Biomedical subjects

S R Petersen

Publications and source records attributed to S R Petersen.

At least 19 recordsLinked to original sources

PubMed2001

Clinical role of polyamine analysis: problem and promise.

Polyamines are ubiquitous cell components for growth. They play an important role in cell proliferation, cell growth and synthesis of protein and nucleic acids. Cells that are stimulated to reproduce demonstrated early increases in biosynthetic enzymes involved in polyamine synthesis and subsequent elevations in polyamine levels. Extracellular fluid polyamine concentrations that reflect the intracellular events may be useful as rapid indicators of therapy in disorders which involve altered cell growth. More complex analytical approaches are required to isolate, identify and quantitate these polyamines. Most of the methods require an extraction procedure to remove interfering amino acid derivatives. Daily monitoring of plasma and urine polyamine levels in many pathological states may provide a non-invasive biochemical marker of the existing disease activity or response to therapy or to screen for drug efficacy. Automated high-performance liquid chromatography, with post or pre-column derivatization and fluorescence or electrochemical detection is frequently used for the simultaneous quantitation of picomolar quantities of polyamines. Recently, a new immuno-cytochemical model system incorporating an enzyme-linked immunosorbent assay for specific polyamines has been developed. The increasing momentum of basic science information in the polyamine discipline may lead clinicians to regard polyamines, their metabolites and antimetabolites as sources of effective treatment.

Biomarkers↗

PubMed2000

The effects of hyperoxia on performance during simulated firefighting work.

This study evaluated the effects of hyperoxia (inspired oxygen fraction = 40%) on performance during a simulated firefighting work circuit (SFWC) consisting of five events. On separate days, 17 subjects completed at least three orientation trials followed by two experimental trials while breathing either normoxic (NOX) and hyperoxic (HOX) gas mixtures that were randomly assigned in double-blind, cross-over design. Previously, ventilatory threshold (Tvent) and VO2max had been determined during graded exercise (GXT) on a cycle ergometer. Lactate concentration in venous blood was assessed at exactly 5 min after both the experimental trials and after the GXT. Total time to complete the SFWC was decreased by 4% (p < 0.05) with HOX. No differences were observed in individual event times early in the circuit, however HOX resulted in a 12% improvement (p < 0.05) on the final event. A significantly decreased rating of perceived exertion (RPE) was also recorded immediately prior to the final event. No differences were observed in mean heart rate or post-exercise blood lactate when comparing NOX to HOX. Heart rates during the SFWC (both conditions) were higher than HR at Tvent, but lower than HR at VO2max (p<0.05). Post-SFWC lactate values were higher (p<0.05) than post-VO2max. These results demonstrate that hyperoxia provided a small but significant increase in performance during short duration, high intensity simulated firefighting work.

Adult↗

PubMed2000

Altered plasma cytokines and total glutathione levels in parenterally fed critically ill trauma patients with adjuvant recombinant human growth hormone (rhGH) therapy.

