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The energy-rich substrates available to the fasting stressed baboon neonate and infant are quantitatively similar to the metabolic fuels presented to the stressed low birth weight human newborn. Within a few hours after birth, fasting arterial plasma glucose levels in the baboon neonate approximate those of 4–6-week-old baboon infants after a 20-hr fast. Lactate levels are high and comparable for both age groups. In contrast, β-hydroxyburyrate is quite low in the immediate neonatal period, but rises to significantly higher levels (P< 0.001) after a fast at 4–6 weeks. In addition, glycerol levels are higher (P< 0.02) in the fasted older infant compared with the fasting neonate.

Summary: The energy-rich substrates available to the fasting stressed baboon neonate and infant are quantitatively similar to the metabolic fuels presented to the stressed low birth weight human newborn. Within a few hours after birth, fasting arterial plasma glucose levels in the baboon neonate approximate those of 4–6-week-old baboon infants after a 20-hr fast. Lactate levels are high and comparable for both age groups. In contrast, β-hydroxyburyrate is quite low in the immediate neonatal period, but rises to significantly higher levels (P < 0.001) after a fast at 4–6 weeks. In addition, glycerol levels are higher (P < 0.02) in the fasted older infant compared with the fasting neonate.Computation of mean cerebral blood arteriovenous differences and oxygen equivalents for animals studied in the first 50 hr of life demonstrates that glucose uptake can account for 50% or less of cerebral oxygen consumption in the newborn period. In confirmation, the respiratory quotient in these animals is 0.52 ± 0.06.Cerebral oxygen consumption in the immediate neonate is greater than can be explained by utilization of glucose and the small quantities of acetoacetate and β-hydroxybutyrate available at this time. At birth, cerebral uptake of lactate is noted, but this phenomenon is not observed at 6 and 12 weeks of ageSpeculation: The baboon model for dynamic studies of neonatal energy metabolism may permit investigations of greater clinical relevance than those in lower mammalian model systems. It is suggested that lactate may be a significant cerebral energy source in the immediate neonatal period.

• Prolonged venous access is desirable in very-low-birth-weight infants and infants for whom feedings are contraindicated. We prospectively evaluated 481 small-diameter venous catheters placed percutaneously in 317 patients over 3 years. Of 478 catheters, 241 (50%) were placed in infants weighing 1 kg or less. Mean catheter stay was 13 days (range, less than 1 to 77 days). Almost half (49%) of the central and thoracic catheters (91% of placements) were removed nonelectively: 43% due to problems such as leaking or clotting and 6% to suspicion of sepsis or venous occlusion. Of the 23 episodes of possible sepsis in the 478 catheter stays, six (1.3%) were confirmed catheter-related sepsis; 12 (2.5%) were confirmed alternate locus sepsis. Three factors specific to percutaneous central venous catheter-ralated sepsis were prolonged catheter stay (3 to 5 weeks), Staphylococcus epidermidis, and weight less than or equal to 1 kg. Four factors specific to alternate locus sepsis were presence of an alternate infection site, earlier infection (1 to 2 weeks), extremely low birth weight, and prolonged clinical instability. Percutaneous central venous catheterizations reduced the need for the stress of repeated venipuncture, resulting in lower complication rates than those reported with surgically placed central venous catheters, and leading to identification of risk factors specific to catheter sepsis and alternate locus sepsis.(AJDC. 1990;144:1246-1250)

Estimates of splanchnic energy substrate exchange in the primate infant have been obtained using a baboon model. The splanchnic bed of the fasting baboon newborn released glucose at an estimated rate of 14.5 ± 5.0 µmol/min·kg body weight. Splanchnic glucose release in the fasting 5-7-wk old baboon infant proceeded similarly at an estimated rate of 15.5 ± 4.5 µmol/min·kg body weight. The principal precursors taken up by the splanchnic bed were lactate, glycerol, and alanine. Uptake of alanine correlated in a linear fashion with glucose release. Lactate was the most important precursor in both age groups. Glucose recycling through lactate is an active mechanism in the primate fetus as well as in the young of other species.

Objective: To review literature identifying a central venous catheter (CVC) as either a primary or a secondary source of sepsis.

