Comparison of substrate utilization by indirect calorimetry during cyclic and continuous total parenteral nutrition.

Five male adult home patients were studied in a randomized order under continuous (24 h/d) and nocturnal cyclic (15 h/d) isocaloric, isonitrogenous total parenteral nutrition (TPN). They received 2626 +/- 265 total kcal/d as 60% dextrose and 40% lipids; the 3-h lipid infusion was followed by the dextrose amino acid infusion on both regimens. Substrate oxidation was measured by indirect calorimetry during four periods on the fourth day of each regimen. During cyclic TPN net lipogenesis occurred with a nonproteic respiratory quotient (npRQ) greater than 1 during dextrose amino acid infusion followed by net lipolysis with an npRQ less than 1 during the nonnourishing phase. In contrast, during continuous TPN net lipogenesis persisted with an npRQ greater than 1 over the 21 h of dextrose amino acid infusion. During the 3-h lipid infusion, fat oxidation was observed during both regimens but was more pronounced during cyclic TPN (p less than 0.05). As a consequence, 24-h lipid oxidation was higher and 24-h dextrose utilization lower during cyclic vs continuous TPN (p less than 0.05). These results suggest that cyclic TPN when alternating between substrate storage and oxidation, mimics the physiological pattern of oral feeding.

Effect of different caloric loads in human jejunum on meal-stimulated and nonstimulated biliopancreatic secretion.

The effects on biliopancreatic secretion of two caloric loads (1.3 and 3.3 kcal/min of Realmentyl: proteins 18%, lipids 27%, carbohydrates 55%), infused into the jejuna of 10 healthy men, were compared with those of a control solution. In one set of experiments (six subjects) when biliopancreatic secretion was not stimulated before infusion, the rate 1.3 kcal/min resulted in mild stimulation whereas the rate 3.3 kcal/min brought about an inhibition of biliopancreatic secretion. In another set of experiments (six subjects) when biliopancreatic secretion was stimulated by ingestion of an homogenized meal (400 mL, 490 kcal) 1 h before the start of infusion, both loads resulted in strong inhibition of pancreatic secretions, the effect being more pronounced with the high caloric load.

Energy and protein metabolism during recovery from malnutrition due to nonneoplastic gastrointestinal disease.

The magnitude of metabolic adaptation to malnutrition is still debated and few studies have investigated the phase of recovery from malnutrition. The aim of the present work was to determine whether refeeding was associated with adaptive changes in 1) energy expenditure, 2) maximal capacity for oxidizing lipids, and 3) whole-body protein turnover. Eleven malnourished patients with nonneoplastic gastrointestinal diseases were studied by using indirect calorimetry and L-[1-13C]leucine infusion while being infused with lipid-rich total parenteral nutrition (TPN). The same study was performed before initiation of TPN and after a mean gain of 6.5 kg body wt. In absolute values, resting energy expenditure (REE) increased after refeeding (4.05 +/- 0.85 compared with 4.60 +/- 1.05 MJ/d). Change in REE adjusted for fat-free mass (FFM) correlated significantly with change in body weight (r = 0.850, P = 0.01) and change in body fat (r = 0.798, P = 0.01) but not with change in FFM (r = -0.06, NS). Lipid oxidation decreased significantly after body weight gain (0.93 +/- 0.28 compared with 0.50 +/- 0.37 mg.kg-1.min-1). When expressed per kg FFM, protein turnover and breakdown increased significantly during body weight gain. Moreover, the change in protein turnover correlated with the rate of change in FFM, suggesting that FFM accretion requires increased interorgan exchange of amino acids. Our data suggest that in patients similar to those studied here and during recovery from malnutrition, the degree of change in adjusted REE during refeeding is correlated with change in fat mass and not with change in FFM, and that there is a decrease in oxidation of infused lipids. These mechanisms may contribute to body fat repletion and regulation during weight gain.

Glutamine metabolism in healthy adult men: response to enteral and intravenous feeding.