OBJECTIVES: Glutathione (GSH) is a potent endogenous antioxidant that serves as one of the body's most important defenses against oxygen metabolites. Plasma levels of GSH are maintained primarily by a balance between secretion from the liver and degradation in the kidney. The ability to maintain and enhance tissue GSH may be of particular importance in controlling cytokine production in response to a stimulus like injury. The interaction after severe trauma between GSH and cytokines, tumor necrosis factor (TNF) -alpha, and interleukin (IL)-6, are not known. The purpose of the study was to investigate the levels of plasma GSH and cytokines TNF-alpha and IL-6 in adult patients admitted to the intensive care unit of our level I trauma center who were treated with recombinant human growth hormone (rhGH) for > or =7 days. DESIGN: Prospective, randomized, controlled trial. SETTING: Trauma intensive care unit. PATIENTS: Twenty-eight patients with multiple injuries and 14 normal postabsorptive controls. INTERVENTIONS: From 48-60 hrs after injury, when resuscitation was complete, a stable hemodynamic status was achieved and the patients were receiving maintenance fluid without nitrogen or calories, a blood sample was drawn for basal, plasma GSH, TNF-alpha, and IL-6 measurement. Intravenous feeding was then started and continued for 7 days. The patients were randomized to receive or not to receive daily intramuscular doses of recombinant human growth hormone (0.15 mg rhGH/kg/day). Daily morning plasma was obtained for analysis of GSH, TNF-alpha, and IL-6 levels. RESULTS: In the early catabolic "flow phase" of severe injury, the plasma levels of GSH were not altered but plasma TNF-alpha and IL-6 levels were increased significantly, compared with uninjured controls. Seven days of total parenteral nutrition alone enhanced plasma GSH levels (76%), but no change in TNF-alpha was observed. Supplementation with rhGH enhanced GSH (180%), and TNF (65%) with no changes in IL-6 levels. There is a significant linear relationship between plasma GSH and TNF-alpha levels in our rhGH-supplemented trauma patients. CONCLUSION: Modification of plasma GSH and TNF-alpha levels by adequate nutritional support with adjuvant rhGH during the postinjury period demonstrates the beneficial role of GSH in enhancing antioxidant defenses.

Adolescent↗

PubMed1999

Release of proinflammatory cytokines by mitogen-stimulated peripheral blood mononuclear cells from critically ill multiple-trauma victims.

This study investigated the alterations in circulating proinflammatory cytokines and cytokine production by peripheral blood mononuclear cells (PBMCs) in response to lipopolysaccharide (LPS) or phytohemagglutinin (PHA) after severe trauma. Plasma and PBMCs were collected from 17 severely injured trauma patients and 10 healthy subjects. Plasma was stored at -80 degrees C and analyzed for cytokines. Isolated PBMCs from each subject were stimulated with LPS or PHA and incubated at 5% CO2 for 24 hours. Supernatants were collected and analyzed for cytokines. There was no significant change in the plasma concentration of free TNF-alpha and IL-1beta between healthy subjects and trauma patients. Plasma IL-6, total TNF-alpha, and total IL-1beta were significantly increased in severely traumatized patients compared with healthy control subjects. PBMCs from trauma patients produced higher levels of TNF-alpha in response to LPS but it showed no significant change in IL-1beta and IL-6 production in response to PHA or LPS in comparison to PBMCs from control subjects. We conclude that severe trauma results in a significant increase in plasma proinflammatory cytokine IL-6. Free TNF-alpha and IL-1beta in plasma remain at levels comparable to those in uninjured controls, while plasma free IL-6 levels in trauma patients remain high. Serious injury is associated with an enhanced production of TNF-alpha by PBMCs stimulated with LPS.

Adult↗

PubMed1999

Substrate fuel kinetics in enterally fed trauma patients supplemented with ornithine alpha ketoglutarate.

BACKGROUND: Ornithine-alpha-ketoglutarate (OKG) is a promising anticatabolic agent and the mechanisms of its potential use in trauma patients are not clearly understood. AIM: To determine the altered whole-body protein, lipid and glucose substrate kinetics in trauma victims in the early flow-phase of injury when they were fed enterally with or without OKG. METHODS: Fourteen adult, multiple trauma patients who were highly catabolic and hypermetabolic were studied. Whole-body protein ((15)N glycine), fat (2 stage glycerol infusion) and glucose ((3H)glucose) kinetics (t/o) and plasma parameters were measured (A) within 48-60 h after injury before starting nutritional support and then (B) after 4 days of enteral feeding. Group A (n=7, control) received a defined enteral formula (Two Cal HN, 1.4 times BEE calories) and Group B (n=7, OKG) received same isonitrogenous diet replacing 2.62gN/d from the enteral diet by OKG-N (20g OKG/d). RESULTS (Mean+/-SEM): Protein turnover is significantly (P<==0.05) increased in OKG treated patients (4.68+/-0. 15 vs 3.90+/-0.23, gP/kg/day) and glycerol turnover is decreased (0. 87+/-0.16 vs 1.46+/-0.16, micro mole/kg/min). Glucose turnover is not changed. Significant (P<== 0.05) increases in circulating plasma levels of hormones (insulin, 44.2+/-8.4 vs 15.7+/-5.0 ulU/ml, growth hormone 1.68+/-0.33 vs 0.92+/-0.16, ng/ml and IGF-1, 106+/-13 vs 75+/-18, ng/ml) and free amino acids (glutamine, 383+/-20 vs 306+/-25, Proline, 203+/-18 vs 146+/-13 and ornithine, 164+/-27 vs 49+/-5 micro mole/l) are found in OKG treated patients, compared to non OKG patients. CONCLUSION: Increased hormone secretion due to OKG and the rapid interaction between the metabolites of OKG at the intermediary metabolism level may be responsible for altered substrate fuel kinetics.