ABSTRACT: Estimates of splanchnic energy substrate exchange in the primate infant have been obtained using a baboon model. The splanchnic bed of the fasting baboon newborn released glucose at an estimated rate of 14.5 ± 5.0 µmol/min·kg body weight. Splanchnic glucose release in the fasting 5-7-wk old baboon infant proceeded similarly at an estimated rate of 15.5 ± 4.5 µmol/min·kg body weight. The principal precursors taken up by the splanchnic bed were lactate, glycerol, and alanine. Uptake of alanine correlated in a linear fashion with glucose release. Lactate was the most important precursor in both age groups. Glucose recycling through lactate is an active mechanism in the primate fetus as well as in the young of other species.

Extract: Measurement of intrarenal distribution of renal blood flow by injection of radionuclides in 3—5-day-old infant monkeys showed a preponderance of outer cortical over inner cortical flow with flow rates of 4.23 and 2.54 ml/min/g, respectively. Intermittent positive pressure ventilation (IPPV) causes a reversal of this flow pattern. The theoretical difference in nephron function in these two areas suggests that this reversal in intrarenal flow induced by IPPV may have important clinical implications.Speculation: Extrarenal stimuli such as IPPV causes a redistribution of intrarenal blood flow in infant primates. Any stimuli that results in increased production of epinephrine or similar compounds may be responsible for this redistribution by a local effect on outer cortical blood vessels. Our data further suggest that antidiuretic hormone may influence intrarenal blood flow in addition to altering tubular membrane permeability.

Objective: To review the literature related to venous access for parenteral infant feeding.

To review literature identifying a central venous catheter (CVC) as either a primary or a secondary source of sepsis.

The age-related changes in fasting arterial levels of energy substrates and insulin were studied at birth and/or 6 wk in eleven baboon infants. In addition, the renal contribution to glucose release in the primate infant was estimated. Arterial blood glucose levels were similar in six fasted newborns and in nine fasted 6-wk-old infants. Arterial blood lactate, alanine, pyruvate, glutamate, and glutamine levels were significantly higher (P< 0.01) in the new born animals, and β-hydroxybutyrate was significantly higher in the older animals (P< 0.001). Arterial plasma insulin levels were low in both groups. Levels of blood glucose in the inferior vena cava below the renal vein were significantly lower than levels in the aorta (P< 0.01). In contrast, levels of blood glucose in the inferior vena cava above the renal vein were significantly higher than in the aorta (P< 0.05). Computed renal vein glucose levels were higher than those in the aorta (P< 0.01). In the newborn infants, there was significant renal uptake of lactate, pyruvate, glycerol, and glutamine (P< 0.01), and release of β-hydroxybutyrate (P< 0.05). In the older animals, there was renal uptake of alanine, lactate, pyruvate, and glycerol (P0.01). Mean cardiac output per kg body weight did not differ significantly in the newborn and 6-wk-old infants.

Measurement of intrarenal distribution of renal blood flow by injection of radionuclides in 3—5-day-old infant monkeys showed a preponderance of outer cortical over inner cortical flow with flow rates of 4.23 and 2.54 ml/min/g, respectively. Intermittent positive pressure ventilation (IPPV) causes a reversal of this flow pattern. The theoretical difference in nephron function in these two areas suggests that this reversal in intrarenal flow induced by IPPV may have important clinical implications.

Gluconeogenesis from lactate may be qualitatively identified in the chronically catheterized baboon fetus in the maternal fed and fasted state. Infusion of 250 μCi U-14C-lactate to the fetus over a 150-min period leads to the appearance of 14C-glucose in the fetal circulation. Little 14C-lactate or glucose appears in the maternal circulation, supporting fetal production of glucose from lactate. Maternal glucose infusion seems to inhibit fetal gluconeogenesis. The mean plateau in percent disintegrations per minute of glucose compared to lactate in the maternal fed state is 14.7 ± 2.2 compared to 16.1 ± 3.0 in the maternal fasting state and 11.1 ± 0.6 during maternal glucose infusion. It is clear that the primate fetus is capable of gluconeogenesis before term. Quantitation of this capacity awaits development of a model permitting assessment of maternal-placental and fetal substrate flux.

