) or saline were given intravenously to fetal sheep at 119 to 137 days of gestation during a one hour period of air administration and a one hour period of hypoxia induced by having ewes breathe 9% O2, 3% CO2 and 88% N2. Fetal carotid PaO2 fell to 13.0 +/- 0.5 mmHg during hypoxia with no change in pH. During hypoxia, plasma cortisol concentration increased significantly more in naloxone-infused fetuses than controls. Ewes, whose fetuses received naloxone, showed a significant increase in cortisol during hypoxia whereas no increase was observed in controls. There were no significant differences between saline and naloxone-infused fetuses during hypoxia in fetal breathing incidence, amplitude, frequency, number of deep inspiratory efforts per hour, heart rate, electrocortical activity or in the rise in plasma glucose caused by hypoxia. Results suggest that endogenous opiates may have a role in modulating cortisol production in the ewe and fetus during hypoxia but do not have a role in mediating the decrease in incidence of breathing activity or rise in plasma glucose. During air administration, naloxone significantly increased fetal breath amplitude, fetal and maternal plasma glucose, fetal heart rate, and the number of electrocortical changes per hour. This suggests endogenous opiates may have a more important role in the normoxic pregnant ewe and fetus.     

Effects of hypoxaemia and hypercapnia on breathing movements and sleep state in sinoaortic-denervated fetal sheep

The role of the systemic arterial chemoreceptors in regulating breathing movements was determined in 7 chronically catheterized fetal sheep with carotid denervation and vagal section. Fetal hypoxaemia (delta PaO2 = -11.4 +/- 0.6 mmHg) decreased significantly the incidence of rapid-eye-movements (control = 26 +/- 1.5 min/h; hypoxia = 12 +/- 2.6 min/h, P less than 0.001) and breathing activity (control = 18 +/- 1.0 min/h; hypoxia = 8 +/- 1.1 min/h, P less than 0.001). However, the lag in onset of inhibition (approximately 8 min) was significantly greater (P less than 0.05) than for normal fetuses. The incidence of low voltage electrocortical activity was not affected. Hypercapnia (delta PaCO2 = 9.5 +/- 1.1 mmHg) increased significantly the incidence of rapid-eye-movements and breathing activity. Hypercapnia also increased the mean amplitude of breathing activity and reduced the average breath interval. Rapid-eye-movements and breathing activity were depressed significantly by hypoxaemic hypercapnia. These observations suggest that hypoxic inhibition does not require afferent activity from the aortic or carotid bodies nor from other chemoreflexes mediated by the vagus. However, such peripheral input may be responsible for a more rapid onset of inhibition in normal fetuses.     

The effects of raising intracranial pressure on breathing movements, eye movements and electrocortical activity in fetal sheep

Extra-dural or cerebroventricular intracranial pressure was measured in 7 unanaesthetized fetal sheep (123-137 days gestation). Basal intracranial pressure was 6.7 +/- 1.7 mmHg, but there were many transient increases of pressure in association with spontaneous changes of amniotic pressure, fetal intrathoracic pressure, and particularly when the fetal nuchal muscles were active. These spontaneous increases of intracranial pressure were often associated with cessation of breathing movements and change of the electrocorticogram from low to high voltage activity. To test whether increased intracranial pressure influenced breathing movements and electrocortical activity, intracranial pressure was raised either by occluding the superior vena cava for 1 min with an implanted extravascular cuff, or by extra-dural injection of 0.3-1.0 ml of 0.9% NaCl. Increasing the intracranial pressure 5-15 mmHg by either method during low voltage electrocortical activity caused cessation of breathing movements, electro-ocular activity, and change of the electrocorticogram from low to high voltage in a significant proportion of trials. We propose that natural fluctuations of intracranial pressure caused by compression of the fetal body or skull, by body movements or by uterine activity, may cause changes in electrocortical activity and breathing movements.     

