To measure the effect of fetal hyperinsulinemia on fetal oxidative metabolic rate and the uptake of fetal oxidative substrates, we operated on 12 near-term ewes under spinal anesthesia and placed catheters in the fetus under local anesthesia. Four days after surgery, we began an 18-h insulin infusion, at the end of which we drew blood samples for analysis of oxygen, glucose, lactate, amino-nitrogen concentrations, blood gases, pH, hematocrit, and plasma insulin concentrations, then injected radiolabeled microspheres to measure umbilical blood flow. Three to five infusions were given to each fetus. Fetal plasma insulin concentrations varied from 0.3 to 60 microU/ml. As fetal plasma insulin concentration rose, the blood concentrations of oxygen, glucose, lactate, and amino-nitrogen fell, but the fetal uptakes of oxygen, glucose, and amino-nitrogen rose. The rise of fetal oxygen uptake occurred by increasing oxygen extraction, resulting in arterial hypoxemia. The increase of the glucose uptake was sufficient to account for an increased fraction of oxidative metabolism, allowing the increased uptake of amino acids to be used for either synthetic or oxidative purposes.
ABSTRACT. We chronically catheterized 15 newborn lambs (9.5 f 2.8 days) and measured the distribution of cardiac output by the radionuclide-microsphere technique at hematocrits ranging from 10 volumes % to 55 volumes %. Seven animals were made progressively anemic and eight polycythemic by means of exchange transfusions. Cardiac output and heart rate increased with decreasing hematocrit while whole body oxygen consumption showed a small decrease during severe anemia. Both cerebral and cardiac blood flow markedly increased during anemia which assured a relatively stable oxygen delivery to both organs. The changes seen for blood flow to the carcass (skin, bones, and muscle) were predictable from the effects of blood viscosity: small decreases in flow at the highest hematocrits and small increases in flow at the lowest hematocrits. Consequently, oxygen delivery was as low as 1 ml of oxygen/min/100 g at a hematocrit of 10 volumes %. Renal blood flow remained unchanged while oxygen delivery fell when hematocrit was decreased. Hepatic oxygenation was measured using a modification of the Fick principle. Hepatic blood flow showed only a small decrease as hematocrit increased and changed minimally during anemia resulting in a falling delivery of oxygen with anemia. A stable hepatic oxygen consumption was assured by a marked increase in oxygen extraction during anemia. Two differing organ responses to changes in hematocrit can be seen in the newborn: the brain and heart vary blood flow to assure an adequate delivery of oxygen while a number of other organs show less blood flow regulation and, most likely, vary oxygen removal from blood. Over a wide range of hematocrits, compensatory responses occur in the newborn which effectively prevent the development of tissue hypoxia. (Pediatr Res 20: 1274-1279, 1986 The physiologic responses that occur with isovolemic anemia and polycythemia reflect the continual interplay between the requirements for tissue oxygenation and the rheologic effects of changes in blood viscosity. While information is available concerning the changes in the distribution of cardiac output for both the fetus (1) and adults (2-8) with anemia and polycythemia, there are little data for the newborn. Two patterns of organ blood flow response can be seen in conditions of decreased oxygen availability: the brain, heart and adrenal glands meet their oxygen requirements by increasing organ blood flows; the majority of other organs regulate the extraction of oxygen by varying capil- lary density and the oxygen diffusion gradient. When both oxygen content and blood viscosity are changing, complex physiologic adjustments are clinically important for the maintenance of a stable oxygen delivery to the organs of the newborn. Both anemia and polycythemia can occur from a variety of causes related to chronic and acute events during pregnancy and delivery. Understanding the limits within which adequate tissue oxygenation occurs offers both prognostic and therapeutic possibilities in the care of infants, especially as we tr...
We chronically catheterized 15 newborn lambs (9.5 +/- 2.8 days) and measured intestinal blood flow (Qi) by the radionuclide microsphere technique at hematocrit levels ranging from 10 to 55%. Seven animals were made progressively anemic and eight polycythemic by means of exchange transfusions. Using the Fick principle, we calculated intestinal oxygen delivery (Di o2), oxygen consumption (Vi o2), and oxygen extraction. Initial base-line values were Qi = 195.5 ml . min-1 . 100 g intestine-1, Di o2 = 22.1 ml . min-1 . 100 g-1, Vi o2 = 4.8 ml . min-1 . 100 g-1, and O2 extraction = 22.5%. As the hematocrit was lowered, Di o2 decreased and O2 extraction increased and vice versa when the hematocrit was raised. Vi o2 remained constant, but Qi did not correlate with changes in hematocrit. However, intestinal blood flow, as a percent distribution of total blood flow, decreased with lower hematocrit levels. At no time was there any evidence of anaerobic metabolism as measured by excess lactate production. Our data indicate that the intestines of neonatal lambs are capable of maintaining their metabolic needs over a wide range of oxygen availability induced by a changing hematocrit. The primary mechanism is through alteration of oxygen extraction. Within the range of our experiments, no critically low oxygen availability was attained at which anaerobic metabolism became significant.
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