Near-term Lambs Research Articles

Effect of indomethacin on cerebral blood flow and oxygenation in the normal and ventilated fetal lamb.

Indomethacin lowers fetal and neonatal brain blood flow and may reduce the risk of periventricular-intraventricular hemorrhage. However, concerns have been raised that cerebral O2 metabolism may be compromised at lower cerebral perfusion pressures. In 17 near-term lamb fetuses, changes in brain blood flow and cerebral O2 metabolism (CMRO2) were measured at mean carotid arterial pressures (MCBP) ranging from 8 to 70 mm Hg. MCBP was adjusted by inflating balloon occluders around the aortic isthmus and brachiocephalic trunk. This was done before and during intrauterine pulmonary ventilation and oxygenation. Nine fetuses were pretreated with indomethacin (1 mg/kg i.v.); eight served as control. Changes in brain blood flow were assessed from carotid arterial blood flow (Qcar, mL/min) measured with flow transducers. In 15 animals, brain blood flow was also measured intermittently by radionuclide-labeled microspheres (Qbrain). Qcar correlated closely with Qbrain (r = 0.94, p < 0.0001); this relationship was not altered by indomethacin or by ventilation with oxygen. In the nonventilated fetuses, indomethacin decreased Qcar at pressures above the lower limit of cerebral autoregulation (43 mm Hg). However, at MCBP below 44 mm Hg, Qcar with indomethacin was not significantly different from controls. CMRo2 fell when MCBP was decreased below 30 mm Hg (range 8-29 mm Hg), but there was no significant difference between control and indomethacin-pretreated fetuses. In the ventilated fetuses, indomethacin reduced the slope of the pressure-flow relationship above the lower limit of cerebral autoregulation (43 mm Hg), suggesting improved cerebral autoregulation. When MCBP was decreased below 44 mm Hg (range 10-43 mm Hg), indomethacin did not lower Qcar or CMRO2 as compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of triiodothyronine administration on the catecholamine content of brown adipose tissue in near-term lambs delivered by caesarean section

The influence of triiodothyronine administration on the catecholamine content of brown adipose tissue in near-term lambs delivered by caesarean section

Effect of ambient temperature during 1st day of life on thermoregulation in lambs delivered by cesarean section

We examined the effect of delivering near-term twin lambs by cesarean section into a warm (30 degrees C) or cool (15 degrees C) ambient temperature on the control of thermoregulation. Heat production was measured 20-30 h after birth during non-rapid-eye-movement sleep at 29 and 14 degrees C. At 29 degrees C there was no difference in heat production between groups, but at 14 degrees C cool-delivered (CD) lambs exhibited a 62% greater metabolic response. Irrespective of delivery temperature, 15 of the 18 lambs used shivering thermogenesis during cold exposure, indicating a reduction in the ability to use nonshivering thermogenesis in brown adipose tissue (BAT). Mean plasma concentrations of thyroxine and triiodothyronine were 35 and 45% greater, respectively, in CD lambs than in warm-delivered lambs. The level of guanosine 5'-diphosphate binding in BAT was lower than in normally delivered lambs and was not different between CD and warm-delivered lambs. Cesarean section delivery prevents the rise in BAT thermogenic activity, which results in an increased reliance on shivering thermogenesis to maintain colonic temperature. Under these conditions, delivery into a cool environment increases the plasma concentration of thyroid hormones, which benefits the neonate by enabling a greater thermogenic response via shivering.

Inhaled nitric oxide reverses pulmonary vasoconstriction in the hypoxic and acidotic newborn lamb.