We examined the effects of maternal sodium ß-hydroxybutyrate (NaBOHB) on the primate fetus to investigate the impact of ketosis not associated with acidosis on fetal metabolism. After a loading dose (600 mg/ kg), NaBOHB was infused for 70 min (300 mg/kg hr) into the maternal femoral vein of eight pregnant baboons, and placental transfer and fetal and maternal metabolic changes were observed during an acute experimental protocol. Maternal arterial levels rose from 0.70 ± 0.21 to 5.42 ± 0.93 mM (p<0.001), and fetal arterial levels from 0.34 ± 0.09 to 2.76 ± 0.64 mM (p<0.01). A maternalfetal gradient of approximately 21 was observed in both baseline and steady-state infusion conditions and is similar to the human maternal-fetal ketone gradient. This is in contrast to the sheep where significantly higher gradients have been described. The elevated lactate, from 1.90 ± 0.34 to 2.88 ± 0.54 mM (p<0.05) and somewhat decreased pO2values in the fetus from 54.8 ± 8.9 to 45.0 ± 3.8 mm Hg (p>0.05<0.1), without change in oxygen consumption (2.00 ± 0.28 versus 1.73 ± 0.15 mM/min) are features common to conditions of increased levels of fetal energy substrate. NaBOHB does not appear to contribute to oxidative energy metabolism of the whole fetus but may contribute to lipid stores. The significance of higher levels of BOHB in the primate fetus compared to the sheep fetus remains to be elucidated

Veno-arterial differences for energy substrates across hindlimb tissues were measured in baboon infants at birth and at 6 weeks. Hindlimb glucose uptake was 2.36 ± 0.80 μM/min in the newly born baboons and 1.81 ± 0.56 μM/min in the 6-week-old infants. The major precursor released by the infant baboon hindlimb was lactate, although release of alanine and glycerol was significant. These studies complement previous data suggesting that glycolysis is a major pathway for energy production in the infant primate.

ABSTRACT: We examined the effects of maternal sodium ß-hydroxybutyrate (NaBOHB) on the primate fetus to investigate the impact of ketosis not associated with acidosis on fetal metabolism. After a loading dose (600 mg/ kg), NaBOHB was infused for 70 min (300 mg/kg hr) into the maternal femoral vein of eight pregnant baboons, and placental transfer and fetal and maternal metabolic changes were observed during an acute experimental protocol. Maternal arterial levels rose from 0.70 ± 0.21 to 5.42 ± 0.93 mM (p<0.001), and fetal arterial levels from 0.34 ± 0.09 to 2.76 ± 0.64 mM (p<0.01). A maternalfetal gradient of approximately 2:1 was observed in both baseline and steady-state infusion conditions and is similar to the human maternal-fetal ketone gradient. This is in contrast to the sheep where significantly higher gradients have been described. The elevated lactate, from 1.90 ± 0.34 to 2.88 ± 0.54 mM (p<0.05) and somewhat decreased pO2values in the fetus from 54.8 ± 8.9 to 45.0 ± 3.8 mm Hg (p>0.05<0.1), without change in oxygen consumption (2.00 ± 0.28 versus 1.73 ± 0.15 mM/min) are features common to conditions of increased levels of fetal energy substrate. NaBOHB does not appear to contribute to oxidative energy metabolism of the whole fetus but may contribute to lipid stores. The significance of higher levels of BOHB in the primate fetus compared to the sheep fetus remains to be elucidated.

