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UBC Theses and Dissertations

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UBC Theses and Dissertations

Substrate utilization in the ovine fetus in utero Kitts, David D.

Abstract

The turnover, interconversion and oxidation of substrates in the ovine conceptus in utero were studied making use of isotope dilution techniques. In Experiment 1, surgical techniques were standardized for the introduction of vascular catheters into the fetuses at approximately 120-130 days of gestation. Based on maternal and fetal blood acid base parameters and metabolite and hormone levels it was possible to obtain chronic fetal preparations which were physiologically stable. In Experiment II, radioactive labelled substrates were injected introvenausly into the fetus and the disappearance of the label from the fetal circulation was monitored against time. Kinetic parameters of substrate metabolism were calculated by graphic analysis of the specific radioactivity-time curves. The pool size, irreversible rate of disposal and volume of distribution of glucose, lactate, and amino acids were estimated. The single injection technique employed in this study facilitated the calculation of 2 additional kinetic parameters not reported hitherto in the literature. These include the mean total residence time and number of cycles the labelled substrates made before being irreversibly lost from the fetal circulation. The finding that lactate and amino acids make more number of cycles into and out of the fetal circulation than glucose provides support to the concept that the placenta on the fetal side is relatively impermeable to the former two substrates. Though the rapid disappearance of isotopes administered into the fetus was recognized by earlier workers, the results of this study have brought to light the significance of recylcing of substrates. It is suggested that this unique dynamic feature serves as a physiological control mechanism to modulate fuel consumption according to nutrient and oxygen availability. On the other hand, there was very little difference in the irreversible rate of disposal when [2-³H] or [U-¹⁴C] glucose was injected indicating that there is only approximately 12.5% of recirculation of glucose within the fetal tissues. The appearance in maternal circulation of only labelled glucose injected into the fetus, but not lactate indicates the inability of lactate to cross the placenta from the fetal side. Though 36% of the administered glucose label appeared in lactate, the methodology used in this study does not differentiate whether the conversion of glucose into lactate occurred in the fetus itself or in the placenta. The recovery of 8.8% of alanine C into glucose, though suggestive of gluconeogenic potential, may have occurred by isotopic cross over rather than true metabolic conversion. In experiment III, the CO₂ production rates were estimated from the plateau specific activity of blood ¹⁴CO2 after the continuous infusion of [¹⁴C] NaHCO₃. The most important findings in this study pertains to the contribution of substrates to oxidative metabolism in the fetus. Contrary to the conclusions based on the Fick principle, the recovery of administered label into ¹⁴CO₂ indicates that glucose, lactate, alanine, acetate and amino acids contribute 15.2, 14.0, 6.8, 1.7 and 8.2% respectively to fetal oxidative metabolism. Though the metabolism of placental tissues may have influenced the above values, the results suggest that the metabolic fuel requirements of the fetus warrant reassessment. The results of these experiments are discussed with reference to the metabolism of the fetus during a period of gestation where the greatest increment in fetal growth occurs.

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