We determined whether inhaling low levels of nitric oxide (NO) gas could selectively reverse hypoxic pulmonary vasoconstriction in the near-term newborn lamb and whether vasodilation would be attenuated by respiratory acidosis. To examine the mechanism of air and NO-induced pulmonary vasodilation soon after birth, we measured plasma and lung cGMP levels in the newly ventilated fetal lamb. Breathing at FIO2 0.10 nearly doubled the pulmonary vascular resistance index in newborn lambs and decreased pulmonary blood flow primarily by reducing left-to-right blood flow through the ductus arteriosus. Inhaling 20 ppm NO at FIO2 0.10 completely reversed hypoxic pulmonary vasoconstriction within minutes. Maximum pulmonary vasodilation occurred during inhalation of > or = 80 ppm NO. Breathing 8% CO2 at FIO2 0.10 elevated the pulmonary vascular resistance index to a level similar to breathing at FIO2 0.10 without added CO2. Respiratory acidosis did not attenuate pulmonary vasodilation by inhaled NO. In none of our studies did inhaling NO produce systemic hypotension or elevate methemoglobin levels. Four minutes after initiating ventilation with air in the fetal lamb lung, cGMP concentration nearly doubled without changing preductal plasma cGMP concentration. Ventilation with 80 ppm NO at FIO2 0.21 increased both lung and preductal plasma cGMP concentration threefold. Our data suggest that inhaled NO gas is a rapid and potent selective vasodilator of the newborn pulmonary circulation with an elevated vascular tone due to hypoxia and respiratory acidosis that acts by increasing lung cGMP concentration.

Regional Cerebral Blood Flow after Hemorrhagic Hypotension in the Preterm, Near-Term, and Newborn Lamb

Developmental changes in regional cerebral blood flow (CBF) responses to hemorrhagic hypotension during normoxia and normocapnia were determined using radioactively labeled microspheres to measure flow to the cortex, brainstem, cerebellum, white matter, caudate nucleus, and choroid plexus in three groups of chronically catheterized lambs: 90- to 100-d preterm fetal lambs (n = 9); 125- to 136-d near-term fetal lambs (n = 9); and newborn lambs 5- to 35-d-old (n = 8). Heart rate, central venous pressure, and arterial blood pressure were monitored continuously and arterial blood gas tensions, pH, Hb, and oxygen saturation together with regional CBF were measured periodically. Hemorrhagic hypotension produced a mean decrease in arterial blood pressure of 27 +/- 4, 23 +/- 2, and 41 +/- 4% in the three groups, respectively, whereas reinfusion of the lamb's blood resulted in a return to control blood pressure within 3% in all three groups. In the pre-term fetal lamb, CBF decreased significantly in all regions during hypotension. In the near-term fetal lamb, only blood flow to the cortex decreased significantly during hypotension. In the newborn lamb, only the choroid plexus demonstrated a significant decrease in blood flow during hypotension. The lower limit of regional CBF autoregulation was identical to the resting mean arterial pressure in fetal life but significantly lower in newborn lambs. These experiments demonstrate for the first time that vulnerability to hypotension decreases with increasing maturity and that the brainstem, the phylogenetically oldest region of the brain, is the least vulnerable to the effects of hypotension at any age in the lamb model.

REGIONAL CEREBRAL BLOOD FLOW IN THE FETUS AND NEWBORN UNDER PHYSIOLOGICAL AND ASPHYXIAL CONDITIONS

Developmental changes in regional cerebral blood flow (RCBF) were determined using radioactively labelled microspheres to measure flow to the cortex (Cx), brainstem (Bs), cerebellum (Cbl), white matter (WM), caudate nucleus (CN) and choroid plexus (CP) in 3 groups of chronically catheterised lambs under physiological and asphyxia, conditions: 90-100 day preterm fetal lambs, 125-136 day near-term fetal lambs and newborn lambs 5-44 days old. In all 3 groups the high flow areas are the CP and CN while the lowest flow area is the WM. There is a different heirarchy of RCBF in utero (Bs and Cbl > Cx) compared to extrauterine life in the newborn lamb (Cx and Cbl > Bs). Analysis of regional cerebral oxygen delivery demonstrated a progressively increasing oxygen transport to the Cx with increasing gestational maturity, and after birth. Oxygen transport to the Bs, Cbl and WM increased with gestational age, but did not increase after birth. RCBF measurements revealed significantly different responses to asphyxia in the 3 groups. With asphyxia, there were significant decreases in oxygen transport to all cerebral regions with the exception of the Bs in the preterm lamb, in contrast to the maintenance of oxygen delivery to the Bs, Cbl, Cx, CN and WM in the near-term and newborn lambs. The response of CBF to hypotension during asphyxia revealed that the preterm brain was the most vulnerable, while the near-term and newborn brains were able to autoregulate regional CBF except in the CP. These experiments demonstrate that maturity of the animal is an important determinant of the response to asphyxia.

