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Biomedical subjects

W W Hay

Publications and source records attributed to W W Hay.

At least 109 records · Page 6Linked to original sources
PubMed1987

Nutrition of the fetus and newborn.

Both the successful development of healthy, long-term animal models to study fetal nutrition and metabolism and the improved survival of low-birth-weight, preterm infants have focused interest and research on fetal and neonatal nutrition and metabolism. Such a focus is important, given the recent emphasis on promoting neonatal growth in preterm infants at "normal" in utero growth rates. Estimates of nutrient requirements for growth in a human fetus remain ill defined, however. Body composition data appear biased toward thin infants. Animal data suggest that fetal nutrition proceeds according to species-specific growth rates, with variations in fat content largely dependent on placental fat permeability and on maternal nutrient supply as regulated by the placenta. After birth, neonatal nutrition is affected primarily by food intake and the functional integrity and capacity of the gastrointestinal tract. Additionally, muscle activity, thermoregulation and stresses of various kinds and degrees modify a neonate's nutritional requirements. Functional deficits of the gastrointestinal tract have been circumvented by a more aggressive use of intravenous nutrition. Both intravenous and enteral nutrient mixtures have been substantially improved in the quantity of all nutrients and have been modified qualitatively toward compositions that are closer to those of human milk. These nutrient mixtures now produce plasma nutrient concentrations that approximate those of a healthy, breast-fed infant. Although such efforts to improve the nutritional balance and growth of preterm infants have been successful, much remains to be learned about the nutritional requirements of sick infants.

Animals↗
PubMed1986

The effect of hyperinsulinaemia on glucose utilization and oxidation and on oxygen consumption in the fetal lamb.

In order to measure the effect of hyperinsulinaemia on fetal glucose metabolism and oxygen consumption, we applied the glucose-clamp technique to experiments in fifteen late-gestation, unstressed, chronically catheterized fetal lambs. In a control period, and immediately thereafter following 2 h of hyperinsulinaemia, we measured fetal glucose utilization and oxidation rates (radioactive tracer methodology) and net fetal uptake rates of exogenous glucose and oxygen uptake rates (Fick principle). During the period of hyperinsulinaemia, fetal glucose concentration was maintained at the average control period value by a variable rate of glucose infusion into the fetus in response to serial 10 min measurements of fetal arterial blood glucose concentration. Hyperinsulinaemia in the fetus (12.12 +/- 1.92 ng X ml-1 (mean +/- S.E.M.) arterial plasma) resulted in a 13% increase in net fetal oxygen uptake rate (0.310 +/- 0.011 to 0.349 +/- 0.012 mmol. min-1 X kg-1), a 106% increase of fetal glucose uptake rate (4.54 +/- 0.43 to 9.35 +/- 0.50 mg X min-1 X kg-1) and an 83% increase of fetal glucose utilization rate (4.94 +/- 0.43 to 9.05 +/- 0.83 mg X min-1 X kg-1). Fetal glucose uptake and utilization rates were not different from each other during the control and the hyperinsulinaemia periods. The fraction of glucose that was oxidized (0.58 +/- 0.05, control; 0.54 +/- 0.05, hyperinsulinaemia) did not change significantly; thus the glucose oxidation rate, the rate of entry of glucose into non-oxidative pathways, and the amount of oxygen used for glucose oxidation all increased in proportion to glucose utilization. These results suggest that insulin promotes the entry of glucose into fetal tissues, thereby increasing fetal glucose utilization and oxidation rates and substituting glucose oxidation for that of other substrates. The insulin-enhanced glucose utilization rate also increases slightly fetal metabolic rate.

Animals↗
PubMed1986

Relationship between glucose utilization rate and glucose concentration in preterm infants.

