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.     

In vivo brown fat response to hypothermia and norepinephrine in the ovine fetus

The goal of this study was to assess the response of fetal brown fat in vivo to hypothermia and norepinephrine infusion. In 10 unanaesthetized, chronically-prepared fetal sheep (133 +/- 2 days of gestation) cold water was passed through tubing encircling the fetus in utero and plasma glycerol concentration was measured as an indicator of brown fat activity. Following cooling for 60 min, amniotic fluid temperature fell 7.79 degrees C to 31.66 +/- 1.73 degrees C (n = 8, P less than 0.001) and maternal temperature fell 0.63 degree C to 38.63 +/- 0.08 degrees C (n = 9, P less than 0.001). Eight of the fetuses were subjected to a second experiment in which norepinephrine was infused intravenously for 15 min. During infusion fetal arterial temperature fell 0.38 degrees C to 39.05 +/- 0.25 degrees C (n = 7, P less than 0.05). Amniotic fluid temperature (n = 7, NS) and maternal arterial temperature (n = 7, NS) remained constant. Glycerol concentration during the infusion increased from 0.73 to 1.27 mg/dl, a 74% increase over control (n = 8, P less than 0.001). Although clearly detectable, these glycerol responses to hypothermia and norepinephrine stimulation are one-third or less of those achieved after birth, indicating that thermogenesis remains quiescent in the near-term fetal sheep, despite powerful stimuli for activation.     

Effects of increase in body temperature on the breathing pattern in premature infants

This study was designed to determine the effects of a mild increase in body temperature within the physiological range (0.8 degrees C) in healthy premature infants. Seven unsedated premature infants (38.4 wk +/- 1.5 postconceptional age) were monitored polygraphically during "morning naps" in an incubator under two different environmental temperatures: (1) normothermia with the incubator temperature set at 25 degrees C and the rectal temperature equal to 36.9 degrees C +/- 0.1; (2) hyperthermia with the incubator temperature set at 35 degrees C and the rectal temperature equal to 37.7 degrees C +/- 0.15. Respiratory frequency and heart rate, respiratory events, i.e., central and obstructive apnea, and periodic breathing with and without apneic oscillations were tabulated. Results for respiratory events were expressed as (1) indices of the total number of respiratory events, and of specific respiratory events per hour of total, quiet and active sleep times; (2) duration of total and specific respiratory events expressed as a percentage of total sleep, quiet and active sleep times. Respiratory frequency and heart rate were significantly increased by hyperthermia (P less than 0.05). Hyperthermia did not significantly modify the indices or the duration of central and obstructive apnea. But the indices and the duration of periodic breathing with and without apneic oscillations were significantly increased by hyperthermia during active sleep (P less than 0.05) but not during quiet sleep. The present study shows that a mild increase in body temperature within the physiological range in premature infants enhances the instability of the breathing pattern during active sleep.     

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.     

Effect of hyperthermia on the plasma concentrations of prolactin and cortisol in the fetal lamb and pregnant ewe during late gestation

Exposing pregnant sheep to an ambient temperature of 43 +/- 1 degree C for 8 h was associated with a 1-1.5 degrees C increase of maternal and fetal core temperatures, and a 11-fold and 3-5 fold increase in maternal and fetal plasma prolactin concentrations respectively. Hyperthermia did not change maternal or fetal plasma cortisol concentrations. We conclude that maternal and fetal hyperprolactinaemia may occur in late pregnancy during hyperthermic conditions and that the increase in fetal plasma prolactin is due to either increased secretion or decreased metabolic clearance of prolactin in the feto-placental compartment.     

