Decreased growth hormone levels in the catabolic phase of severe injury.

BACKGROUND: Human growth hormone (hGH) is a potent anabolic agent, which has profound effects on protein, carbohydrate, and lipid metabolism. The role of this primarily anabolic hormone in the severe catabolic state of trauma is not known. METHODS: In a group of young, obese, and elderly patients with multiple traumas, plasma hGH levels were measured in the catabolic "flow" phase of injury, once before and then after 4 to 6 days of nutritional support sufficient to match their initial loss of calories and nitrogen. RESULTS: A decreased hGH level was noted in the hyperglycemic and hypercatabolic injured state, particularly in victims of trauma who were young and not obese, compared to respective volunteers. A significant (p = 0.025) inverse relationship was observed between age and plasma hGH levels in this group of patients who had experienced trauma. Nutritional therapy improved the protein and fat metabolism but could not reverse to the normal state. In young patients who had experienced trauma and who were not obese, the hGH levels were significantly improved because of dietary intake, whereas in elderly patients or patients who were obese no change was noted. CONCLUSION: These results are consistent with less lipid mobilization and inefficient utilization of fatty acids in the elderly patients or patients who were obese who had abundant fat sources to spare. Elevation of hGH level by exogenous administration may improve the nitrogen economy and lipid mobilization, particularly so in the elderly patients or patients who were overweight. Our study supports the view that provision of adequate nutrition with daily administration of human hGH in the first week after trauma would enhance the metabolic status of the patient, resulting in reduced morbidity and earlier discharge from the hospital.

Efficacy of ornithine-alpha-ketoglutarate (OKGA) as a dietary supplement in growing rats.

New substrates of potential benefit to critically ill patients receiving traditional nutritional support have been suggested to meet organ or tissue specific needs. The addition of an anabolic stimulus during nutritional support therefore appears to be a reasonable adjunct to augment protein synthesis. The purpose of this investigation was to evaluate the efficacy of the neutral salt ornithine alphaketoglutarate (OKGA) as a dietary supplement to promote growth in young rats by enhancing protein metabolism. A group of 16 male Sprague-Dawley rats (150-170g) were housed in individual metabolic cages and after dark-light cycle adaptation were fed ad libitum an oral liquid diet for 7 days. Half of the animals were given the control diet and the other half was fed a test diet. This isonitrogenous test diet contained the control diet with 2.3% of nitrogen (N) replaced by N from OKGA. Daily weight, food intake and urinary excretions of N, creatinine, urea, orotic acid, polyamines and amino-acids were determined. At the end of 7 days of free-feeding, the rats were sacrificed and blood was collected for free amino-acids. Rats fed the OKGA supplemented diet consumed 16% more diet, retained 11% more nitrogen and gained 15% more weight. The accelerated protein metabolism is reflected in the changes in plasma and urinary free amino-acid levels. Enhanced protein anabolism is evident from the increased urinary excretion of polyamines in the OKGA fed rats. The increased ratio of urinary urea N to total N and the decreased orotic acid excretion in OKGA fed rats suggests thata NH(4)(+) was efficiently diverted through urea cycle. It is concluded that in growing rats, supplementing isonitrogenous diet with OKGA significantly stimulates food intake compared to controls. This results in better weight gain and improvement in protein metabolism.

Nutritional influence on the plasma and urine-free alkaline ribonuclease levels in severe trauma victims.

The significance of free alkaline ribonuclease (RNase) activity as a criterion of protein metabolism and nutrition in traumatized man is evaluated in this report. Plasma and urinary levels of RNase were measured in severely injured, hypermetabolic patients and in normal controls. Significant increases in the plasma and urinary RNase levels were seen in these polytrauma victims and they were positively correlated. Plasma RNase levels were also significantly related to blood urea nitrogen and daily urinary nitrogen excretion. Urinary clearance of RNase was increased by 220% in trauma victims, although the creatinine clearance was not affected by trauma. In a subgroup of eight patients who were fed intravenously (1.4 times basal energy expenditure calories and 250-300 mg of N per kilogram per day) for 6 days, the daily excretions of urinary RNase, nitrogen, 3-methylhistidine, creatinine, and catecholamines were measured. There was a significant negative correlation between daily urine RNase and nitrogen balance. A general increase in all the metabolic parameters on the first day of feeding was seen, suggesting a nutritional stress superimposed on the trauma-induced metabolic stress. Excretion of RNase, 3-methylhistidine, and creatinine peaked on the first day of feeding and then decreased. The normal levels could not be reached even after 6 days of adequate nutrition. The results suggest that RNase levels could be used as a biomarker of protein metabolism.

Mild orotic aciduria and uricosuria in severe trauma victims.

Hypermetabolic responses with respect to pyrimidine and purine kinetics in trauma victims were investigated during the catabolic phase before and after nutritional support. Orotic acid and uric acid excretions were measured in 32 adult, severely traumatized, hypermetabolic, and highly catabolic patients while they were receiving fluids with no calories or nitrogen. Patients were then fed intravenously amino acids and glucose or glucose alone or fed enterally for 5-6 d. Daily excretions of orotic acid, uric acid, urea, nitrogen, and creatinine were monitored. Mild orotic aciduria and uricosuria with hypouricemia were the basal-trauma responses. The significant (P = 0.001, r = 0.70) positive correlation between orotic and uric acid excretion demonstrates the parallelism between pyrimidine and purine metabolism. Feeding for 5-6 d could decrease but not readily abolish the injury-induced metabolic changes in nitrogen, pyrimidine, and purine metabolism. Glucose infusion alone may be sufficient to counteract the metabolic effects of trauma in the early flow phase of injury.

