The Effects of Sepsis and Endotoxemia on Gut Glutamine Metabolism (original) (raw)
Related papers
Glucose and glutamine metabolism in the small intestine of septic rats
PubMed, 1990
The intestinal metabolism of glucose and glutamine was studied in rats made septic by cecal ligation and puncture technique. Sepsis resulted in negative nitrogen balance and produced increases in the concentrations of blood pyruvate, lactate, alanine, and glutamine, and decreases in those of 3-hydroxybutyrate and acetoacetate. Both plasma insulin and glucagon concentrations were increased by 2.2- and 3.2-fold in septic rats, respectively. Portal-drained visceral blood flow increased in septic rats, and was accompanied by a decrease in the rates of utilization of glutamine and production of lactate, glutamate, and ammonia compared with those rates in sham-operated animals. Enterocytes isolated from septic rats showed decreased rates of glucose and glutamine utilization compared with cells isolated from corresponding controls. The maximal activities of hexokinase, 6-phosphofructokinase, pyruvate kinase, and glutaminase were decreased in intestinal mucosal scrapings of septic rats. It is concluded that a moderate form of sepsis decreases the rates of glucose and glutamine utilization (both in vivo and in vitro) by the epithelial cells of the small intestine. This may be caused by changes in the maximal activities of key enzymes in the pathways of glucose and glutamine metabolism in these cells as a metabolic adaptation to spare glucose and glutamine for use by other tissues.
Saudi medical journal, 2012
To investigate the effects of enteral and parenteral glutamine (Gln) usage on rats in sepsis. This study was conducted in Istanbul University Experimental Medical Research Institution (DETAE) laboratory, Istanbul University, Istanbul, Turkey between June and September 2009. The levels of blood Gln, tumor necrosis-alpha (TNF-alpha) and interleukin (IL)-10 was measured. Samples of tissue were obtained from the mesenteric lymph nodes, liver, and lower lobe of the right lung to evaluate the reproduction of bacteria, and samples of tissue were also obtained from the small intestine to evaluate blood and villus atrophy. Bacteremia of Group EP (combined group) were found lower than Group C (control) (p=0.007). Villous atrophy rates of all groups were lower than Group C: between Group E (enteral) and C (p=0.003); between Group P (parenteral alanine) and C (p=0.019); and between Group EP and C (p=0.001). The values of serum TNF-alpha and IL-10 of Group EP and P were lower than the other grou...
Clinical Science, 2001
We have investigated sequential changes in skeletal muscle and hepatic protein synthesis following sepsis, and their relationship to changes in circulating and tissue glutamine concentrations. Male Wistar rats underwent caecal ligation and puncture (CLP) or sham operation, with starvation, and were killed 24, 72 or 96 h later. A group of non-operated animals were killed at the time of surgery. Protein synthesis was determined using a flooding dose of L-[4-3 H] phenylalanine, and glutamine concentrations were measured by an enzymic fluorimetric assay. Protein synthesis in gastrocnemius muscle fell in all groups. Gastrocnemius total protein content was reduced after CLP and at 72 and 96 h after sham operation. After CLP, protein synthesis was lower at 24 h, and total protein content was lower at 72 and 96 h, than in shamoperated animals. CLP was associated with increased liver protein synthesis at all time points, whereas there was no change after sham operation. Liver protein content did not change after CLP, but was lower at 72 and 96 h after sham operation than in non-operated animals. Plasma glutamine concentrations were reduced at 24 h after sham operation, and at 72 and 96 h after CLP. Muscle glutamine concentrations were reduced in all groups, with the decrease being greater following CLP than after sham operation. In the liver, glutamine concentrations were unchanged after CLP, but increased after sham operation. In rats with sepsis, decreases in muscle protein synthesis and content are associated with markedly reduced muscle glutamine concentrations. Plasma glutamine concentrations are initially maintained, but fall later. In liver, protein synthesis is increased, while glutamine concentrations are preserved. These results support a peripheral-to-splanchnic glutamine flux in sepsis.
Pulmonary glutamine production: effects of sepsis and pulmonary infiltrates
Intensive Care Medicine, 2003
To define the role of the lung in the production of glutamine in the critically ill and to determine the effects of the presence of pulmonary infiltrates and the presence and severity of sepsis. Design and setting: Prospective clinical study in a single center; interdisciplinary intensive care unit at a university hospital. Patients: Eleven critically ill patients were compared to ten patients prior to cardiac bypass surgery. Measurements and results: Fluxes of glutamine and other amino acids were measured. Chest radiography was performed, and APACHE II and multiple-organ failure scores were calculated. Septic patients showed significantly higher glutamine efflux from the lungs than controls. At least one-half of this glutamine is estimated to result from protein breakdown. Severity of illness had no impact on glutamine fluxes. In the presence of pulmonary infiltrates on chest radiographs glutamine efflux did not differ from zero. Conclusions: The lungs produce significant amounts of glutamine in septic patients. Pulmonary infiltrates decrease the glutamine efflux from the lung in septic patients. We suggest that this is caused by uptake of glutamine by white cells in the lung exerting immunological functions.