Temperature effects on oxygen affinity of human fetal blood

In an effort to understand the effects of temperature changes on fetal oxygenation, the temperature effects were measured on oxygen affinity of whole blood from term human fetuses. The blood obtained was tonometered at delivery in two flasks gassed with 95% N2 (+ 5% CO2 or 20.9% + 5% CO2, and mixed aliquots from each flask in different proportions to obtain samples for analysis of PO2 and percent saturation. The oxyhaemoglobin dissociation curve was constructed and P50 determined at two or three different temperatures for each batch of blood. As temperature increased from 30 to 41 degrees C, human fetal blood bound O2 less avidly, the temperature coefficient for changes in P50 being 0.0255 per degree C. This temperature effect was similar to that in adult blood, although at any temperature O2 affinity of fetal blood was greater than that of the adult. Placental oxygen exchange could be significantly affected by changes in temperature such as occur during hypo- or hyperthermia, as with maternal exercise.     

Effects of hyperthermia on fetal breathing movements

High environmental temperature is known to impair fetal growth and development. We now report long lasting changes in fetal breathing activity following the exposure of pregnant ewes to an ambient temperature of 43 degrees C for 8 h. In 16 trials in 10 ewes (119-138 days gestation) heat exposure increased maternal and fetal core temperatures 1.5-2.0 degrees C, and the hyperventilation by the ewe produced a fall in fetal PaCO2 from 53.5 +/- 1.3 to 34.8 +/- 5.3 mmHg (P less than 0.05). Fetal breathing movements decreased in incidence during the hyperthermia but remained episodic (present during low-voltage electrocortical activity) with occasional brief episodes of breathing at high rates (greater than 4 breaths/s). However, 1-2 h after the end of heating, when maternal and fetal core temperature and PaCO2 had returned to normal, fetal breathing movements became continuous, and were augmented 30-100% in amplitude. Fetal breathing movements occurred during both low- and high-voltage electrocortical activity. The results show that a heat load similar to that experienced by sheep in sub-tropical regions in the summer months cause prolonged changes in the central regulation of fetal breathing.     

Metabolic and hormonal responses to cooling the fetal sheep in utero

The metabolic and hormonal effects of cooling 10 fetal sheep in utero (115-142 days of gestation) for 2h were studied. The fetal core temperature fell by 2.81 +/- 0.14 degrees C while the maternal temperature fell 0.86 +/- 0.15 degrees C. This hypothermia caused a significant rise in the fetal and maternal plasma glucose concentrations (P less than 0.001) and a fall in the fetal insulin concentrations (P less than 0.01). The fetal plasma lactate and cortisol concentrations rose rapidly (P less than 0.01) while the growth hormone fell (P less than 0.01) and remained low until cooling ceased when a rapid rebound occurred. There was no significant change in any of the fetal iodothyronines and no elevation of nonesterified free fatty acid concentrations, in contrast to the rapid rise (P less than 0.01) which occurred when newborn lambs were cooled. These observations demonstrate that appropriate glucose, insulin, lactate and cortisol responses to hypothermia have differentiated by 120 days of gestation. However, neither a thyroid hormone response nor an elevation in free fatty acid levels was observed. Thus not all components of the thermogenic response to hypothermia can be demonstrated in the late gestation fetail sheep in utero.     

Heat stress-induced alterations in the synthesis and secretion of proteins and prostaglandins by cultured bovine conceptuses and uterine endometrium

Effect of in vitro heat stress on protein and prostaglandin synthesis and secretion by bovine conceptuses and endometrium was examined. Conceptuses (n = 11) and endometrium (n = 10) obtained on Day 17 of pregnancy were cultured at thermoneutral (39 degrees C, 24 h) or heat stress (39 degrees C, 6 h; 43 degrees C, 18 h) temperatures in medium supplemented with L-[4,5-3H]leucine (100 microCi) and arachidonic acid (10 micrograms/ml). Radiolabeled protein secreted into culture medium increased with time in both groups. Heat stress reduced (p less than 0.001) incorporation of [3H]leucine into intracellular and secreted proteins by conceptuses but did not alter incorporation of [3H]leucine by endometrium. In particular, heat stress reduced by 72% the secretion of bovine trophoblast protein-1, the conceptus polypeptide believed to cause extension of luteal lifespan. Two-dimensional, sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that heat stress altered the array of proteins in endometrial and conceptus tissues, as evidenced by the induction of "heat-shock proteins." Endometrial secretion of prostaglandin F (p less than 0.001) and conceptus secretion of prostaglandin E2 (p less than 0.05) increased in response to heat stress. Sensitivity of bovine conceptuses and endometrium to heat stress in vitro suggests that infertility associated with maternal heat stress may be caused, partially by alterations in signals required for maintenance of the corpus luteum during early pregnancy.     