Summary: The age-related changes in fasting arterial levels of energy substrates and insulin were studied at birth and/or 6 wk in eleven baboon infants. In addition, the renal contribution to glucose release in the primate infant was estimated. Arterial blood glucose levels were similar in six fasted newborns and in nine fasted 6-wk-old infants. Arterial blood lactate, alanine, pyruvate, glutamate, and glutamine levels were significantly higher (P < 0.01) in the new born animals, and ß-hydroxybutyrate was significantly higher in the older animals (P < 0.001). Arterial plasma insulin levels were low in both groups. Levels of blood glucose in the inferior vena cava below the renal vein were significantly lower than levels in the aorta (P < 0.01). In contrast, levels of blood glucose in the inferior vena cava above the renal vein were significantly higher than in the aorta (P < 0.05). Computed renal vein glucose levels were higher than those in the aorta (P < 0.01). In the newborn infants, there was significant renal uptake of lactate, pyruvate, glycerol, and glutamine (P < 0.01), and release of ß-hydroxybutyrate (P < 0.05). In the older animals, there was renal uptake of alanine, lactate, pyruvate, and glycerol (P 0.01). Mean cardiac output per kg body weight did not differ significantly in the newborn and 6-wk-old infants.Lactate uptake was potentially responsible for 59% of mean renal glucose output in the newborn and 76% of mean renal glucose output in the older infant. Net renal glucose release in eight 6-wk-old infants was estimated to be 3.5 ± 1.1 µM/min · kg (95% confidence limits, 0.7 < 3.5 < 6.2). Net renal glucose release in three newborn infants was 4.7, 5.4, and 19.8 µM/min · kg. There was a significant linear relationship between arterial lactate levels and renal glucose production in the older infants (P < 0.05). Extremely low arterial pH was associated with increased renal glucose release in the newborn, and high arterial pH with decreased or absent glucose release in the 6-wk-old animals.Speculation: The primate infant kidney has a capacity for gluconeogenesis which is apparently enhanced by acidosis and lactate availability. In the stressed human neonate, it is possible that renal gluconeogenesis could be a significant and uncontrolled source of new glucose, leading to hyperglycemia.

We have reviewed 934 perinatal deaths from 1976 through 1983 among 28,000 inborn births in an urban perinatal center hospital. During perinatal mortality review the principal cause of death was assigned by one individual (JBP) into 7 fetal and 7 neonatal major diagnostic groupings; autopsy information contributed to assignment in 80%. Perinatal asphyxia accounted for approximately 50% of the neonatal deaths; over time there tended to be a redistribution with increased contribution from the 500-750g group. Congenital anomalies decreased from 11.7% to 9.1% while infection tripled from 8.3% to 25%. The most impressive change was the decrease in immaturity as the principal cause from 21% to 4.5%; this change may represent an artifact of having more information available for the review process. For 33% of fetal deaths cause was undetermined. The next common cause was placental abruption, 18.5% overall, with no real change over time; in contrast maternal disease and Rh disease decreased from 12% to 10% respectively to 2.3% for each group. The wt specific distribution of perinatal mortality, except for >2500g, has been progressively towards the <1000g infant, now accounting for over 2/3 of perinatal mortality and clearly identifying prematurity as the most important unsolved problem. In addition, these data identify other causes of death to direct education and intervention programs to improve outcome for both the fetus and newborn.

To plan appropriate obstetric and pediatric intervention for pregnancies resulting in VLBW infants, the physician needs to be informed of outcome data at the delivering institution. We reviewed 9552 live births from Jan ′82 through Aug ′84 when our crude neonatal mortality rate was 15.5 and our VLBW rate was 3.8%. Because of rapidly improving outlook for VLBW infants, BW and GA specific mortality analysis by 100g increments or 1 week GA intervals is essential. Of 137 neonates, weighing 600-1499g, with Apgar score of 4 or more, the survival was 93%. For 190 neonates between 23 & 32 weeks GA, with 1 min. Apgar score of 4 or more, survival was 94%. g ao When the 1 min Apgar score was 3 or less, survival was 51% and 57% for comparable BW and GA groups. Prolongation of pregnancy is the most important factor to improve outcome for the VLBW infant; when this is not possible assuring optimal condition at birth becomes the highest priority.

Glucose (Glu) levels are exceedingly low in the ovine fetus and the ungulate liver has little measurable glucokinase. Nonetheless, at term, the fetal (Fet) sheep liver contains significant glycogen stores. Recent suggestions that glycogenesis in the adult may proceed through the gluconeogenic pathway led us to examine the capacity of lactate (Lac) to serve as a glycogenic precursor in the chronically catheterized Fet sheep. Six ovine fetuses were prepared with aortic (Ao) and inferior vena cava (IVC) catheters. On day 5 post surgery, after a maternal (Mat) 48 hour fast, a steady state Mat venous infusion of Glu was begun sufficient to raise Mat blood Glu from 19.41.6 mg/dl to 48.6±6.2 mg/dl. A simultaneous infusion of 300 uC (U-14C) Lac was administered to the Fet IVC over a 5 hour period to steady state. Six Fet Ao and Mat art. samples were obtained q 10 min during the last 60 min of the infusion. The fetus and ewe were then sacrificed and liver removed for determination of glycogen and 14C glycogen enrichment. Minimal radiolabel was found in Mat blood or liver glycogen. Fet blood levels were Lac 13.6±1.3 mg/dl (SA 42±9 uc/mg×103), fructose 70.2±10.4 mg/dl (SA 1.0±.2 uc/mg×103), Glu 23.2±4.3 mg/dl. No Lac-derived labelled Fet Glu could be reliably detected. Fet hepatic glycogen was 40.0±6.5 mg/g liver (SA 1.4±.5 uc/mg×103). The SA of glycogen and absent Glu labelling suggests that Lac is a precursor of Fet glycogen through the gluconeogenic path. This is teleologically important, since placental conversion of Mat Glu to Lac maintains higher levels of Lac in the Fet circulation and seems to be a means for Fet conservation of energy stores.

