Effect of Birth-Related Events on Metabolism in Fetal Sheep

Abstract

ABSTRACT. At birth, changes in utilization of metabolic substrates occur as the fetus, dependent upon carbohydrates and amino acids available continuously from the placenta, becomes a neonate, dependent primarily upon fat obtained intermittently by suckling. In addition to changes in substrates, at birth, metabolic rate increases dramatically as the activity of several organs and thermoregulatory mechanisms increase. To determine whether metabolic changes are related to certain events that occur at birth, we studied 15 fetal sheep instrumented chronically with vascular catheters and an endotracheal tube at 133 to 137 d gestational age. We measured blood flow with radionuclide-labeled microspheres and arteriovenous concentration differences for oxygen content, blood glucose, and lactate across the placental, cerebral, myocardial, and hindlimb circulations at rest, during in utero ventilation of the fetal lungs with 3% 02, during in utero ventilation with 100% 02, and during ventilation with 100% OZ and umbilical cord occlusion. Ventilation with 3% 0 2 decreased oxygen uptake by the fetus and by the cerebral circulation but produced no other significant changes. Ventilation with the low and high oxygen gas mixture reduced glucose uptake by the fetus from the placental circulation dramatically to zero. In contrast, blood glucose concentrations increased and glucose uptake by the fetal brain, heart, and hindlimb were not altered significantly. These data indicate that, for a short time at least, complete cessation of glucose supply to the fetus from the placenta is not associated with decreases in blood glucose concentrations or utilization of glucose by a major portion of the fetal body. (Pediatr Res 30: 158-164,1991) Oxygen consumption increases abruptly at birth (1-3). Important factors that increase oxygen consumption in the neonate are a decrease in environmental temperature, an increase in muscle activity, and appropriate hormonal stimulation (1, 3-7). An increase in oxygen delivery per se does not appear to increase oxygen consumption. Contrary to the notion that the fetus is hypoxemic and fetal oxygen delivery normally limits fetal oxygen consumption, an increase in oxygen delivery to the fetus does not increase fetal oxygen consumption (8, 9).Shortly after birth, certain tissues alter the substrates they utilize. In the fetus, the major substrates consumed are carbohydrates supplied by the mother (2). After birth, the continuous nutrient supply from the placenta ceases. The newborn mobilizes its fat and glycogen reserves, and blood glucose, lactate, and FFA concentrations increase (10). Thus, the substrates available change, and several organs utilize fats instead of carbohydrates. Concurrently, the function and metabolic demands of several organs change.The events that initiate changes in regional oxygen and sub-I strate utilization at birth are not known. Many previous studies that have examined aspects of regional metabolism are based on in vitro measurements of metabolism of tissues derived from fetu...

Maternal hyperoxygenation for the human fetus: should studies be curtailed?

“…However, as mentioned above, based on the studies in fetal lambs, increasing oxygen concentration in cerebral arterial blood results in vasoconstriction with reduction in cerebral blood flow. 17 Although cerebral oxygen delivery and consumption are maintained, glucose delivery and consumption are markedly reduced. The reduction in substrate could interfere with cerebral development, despite an adequate oxygen supply.…”

“…We examined the effect of acute change in oxygen saturation on cerebral blood flow and metabolism. 17 Fetal sheep were prepared with indwelling vascular catheters and a tracheal tube. After recovery for 2-3 days studies were conducted on the fetuses in utero; blood flows to organs were measured by the radionuclide-labeled microsphere technique.…”

Hypoplastic Left Heart Syndrome: Is There a Role for Fetal Therapy?

“…One study reported that chronic MH may be associated with growth restriction (63), whereas another group had concerns regarding fetal brain and placental development (16). In animal models using fetal sheep it could also be shown that hyperoxygenation led to reduced cerebral perfusion resulting in significantly decreased cerebral glucose delivery and consumption (68). Other fetal complications like constriction of the arterial duct or retinopathy may also be considered but were not reported in human studies on chronic MH.…”