Adult↗

PubMed1999

Skeletal muscle metabolism during short-term, high-intensity exercise in prepubertal and pubertal girls.

To test the hypothesis that glycolytic metabolism in muscle is attenuated in prepubertal children, (31)P-magnetic resonance spectroscopy was used to determine calf muscle intracellular pH (pH(i)) in nine prepubertal (Pre) and nine pubertal female swimmers (Pub). Maximal plantar flexion work capacity (100% MWC) was established by using a graded exercise test. Between 5 and 10 days later, calf muscle images (magnetic resonance imaging) and phosphorus spectra were acquired at rest, during 2 min of light exercise (40% MWC), and during 2 min of supramaximal exercise (140% MWC) in a 3.0-T NMR system. End-exercise pH(i) was 6.66 +/- 0.11 and 6.76 +/- 0.17 for Pub and Pre, respectively. No significant differences in the mean values for pH(i) or the P(i)-to-phosphocreatine ratio were observed between groups during the protocol; however, an interaction effect was found for the P(i)-to-phosphocreatine ratio during the supramaximal exercise challenge. Cross-sectional area of gastrocnemius was 15.12 +/- 0.46 and 9.37 +/- 0.37 cm(2) for Pub and Pre, respectively (P < 0.05). Differences in muscle size must be considered when interpreting the unlocalized magnetic resonance spectroscopy data. These results suggest that glycolytic metabolism in physically active children is not maturity dependent.

Adolescent↗

PubMed1998

Amelioration of the protein metabolic response in spermidine-supplemented trauma rats.

Polyamines are biologically active, small, positively charged ubiquitous compounds that play an important role in initiating adaptive changes in cell proliferation, cell growth, and synthesis of proteins and nucleic acids. The potential for exogenous dietary polyamine to significantly contribute to whole-body growth and health has not been explored. This study evaluates the efficacy of feeding a liquid diet supplemented with 0.05% spermidine in injured rats. Rats traumatized by bilateral femur fracture (n = 12) and pair-fed uninjured controls (n = 12) were starved for 2 days and then refed for 4 days with a liquid diet containing 0.05% spermidine or an isonitrogenous control diet. Daily urine and body weight data were collected. At the end of refeeding, the rats were killed, and blood, cerebrospinal fluid (CSF), muscle, and brain tissue were collected. Spermidine supplementation (0.05%) was found to be tolerated well by the rats and (1) did not affect voluntary food intake by traumatized rats, (2) did not alter the growth rate, (3) increased protein utilization efficiency, and (4) decreased leucine, isoleucine, and valine levels in plasma and muscle. The profound effect of trauma on plasma amino acid metabolism seen in rats fed the basal diet was absent in spermidine-supplemented rats. Depletion of plasma glutamine (GLN) levels due to trauma was significantly less in rats with spermidine supplementation (11% v 33%), indicating a beneficial effect to counteract trauma responses. The results suggest that spermidine supplementation improves protein utilization efficiency and ameliorates trauma effects on amino acid levels.