Fetal and maternal body temperatures measured by radiotelemetry in near-term sheep during thermal stress.

Using implanted radiotelemeters, we have measured amniotic temperature and fetal lamb and pregnant ewe body temperatures continuously over the last 34 days of gestation and during conditions of thermal stress. Body temperature of the fetus was approximately 0.6 degrees C higher than that of the mother, and the fetomaternal temperature difference remained constant over the last 25 days of gestation, until the immediate prepartum period, when it rose. During exposure to mild heat stress (35 degrees C dry-bulb temperature, 24 degrees C wet-bulb temperature), ewe and fetal body temperatures rose, but fetal temperature rose at a slower rate. Thus the fetomaternal temperature gradient fell significantly in the initial exposure period. In an environment of 4 degrees C, body temperature of the pregnant ewes fell, but the fetomaternal gradient did not change significantly. During maternal fever, heat loss from the fetus was compromised; body temperature of the fetus rose more than that of the mother, and the fetomaternal temperature gradient rose significantly. We suggest that mild heat or cold exposure in pregnant animals constitutes little risk of fetal thermal stress. During maternal fever, however, the fetus may be at risk of thermal injury.     

Effect of temperature and monensin on the level of intracellular sodium and pH in perfused RIF-1 cultured cells

The direct measurement of temperature in subcutaneously (sc) implanted tumors shows that the actual tumor temperature is by 3-4 degrees C lower than the normal body temperature. Thus, the temperatures usually used for tumor hyperthermia are in fact heating the sc-tumors from 33 to 37 degrees C. The temperature increase during the perfusion of radiation-induced fibrosarcoma (RIF-1) cells from 33 to 37 degrees C caused a reversible increase in intracellular 23Na ([Na+]i) NMR signal intensity by 50-60%. This heating significantly decreased the intracellular pH (pH) in 5 min, but it returned back to the baseline level during the heating period. The 3ATP/P(i) remained generally unchanged throughout the experiment. Monensin, an antitumoral drug and Na+ ionophor, increased [Na+]i by 20% during cell superfusion without heating. When combined, monensin did not increase the heating effect on [Na+]i. However, when monensin was added to the superfusion media, the [Na+]i level did not return to baseline during post-heating recovery, but instead started to increase again. Monensin did not significantly change pH(i) and betaATP/P(i). Our data and the literature show that monensin can accelerate the processes leading to the collapse of the transmembrane Na+ gradient and thus can increase the thermo-sensitivity of tumor cells.     

Measurement of fetal heat production using differential calorimetry

These experiments were undertaken to measure heat production of fetal lambs in utero by using differential calorimetry. We used the principle that fetal heat production, H(fetus), can be calculated from measurements of base-line temperature difference between mother and fetus, delta T(fetus), heat introduced from an external source, H(heater), and the increase in body temperature, delta T(heater), that results, i.e., H(fetus) = H(heater) X delta T(fetus)/delta T(heater). We placed microheaters (1.8 mm diam) in the inferior vena cavae of eight near-term lambs and placed thermistors and catheters into maternal and fetal vessels and amniotic fluid. Five days later, fetal arterial temperature averaged 0.54 +/- 0.02 degrees C (SE) higher than maternal arterial temperature. When the heater was turned on to dissipate 29-103 cal/min, fetal temperature increased to approach 0.1-0.5 degrees C higher than control; the final temperature was estimated using the rate of increase during the first 20 min. Fetal heat production averaged 47.1 +/- 4.1 cal X min-1 X kg-1 during the warming phase in these lambs, which weighed 3.26 +/- 0.36 kg. This value would be 3-4% less if corrected for the increase in metabolic rate caused by heating, assuming a Q10 of 2.5. Fetal heating did not alter fetal heart rate, blood pressure, or blood gas values significantly, nor was hemolysis visible in plasma samples. When heat production was calculated from the decrease in fetal temperature after the heater was turned off, an average value of 41.2 +/- 2.5 cal X min-1 X kg-1 was found. Because this value is comparable to the heating phase, fetal metabolic rate and the insulating properties of the fetal shell are not likely to have been changed by the heating.     

