Induced Hyper and Hypo Amino Acidemia in the Ovine Fetus Near Term: Effects on Electrocortical Activity

Abstract

Amino acid infusate (Primene) and insulin euglycemic (insulin + 10% dextrose) clamp techniques were used in the ovine fetus near term and the impact on the incidence of low-voltage and high-voltage electrocortical (ECOG) activities was determined. Fetal sheep were studied over a 2-hour control period and a subsequent 6-hour experimental period.With the Primene infusion, the basic and neutral amino acids were increased by 43% and 25%, respectively, whereas the acidic amino acids showed little change. With the insulin/dextrose infusion, the basic and neutral amino acids decreased by 48% and 30%, respectively, whereas the acidic amino acids were again little changed. A small fall in arterial oxygen saturation and an increase in fetal heart rate for both groups can be attributed to an insulin-mediated increase in fetal metabolic rate. Despite the moderate increases and decreases in circulating amino acid levels, there was no significant change in the mean percent time or duration of fetal ECOG activities for either study group.

Cerebral Protein Synthesis in the Ovine Fetus Near Term with Amino Acid Infusion and Insulin-Induced Hypoaminoacidemia

“…Not all measurements were obtained for each animal. The effects of amino acid and insulin/dextrose infusions on cardiovascular and ECOG activity for these animals have previously been reported [18] .…”

“…There was no evidence of a differential effect of increases versus decreases in circulating amino acids on cerebral protein synthesis as studied, which may be attributed to the saturable nature of the BBB transporters for amino acids [6] , although this has not been studied for the ovine fetus. This would indicate that protein metabolism in the brain is less sensitive to systemic amino acid change than other organ tissues, and most certainly for carcass/muscle [12][13][14][15][16][17][18] , which would be important for the developing brain when the relatively high rates of protein synthesis/degradation with tissue growth and remodeling would be more vulnerable to changes in amino acid availability.…”

“…Blood glucose measurements were made in duplicate with membrane-bound glucose oxidase and D -lactate dehydrogenase, respectively (YSI 2300 Stat Plus; Yellow Springs Instruments, Yellow Springs, Ohio, USA). Plasma amino acid analysis was performed as previously described [18] .…”

“…The enrichment of [ 13 C]-leucine within arterial plasma (MPE P ) was determined using the steady-state measurements obtained over the last 4 h of experimental study for both the amino acid and insulin/dextrose infusate groups, during which time the changes in plasma leucine values had largely stabilized [18] . The enrichment of [ 13 C]-leucine within brain tissue protein-bound (MPE PB ) and intracellular free (MPE IF ) were determined using the tissue measurements obtained from the pellet and supernatant, respectively.…”

“…A mixed amino acid infusate and an insulin euglycemic clamp technique were used to induce increases and decreases in circulating amino acid levels, respectively, of ϳ 30 to 40% on average as we [18] and others [13,14,19,20] have previously described. Protein FSR values within the brain were calculated from the enrichment of protein-bound [ 13 C]-leucine as measures of cerebral protein synthesis.…”