Amino Acids↗

PubMed1998

Effects of endurance training on transient oxygen uptake responses in cyclists.

The aim of this study was to determine the alterations in oxygen uptake kinetics following endurance training in previously trained athletes. Sixteen competitive cyclists completed 8 weeks of supervised endurance cycle training. Ventilatory threshold, maximal oxygen uptake (VO2max), oxygen uptake kinetics and simulated 40-km time-trial tests were performed three times over a 4-week period before training, and then after 4 and 8 weeks of training. The protocol for measuring oxygen uptake kinetics consisted of three square-wave increments from unloaded cycling to a power output of 78 W followed by a single increment from 78 to 156 W. No significant differences in any variables were observed over the pre-training period. The ventilatory threshold and VO2max increased, and the time for 40 km decreased (P < 0.05) with training. Shorter VO2 time constants and lower heart rates were observed during the protocol for measuring oxygen uptake kinetics (same absolute power output) post-training. These results indicate that oxygen uptake kinetics may be improved with endurance training in previously trained athletes.

Adult↗

PubMed1998

Thyroid hormone concentrations and muscle metabolism in amenorrheic and eumenorrheic athletes.

The relationship between resting thyroid hormone concentrations and exercise muscle metabolism was examined among eumenorrheic endurance-trained (n = 11), amenorrheic endurance-trained (n = 8), and eumenorrheic nonathletic (n = 13) subjects. Muscle metabolism was assessed with 31Phosphorous magnetic resonance spectroscopy by measuring changes in phosphocreatine (PCr), inorganic phosphate (Pi), and pH during plantar flexion exercise and recovery. All groups had similar Pi/PCr ratios and pH changes during exercise. Eumenorrheic endurance-trained subjects had faster recovery rates for PCr and Pi/PCr following exercise compared to the nonathletes (p < .05) and faster recovery rates for PCr compared to amenorrheic subjects (p < .05). Thyroxine (T4) and triiodothyronine (T3) levels were significantly lower in amenorrheic subjects compared to both eumenorrheic groups (p < .05). It was concluded that routine training enhances muscle metabolism, as measured by phosphate recovery kinetics. This enhancement was not evident in amenorrheic athletes with reduced T3 and T4 concentrations.

Adult↗

PubMed1997

The influence of maximal aerobic power on recovery of skeletal muscle following anaerobic exercise.

Phosphorus magnetic resonance spectroscopy (31P-MRS) was used to investigate the influence of maximal aerobic power (VO2max) on the recovery of human calf muscle from high-intensity exercise. The (VO2max) of 21 males was measured during treadmill exercise and subjects were assigned to either a low-aerobic-power (LAP) group (n = 10) or a high-aerobic-power (HAP) group (n = 11). Mean (SE) VO2max of the groups were 46.6 (1.1) and 64.4 (1.4) ml.kg-1.min-1, respectively. A calf ergometry work capacity test was used to assign the same relative exercise intensity to each subject for the MRS protocol. At least 48 h later, subjects performed the rest (4 min), exercise (2 min) and recovery (10 min) protocol in a 1.5 T MRS scanner. The relative concentration of phosphocreatine (PCr) was measured throughout the protocol and intracellular pH (pHi) was determined from the chemical shift between inorganic phosphate (Pi) and PCr. End-exercise PCr levels were 27 (3.4) and 25 (3.5)% of resting levels for LAP and HAP respectively. Mean resting pHi was 7.07 for both groups, and following exercise it fell to 6.45 (0.04) for HAP and 6.38 (0.04) for LAP. Analysis of data using non-linear regression models showed no differences in the rate of either PCr or pHi recovery. The results suggest that VO2max is a poor predictor of metabolic recovery rate from high-intensity exercise. Differences in recovery rate observed between individuals with similar VO2max imply that other factors influence recovery.

