Margaret R. Ball

Substrate interaction in intravenous feeding: comparative effects of carbohydrate and fat on amino acid utilization in fasting man.

Data are presented on the metabolic and endocrine effects of intravenous infusions in normal fasting man observed under highly controlled conditions over a period of six to eight days duration. There are comparative data on a variety of intravenous feeding programs. The data on total starvation are based on studies from the literature, some of which were carried out in this laboratory. The data on low dose glucose, high dose glucose, glycerol, fat emulsion, and amino acids, each given separately, demonstrate changes seen with simple infusion of a single substrate in fasting. These data are now compared with the utilization of amino acid infusions when accompanied by low dose glucose, high dose glucose, glycerol, and fat emulsion. In all, nine experimental intravenous feeding programs are presented, based on data from 35 subjects observed over a total of 370 subject-days. The findings show a strong interaction between glucose or lipid and protein metabolism. In fasting, glucose had protein sparing effect, most evident when given at high dose. Glycerol, in an amount equal to that contained in 2000 ml of ten per cent fat emulsion, had a mild protein sparing effect. Fat emulsion was no more effective. When amino acids were given alone, normal fasting human subjects were always in negative nitrogen balance with the daily nitrogen loss half that seen in starvation alone. Although amino acids given alone have a protein sparing effect, this is accomplished only at the expense of a high nitrogen excretion including an amount equivalent to the entire infusion plus an additional loss from the bodys native proteins.The provision of energy yielding non-protein substrates with the amino acids markedly improved nitrogen economy in the following order: glycerol, low dose glucose, fat emulsion and high dose glucose. When caloric provision with glucose approached the isocaloric level for normal diet, the utilization of amino acids was maximized. When given with amino acids, fat emulsion was more effective than the available glycerol alone.The accompanying endocrine and biochemical changes suggest that the milieu for ideal utilization of infused amino acids is variable: ketones at low range (carbohydrate) or moderately elevated (fat emulsion); insulin elevated (carbohydrate) or unchanged (fat emulsion). The utilization of the infused amino acids was markedly improved in both endocrine settings, suggesting that it is the provision of energy as substrate as well as the endocrine setting that determines amino acid utilization. There were other changes in plasma intermediates, particularly fatty acids, glucose and urea, all consistent with the concept that when amino acids are given without other substrates, the amino acids must be maximally utilized for gluconeogenesis. When other substrates are provided (particularly glucose at high dose) then this mandate no longer exists and protein synthesis from the amino acids is favored.Several of the plasma amino acid concentrations responded to glucose when added to amino acid infusion. Amino acids alone produced increases in concentration of all the amino acids found in the infusion with the exception of alanine, arginine, and threonine. Many of these increases were abated by the addition of glucose to the amino acid infusion, suggesting an increased utilization rate. Glycerol and fat emulsion, while modulating increases in the plasma amino acid concentration, did so to a lesser extent than did glucose. This lowering of amino acid concentration was unaccompanied by an increase in urinary excretion. The assumption is therefore made that the provision of the added glucose favors the incorporation of amino acid into protein. There is no evidence from these data to suggest that a rising concentration of ketones in the blood favors amino acid utilization or protein synthesis.

Circadian variation in response to potassium infusion.

The response of 5 normal men to an intravenous infusion of potassium chloride was compared at midday and midnight. Each subject was maintained on strict supine bedrest with oral intake limited to 100 ml distilled waterlhr for the 9 hr before and after each infusion. Potassium chloride, 37 mEq, (with an added label of 200 µCi 42KCl) in iso‐osmolar solution was administered via a central venous catheter over 1 hr starting either at midday or midnight. Plasma potassium concentration was elevated by 40% more at midnight than at midday, and plasma 42K activity also rose to a higher level at midnight. These differences were reflected by greater T wave elevations of the electrocardiogram at midnight than at midday, although urinary potassium excretion (total and 42K labeled) was higher at midday than at midnight, indicating that there was reduced renal excretory responsiveness to elevations in plasma potassium concentration at midnight compared with midday. Plasma aldosterone concentration rose during the potassium infusions at both midday and midnight by a similar amount, which suggests that the induced increments in aldosterone secretion were not a major determinant of the differing renal response. These findings indicate that circadian modulations in the physiologic mechanisms which regulate potassium homeostasis profoundly influence the response to exogenous potassium loads. Special caution must therefore be taken in administering potassium infusions at night.

Intravenous Amino Acids as the Sole Nutritional Substrate: Utilization and Metabolism in Fasting Normal Human Subjects

The fasting normal human volunteer subject provides an ideal experimental setting for the initial investigation of foodstuffs whose use is proposed for the acutely ill surgical patient. In the normal human subject many variables can be controlled; the achievement of an ideal body fuel economy is quite simple; if a favorable utilization of injected foodstuffs cannot be achieved in this setting, it is unlikely, and remains to be proven, that utilization will be satisfactory under the challenges of acute surgical trauma. In this experimental model, employing four normal human volunteer subjects, nutrition has been provided by the intravenous infusion of isotonic amino acids (FreAmine(R) II) at a 3.4% concentration. No other source of calories or nutrients was provided. In this setting, utilization was very poor; the subjects were in negative nitrogen balance throughout. The nitrogen excretion was significantly greater than the total of infused nitrogen. The changes in protein, fat and carbohydrate intermediates, as well as the alteration in hormone concentrations, suggest the following endocrine governance of fuel economy in this setting: a sharp rise in glucagon with maintenance of insulin concentration; rapid gluconeogenesis at the expense of both injected and endogenous amino acids; a progressive ketosis without any associated improvement in protein economy; fat oxidation to meet caloric need. The changes in plasma amino acid concentrations are of outstanding interest. They demonstrate changes appropriate to the infusion gradient with the exception of three amino acids whose concentrations did not respond to high infusate levels (serine, lysine, and alanine); likewise, by the fact that methionine rose remarkably though present in only low concentrations in the infusion. These data, taken with other information reported in the literature, as well as continuing studies in these laboratories, strongly suggest that the utilization of infused amino acids for protein synthesis is favored by the provision of an additional caloric source such as glucose.

Body composition in the dog. I. Findings in the normal animal.

Summary o 1. A technique is presented for the simultaneous measurement of total body water, extracellular fluid, red cell volume, plasma volume, exchangeable sodium, exchangeable chloride and exchangeable potassium in the dog. The method requires five venipunctures and 60 to 80 ml. of blood for sampling. 2. The reproducibility of the technique has been examined by means of five repeated measurements in three dogs at weekly intervals. The errors of the method are small, and approximate the expected statistical errors due to counting and chemistry. 3. The body compositional findings in the normal dog are contrasted briefly with those found in man. These dogs had less body fat than is seen in the normal adult female human subject; within the aqueous phase of body composition a larger fraction of water is occupied by cellular tissue than in the human being; body tonicity as exemplified in the ratio Na e +K e /TBW is approximately 10 mEq./L. higher in the dog than in man; this latter fact is correlated with the higher concentration of sodium in the serum found in the dog. 4. For long-term observation of changes in the animals body composition as a result of disease, the isotope dilution technique for body composition appears preferable to the metabolic balance method.