Acta Cirurgica Brasileira, 2010
PURPOSE: To evaluate the metabolic changes induced by pre-administration of L-alanyl-glutamine (L-Ala-Gln) and omega-3 (ω-3) in rats subjected to sepsis. METHODS: Eighteen male Wistar rats were randomized into three groups (n=6) and treated with saline (group Control-G-1), L-Ala-Gln (0.75 mg /kg , G-2) or ω-3 (0.2 g /kg, G-3 ) administered intravenously 3, 2 and 1 day and 30 minutes before induction of sepsis. Samples (blood, striated muscle and liver) were collected 48 hours after induction of sepsis, to measure the concentrations of metabolites (pyruvate, lactate, glucose and ketone bodies. RESULTS: There was a significant increase in muscle glycolysis and gluconeogenesis in the liver in rats treated with L-Ala-Gln and ω-3, compared to the control group, 48 hours after induction of sepsis. CONCLUSION: Pre-administration of L-Ala-Gln or ω-3 to rats subjected to sepsis resulted in similar metabolic changes, by rising glycolysis in peripheral tissues and stimulating hepatic gluconeog...
Understanding the mechanisms of glutamine action in critically ill patients
Anais da Academia Brasileira de Ciências, 2010
Glutamine (Gln) is an important energy source and has been used as a supplementary energy substrate. Furthermore, Gln is an essential component for numerous metabolic functions, including acid-base homeostasis, gluconeogenesis, nitrogen transport and synthesis of proteins and nucleic acids. Therefore, glutamine plays a significant role in cell homeostasis and organ metabolism. This article aims to review the mechanisms of glutamine action during severe illnesses. In critically ill patients, the increase in mortality was associated with a decreased plasma Gln concentration. During catabolic stress, Gln consumption rate exceeds the supply, and both plasma and skeletal muscle pools of free Gln are severely reduced. The dose and route of Gln administration clearly influence its effectiveness: high-dose parenteral appears to be more beneficial than low-dose enteral administration. Experimental studies reported that Gln may protect cells, tissues, and whole organisms from stress and injur...
Annals of Surgery, 1998
To quantify the sequential changes in metabolic response occurring in patients with severe sepsis after the onset of peritonitis. Summary Background Data Understanding the changes in energy expenditure and body composition is essential for the optimal management of severely septic patients; however, they have not been quantified in the context of modern surgical care. Methods Twelve patients with severe sepsis secondary to peritonitis (median APACHE 11 score = 21.5) had measurements of energy expenditure and body composition as soon as they were hemodynamically stable and 5, 10, and 21 days later. Sequential measurements of acute-phase proteins and cytokine responses were also made. Results Resting energy expenditure rose to 49% above predicted and remained elevated throughout the study period. Total energy expenditure was 1.25 x resting energy expenditure. Body fat was oxidized when energy intake was insufficient to achieve energy balance. There was a positive fluid balance of 12.5 over the first 2 days after onset of sepsis; thereafter, body water changes closely paralleled body weight changes and were largely accounted for by changes in extracellular water. During the 21-day study period, there was a loss of 1.21 kg (13%) of total body protein. During the first 10 days, 67% of the protein lost came from skeletal muscle, but after this time it was predominantly from viscera. Intracellular potassium levels were low but did not deteriorate further after hemodynamic stability had been reached. There was a reprioritization of hepatic protein synthesis that was obligatory and independent of changes in total body protein. The cytokine responses demonstrated the complexity, redundancy, and overlap of mediators. Conclusions The period of hypermetabolism in severely septic patients is similar to that previously described, but the fluid changes are larger and the protein loss is greater. Protein loss early on is predominantly from muscle, thereafter from viscera. Fat loss can be prevented and cell function preserved once hemodynamic stability is achieved. Patients with severe sepsis demonstrate a characteristic picture in which hypermetabolism occurs, protein and fat are consumed, and body water and salt are conserved.' These fundamental changes lie at the heart of present management of the severely septic patient; however, many of the changes described have not been quantified in the context of modem surgical care. The availability of body composition methodology, which has been adapted for use in
Sepsis impairs gut amino acid absorption
The American Journal of Surgery, 1993
Sepsis has been shown to adversely affect the barrier and metabolic functions of the small intestine as well as to reduce mesenteric blood flow and cause histologic damage. However, the effect of sepsis on gut absorptive function has been largely ignored. In this study, intestinal absorption of arginine and an amino acid analogue, aminoisobntyric acid, was studied using in vivo and in vitro techniques in an experimental model of sepsis. In vivo studies showed a significant impairment in the absorption of both amino acids from the intestinal lumen 24 and 72 hours after cecal ligation and puncture. Uptake of these amino acids by everted gut sacs prepared from septic animals was also significantly reduced. This reduction in absorptive capacity of the gut may limit the ability of enteral feeding alone to supply nutritional requirements during sepsis and may also contribute to the associated morbidity and mortality.