Within the neonatal euglycemic range, we studied the relationships among total glucose entry, intravenous glucose infusion, endogenous glucose production, glucose disposal rate and blood glucose concentration in infants less than or equal to 32 weeks gestation. [U-13C]-glucose was used as a tracer of glucose metabolism, administered as a primed constant infusion. Using a glucose clamp technique, at least one steady-state period of blood glucose concentration in 10 infants and two steady-state periods of blood glucose concentration in 6 infants were achieved. In the 6 infants studied at 2 glucose concentrations, glucose disposal rate increased with blood glucose concentration, r = 0.95, p less than 0.01, slope = 0.091 +/- 0.058 (SD) mg X min-1 X kg-1 per mg X dl-1 of glucose concentration increase. In all infants studied, intravenous glucose infusion rate was not different from glucose disposal rate, suggesting the absence of endogenous glucose production.

Blood Glucose↗
PubMed1985

Placental, fetal, and neonatal carbohydrate metabolism.

In summary, glucose metabolism in the placenta and fetus is characterized by a fairly exact balance between exogenous glucose supply from the mother and placental and fetal glucose utilization (directly and as lactate produced from glucose). The rate of glucose utilization and its rate of oxidation are largely determined by the maternal glucose concentration and are mediated in part by insulin. Thus, glucose and insulin act together to substitute glucose oxidation for the oxidation of other energy substrates and to direct glucose carbon into glycogen, fat, and protein accretion. After birth, endogenous glucose production and dietary glucose intake (as glucose or as galactose) must account for the maintenance of glucose supply. In many cases, however, the balance among glucose intake, glucose production, and glucose utilization is inexact in the transition from intrauterine to extrauterine life, leading to both hypoglycemia and hyperglycemia. Basic measurements of the glucose production rate and the glucose utilization rate can be made now in the fetus as well as in the neonate, but the factors producing perturbations in glucose supply and utilization and in regulating the responses to these perturbations remain to be measured.

Animals↗
PubMed1985

Effect of insulin on glucose uptake in near-term fetal lambs.

Glucose clamp experiments were performed in 27 chronically catheterized, late-gestation fetal lambs in order to measure the effect of fetal insulin concentration on fetal glucose uptake at a constant glucose concentration. Fetal arterial blood glucose concentration was measured over a 30-min control period and then maintained at the control value by a variable glucose infusion into the fetus while insulin was infused at a constant rate into the fetus. Plasma insulin concentration increased from 21 +/- 10 (SD) to 294 +/- 179 (SD) microU X ml-1. The exogenous glucose infusion rate necessary to maintain constant glycemia during the plateau hyperinsulinemia averaged 4.3 +/- 1.6 (SD) mg X min-1 X kg-1. In a subset of 13 animals, total fetal exogenous glucose uptake (FGU; sum of glucose uptake from the placenta via the umbilical circulation plus the steady-state exogenous glucose infusion rate) was measured during the control and hyperinsulinemia period. FGU was directly related to insulin concentration (y = 4.24 + 0.07x) at insulin levels less than 100 microU/ml and increased 132% above control at insulin levels above 100 microU/ml. Hyperinsulinemia did not affect fetal glucose uptake from the placenta via the umbilical circulation. These studies demonstrate that insulin concentration is a major factor controlling glucose uptake in the near-term fetal lamb, and that an increase of fetal insulin does not affect the transport of glucose to the fetus from the placenta.

Animals↗
PubMed1984

Fetal glucose uptake and utilization as functions of maternal glucose concentration.

Seventeen studies were performed in 12 pregnant sheep to examine the relationship among simultaneously measured glucose uptake via the umbilical circulation, fetal glucose utilization (mg X min-1 X kg-1), and maternal arterial glucose (Gm, mg/dl). Fetal glucose utilization was measured by means of tracer glucose infused into the fetus or both mother and fetus. By fasting the ewe, Gm was varied in the 62-22 range. A decrease in Gm was accompanied by a significant (P less than 0.001) decrease in umbilical uptake (uptake = 0.09 Gm - 0.96, r = 0.82) and in fetal utilization, measured either by [U-14C]glucose (utilization = 0.062 Gm + 0.91, r = 0.90) or [6-3H]glucose (utilization = 0.065 Gm + 0.51, r = 0.91). At uptake greater than 3 mg X min-1 X kg-1, utilization and uptake were not significantly different. At lower uptakes, utilization did not decline as much as uptake. The results demonstrate that maternal fasting decreases both the umbilical uptake and the fetal utilization of glucose and suggest that fetal glucogenesis increases when the availability of exogenous glucose is markedly reduced.