Altered plasma free amino acid levels in obese traumatized man.

Obesity is a major nutritional disorder that produces many abnormal metabolic responses. The effect of injury-induced stresses acting synergistically with the state of excessive body fat is not well known. Plasma levels of circulating free amino acids reflect the net status of protein breakdown and utilization. Hypoaminoacidemia is a common finding in severe injury and its significance in obese subjects was investigated. We measured in 10 obese (body mass index [BMI] greater than 30) and 10 non-obese (BMI less than 30) traumatized (Injury Severity Score [ISS] 17 to 50) patients, the plasma levels of free amino acids in the early "flow" phase of injury when subjects were receiving maintenance fluids without calories or nitrogen. Postabsorptive control samples were obtained from 10 obese and 10 non-obese volunteers. Obese controls showed an increase in valine, leucine, isoleucine, and glutamic acid levels, and a decrease in glycine, tryptophan, threonine, histidine, taurine, citrulline, and cystine levels compared with lean controls. Hypoaminoacidemia was equally seen in traumatized obese and non-obese patients, and it was mainly due to a 24% decrease in nonessential amino acids. Remarkably, essential amino acid levels were the same in all groups. Arginine and ornithine levels were significantly different in traumatized obese compared with non-obese patients. The hypoglycinemia seen in non-obese trauma patients was absent in obese patients. The changes in levels of sulphur-containing amino acids also suggest that monitoring of these levels should be included in the nutritional management of obese trauma patients.

Elevated urinary C-peptide excretion in multiple trauma patients.

A simple, indirect method of estimating integrated insulin secretion is the measurement of C-peptide, a byproduct of insulin biosynthesis, in plasma and in 24-hr urine samples. We determined, in 29 severely injured hypermetabolic and highly catabolic multiple trauma patients, the plasma level and daily excretion rate of C-peptide, 48-72 hrs postinjury. Data from a set of eight patients who underwent glucose-based total parenteral feeding for 6 days were analyzed for the course of changes in the excretory pattern of C-peptide and catecholamines. The molar ratio of plasma C-peptide to insulin in the trauma patients was similar to that in unstressed controls, indicating that the rate of hepatic insulin extraction is not appreciably altered due to trauma. This is also evident from a significant correlation (p = 0.001) between the plasma C-peptide and insulin levels. The excretion of C-peptide was elevated to three times the normal both in absolute terms and when normalized to creatinine excretion. This was also accompanied by a twofold increase in the plasma levels, indicating an enhanced secretion rate of C-peptide and hence of insulin in response to trauma. Injury-induced insulin resistance does not seem to be due to a decreased insulin secretion. An increase in insulin output would appear to be a significant and desirable response for a continued anabolic stimulus coexistent with the net catabolic phase. Parenteral feeding augmented the excretion of C-peptide and catecholamines and this effect peaked on the fourth day of nutritional therapy.

Effect of major trauma on plasma free amino acid concentrations in geriatric patients.

Age-associated decrease in lean body mass may lead to varied responses to severe trauma. Hypoaminoacidemia is generally common among trauma victims. We measured the plasma free amino acids in the early "flow," ie, catabolic, phase of injury in 9 elderly (aged 61-81 y) and 13 young (aged 20-38 y) traumatized patients. Postabsorptive control samples were obtained from 8 elderly and 10 young volunteers. The results were analyzed for age-related responses to major trauma. Older healthy control subjects showed a decrease in total amino acids, essential amino acids, proline, histidine, taurine, and cystine. The hypoaminoacidemia was less pronounced in geriatric trauma, mainly because of a larger decrease in nonessential amino acids in young trauma victims. Significant decreases in arginine and methionine and increases in ornithine and citrulline concentrations were seen in geriatric trauma. These results suggest a sluggish protein metabolic response to trauma in elderly individuals, which should be considered in their nutritional management.

A rapid, automated micromethod for measuring free fatty acids in plasma/serum.

The investigation of mobilization and utilization of fat as fuel in human subjects requires the quantification of free fatty acids (FFA) in the circulating plasma. Methods in current use involve tedious extraction and titration, or enzymatic reaction with colorimetric or fluorometric detections. A rapid and reliable micro-technique is needed. We have adapted the manual enzymatic method of the Wako NEFAC kit to an automated rapid assay performed with a micro-centrifugal analyzer. This method depends upon the specific acylation of CoA by FFA, followed by oxidation and condensation to form a purple adduct measurable at 550 nm. The acylation step requires incubation at 37 degrees C for 10 min, a critical step for serum/plasma analysis. Only 4 microL of plasma is needed, and 20 tests can be performed in 20 min. The precision (CV) of sample analysis is within 2%. The results for the samples analyzed by this technique are within 4% (SEM 1%) of results by the manual method. Thus accurate results are achieved at reduced cost, time, and sample size.

Aminoaciduria of severe trauma.

Plasma and urine levels of free amino acids were measured in 15 severely traumatized adult patients while they were receiving fluids free of calories and nitrogen. Endogenous plasma clearance and the relative rates of reabsorption of free amino acids from renal tubules were calculated. These data were compared with similar studies of eight control subjects. Multiple injury provoked distinct patterns of free amino acids in plasma and urine. Hypoaminoacidemia and hyperaminoaciduria were seen in severe trauma. There was a marked depletion of nonessential amino acids in plasma of trauma victims. In contrast, the urinary loss of all amino acids was increased 5-10 times. This enhanced loss in patients, however, represented only 2.1% of total N excreted compared with 0.7% in control subjects. Considerable variations were seen in the selectivity with which various amino acids were reabsorbed by renal tubules. This may partly be due to the abnormal pattern of amino acids presented to renal tubules.