Ovine Abortion Due to Coxiella Burnetii Infection

9The organism is an obligate intracytoplasmic parasite in the family Rickettsiaceae. It causes Q fever in man and occasionally outbreaks of abortions in food animals such as sheep, goats, and dairy cows. The purpose of this report is to describe the pathology and microbiologic findings of a recent outbreak of abortion in sheep from northcentral California. Four aborted near-term lambs and 2 placentas were submitted for diagnostic examination to the Animal Disease Research and Diagnostic Laboratory of South Dakota State University, Brookings, South Dakota, in January 1987. They were submitted from a north-central California flock that had abortions occurring since October of the previous year. The disease appeared to be highly contagious, with the abortion rate varying from 10 to 60% within groups of the flock. Lambs were either aborted near term or born weak. Standard diagnostic procedures for ovine abortions were employed, including gross examination and collection of lung, liver, myocardium, brain, and placenta for histopathology in 10% neutral buffered formalin. For electron microscopy, formalin-fixed tissue was rinsed and postfixed in 2% glutaraldehyde and 1% osmium tetroxide and processed by standard procedures. Lung, placenta, and stomach contents were cultured by standard aerobic and microaerophilic methods. Impression smears were prepared from placental cotyledons and stained with Gimenez stain. Fluorescent antibody tests were done on frozen placental sections using Chlamydia groupspecific conjugate” and conjugate specific for C. burnetii.

Reactive oxygen metabolites relax the lamb ductus arteriosus by stimulating prostaglandin production.

To determine whether oxygen metabolites can cause ductus relaxation, we used rings of fetal ductus obtained from 36 near-term lambs and measured the effects of the oxygen metabolites generated by the combination of hypoxanthine and xanthine oxidase. The oxygen metabolites produced by hypoxanthine plus xanthine oxidase caused relaxation of the ductus that was inhibited by catalase (hydrogen peroxide scavenger) but not by superoxide dismutase (superoxide anion scavenger). In addition, hypoxanthine plus xanthine oxidase produced a 14-fold increase in prostaglandin (PG) E2 production with only twofold increase in 6-keto-PGF1 alpha (the stable metabolite of PGI2). PGE2 is the most potent relaxant of the ductus arteriosus. The presence of either catalase or indomethacin blocked both the increase in prostaglandin production and the relaxation. We conclude that reactive oxygen metabolites relax the ductus arteriosus and oppose the normal constriction that occurs after birth. However, the vasoactive effects of reactive oxygen metabolites in the ductus appear to be mediated exclusively through the generation of PGE2.

Development of pulmonary vascular response to oxygen.

The ability of the pulmonary circulation of the fetal lamb to respond to a rise in oxygen tension was studied from 94 to 146 days of gestation. The unanesthetized ewe breathed room air at normal atmospheric pressure, followed by 100% oxygen at three atmospheres absolute pressure in a hyperbaric chamber. In eleven near-term lambs (132 to 146 days of gestation), fetal arterial oxygen tension (PaO2) increased from 25 +/- 1 to 55 +/- 6 Torr (mean +/- SE), which increased the proportion of right ventricular output distributed to the fetal lungs from 8 +/- 1 to 59 +/- 5%. In five very immature lambs (94 to 101 days of gestation), fetal PaO2 increased from 27 +/- 1 to 174 +/- 70 Torr, but the proportion of right ventricular output distributed to the lung did not change, 8 +/- 1 to 9 +/- 1%. In five of the near-term lambs, pulmonary blood flow was measured. It increased from 34 +/- 3 to 298 +/- 35 ml.kg fetal wt-1.min-1, an 8.8-fold increase. We conclude that the pulmonary circulation of the fetal lamb does not respond to an increase in oxygen tension before 101 days of gestation; however, near term an increase in oxygen tension alone can induce the entire increase in pulmonary blood flow that normally occurs after the onset of breathing at birth.

Central stimulation of breathing movements in fetal lambs by prostaglandin synthetase inhibitors.

