Characterization of the alteration of nutritional state in brain injury induced by fluid percussion in rats.

OBJECTIVE: Patients suffering from traumatic brain injury (TBI) undergo rapid weight loss with negative nitrogen balance and enhanced whole-body protein breakdown, with protein wasting causing morbidity and increased mortality. Many experimental models of TBI have been used to evaluate strategies to improve the outcome of these patients, but nutritional status has not been considered in experiments published to date, although this may have great importance and influence the results obtained with TBI models. This study characterized the hypercatabolism level and nutritional status of TBI rats. DESIGN: Twenty-four male Wistar rats were randomized into three groups. Rats from the TBI group were anesthetized and fluid percussion was applied. The pair-fed (PF) group was healthy but was pair-fed to the TBI group. The ad libitum (AL) group was healthy and fed ad libitum. The study was performed over 10 days post-TBI. MEASUREMENTS AND RESULTS: TBI in rats was characterized by remarkable long-lasting anorexia, renal failure (creatinine clearance: AL 1.8+/-0.2 and PF 1.5+/-0.1 vs. TBI 0.9+/-0.1 l/24 hour), anorexia (appetite depressed throughout the study), increased myofibrillar proteolysis (3-methylhistidine/creatinine ratio (day 2: AL 36+/-1 and PF 38+/-2 vs. TBI 54+/-5 micromol/mmol), and intestinal atrophy (ileum: AL 29.3+/-2.5 and PF 28.7+/-1.1 vs. TBI 22.5+/-1.4 mg/cm). In addition, anorexia led to muscular atrophy and decreased nitrogen balance. The metabolic alterations described above can increase morbidity and mortality. CONCLUSIONS: TBI by fluid percussion in rats is a model reproducing the metabolic and nutritional alterations observed in clinical practice and is suitable for further studies exploring the efficacy of optimized nutritional support.

Does dietary ornithine alpha-ketoglutarate supplementation protect the liver against ischemia-reperfusion injury?

Nutritional supplementation with glutamine, arginine and their precursors has been proposed to contribute to the protection against ischemia-reperfusion-related injuries. The aim of this study was to evaluate in an isolated perfused rat liver model the preventive effect of a 4-day oral ornithine alpha-ketoglutarate (OKG) supplementation against warm ischemia-reperfusion (I-R) injury, and the involvement of nitric oxide synthesis. Rats were fed a controlled regimen supplemented with either OKG (5 g kg(-1); n=15) or an isonitrogenous mixture of non-essential amino acids (Control; n=6) for 4 days. Livers were subsequently prepared for isolated perfusion experiments, including a 45 min no-flow ischemic period. The OKG-treated group was divided into two groups according to the absence (OKG; n=8) or presence of a NO-synthase inhibitor, L-N(omega)-nitro-arginine methyl ester (OKG L-NAME; n=7) during liver perfusion. Liver cytolysis after ischemia was demonstrated by an elevated alanine aminotransferase release during the last 15 min of reperfusion that was significantly higher in the OKG-L-NAME group. Tumor necrosis factor alpha (TNF(alpha)) production was transiently increased only in the control group just after ischemia. At the end of the reperfusion period, liver superoxide dismutase activity was significantly lower in the OKG-L-NAME group compared to control animals. Dietary OKG administration had only a limited effect in this model of mild hepatic I-R, leading mainly to reduced TNF(alpha) production. As the content of lipid peroxidation products was not modified, it seems that OKG acts on the inflammatory response rather than on oxidative reactions. This action can tentatively be attributed to the role of OKG as a glutamine precursor rather than to the synthesis of arginine and nitric oxide.

Evaluation of a glycine-rich amino acid solution for parenteral nutrition in endotoxemic rats.

OBJECTIVE: It has been shown recently that high amounts of glycine might have some pharmacologic effects (reduction of injury and mortality in endotoxemic rats), but its effects on the nutritional status and protein metabolism during injury are still unknown. The aim of this study was to compare the nutritional effects of a glycine-rich amino acid solution for parenteral nutrition (AFD) with a standard one (Vintene) (glycine, 15 vs. 9 g/L) in endotoxemic rats. DESIGN: Laboratory investigation. SETTING: University laboratory. SUBJECTS: Male Wistar rats (198 +/- 11 g). INTERVENTIONS: Rats were operated to receive total parenteral nutrition (250 kcal/kg/day, 2 g N/kg/day) with amino acids supplied by either AFD (n = 9) or Vintene (V, n = 6). One day after surgery, corresponding to day 0 of the experiment and to the first day of full-strength total parenteral nutrition, the AFD and V group rats received an endotoxemic shock by intraperitoneal injection of lipopolysaccharide (Escherichia coli, 8 mg/kg). The rats were then studied over 3 days and compared with a healthy ad libitum-fed group (AL, n = 10). MEASUREMENTS AND MAIN RESULTS: The rats were weighed and urine was collected daily to determine nitrogen balance and 3-methylhistidine excretion. On day 3, the thymus, spleen, liver, intestinal mucosa, and muscles were weighed, and amino acids from plasma and tissues were analyzed. Lipopolysaccharide caused the classic endotoxemic shock, of similar intensity in the V and AFD groups (V and AFD not equal AL, p < .05): no weight gain, decreased nitrogen balance (day 3, AL 558 +/- 21, V 83 +/- 28, AFD 123 +/- 25 mg N/day), increased urinary 3-methylhistidine/creatinine excretion (day 3, AL 51 +/- 2, V 91 +/- 13, AFD 87 +/- 14 mumol/mmol), soleus (V -15% and AFD -26 % vs. AL) and thymus atrophy (V -36% and AFD -33%), and spleen hypertrophy (V 51% and AFD 83%). Compared with V solution, AFD has a reduced content of some essential amino acids and proline and an elevated content of glycine, aspartate, and glutamate. These differences were not reflected in tissue or plasma amino acids, except for plasma glycine, which in the AFD group was restored to the level of the AL group (AL 426 +/- 12 and AFD 379 +/- 50 vs. V 251 +/- 31 mumol/L, p < .05). CONCLUSIONS: In endotoxemic rats, the nutritional effects of a glycine-rich AFD solution are similar to those of a standard amino acid solution for parenteral nutrition.