Behavioral activity during prolonged hypoxemia in fetal sheep

Experiments were conducted in unanesthetized, chronically catheterized pregnant sheep to determine the fetal behavioral response to prolonged hypoxemia produced by restricting uterine blood flow. Uterine blood flow was reduced by adjusting a vascular occluder placed around the maternal common internal iliac artery to decrease fetal arterial O2 content from 6.1 +/- 0.3 to 4.1 +/- 0.3 ml/dl for 48 h. Associated with the decrease in fetal O2 content, there was a slight increase in fetal arterial PCO2 and decrease in pH, which were both transient. There was an initial inhibition of both fetal breathing movements and eye movements but no change in the pattern of electrocortical activity. After this initial inhibition there was a return to normal incidence of both fetal breathing movements and eye movements by 16 h of the prolonged hypoxemia. These studies indicate that the chronically catheterized sheep fetus is able to adapt behaviorally to a prolonged decrease in arterial O2 content secondary to the restriction of uterine blood flow.     

Effect of asphyxia on respiratory activity in fetal sheep

Hypoxia in fetal sheep depresses respiratory activity. To determine if this effect is counterbalanced by hypercarbia we studied the effects of two levels of asphyxia produced by occlusions of the maternal uterine artery. Moderate asphyxia (PaO2 16.8 +/- 1.6 (SEM) PaCO2 48.9 +/- 1.0 torr) produced no changes in the percent time fetal breathing movements occupied each hour which ranged from 25.6 +/- 7.0 to 32.4 +/- 6.2%. However, a more marked asphyxia (PaO2 12.0 +/- 0.3, PaO2 57.0 +/- 1.6) resulted in a decrease in fetal respiratory activity to 8.7 +/- 3.7% during the first hour. This depression was sustained over the next 2 h but by the 5th hour breathing had returned to 26.2 +/- 7.3%. We concluded that hypercarbia can offset the respiratory inhibition of acute moderate hypoxia, but not that of a more marked lowering of PaO2 in fetal sheep. Severe asphyxia causes an initial inhibition of respiration which is followed by a return to normal respiratory activity.     

Indomethacin reversal of ethanol-induced suppression of ovine fetal breathing movements and relationship to prostaglandin E2

The effects of indomethacin on the ethanol-induced suppression of fetal breathing movements and fetal arterial plasma and cerebrospinal fluid (CSF) PGE2 concentrations and maternal arterial plasma PGE2 concentration were determined in the near-term fetal lamb. Eight conscious instrumented pregnant ewes (between 130 and 133 days of gestation; term, 147 days) received 1-h maternal intravenous infusion of 1 g ethanol/kg total body weight, and the fetus received 6-h intravenous infusion of indomethacin (1 mg/h per kg fetal body weight) commencing 30 min later. Serial fetal and maternal arterial blood samples (n = 8) and fetal CSF samples (n = 5) were collected at selected times throughout the 12-h study for the determination of PGE2 concentration. Fetal breathing movements were monitored continuously throughout the experimental period. Maternal ethanol infusion resulted in initial suppression (P less than 0.05) of fetal breathing movements for 2 h below pretreatment value, followed by a rapid increase in the incidence of fetal breathing movements after the onset of fetal indomethacin treatment. Fetal and maternal plasma PGE2 concentrations and fetal CSF PGE2 concentration were increased (P less than 0.05) above the pre-infusion value during the administration of ethanol and 1 h thereafter. Fetal indomethacin treatment suppressed (P less than 0.05) to undetectable levels fetal plasma and CSF PGE2 concentrations, which then became similar (P greater than 0.05) to pretreatment by 12 h. There was a positive correlation between fetal plasma and CSF PGE2 concentrations. There was an inverse correlation between the incidence of fetal breathing movements and fetal CSF PGE2 concentration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of moderate hypoxia on fetal electrocortical activity, eye movements, and breathing activity in sheep

Isocapnic hypoxaemia (delta PaO2 = -8.0 +/- 0.5 mmHg; delta CaO2 = -2.86 +/- 0.20 ml/dl) was produced in fetal sheep by having the ewe breathe for one hour a gas mixture (v/v) of 10.5% O2 and 1.5% CO2 in N2. Mean fetal heart rate, blood pressure, and incidence of low voltage electrocortical activity were not affected. However, the incidence of rapid-eye-movements and breathing activity was reduced by about 40%. Breathing movements during hypoxaemia had a mean inspiratory time, breath interval, and tracheal pressure amplitude which did not differ significantly from those during control experiments in which the ewe breathed air from the plastic bag. These observations suggest that hypoxia decreases the incidence of breathing movements but does not affect the amplitude or pattern of breathing activity and that it may reduce the incidence of eye movements and breathing activity through a common mechanism.     