In unanaesthetized fetal lambs at 125-135 days gestation in utero central acidosis caused by perfusion of the cerebral ventricular system with a solution containing less than 1 mM-HCO3- (cerebrospinal fluid (c.s.f.) pH 6.98) or intravenous infusion of ammonium chloride (c.s.f. pH 7.1) produced an increase in the depth and frequency of episodic breathing but no change in electrocortical activity, heart rate or arterial pressure. Administration of prostaglandin synthetase inhibitors, sodium meclofenamate (0.8-10 mg/kg I.V. or 0.6-2.6 mg/kg intracerebrally) or acetylsalicylic acid (6.7 mg/kg I.V.) caused prolonged episodes of fetal breathing during low and high voltage electrocortical activity, with a large increase in breath amplitude. Blood gas values, heart rate, blood pressure, electrocortical activity and eye movements were not altered. In fetuses whose brain stems had been sectioned in the upper pons or the inferior colliculus, sodium meclofenamate induced prolonged deep breathing. Intravenous prostaglandin E2 abolished the continuous breathing induced by meclofenamate, but not breathing movements enhanced by hypercapnia or hypoxia. It is concluded that the central chemoreceptors respond to acidosis in near-term lamb fetuses qualitatively as in adult animals. Secondly, the results suggest that prostaglandin E2 and the inhibitors of prostaglandin synthesis also act centrally in the lower pons or medulla to modulate fetal breathing.

267 OXYGENATION DOES NOT STIMULATE HEPATIC GLUCOSE PRODUCTION IN FETAL LAMES

Previous studies have demonstrated zero glucose flux and absence of gluconeogenesis by the fetal liver. Shortly after birth, however, the newborn liver releases glucose both by glycogenolysis and by gluconeogenesis. Warnes et al have suggested that oxygen availability stimulates hepatic gluconeogenesis at birth. To test whether an increase in blood pO2 stimulates hepatic release of glucose, we studied 6 healthy fetal lambs at 136.5 days which had catheters chronically maintained in the right or left hepatic vein (HV), umbilical vein, inferior vena cava, and fetal descending aorta (FA), and a large tube in the trachea. We ventilated the lambs in utero, first with 57.CO2, 3%O2, 92%N2 and then with 95X02, 5ZC02- We measured hepatic blood flow by the microsphere method and hepatic glucose (Glu) flux by the Fick method. Our results (mean±SD) are as follows: These near-term lambs did demonstrate hepatic glucose production in the control period. However, although the results suggest that oxygenation increases HV Glu concentration, and decreases liver blood flow, the differences are not significant, and oxygenation did not change hepatic glucose flux. (Supported by HL24056.)

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.

INPUT IMPEDANCE OF FETAL AND NEONATAL LEFT PULMONARY ARTERIAL CIRCULATION

Interpretation of the change in pulmonary vascular resistance at birth ignores the hemodynamic consequences of pulsatile pressure and flow. Whereas, impedance analysis can account for such changes. We studied changes of input impedance (Zin) in the left pulmonary arterial circulation (LPAC) before and immediately after birth in four near-term lambs. Epochs of pressure and flow in the LPAC were obtained from a micromanometer and an electromagnetic flowmeter. A computerized spectral analysis program provided Zin in terms of a modulus spectrum [Zin] and phase spectrum (Oin). The [Zin] spectra of the fetus and newborn are qualitatively similar to those obtained by others in adult vascular beds, ie, as a consequence of a pulsatile flow at a given heart rate, the effective circulatory load at the entrance of the LPAC is less than Rp, the resistance of the arteriolar bed(decoupling phenomena). We interpret this as the LPAC presenting a similar hydraulic load to pulsatile potential hydraulic power. We conclude that the fetal and neonatal LPAC may not differ markedly in how it accomodates pulsatile hydraulic power at harmonics equal to heart rate.

Cardiovascular effects and clearance of arginine vasopressin in the fetal lamb.