To assess the effect of feeding on glutamine kinetics, six healthy men received 4-h intravenous infusions of L-[2-15N]glutamine and L-[1-13C]leucine on 3 separate days: 1) in the postabsorptive state, 2) over the course of an 8-h nasogastric infusion of a small peptide-based nutrient mixture, and 3) during an 8-h isonitrogenous, isoenergetic intravenous infusion (1.5 g amino acid.kg-1.d-1; 130 kJ.kg-1.d-1, or 31 kcal.kg-1.d-1; 58% carbohydrate and 42% fat). Regardless of the route, nutrition increased leucine appearance rate (Ra) and oxidation, stimulated protein synthesis, and improved leucine balance; apparent rates of protein breakdown decreased during enteral nutrition only. Glutamine Ra increased 16.8% (NS) and 26.2% (P < 0.01) with parenteral and enteral feeding, respectively, over postabsorptive values. The present findings are consistent with a major role of glutamine in interorgan nitrogen transport in the fed state and further suggest that increased availability of precursors may stimulate glutamine synthesis de novo, and enteral infusion of peptide-bound amino acids may be an effective route to provide free glutamine to the rest of the body.

Glutamine metabolism after small intestinal resection in humans.

Glutamine and leucine kinetics were measured using stable isotopes in five enterectomized patients (residual small bowel, 80 +/- 25 cm [mean +/- SE]) who were in a near normal nutritional status at distance from surgery. While parameters of leucine metabolism were normal, rates of whole body glutamine utilization were reduced by 20% in the patients. The data suggest that the small intestine plays a prominent role in glutamine utilization in vivo in humans.

Energy and protein metabolism in malnutrition due to nonneoplastic gastrointestinal diseases.

Although a reduction in both energy expenditure and protein turnover has been demonstrated in starved volunteers, few metabolic data are available for patients in whom malnutrition is due to nonneoplastic gastrointestinal diseases. Chronically malnourished, unstressed adult patients with nonneoplastic gastrointestinal diseases (body mass index, 15.8 +/- 2.5 kg/m2, n = 13) and healthy control subjects (n = 10) were studied in the postabsorptive state using indirect calorimetry, as well as substrate fluxes of L[1-13C]leucine, L-[2-15N]glutamine (seven patients and six controls), and D[6,6-2H2]glucose (seven patients and eight controls). Resting energy expenditure (REE) expressed in kilocalories per 24 hours was significantly lower in patients than in controls; REE expressed per unit of fat-free mass (FFM) was not significantly different in both groups. Whole-body leucine turnover, oxidation, and nonoxidative disposal rates, based on either 13C-leucine or 13C-alpha-ketoisocaproic acid (KIC) enrichments, and glucose turnover rate were not significantly different between malnourished patients and controls. Moreover, glutamine turnover was increased by 28% in malnourished patients as compared with normal volunteers (429.8 +/- 86.8 v 334.9 +/- 15.9 mumol/kg/h, P = .02). These results suggest that hypometabolic adaptation, although previously documented in starved volunteers, is not operative during states of chronic malnutrition due to gastrointestinal disease. The increase in glutamine turnover rate might represent an adaptative mechanism to malnutrition for preservation of visceral mass or function.

Amino acid exchange between plasma and erythrocytes in vivo in humans.

To study amino acid exchange between plasma and erythrocytes in vivo, 4-h primed, continuous intravenous infusions of L-[1-13C]leucine, [15N]glycine, and L-[15N]alanine were administered to five healthy young men in the postabsorptive state. Stable isotope enrichments and amino acid levels were determined by gas chromatography-mass spectrometry in both plasma and whole blood and estimated (using hematocrit) in erythrocytes. A high concentration gradient across the erythrocyte membrane was consistently found for glycine (552 +/- 268 microM in erythrocytes vs. 155 +/- 35 microM in plasma), but not for leucine or alanine. A steady-state isotopic enrichment was observed in whole blood as well as plasma for each amino acid in every subject. Steady-state [13C]leucine enrichment in erythrocytes did not differ from plasma enrichment at steady state, the ratio of erythrocyte to plasma enrichment being 1.03 +/- 0.20 (95% confidence limits = 0.78-1.28); in contrast, this ratio reached only 0.23 +/- 0.04 and 0.59 +/- 0.09 (confidence limits 0.18-0.28 and 0.48-0.70) for [15N]glycine and [15N]alanine at steady state, respectively. These results suggest that most of erythrocyte leucine is exchangeable with plasma, whereas only a fraction of erythrocyte glycine and alanine is involved in exchange with plasma in vivo.