Effect of cooling and heating on the regional distribution of blood flow in fetal sheep

This is a study on the effect of cooling and heating amniotic fluid on blood flow to fetal tissues and organs. In 8 unanaesthetized, chronically-catheterised fetal sheep (129-137 days gestation) cold or warm water was passed through tubing encircling the fetus in utero and blood flow was measured using the radionuclide-labelled 15 mu spheres. Following cooling for 30 min, amniotic fluid temperature fell 9.6 degrees C to 29.9 +/- 2.1 degrees C (SEM) fetal arterial temperature fell 2.37 degrees C to 37.30 +/- 0.36, and maternal arterial temperature fell 0.53 degrees C to 38.58 +/- 0.16. Blood flow through the fetal skin fell 60% (P less than 0.01) to 13.6 ml/min per 100 g tissue. Blood flow to the brown fat increased 186% (P less than 0.05) to 99.6 ml/min per 100 g. Following warming for 20 min, fetal temperature rose to 40.43 +/- 0.19 degrees C, and skin blood flow did not change significantly relative to initial control period but rose 200% above that during cooling (P less than 0.01). During both cooling and heating, blood flow to the adrenals rose significantly (P less than 0.05) whereas flow to the carcass, brain, kidneys, and placenta was not altered detectably. Continuous sampling of blood from the inferior vena cava during microsphere injection failed to detect any evidence of arterio-venous shunting through the skin at any temperature studied. Overall, the blood flow responses are consistent with a thermoregulatory role for the skin and brown fat in the near-term fetal sheep.     

Body temperature and plasma prolactin and norepinephrine relationships during exercise in a warm environment: effect of dehydration

The effects of euhydration (Eh) and light (Dh1) and moderate (Dh2) dehydrations on plasma prolactin (PRL) levels were studied in 5 young male volunteers at rest and during exercise to exhaustion (50% of VO2max) in a warm environment (Tdb = 35 degrees C, rh = 20-30%). Light and moderate dehydrations (loss of 1.1 and 1.8% body respectively) were obtained before exercise by controlled hyperthermia. Compared to Eh, time for exhaustion was reduced in Dh1 and Dh2 (p less than 0.01) and rectal temperature (Tre) rose faster in Dh2 (p less than 0.05). Both venous plasma PRL and norepinephrine (NE) increased during exercise at any hydration level (p less than 0.05). Plasma PRL reached higher values after 40 and 60 min in Dh2 and Dh1 (p less than 0.05). Plasma NE values were higher in Dh2 at rest and at the 40th min during exercise (p less than 0.05). Plasma PRL was linearly correlated to Tre and plasma NE (p less than 0.001) but unrelated to plasma volume variation and osmolality. Our results provide further evidence for the major effect of body temperature in exercise-induced PRL changes. Moreover, the plasma PRL-NE relationship suggests that these changes may result from central noradrenergic activation.     

Efficiency of thermoregulatory system in man under endogenous and exogenous heat loads