Increased fetal secretion of arginine vasopressin (AVP) occurs in association with complicated pregnancies, asphyxia, and meconium-stained amniotic fluid (AF); yet, the role of AVP in fetal homeostasis remains unclear. Using chronically instrumented, near-term lamb fetuses (n = 8), we have ascertained the cardiovascular responses to doses of AVP ranging from 1.94 to 8.73 mU/min, the clearance of AVP from plasma, and the occurrence of meconium release into AF during AVP infusions. AVP administration resulted in a dose-related rise in arterial pressure; although heart rate fell, the decline was not dose-related and occurred before the pressor response. Clearance of plasma AVP was 60 +/- 8.7 ml X kg-1 X min-1, and the half-time in plasma was 2.8 min. AVP was not cleared across the fetal placenta nor by fetal-maternal transport. However, the AF concentration of AVP rose fourfold after the infusion of AVP was stopped. Meconium release into AF occurred in fetuses infused with AVP at rates greater than or equal to 7.76 mU/min. AVP has hemodynamic effects that mimic fetal responses to intrauterine "stress" and may be causally associated with the fetal release of meconium into AF. Furthermore, plasma AVP is cleared in part by the fetal kidney.

Effect of gestational age on ductus arteriosus response to circulating prostaglandin E 2

Premature newborn lambs with a patent ductus arteriosus have higher plasma prostaglandin E2 concentrations than near-term newborn lambs with a contricted ductus arteriosus. To see whether these concentrations of PGE2 could produce patency of the ductus arteriosus, we studied eight near-term lambs (with constricted ductuses) delivered by cesarean section, paralyzed, and mechanically ventilated. After ductus arteriosus resistance and plasma PGE2 concentrations had stabilized, a continuous PGE2 infusion into the superior vena cava was started to determine threshold concentrations needed to dilate the ductus in vivo. By two hours after birth, circulating PGE2 concentrations in near-term lambs were considerably less then the threshold concentration, and the ductuses were constricted. In five premature newborn lambs, significantly lower concentrations of PGE2 were required to dilate the ductus: threshold and ED50 concentrations were one sixth and one third, respectively. In these premature lambs during the first two hours after birth, circulating PGE2 concentrations were twice as high as the calculated in vivo threshold level. Therefore, circulating PGE2 concentrations probably played a significant role in the patency of the ductus arteriosus in these premature lambs.

Glucose metabolism and its regulation in pieces of perirenal adipose tissue from foetal lambs.

1. The following were measured in pieces of perirenal adipose tissue obtained from foetal lambs at about 120 days of gestation or within 3 days of term, and 9-month-old sheep: the rates of synthesis from glucose of fatty acids, acylglycerol glycerol, pyruvate and lactate; the rate of glucose oxidation to CO2 and the proportions contributed by the pentose phosphate cycle, pyruvate dehydrogenase and the tricarboxylic acid cycle; the activities of hexokinase, glucose 6-phosphate dehydrogenase, phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase. 2. The total rate of glucose utilization was lower in pieces of adipose tissue from near-term lambs than 120-day foetal lambs and the pattern of glucose metabolism differed, with, for example, a much smaller proportion of glucose carbon being used for fatty acid synthesis, whereas a greater proportion of glucose oxidation occurred via the tricarboxylic acid cycle in the near-term lambs. In general, these differences in glucose metabolism were not associated with differences in the activities of the various enzymes listed above. 3. The rates of glucose utilization per fat-cell by 120-day foetal lambs and 9-month-old sheep were very similar but, again, the proportions metabolized to the various products differed. In particular, there was a smaller proportion of glucose oxidized via the pentose phosphate cycle and a greater proportion oxidized via pyruvate dehydrogenase and the tricarboxylic acid cycle in adipose tissue from foetal lambs. These differences were matched by a lower activity of glucose 6-phosphate dehydrogenase and a higher pyruvate dehydrogenase activity in fat-cells from the foetal lambs.

Measurement of visual evoked potential in the asphyctic fetus and during neonatal survival

Visual evoked potentials were measured in eight exteriorized near-term fotal lambs prior to and during 8 minutes of asphyxia and during 1 hour of newbom survival. Four of the lambs were then extubated, and measurements were continued while the lambs were observed for behavior and gross motor function. Early in the aspnyctic period marked changes in the visual evoked potential occurred in association with a fall in Po2, whereas during the postexposure period the visual evoked potential appeared to recover independently of caidiovascular or arterial blood gas values. Moreover, early wave components of the visual evoked potential were more resistant to asphyxia than were later components and resporded more quickly to resuscitative efforts. During the survival period the visual evoked potential did not correlate with gross motor function when animals were exposed to moderate acidosis. After severe acidosis abnormal visual evoked potentials were seen during periods of clinical deterioration.