Effect of beta-endorphin on fetal breathing movements in sheep

It has been suggested that endogenous opioids, such as beta-endorphin (beta-EP), act to depress respiration in the fetus and newborn. We have investigated the effect of infusing beta-EP either intravenously or into a lateral cerebral ventricle on breathing movements and electrocortical activity in eight fetal lambs between 116 and 133 days gestation. Intravenous infusion of beta-EP (200 or 500 micrograms over 1 h) increased plasma beta-EP concentrations 2- to 230-fold and was associated with a small decrease in the percent time spent breathing, from 57.8 +/- 9.1 to 51.3 +/- 8.2%/h (n = 6 exp). There was no change in the amount of high- or low-voltage electrocortical activity. Intracerebroventricular beta-EP infusion (1 or 2 micrograms beta-EP/min for 120 min) was not associated with any change of breathing movements (n = 5 exp) during the period of the infusion. However, in four experiments, in the 6-h period after the end of the beta-EP infusion there were episodes of 2-4 h when the percent time per hour spent breathing exceeded 70%. Electrocortical activity increased in amplitude and distinct episodes of high- and low-voltage activity were sometimes lost in these experiments. We conclude that high concentrations of beta-EP in plasma or cerebrospinal fluid do not totally suppress fetal breathing directly in the fetal lamb.     

Fetal swallowing: response to graded maternal hypoxemia.

A computer-based system, incorporating electromyography (EMG) and esophageal fluid flow measurement, was used to determine fetal breathing and swallowing responses to graded maternal hypoxemia. Five chronically prepared ewes with singleton fetuses at a gestational age of 130 +/- 2 (SE) days were subjected to successive 30-min periods of mild and moderate hypoxemia (inspired O2 fraction = 0.16 and 0.13, respectively). Mild and moderate maternal hypoxemia evoked significant reductions in fetal arterial PO2 (21 +/- 1 to 17 +/- 1 and 13 +/- 1 Torr, respectively), while fetal arterial pH, hematocrit, plasma osmolality, heart rate, and mean blood pressure did not change. Moderate hypoxemia was associated with significant increases in fetal plasma arginine vasopressin and renin activity and significant reductions from basal values in percent time breathing (53 +/- 4 to 25 +/- 12%), percent time swallowing (11.5 +/- 3.1 to 1.3 +/- 0.7%), and volume swallowed (21.3 +/- 2.1 to 4.8 +/- 2.7 ml/30 min). Fetal swallowing activity was better correlated with arterial PO2 (r = 0.8) than breathing activity (r = 0.45). We conclude that fetal swallowing is suppressed during mild and moderate hypoxemia. It is suggested that several sites and/or mechanisms may account for the hypoxemic inhibition of fetal activities.     

Fetal breathing, sleep state, and cardiovascular responses to adenosine in sheep

The possibility that adenosine mediates hypoxic inhibition of fetal breathing and eye movements was tested in nine chronically catheterized fetal sheep (0.8 term). Intracarotid infusion of adenosine (0.25 +/- 0.03 mg.min-1.kg-1) for 1 h to the fetus increased heart rate and hemoglobin concentration but did not significantly affect mean arterial pressure or blood gases. As with hypoxia, adenosine decreased the incidence of rapid eye movements by 55% and the incidence of breathing by 77% without significantly affecting the incidence of low-voltage electrocortical activity. However, with longer (9 h) administration, the incidence of breathing and eye movements returned to normal during the adenosine infusion. Intravenous infusion of theophylline, an adenosine receptor antagonist, prevented most of the reduction in the incidence of breathing and eye movements normally seen during severe hypoxia (delta arterial PO2 = -10 Torr). It is concluded that 1) adenosine likely depresses fetal breathing and eye movements during hypoxia and 2) downregulation of adenosine receptors may contribute to the adaptation of breathing and eye movements during prolonged hypoxia.     

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

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