Duodenal vs. gastric administration of labeled leucine for the study of splanchnic metabolism in humans.

Low-rate (6 ml/h) intragastric infusion of stable, isotope-labeled amino acids is commonly used to assess the splanchnic handling of amino acids in humans. However, when used in the postabsorptive state, this method yields unreliable plasma isotopic enrichments, with a coefficient of variation >10%. In this metabolic condition, we confirmed in six subjects that an intragastric infusion of L-[(2)H(3)]leucine at 6 ml/h yields an unreliable isotopic steady state in plasma amino acids with a coefficient of variation of 43 +/- 12% (mean +/- SD). In five additional subjects, we assessed the effects of 1) increasing the rate of delivery of a leucine tracer in an isotonic plasmalike solution at 240 ml/h into the gastric site, and 2) changing the site of infusion from gastric to duodenal with this same high rate of delivery. In contrast to the gastric route, and regardless of the rate of delivery, only the intraduodenal route allowed 1) isotopic plasma steady state (i.e., coefficients of variation were <10%: 5 +/- 3%), and 2) reproducible leucine extraction coefficients (22 +/- 5%). We conclude that an infusion site that bypasses the gastric emptying process, i.e., the duodenal route, along with delivery of a plasmalike solution, is necessary to reach isotopic steady state in plasma when labeled leucine is infused into the gastrointestinal tract in the postabsorptive state.

Intestinal absorption of amiodarone in man.

The jejunal absorption rate of amiodarone and the influence of lipids on it were studied in human volunteers using the intestinal perfusion technique. A nutrient solution (Realmentyl, Sopharga Laboratories, France) with 300 mg of the drug was infused for 120 minutes at the ligament of Treitz. The segment tested was 25 cm long. Two caloric loads of the nutrient solution, 3.3 Kcal/min (solution A) and 1.3 Kcal/min (solution B), A containing total lipid and caloric load 2.5 times higher than B, were administered. Minor interindividual differences in amiodarone absorption rate were observed (20.2 to 31.7%) with solution A. Amiodarone absorption correlated with lipid absorption significantly. Since the maximal plasma concentrations of the drug and the area under the curve (AUC/24 hours) did not correlate with the amount of amiodarone absorbed, the wide fluctuations of amiodarone pharmacokinetics must mainly be due to amiodarone tissue distribution and metabolic pathway.

Use of a ventilated canopy for assessment of [13C]leucine oxidation in patients receiving total parenteral nutrition.

Rates of oxidation of infused 13C-labeled substrates are calculated from CO2 production and 13C enrichment in breath CO2. Breath sampling through a mouthpiece is not appropriate in severely ill patients; the authors therefore validated the use of direct air sampling from the ventilated canopy of an indirect calorimeter for measuring the oxidation of 13C-labeled substrates. Infusions of H13CO3Na or L-[1-13C]leucine were performed in four healthy postabsorptive adults and six malnourished patients receiving total parenteral nutrition (TPN). At each sampling point, air was collected from the canopy to compare with breath air sampled through a mouthpiece and 13CO2 enrichment determined by isotope ratio mass spectrometry. Despite five-fold dilution of expired air by room air within the canopy (a dilution required to maintain safe CO2 levels in inspired air): (1) Breath 13CO2 enrichment was accurately predicted using samples from the canopy, with a correction taking into account the measured CO2 fractions in canopy and room air; (2) the precision in isotopic determination was similar with both methods (SD/mean of 12 determinations = 2.5 +/- 1.0% vs 3.0 +/- 1.0%). These data demonstrate that the use of a ventilated canopy allows for combined assessment of energy expenditure and rates of oxidation of 13C-labeled substrates even in sick, debilitated patients receiving total parenteral nutrition.