Subhuman primates are frequently used as models of human perinatal physiology and pathology. In order to obtain normal data for organ growth and blood flow 65 measurements were made on baboons from 115 days gestation (term 184 days) to age 8 weeks during acute surgical experiments using the radioactive microsphere method to estimate cardiac output and organ blood flow.From 115 days to term, while body weight triples, biventricular cardiac output per kg body weight increases by about 50% -- a level that is maintained postnatally from birth to 8 weeks while body weight increases about 50%. Brain weight increases by about 150% during the last third of pregnancy while blood flow increases almost 6-fold. There is a significant decrease in cerebral blood flow in the transition from fetus to neonate but increased blood oxygen content maintains oxygen delivery at the prepartum level. Postnatally there is a 25% increase in brain weight and a comparable increase in blood flow with all of the increase in blood flow distributed to the cerebral cortex. In contrast, renal growth and blood flow over the age-span studied parallel changes in total body growth accounting for about 0.6% of body weight and about 4% of biventricular cardiac output.

Chicago has shown a decrease in PM over the past decade more gradual than the Nation as a whole. We looked for an explanation to PM data over the past decade 1973-83 for our Perinatal Center (74,589 deliveries) which serves a large high-risk population. In 1979, maternal transfers/transports began to impact on delivery populations, a trend which has accelerated to the present. Crude PM rate dropped from 39 to 30. Deliveries <1500g (VLBW) increased from 3.2% to 4.9%; PM <1500g has dropped from 708 to 469. Deliveries <750g increased from 1.4 to 2.0%, while their contribution to PM rose from 36% to 58%; for every higher weight category the contribution to PM decreased. In particular between 750-1500g PM decreased from 542 to 170. Neonatal mortality improved for each 250g weight group <1500g while each group contributed a larger fraction to the delivery population. The net effect on crude neonatal mortality, 16.2 to 16.9, is less dramatic considering the improvements in perinatal care. In contrast, in our network of hospitals neonatal mortality went from 19.5 in 1978 to 14.5 in 1983. There has been a dramatic redistribution of VLBW deliveries with the Center increasing from 2.8 to 3.5% of live births while the Network has decreased from 2.6 to 1.2% with a System wide decrease of less than 0.5% VLBW. These data demonstrate that improved perinatal care and regionalization can affect weight-specific outcome; a major impact on overall survival awaits significant reduction of VLBW rates.

Cytochrome P-450 mediated mixed function monooxygenases (P-450) are a group of enzymes which metabolize many substrates including steroids, environmental chemicals and drugs. P-450 in animals has been shown to be important in certain chemical induced birth defects, cancer, mutations and organ damage. Select P-450 isozymes can be induced by exposure to certain chemicals. We and others have shown that P markedly decreases maternal hepatic P-450 function. To further investigate the effect of P on P-450 we used an HPLC method (PNAS 77:6473 1980) to analyze tlhe profile of P-450 during P. Solubilized hepatic microsomes from non-pregnant female and pregnant C57BL/6 mice were compared. Comparison of elution profiles of P-450 from nonpregnant and pregnant mice show a marked increase during P in a specific peak (P-450-P) as shown. P-450-P did not co-chromatograph with the classical P-450 isozyme peaks induced by phenobarbital, 3 methylcholanthrene, or pregnenolone-16 ∝ carbonitrile. P-450-P is detectable by day 6 of gestation and remains elevated at least through post partum day 3. In summary, P induces in mice a new major P-450 isozyme peak, P-450-P, which does not co-chromatograph with the classical forms of P-450.