Animals↗
PubMed1984

Maternal-fetal glucose exchange: necessity of a three-pool model.

Tracer glucose was infused simultaneously into mother ( [6-3H]glucose) and fetus ( [U-14C]glucose) in pregnant sheep in the last month of gestation to study the exchange of glucose molecules between maternal and fetal blood. Net rates of entry and exit of tracer glucose via the uterine and umbilical circulations were measured by application of the Fick principle under steady-state conditions. The net flux of fetal tracer to the uteroplacenta from the fetus was 53.4 +/- 3.1% of the fetal tracer infusion. The net flux of fetal tracer into maternal blood was 43.8 +/- 5.0% of the net flux of fetal tracer to the uteroplacenta from fetal blood. The net flux of maternal tracer to the uterus from the mother was 31.7 +/- 2.8% of the maternal tracer infusion. The net flux of maternal tracer into fetal blood was 40.5 +/- 4.4% of the net flux to pregnant uterus from maternal blood. This evidence demonstrates that the uteroplacental tissue mass constitutes a glucose pool that is interposed between the maternal and fetal glucose pools and rapidly metabolizes glucose molecules derived from both maternal and fetal blood. Calculations based on a three-pool model show that the fetal glucose pool contributes approximately 40% of the glucose that is metabolized by the placenta. The comparison of the three-pool model with a previously proposed two-pool reversible model shows that the latter lumps the placental utilization of fetal glucose with fetal glucose utilization and overestimates the rate of fetal glucose metabolism by approximately 60%.

Animals↗
PubMed1984

Glucose turnover rates in chronically catheterized non-pregnant and pregnant rabbits.

Glucose turnover rates have been measured in conscious, chronically catheterized, non-pregnant and pregnant rabbits. Non-pregnant rabbits were studied weekly for 4 wk. Pregnant animals were studied once while non-pregnant and then weekly for up to 4 wk during pregnancy. Glucose turnover rate was measured using a primed-constant infusion of [U-14C]glucose and [6-3H]glucose. The weight of the rabbits did not vary throughout the 4-5 wk of study in either the non-pregnant or pregnant group. Seven pregnant rabbits delivered pups which weighed an average of 61 g each. In non-pregnant rabbits, blood glucose concentration did not vary with time. In the pregnant rabbits, blood glucose concentration fell by the end of gestation to an average value of 74.6 +/- 2.7 mg/dl, significantly less (P less than 0.01) than the glucose concentration in the same animals before pregnancy, 88.2 +/- 2.4 mg/dl. The weight specific glucose turnover rate did not vary with time in either the non-pregnant (4.38 +/- 0.16 mg X min-1 X kg-1) or pregnant rabbits (3.89 +/- 0.29 mg X min-1 X kg-1). Blood glucose clearance did not change over time in the non-pregnant rabbits but did increase in the pregnant rabbits in late pregnancy. Blood glucose clearance was inversely related to the fall in blood glucose concentration.

Animals↗
PubMed1984

Some aspects of maternal metabolism throughout pregnancy in the conscious rabbit.

Studies of maternal metabolism during pregnancy have focused principally upon the latter half of gestation. However, maternal metabolic adaptations to pregnancy may occur at all stages of pregnancy. To study maternal metabolism throughout pregnancy, we developed a chronically catheterized rabbit model in which animals could be studied under conscious, stress-free conditions when nonpregnant and then serially throughout pregnancy. Anesthesia produced marked hyperglycemia. In contrast, chronic catheterization and daily handling did not affect blood concentrations of glucose, lactate, ketone bodies, or free fatty acids, or food intake. Glucose concentration decreased with pregnancy to a value at term equal to 85% of the prepregnancy value. Lactate concentration rose significantly in the second half of pregnancy but changes in free fatty acids and ketoacid levels were not significant. These results are discussed from a comparative physiologic point of view, emphasizing the unique aspects of rabbit metabolism during pregnancy and the importance of performing such studies under conscious, stress-free conditions.