The aim of the present work was to estimate the dynamics and efficiency (eta sw) of sweating, and thermoregulatory index (TI) defined as a ratio of heat loaded the body to the heat removed to the environment. In the first part of this work 22 men exercised with an intensity of 50% VO2 max. in 22 degrees C, 16 men were exposed to 40 degrees C at rest, and 9 men exercised at the level of 50% VO2 max. at 30 degrees C. In the second part, 8 men and 8 women were exposed to 40 degrees C before and after dehydration (1% of body mass, approximately), 8 men exercised at 23 degrees C before and after hyperhydration (35 ml/kg of body mass) and 22 men exercised before and after 3 months of endurance training. Body heat balance, rectal (Tre), tympanic (Tty) and mean skin (Tsk) temperatures were measured in all subjects. TI was greater during simultaneous (0.84) than during separate endo- (0.76, p less than 0.01) or exogenous (0.67, p less than 0.001) heat loads. The respective values of eta sw were 0.82; 0.57 (p less than 0.001) and 0.78 (p less than 0.001). No difference in TI was found between men and women. Dynamics of sweating was greater in men but efficiency of sweating was greater in women. Dehydration before heat exposure decreased both dynamics of sweating and TI but it increased eta sw in men. As a result Tre was greater in dehydrated (0.45 degrees C) than in normally hydrated men (0.31 degrees C, p less than 0.002). Dehydration did not affect the measured variables in women. Hyperhydration of exercising men caused an increase in TI from 0.72 to 0.82 (p less than 0.05) and in eta sw from 0.57 to 0.81 (p less than 0.01). In men exercising after endurance training the onset of sweating was shortened from 4.0 to 0.9 min (p less than 0.002). TI increased from 0.76 to 0.89 (p less than 0.001), eta sw increased from 0.57 to 0.74 (p less than 0.02) whereas Tty was lower (1.10 and 0.58 degrees C, p less than 0.001, respectively). It is concluded that dynamics and efficiency of sweating, as well as the thermoregulatory index depend on the type of heat load. Men and women tolerate dry heat equally well. Dehydration changes thermoregulatory function in men but not in women. Hyperhydration before exercise and particularly endurance training increase tolerance of endogenous heat.(ABSTRACT TRUNCATED AT 400 WORDS)     

Switching maternal dietary intake at the end of the first trimester has profound effects on placental development and fetal growth in adolescent ewes carrying singleton fetuses.

The aim was to investigate whether placental growth and hence pregnancy outcome could be altered by switching adolescent dams from a high to a moderate nutrient intake, and vice-versa, at the end of the first trimester. Embryos recovered from adult ewes inseminated by a single sire were transferred in singleton to peripubertal adolescents. After transfer, adolescent ewes were offered a high (H, n = 33) or moderate (M, n = 32) level of a diet calculated to promote rapid or moderate maternal growth rates, respectively. At Day 50 of gestation, half the ewes had their dietary intakes switched, yielding 4 treatment groups: HH, MM, HM, and MH. A subset of ewes were killed at Day 104 of gestation to determine maternal body composition in relation to growth of the products of conception. Maternal body composition measurements revealed that the higher live weight in the high-intake dams was predominantly due to an increase in body fat deposition, with a less pronounced increase in body protein. At Day 104, HH and MH groups (high intake during second trimester) compared with MM and HM groups (moderate intake during second trimester) had a lower (p < 0.002) total fetal cotyledon weight; but fetal weight, conformation, and individual organ weights were not significantly influenced by maternal dietary intake. In ewes delivering live young at term, a high plane of nutrition from the end of the first trimester (HH and MH groups) compared with moderate levels (MM and HM groups) was associated with a reduction in gestation length (p < 0.009), total placental weight (p < 0.002), total fetal cotyledon weight (p < 0.001), and mean fetal cotyledon weight per placenta (p < 0.001). Fetal cotyledon number was dependent on maternal dietary intake during the first trimester only and was lower (p < 0.007) in HH and HM ewes compared to MM and MH ewes. The inhibition of fetal cotyledon growth in HH and MH groups was associated with a major decrease (p < 0.001) in lamb birth weight at term relative to the MM and HM groups. Thus, reducing maternal dietary intake from a high to a moderate level at the end of the first trimester stimulates placental growth and enhances pregnancy outcome, and increasing maternal dietary intake at this time point has a deleterious effect on placental development and fetal growth.     