Adult↗

PubMed1997

Nutritional and metabolic effects and significance of mild orotic aciduria during dietary supplementation with arginine or its organic salts after trauma injury in rats.

The effects of acute food deprivation and subsequent refeeding with isonitrogenous oral liquid diets supplemented with arginine (ARG), ARG alpha-ketoglutarate (AKG), or ARG alpha-ketoisocaproate (AKIC) were examined in a Sprague-Dawley rat trauma model (bilateral femur fracture). Both control and trauma rats were starved for 2 days and then pair-fed for 4 days with one of four liquid isonitrogenous diets: diet 1 was a basal casein-based diet, and diets 2, 3, and 4 were the basal diet in which 10% of the nitrogen was replaced by ARG, AKG, or AKIC nitrogen. Two days of starvation resulted in a 13% loss of body weight and also a 27% decrease in the excretion of orotic acid (OA) in control and trauma rats. Although the ARG content of diets 2, 3, and 4 was the same, ARG- and AKIC-supplemented rats excreted significantly (P < .05) more OA than AKG-fed rats. The low level of OA excretion in AKG-fed rats indicates greater use of ARG for metabolic purposes, including efficient urea cycle operation. The metabolic adaptation and nutritional efficacy, i.e., Increased nitrogen retention, larger weight gain, and altered amino acid (AA) metabolism, of AKIC rats seem to be better than in ARG- or AKG-fed rats.

Amino Acids↗

PubMed1997

Nutritional efficacy of a spermidine supplemented diet.

Polyamines (PA) are ubiquitous cell components essential for growth. Dietary PAs are directed preferentially to tissues and organs that have been stimulated to grow by metabolic signals. Nutritional efficacy and growth potential of an oral PA supplement, spermidine (SD), was examined in growing rats. A group of 24-male Sprague-Dawley rats (200-220 g) was adapted to our vivarium conditions for 3 d, then fed ad libitum continuously for 14 d. During feeding they received either a basal diet (n = 8) or a test diet containing the basal diet with 0.05% SD (test diet 1, n = 8) or 0.10% SD (test diet 2, n = 8). This dose of SD corresponds to an intake of 54 and 108 mumol of SD per rat per day. At the end of 14 d of feeding, the animals were sacrificed and plasma, cerebral spinal fluid (CSF) and tissues (muscle, brain, and liver) were harvested for amino acid analysis. Voluntary food intake, body weight gain, and nitrogen excretion and balance were significantly decreased in test diet 2 fed rats compared to test diet 1. The opposing trends in the accumulation/depletion of free amino acids (AA) in muscle and plasma suggests that the exogenous supply of SD blocks the transport of amino acids, as well as PAs from the cells, since AA and PA share the same transport systems. A trend toward decreased weight gain and feeding efficiency was observed when high concentrations of SD were fed. It was concluded that feeding of SD at moderate intake is not toxic and does not retard growth. Oral administration of a smaller dose (<0.05%) of SD may promote further growth. The optimal level of SD dietary supplementation has thus yet to be established.

Amino Acids↗

PubMed1997

Reprioritization of liver protein synthesis resulting from recombinant human growth hormone supplementation in parenterally fed trauma patients: the effect of growth hormone on the acute-phase response.