Anesthesia↗
PubMed1984

Effect of insulin on glucose uptake by the maternal hindlimb and uterus, and by the fetus in conscious pregnant sheep.

Previous studies have demonstrated the presence of insulin receptors on the maternal surface of the placenta in several species and the specific binding of insulin to the placenta in sheep. However, both in-vitro and in-vivo studies have produced conflicting evidence concerning the effect of insulin on placental glucose uptake. To clarify this problem, we measured maternal hindlimb, uterine and fetal glucose and oxygen extractions and glucose/oxygen quotients in chronically catheterized, non-stressed, late-gestation pregnant sheep over 1 h at a constant concentration of arterial plasma glucose, and again during the next 2 h at the same glucose level but at a higher insulin concentration using glucose 'clamp' methodology. Insulin produced a 4.9-fold increase in glucose extraction and a 3.5-fold increase in glucose/oxygen quotient across the hindlimb; in contrast, insulin did not significantly affect uterine or fetal glucose extraction or glucose/oxygen quotient. We conclude that in contrast to other tissues of the pregnant ewe, placental glucose uptake and transfer are insensitive to variations in maternal insulin concentration.

Animals↗
PubMed1984

Fetal CO2 kinetics.

Knowledge of CO2 kinetics in the fetus is important for the design and interpretation of fetal metabolic studies that use carbon-labelled tracers. To study fetal CO2 kinetics, four fetal sheep were infused at constant rate with NaH14CO3 to simulate a constant rate of fetal 14CO2 production from the metabolism of a 14C-labelled substrate. Uterine and umbilical blood flows, and concentrations of 14CO2 and total CO2 in umbilical arterial and venous blood and in uterine arterial and venous blood were measured. During steady state, the excretion of 14CO2 via the umbilical circulation was 99.6 +/- 1.0 (SEM)% of the NaH14CO3 infusion rate. The irreversible disposal rate of CO2 molecules from the fetal CO2 pool was approximately 5 times greater than the metabolic production of CO2 by the fetus. This evidence demonstrates that measurements of fetal 14CO2 excretion via the umbilical circulation can provide an accurate measurement of fetal 14CO2 production and that the exchange rate of CO2 molecules between placenta and fetal blood is much greater than the net rate of excretion of CO2 molecules from fetus to placenta.

Animals↗
PubMed1983

Partition of maternal nutrients to the placenta and fetus in the sheep.

Utilizing the Fick Principle, the fluxes of oxygen and glucose leaving the uterine circulation and entering the fetal umbilical circulation were measured simultaneously in 35 chronically catheterized sheep. Additionally, the distribution of placentally produced lactate into the uterine and umbilical circulations was measured by the same techniques. Under unstressed conditions, placental oxygen consumption accounted for approximately half the oxygen exiting the uterine circulation. Placental glucose consumption averaged 75% of the glucose exiting the uterine circulation, and this proportion increased with decreasing glucose concentration in the maternal artery. Lactate was produced at a high rate by all placentae, and distributed disproportionately to the fetus, in spite of higher fetal lactate concentration. Fetal metabolism was aerobic, as demonstrated by a high rate of net oxygen consumption and a high rate of net lactate consumption. Fetal oxygen metabolism correlated well with fetal weight and with the sum of net fetal lactate and glucose consumption.

Animals↗
PubMed1983

Partition of maternal glucose production between conceptus and maternal tissues in sheep.

Experiments were conducted in late-gestation, conscious, pregnant ewes to measure maternal glucose production and the net glucose uptake by the uterus, fetus, uteroplacenta, and nonuterine maternal tissues. Glucose concentration in the ewes varied naturally or decreased in response to fasting. Normoglycemic ewes (63.8 +/- 8.7 mg/dl) had a glucose production rate of 178.7 +/- 44.5 mg/min compared with a rate of 76.9 +/- 20.6 mg/min for hypoglycemic ewes (34.7 +/- 7.4 mg/dl). Uterine glucose uptake (56.5 +/- 16.8 mg/min), fetal glucose uptake (15.7 +/- 5.2 mg/min), uteroplacental glucose uptake (40.8 +/- 13.4 mg/min), and nonuterine maternal glucose uptake (122.2 +/- 27.7 mg/min) in the normoglycemic ewes were significantly greater than in the hypoglycemic ewes (28.7 +/- 5.4, 7.5 +/- 4.4, 21.2 +/- 6.6, and 48.2 +/- 15.2 mg/min, respectively). The fractional distribution of maternally produced glucose among nonuterine maternal tissues, the fetus, and the uteroplacenta was not altered markedly by hypoglycemia despite a 57% reduction in maternal glucose production.