Influence of cortisol on prostaglandin synthesis by fetal membranes, placenta, and uterus of pregnant rabbits

Two experiments were designed to assess the effects of cortisol on prostaglandin formation in amniotic fluid and the prostaglandin-forming cyclooxygenase in 4 gestational tissues of rabbits. Cortisol treatment (12 mg/kg body wt/h) was initiated on Day 21 of pregnancy and continued for a 24-h period. Each experiment included 5 treated and 5 vehicle-injected controls, killed at 48 (Experiment 1) or 62 h (Experiment 2) after initial injection. In both experiments, amniotic fluid was collected; cortisol, prostaglandin F (PGF), and prostaglandin E2 (PGE2) were quantified by radioimmunoassay. Microsomes prepared from amnion, yolk sac splanchnopleure, uterus, and placenta were analyzed for prostaglandin-forming cyclooxygenase activity. In Experiment 2, blood drawn at 12-h intervals was quantified for PGF, PGE2, and progesterone. In cortisol-treated rabbits, plasma progesterone decreased (p less than 0.01) from 7.2 +/- 0.8 ng/ml on Day 21 (pre-treatment) to 1.6 +/- 0.2 ng/ml on Day 23, 48 h after the initiation of cortisol treatment. By 62 h, PGF, PGE2, and cortisol concentrations were all significantly higher (p less than 0.05) in the amniotic fluid of treated animals. However, prostaglandin-forming cyclooxygenase activity had not increased in most fetal or maternal tissues at either 48 or 62 h. Therefore, even though increased prostaglandin production may be responsible for the cortisol-induced abortion, increased cyclooxygenase activity in the fetal membranes, placenta, or uterus probably is not the primary stimulus for the increased prostaglandin synthesis.     

Effects in mice of high and low environmental temperature on the maternal and fetal toxicity of 2-sec-butyl-4,6-dinitrophenol (dinoseb) and on disposition of [14C]-dinoseb(12).

Swiss-Webster female mice were treated with 2-sec-butyl-4,6-dinitrophenol (dinoseb) and maintained in an increased environmental temperature (32 degrees C) for 24 h or a decreased temperature (0-6 degrees C) for 1.5-4 h. In two experiemtns animals maintained at low temperature were kept wet during the cold exposure, to enhance the reduction in body temperature, by rinsing them with water at approximately 30 min intervals. Results from nonpregnant females indicated that increased temperature lowered the LD50 for single injections of dinoseb from 20.2 to 14.1 mg/kg and that reduced temperature for 4 h had no effect on the LD50. A 24 h exposure to 32 degrees C enhanced the effect of 3 daily dinoseb treatments of pregnant mice; it increased maternal mortality, decreased fetal body weight, and increased frequency of fetal anomalies. Fetal body weight and the frequency of malformations were the same in groups exposed to low temperature and maintained at room temperature. Disposition of [14 C] dinoseb was also determined in nonpregnant mice exposed to temperatures of 0, 24, and 32 degrees C. The periods of environmental temperature studied (3-24 h) had no effect on the rate of disappearance of dinoseb from plasma or other tissues examined.     

Haemodynamic and catecholamine responses to hypothermia in the fetal sheep in utero

Chronically catheterised fetal sheep (117-134 days) were cooled in utero via a tubing coil placed around the fetal trunk through which cold water was circulated for one hour. The fetal core temperature was reduced by 5.51 +/- 0.61 degrees C. This hypothermia was associated with tachycardia (P less than 0.001) and hypertension (P less than 0.001) (n = 12). The tachycardia was abolished by treatment with propranolol (n = 4) and the hypertension by treatment with phentolamine (n = 5). Blood flow in the left umbilical artery was measured by an electromagnetic flow probe in 4 fetuses and rose (P less than 0.001) with fetal cooling. The increase in blood flow was abolished by treatment with either phentolamine or propranolol. These observations are consistent with a redistribution of fetal blood flow from peripheral tissues to placental and thermogenic tissues during cooling. Fetal plasma adrenaline and noradrenaline concentrations rose (P less than 0.01) during fetal cooling (n = 5). These studies demonstrate that catecholamine and cardiovascular responses to environmental hypothermia have differentiated prior to birth in the sheep fetus.