Regulation of gluconeogenesis has been studied in 4 baboon fetuses (135-140 d.) with catheters chronically placed in the inferior vena cava and aorta, using a single isotope-labeled precursor technique. A primed infusion of [u-14C] lactate (Lac) was administered to the fetus to steady state over 150 min. Net Lac to glucose (Glu) conversion was evaluated by comparing fetal (Fet) and Maternal (Mat) dpm and specific activity (S.A.) of Lac and Glu during Mat fed (4), fasting (4), and Glu infusion (1) (Iglu).Mat/Fet Glu dpm were 36.0±1.9% fed, 51.4±3.1% fasting (p<.001) and 9.2% during Iglu. Mat/Fet Glu S.A. was 27.6±2.4% fed, 44.7±5.2% fasting (p<.001) and 9.5% during Iglu. Fet to Mat placental transfer of Glu and Lac is more efficient in the baboon than in the sheep, but higher Fet than Mat 14C Glu enrichment confirms the capacity of the primate fetus for gluconeogenesis. Fet gluconeogenesis from Lac is regulated by Mat nutrient status and substrate supply.

In order to assess the contribution of the direct [phosphorylation(P) of glucose] vs indirect [P of other precursors) pathway of glycogenesis in the fetus(fet), ten baboon fet of 140 d gestation were studied after placement of femoral artery (FA) and umbilical vein(UV) catheters. On day 4 post surgery, after a 24h fast, maternal(mat) baboons were sedated and mat plasma glucose(G) was raised to 68±3 mg/dl with 10%G to mat vein. A primed dose of 50 uc/h U-14C L and 2-3H G (n=5), or U-14C F and 3-3H G(n=5) was infused to steady state into the UV over 3h. Six FA samples were obtained 90-180 min, the fet was sacrificed under mat-fet general anesthesia, and kidney and liver removed for determination of glycogen (gly) and 14C, 3H gly enrichment. Fetal blood 14C G derived from L SA was 4.0±.5, 14C G from F SA was 11.0±1.5, 2-3H G SA was 42.0+2.5, and 3-3H G SA, was 35.0±5.(uc/mg(103). Organ gly SA was calculated as uc/mg(103):SA organ gly/SA G reflects the fraction of gly derived from label. 14C SA kidney gly/SA G was greater than 2-3H or 3-3H ratio for F and L fet(p<.004). 14C SA liver gly/SA G was greater for F vs 2-3H, 3-3H(p<.002, p<.05) and L vs 2-3H(p<.002), but similar for L fet vs 3-3H. This is more than can be explained by intraorgan futile cycling. The indirect pathway may be an important route of glycogenesis in gluconeogenic organs of the fetus.

Adequate calorie intake, 120 cal/kg/day, was maintained from age 48 hours in two groups of low birth weight infants, 1001-1250g. and 1251-1500g., by continuous duodenal or proximal jejunal infusion(NJ) of commercial infant formula. The neonatal course of these infants was compared with a control group(C) fed conventionally by intermittent gavage feedings. The NJ groups were comparable to controls in birth weight, discharge weight and mortality; however, maximum weight loss was reduced by about 50% in the NJ groups with a comparable reduction in the time to regain birth weight. Hospital stay was reduced in the lower but not in the higher infant weight group. No significant complications of the feeding tube or the accelerated feeding program were encountered.Early malnutrition may have a detrimental effect on developmental potential; this technique permits greater control over the duration and severity of catabolism in the early neonatal period.

The response of the fetus to systemic acidosis has been studied in 8 fetal baboons age 160 gestation. Lactic acid 4meq/kg fetal weight) was infused over a 15 min. period. pH, pCO2, HCO3, base excess and lactate were measured in fetal blood and urine, amniotic fluid and maternal blood and urine. TA and NH4were measured in amniotic fluid and in fetal and maternal urine Fetal femoral artery blood pH fell from 7.22 to 7.16 after lactic acid infusion. After 18 min., the fetal blood pH had returned to control values. Fetal UpH did not significantly change from the mean control value and there was no increase in TA or NH4. The infused acid was distributed as follows during 75 min. following the infusion.These data support our hypothesis that fetal acid-base balance is primarily maintained by placental clearance of H+ as more than 82% of the infused acid is rapidly cleared by this organ. Fetal-amniotic fluid exchange is also an important homeostatic mechanism. The clearance of only 0.2% of the infused acid by the kidneys indicates no significant participation in acid-base homeostasis in utero by these organs. This is not inconsistent with our previous demonstration of a mature H+secretory capacity for the fetal kidney.