Animals↗
PubMed1983

Glucose and lactate oxidation rates in the fetal lamb.

Both glucose and lactate are nutrients of the ovine fetus. Each may be used by the fetus as a fuel for oxidation or as a source of carbon for energy storage and net tissue accretion. The present report describes the oxidation rates of glucose and lactate in vivo for the fetal lamb over a relatively short time period. The fraction of fetal glucose or lactate oxidized was defined as the ratio of 14CO2 excretion across the umbilical circulation to the net entry of [14C]glucose or [14C]lactate into fetal tissues. The fraction of glucose oxidized over a 3-hr study averaged 61.2%, accounting for 2.55 mg X min-1 X kg-1 of glucose oxidized and for 28% of the simultaneous net oxygen uptake. The fraction of lactate oxidized averaged 71.5%, accounting for 4.12 mg X min-1 X kg-1 of lactate oxidized. Oxidation fractions and rates for both glucose and lactate increased with their concentrations in fetal blood suggesting sparing of other fuels for oxidation at higher glucose and lactate concentrations.

Animals↗
PubMed1983

The "eyetone" blood glucose reflectance colorimeter evaluated for in vitro and in vivo accuracy and clinical efficacy.

We evaluated the performance of a blood glucose reflectance colorimeter ("Eyetone," Ames Co.) for accuracy and precision with use of "Dextrostix" (Ames Co.) glucose oxidase reagent strips for blood samples with known and unknown concentrations of glucose covering the usual range of neonatal blood glucose (200-800 mg/L). The meter was calibrated and tested by research nurses and one clinical chemist. Five unknowns were tested for accuracy and precision (56-92 determinations per unknown) and compared with Beckman Astra values (plasma and calculated whole blood). Eyetone/Dextrostix values differed (gave lower values) from the calculated whole-blood values only at concentrations less than 300 mg/L. On 258 clinical specimens from newborn infants, Eyetone/Dextrostix values were not different from calculated whole-blood values (p less than 0.05, r = 0.80). Operator training to develop a consistent procedure was the most critical factor in achieving accurate and precise results.

Autoanalysis↗
PubMed1982

Simultaneous measurements of lactate turnover rate and umbilical lactate uptake in the fetal lamb.

Lactic acid represents a major exogenous nutrient for the developing fetal lamb in utero. Our study was undertaken (a) to quantitate the net consumption of lactate by the fetus, (b) to quantitate the net lactate production and metabolism by the placenta, and (c) to compare the net fetal lactate consumption with fetal lactate use, measured simultaneously with radioactive tracers. 14 pregnant sheep were prepared with catheters in the maternal femoral artery and uterine vein and in the fetal aorta and umbilical vein. By simultaneous application of the Fick principle to the uterine and umbilical circulations, placental glucose consumption and placental lactate production were rapid, averaging 39.8 +/- 5.1 and 11.8 +/- 0.7 mg.min-1. Net lactate umbilical uptake averaged 1.95 +/- 0.16 mg-1.kg.min-1. During infusion of L-[14C(U)]lactate, fetal lactate turnover was much more rapid, averaging 6.5 +/- 0.8 mg.kg-1.min-1, and lactate utilization within the anatomic fetus was 5.9 +/- 0.7 mg.kg-1.min-1. During infusion of tracer glucose, endogenous fetal lactate production from glucose and nonglucose substrates averaged 3.0 and 1.5 mg.kg-1.min-1, respectively. The present studies have quantitated under well oxygenated, steady-state conditions, the rapid placental metabolism and production of lactate, the net fetal consumption of lactate, and the rapid endogenous fetal lactate production from glucose and nonglucose substrates.

Animals↗