Prostaglandin D 2 reverses induced pulmonary hypertension in the newborn lamb

We investigated the effects of PGD2 in six near-term newborn lambs with induced pulmonary hypertension (mean pulmonary arterial pressure equal to mean systemic arterial pressure). In each lamb PGD2 decreased mean pulmonary arterial pressure, increased pulmonary blood flow, and therefore decreased pulmonary vascular resistance without changing mean systemic arterial pressure. A bolus dose of 20 micrograms PGD2 decreased pulmonary arterial pressure by 30%, increased pulmonary blood flow by 45%, and decreased pulmonary vascular resistance by 54%; systemic arterial pressure increased by 4%. At all doses, pulmonary vascular resistance fell further than systemic vascular resistance, the ratio of percent change in pulmonary vascular resistance to percent change in systemic vascular resistance was approximately 2:1. Similar changes occurred with continuous infusions of PGD2. These effects suggest a role for PGD2 in the normal regulation of pulmonary vascular resistance and blood flow at birth. In addition, because PGD2 in these circumstances increases pulmonary blood flow and reduces pulmonary arterial pressure, it may merit further trials in nonhuman primates; it may be an appropriate agent for treating newborn infants with persistent pulmonary hypertension.

Developmental aspects of the renal response to hypoxemia in the lamb fetus.

The effects of fetal hypoxemia on renal hemodynamics and renal function were studied in two groups of chronically catheterized young (< 120 days of gestation) and near-term lamb fetuses (> 130 days). Fetal hypoxemia produced, in both groups, a significantly decrease in renal blood flow (RBF) and a significant increase in the filtration fraction. However, the glomerular filtration rate (GFR) did not change significantly suggesting that the renal vasoconstriction associated with fetal hypoxemia was more important at the efferent than at the afferent arteriolar level. In the group of near-term fetuses, the decrease in RBF correlated closely with changes in plasma renin activity (PRA) (r = 0.77). No changes in PRA were observed during hypoxemia in the group of young fetuses. After hypoxemia, reactive hyperemia associated with a significant increase in urinary prostaglandin excretion (PGE and PGF2 alpha) was observed in near-term fetuses but not in young fetuses. It also was demonstrated that fetal hypoxemia produced a significant increase in fetal plasma concentrations of vasopressin associated with an antidiuresis in all but one near-term fetus and in 50% of the young fetuses, suggesting that the ability of the fetal kidney to reabsorb free water is more developed in near-term fetuses. Finally, fetal hypoxemia had no effect on mean arterial pressure and heart rate in young fetuses; however, in near-term fetuses, a significant increase in blood pressure and a decrease in heart rate were observed. In summary, it appears that the response of the fetal kidney to hypoxemia depends on the degree of fetal maturation.

Intracranial hemorrhage following intravenous administration of sodium bicarbonate or saline solution in the newborn lamb asphyxiated in utero.

The effects of intravenously administered sodium bicarbonate were studied in near-term neonatal lambs asphyxiated in utero by maternal hypotension. Following tracheal intubation and manual ventilation with 100 per cent oxygen, the extracellular base deficits of ten neonates were corrected with sodium bicarbonate, 4.2 per cent, in 5 per cent dextrose (964 mOsm/1). Nine neonates alternatively received an isovolumic infusion of physiologic saline solution, 0.5 percent, in 2.5 per cent dextrose (314 mOsm/1). Following sodium bicarbonate infusion (mean dose 6.7 mEq/kg), serum sodium and osmolality immediately increased to 160 mEq/1 and 335 mOsm/1, respectively. However, sodium values were similar in the two groups by 15 min after infusion. Although significant differences in PAO2 values were not found between groups after infusion, sodium bicarbonate therapy was associated with a significantly higher PAO2 value (175 ± 60 torr) than was treatment with saline solution (51 ± 8 torr) in neonates with pHa