Uptake of glucose and release of gluconeogenic precursors by the hindlimb of the fasting baboon infant was evaluated in 6 baboon neonates after delivery by cesarean section at term and 8 6-week-old baboon infants. Arteriovenous (AV) differences across the hindlimb were determined by measuring substrate levels in the aorta and the inferior vena cava below the level of the renal veins and above a unilaterally occluded femoral vein.There were no significant AV differences for pyruvate, beta-hydroxybutyrate, glutamate or glutamine. Production and uptake was calculated using hindlimb blood flows determined by the radioactive microsphere method. Glucose consumption by the hindlimb in the neonate was 2.4 μM/min. Uptake by the entire carcass was estimated to be 9.6 μM/min, almost twice the previously estimated cerebral cortex glucose consumption (5.6 μM/min). Estimated splanchnic and renal glucose production (15.7 μM/min) could account for all (15.2 μM/min) of estimated cerebral and carcass glucose uptake. The fasting neonate has a substantial glucose utilization rate exclusive of the requirement of the central nervous system.

Serial hemodynamic changes following intravenous E. coll 0111B4 endotoxin were evaluated in 28 puppies, 1-18 days and 270-1800 grans. Serial cardiac outputs were measured by a modified reinfusion dye dilution technique. Heart rate and systemic arterial pressures also were measured. Changes were recorded at 5 min, 10 min and at 10 min intervals thereafter for 1 hour following endotoxin. Heart rate dropped from 210/min to 141/min at 5 min and stabilized at a slightly higher level thereafter (p < 0.01). Mean systemic pressure decreased gradually from 70 mm Hg to 42 mm Hg at 1 hour (p < 0.01). Cardiac index decreased from 266 ml/min/kg to 131 ml/min/kg at 5 min and continued to decline to 115 ml/min/kg at 1 hour (p < 0.01). Systemic vascular resistance rose from 0.467 unit to 0.846 unit at 5 min and remained elevated at slightly lower level at 1 hour (p < 0.01). Minute work decreased at 5 min from 0.301 Kg-m/kg to 0.134 Kg-m/kg and to 0.066 Kg-m/kg at 1 hour (p < 0.01). Mean ejection rate decreased from a control of 10.89 ml/kg/sec to 6.69 ml/kg/sec at 1 hour (p < 0.01). Puppies were divided into 3 groups by weight: 270-400 gm (group A), 401-800 gm (group B) and 801-1800 gm (group C). Cardiac function was comparatively more depressed in group C than in groups A and B. We conclude that 1) E. coli endotoxin has negative inotropic and chronotropic effects on the myocardium of newborn puppies, 2) depression of cardiac function is greater in the older, larger puppies.

Net cerebral uptake of energy substrates was measured by repetitive arteriovenous sampling in 9 baboon neonates in the first 3 days of life. Catheters were placed in the aorta, left ventricular outflow tract, and in the superior sagittal sinus. Cardiac output and cerebral cortex blood flow were determined by the radioactive microsphere method. Glucose (G) uptake was 9.4±2.1 µM/min/kg body weight or 11.2±2.6 µM/min/100 g cerebral cortex. Cerebral uptake of alanine was detected in 4/4 animals, and of lactate in 3/9 animals. There was no net lactate release and no net uptake or release of glycerol. Infusion of Na DL-ßhydroxybutyrate (ßOHB) to steady state levels of 2-6 mM total KB (acetoacetate + D-ßOHB) did not alter G, lactate, or O2uptake. However, KB uptake was correlated in a linear fashion with arterial KB to levels of 8 mM.Although G/O2ratios less than 1 suggest that substrates other than glucose are utilized by the brain of the baboon neonate, cerebral KB uptake does not necessarily reflect oxidative metabolism of acetoacetate and D-ßOHB.