BACKGROUND: One of the major components of the metabolic response to severe trauma is the alteration in concentrations of a large number of plasma proteins referred to as acute-phase proteins (APP). The principle mediators of these liver-synthesized APP are mainly the cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). METHODS: We have measured the plasma levels of IL-6, TNF alpha, and 20 APP in 24 adult, severely injured, hypermetabolic and highly catabolic patients with multiple injuries within 48-60 hours after injury, when they were receiving maintenance fluids without calories or nitrogen, and subsequently during 7 days of total parenteral nutrition with (n = 12) or without (n = 12) recombinant human growth hormone supplementation (rhGH, 0.15 mg/kg/d). RESULTS: Baseline positive APP due to severe trauma include C-reactive protein (CRP), alpha-1 antichymotrypsin, alpha-1 acid glycoprotein, alpha-1 antitrypsin, fibronectin, and factor B. Negative APP include IgG, IgM, complement-3, prealbumin, transferrin, ceruloplasmin, and albumin. Except for CRP, alpha-1 antichymotrypsin, and albumin, all the APP levels increase during 7 days of nutritional support. Plasma levels of cytokines IL-6 and TNF-alpha, although initially markedly increased after injury, decrease with parenteral refeeding. There is a linear correlation between CRP and IL-6 levels and also between the transport proteins prealbumin and transferrin. Trauma-induced increases in CRP and IL-6 levels decreased with nutrition alone, but did not change with rhGH supplementation. An immunosuppressed state of injury is evident from the decreased immunoglobulin levels (IgG, IgM, IgA) in the trauma patients. Total parenteral nutrition alone increases the immunoglobulin levels to normal. However, with adjuvant rhGH, only IgA levels are normalized. CONCLUSIONS: Adjuvant rhGH therapy does not attenuate the reprioritization of acute liver protein synthesis and results in only limited restoration of host defenses. The clinical implications of these findings await further study.

Acute-Phase Proteins↗

PubMed1996

The effect of salbutamol on performance in endurance cyclists.

The effect of salbutamol (S) on cycling performance was examined in 15 highly trained non-asthmatic male cyclists. A double-blind, randomized cross-over design was used with S or placebo (P) administered using a metered-dose inhaler and a spacer device 20 min before each testing session. The S dose was 400 micrograms (four puffs), which is twice the normal therapeutic level. Subjects were habituated to all the laboratory procedures in the week prior to actual data collection. The subjects performed four tests under S and P conditions on separate days over 2 weeks. These included measurement of maximal O2 uptake (VO2max) (cycle ergometry) with assessment of pulmonary function before and after, a submaximal (90% of ventilatory threshold) square-wave work transition from a base of unloaded cycling, a 60-s modified Wingate test, and a simulated 20 km time trial. No significant differences were observed in any of the dependent variables related to aerobic endurance or cycling performance between the S and P conditions. These results support other findings that an acute dose (400 micrograms) of S has no performance-enhancing properties.

Adrenergic beta-Agonists↗

PubMed1996

Adjuvant recombinant human growth hormone does not augment endogenous glucose production in total parenteral nutrition-fed multiple trauma patients.

Hyperglycemia and insulin resistance are well-known, consistent responses to severe injury. The purpose of this study was to investigate the mechanism for the further exaggerated hyperglycemia due to adjuvant recombinant human growth hormone (rhGH) treatment in multiple trauma patients. We have measured in 20 adult severely injured, highly catabolic, hypermetabolic multiple trauma patients, the glucose kinetics (appearance, clearance, oxidation, and recycling) once in the basal state (study I), 48 to 60 hours after injury but before starting nutritional therapy, and again (study II) after 7 days of intravenous nutrition (1.1 times resting energy expenditure, 250 mg nitrogen [N]/kg/d) with or without adjuvant rhGH. Group H (n = 10) randomly received daily (8 AM) rhGH (0.15 mg/kg/d) and group C (n = 10) received the vehicle of infusion. Adjuvant rhGH treatment in intravenously fed trauma patients (1) increases plasma insulin-like growth factor-1 (IGF-1) and insulin concentrations, (2) improves N balance, and (3) exaggerates the hyperglycemic response without affecting endogenous glucose output, glucose oxidation, or recycling. The mechanism for the hyperglycemic hyperinsulinemia in trauma may be due to a defective nonoxidative glucose disposal, as well as inhibition of glucose transport activity into tissue cells.

Adjuvants, Pharmaceutic↗

PubMed1996

Evaluation of pancreatic injury after blunt abdominal trauma.

Pancreatic injury after blunt abdominal trauma can be subtle and delayed in its onset. We present a 24-year-old man who became jaundiced 16 days after he experienced blunt trauma. He was found to have an isolated pancreatic contusion. We discuss the initial evaluation for blunt pancreatic injury, the differential diagnosis of jaundice resulting from the trauma, and, finally, three methods of treating pancreatic contusions that cause jaundice.

Abdominal Injuries↗

PubMed1996

Ornithine-alpha-ketoglutarate (OKG) supplementation is more effective than its component salts in traumatized rats.

Addition of an anabolic stimulus during nutritional support seems to be a reasonable adjunct to augment protein synthesis. Ornithine-alpha-ketoglutarate (OKG) has been used for this purpose in many pathological situations, but the mechanism of action is poorly understood. We have evaluated the relative metabolic efficacy of four isonitrogenous diets with or without the addition of alpha-ketoglutarate (alpha KG) or ornithine (ORN), in a rat trauma (bilateral femur fracture) model. Both control and traumatized rats were starved for 2 d. Then for 4 d, the control rats were pair-fed to the traumatized rats, one of the four isonitrogenous diets: the basal diet was a casein-based liquid diet; the ORN and OKG diets were the basal diet in which 10% of the dietary nitrogen was replaced by ORN- or OKG-nitrogen, respectively; the alpha KG diet contained equivalent amounts of alpha KG as were present in the OKG diet. Body weight gain per gram of nitrogen intake was similar in all four diet groups of both control and traumatized rats. The fraction of nitrogen intake that was retained in the body was significantly higher in OKG-fed traumatized rats (23%) than in the corresponding basal diet-fed rats. Plasma and muscle free amino acid concentrations were comparable in OKG- and ORN-fed rats but not in OKG- and alpha KG-fed rats. Our data suggest that the mechanism of OKG action may be associated with increases in growth hormone and insulin, as well as the production of metabolites of ORN and alpha KG. OKG has better metabolic benefits than its two components given separately in the nutritional support of injured rats.

Amino Acids↗

PubMed1996

Arterial-jugular vein free amino acid levels in patients with head injuries: important role of glutamine in cerebral nitrogen metabolism.

Traumatic brain injury is the single largest contributor of trauma center deaths. Injury to the brain cannot be considered as an isolated event, affecting only this organ. Profound hypoglutaminemia commonly seen in patients with head injuries may be caused by the diminished release of glutamine from the brain to the systemic circulation. To assess this hypothesis, we have simultaneously measured the free amino acid (AA) levels in systemic arterial (A, radial artery), cerebral venous (JV, jugular bulb), and systemic venous (PA, pulmonary artery) plasma in 11 adult patients with severe head injuries once within 48 hours of the initial injury before starting nutritional support and again after 3 to 4 days of enteral feeding. Cerebral organ (A-JV) changes of AA levels were compared with whole body systemic (A-PA) changes. Arterial total AA levels when compared with reported normal values are diminished by 46% in patients with isolated severe injuries. Cerebral outflow of glutamine is 6% of the total AA output compared with 73% in normals. The systemic outflow of glutamine in patients with brain injuries is 28% of total AA flow. Despite this high systemic output, significant hypoglutaminemia persists. Feeding for 3 days did not appreciably change the arterial plasma AA levels except that of glutamate and citrulline. A significant (p = 0.01) linear relationship between glutamine (product) and glutamate (precursor) was seen in JV samples but not in A or PA samples. The ratio of plasma glutamine to glutamate was decreased significantly only in JV during nutritional support, and this was caused mainly by an increase in glutamate levels. This may be owing to defective amidation to glutamine, inasmuch as gamma aminobutyric acid (GABA) levels were only minimally affected. Nutritional support improves the net release of glutamine from the brain. This suggests that supplementing the diet with glutamine may be beneficial to support systemic requirements in patients with severe head injuries.

Adolescent↗