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The effects of thermal injury in rats on glucose utilization (Rg) by skin, wound, small intestine, and muscle in vivo has been determined using 2-[18F]-fluoro-2-deoxy-D-glucose (18FDG) 6 hours, 24 hours, and 3 weeks after injury. These results were compared with serum glucose and insulin levels at the same time points and with hexokinase activity in the tissues. Thermal injury had no significant effects on serum glucose levels; however, serum insulin levels were lower than sham values 6 hours after injury, the same as sham values 24 hours after injury, and significantly higher than sham values 3 weeks after injury. Rg of unburned skin was not changed at 6 or 24 hours after injury, but was increased at 3 weeks after injury. The Rg of the wound was almost zero at 6 and 24 hours after injury; however, at 3 weeks after injury, the wound area had a Rg two to three times higher than that of the normal skin of sham animals. Small intestine Rg was decreased 6 and 24 hours after injury, but was essentially normal by 3 weeks after injury. The Rg of muscle was unchanged at all of the time points tested. Total Rg was significantly higher in the animals 3 weeks after injury, with the increase primarily due to the increases in skin and wound. The increases in Rg were associated with changes in tissue hexokinase activity. The present data suggest that thermal injury to rats results in dramatic alterations in glucose utilization by the skin and wound, changes that may contribute to the overall alterations in carbohydrate metabolism during burn trauma.

Background: Exogenous antigenic peptides are presented to T cells by class II major histocompatibility complex (Ia) molecules on the surface of antigen-presenting cells. Class II-associated invariant chain (Ii) is also required for effective antigen presentation. Because messenger RNAs (mRNAs) for Ii chain and for class II I-A beta chain appear in the mouse intestinal epithelium after weaning, experiments were conducted to test the effect of age of weaning and diet on the appearance of Ia and Ii mRNA., Methods: Four litters were split at day 17; one half was weaned and the other remained with the mother until day 24. On day 23, 25, 27, and 29, enterocytes were isolated from full-length small intestine by vascular perfusion with 30 mmol/L ethylenediaminetetraacetic acid, and the RNA was extracted., Results: Appearance of Ii and I-A beta was significantly delayed by late weaning, as judged by RNA hybridization blots (Ii chain) and complementary DNA amplification (I-A beta chain). In mice on elemental diets, the appearance of Ii and I-A beta chain was delayed compared with littermates reared on standard chow. Ii mRNA failed to appear in mice maintained on the elemental diet by day 40, despite normal growth., Conclusions: Appearance of mRNA for both Ia and Ii depends on the introduction of a complex diet and not the "stress" of weaning or elimination of breast milk. Introduction of foreign dietary antigens or development of an altered intestinal flora may contribute to this process.

The interactions between bacteria and the host's intestinal barrier appear to be important regulators of bacterial colonization. In this study we investigated the effect of prenatal corticosteroids, known to accelerate the intestinal maturation of newborn rats, on bacterial colonization in the rat pup. Pregnant rats were treated with either cortisone acetate or normal saline on days 18-21 of gestation and were allowed to deliver spontaneously. The pups, after normal delivery, were sacrificed at different times during the first 10 days of life. The entire small intestine was removed, and each lumen was flushed to exclude nonadherent, transient organisms and homogenized. Tenfold dilutions were plated on horse-blood agar (total bacteria) and MacConkey's medium (gram-negatives). Quantitation and bacterial typification was determined after 24 h of incubation at 37 degrees C. Total bacteria and gram-negatives found in association with the mucosa were significantly lower in pups prenatally treated with steroids. These changes were not related to any changes in motility or intraluminal digestion. This suggests that the developmental condition of the host's intestinal barrier may be an important regulator of the bacterial microenvironment of the newborn small intestinal mucosa.

The pathway which results in a loss of intestinal barrier function and transepithelial transfer of macromolecules after cutaneous thermal injury is unknown. To determine the enhanced absorption pathway, transepithelial transport of horseradish peroxidase (HRP) was examined ultrastructurally after a thermal injury. Within 6 h after the injury, increased HRP uptake was seen in the portal and systemic blood with the maximal increase in uptake measured at 18 h postinjury; permeability returned to normal by 72 h postinjury. Morphologically, the increased uptake was found to be transcellular through ultrastructurally normal intestinal absorptive cells. Occasional focal regions of enhanced HRP uptake were found and this enhanced uptake was attributed to focal intestinal epithelial disruptions. This increase in intestinal permeability represents a transient loss of intestinal barrier function and potentially allows absorption of macromolecules such as endotoxin from the intestinal lumen into the portal circulation early after thermal injury.

Platelet-activating factor (PAF) was injected into conventional mice, endotoxin-resistant mice (C3H/HEJ), conventional rats, germ-free rats and specific-pathogen-free (SPF) mice. The PAF resulted in significant necrosis and damage to the small intestines of all the animals tested. In general, the frequency and severity of the lesions were similar in all groups. All the conventional rats and mice, as well as the endotoxin-resistant HEJ mice, were dead 18 h after the injection of the PAF, while all the germ-free rats and the SPF mice survived. These data demonstrate that development of massive intestinal lesions, in the absence of aerobic bacteria, is not sufficient to cause the death of the host from septic shock and endotoxaemia.

Ethanol may have profound effects on both the distribution of perfusion and substrate utilization by the liver and heart due to its vasodilating properties and the generation of high levels of circulating acetate and lactate. Since fatty acids are highly extracted by the heart and liver under normal circumstances, changes in the relationship of perfusion/fatty acid uptake may be a sensitive indicator of both altered perfusion and changes in metabolic substrate availability. To test this hypothesis, studies were performed in rats fed 3.1, 6.2, and 9.3 g/kg doses of ethanol. Fatty acid uptake was estimated with a 3-methyl substituted reagent with a chain length equivalent to 17 carbons. The methyl group in the three position prevented beta oxidation and prolonged the residence of fatty acids in the tissue. Eighteen hours after acute alcohol administration, fatty acid uptake was reduced in the heart and the small intestine; in the liver uptake was increased or unchanged. Acute ethanol administration also resulted in increased perfusion, as indicated by enhanced uptake of 201thallium by the heart, liver, and small intestine. The fatty acid extraction of the heart, liver, and small intestine, defined as the concentration of fatty acid divided by the concentration of 201thallium, was markedly decreased by alcohol ingestion. These alcohol effects were dose-dependent and temporally related. The data suggest that ethanol ingestion could potentially alter heart function during exercise or following a prolonged fast, when the heart relies primarily upon fatty acids extracted from the circulation to generated adenosine triphosphate (ATP).

We have examined the role of neutrophils in the alterations observed in the intestines of rats subjected to 40 per cent surface area scald injury. Histologically, there was no evidence of neutrophilia in the intestinal tissue, and myeloperoxidase activity in mucosal scrapings was not elevated. The distribution of labelled human neutrophils injected into the burned rats showed no enhancement of uptake in the intestines, although there was increased uptake by the lung. The present data suggest that neutrophil migration may not play a role in the alterations in small intestinal function and morphology seen in burn trauma in the rat, but may be a factor in lung damage associated with thermal injury.

Small intestinal mucosal weight and nutrient absorption are significantly diminished early after cutaneous thermal injuries. Because these intestinal properties are highly dependent on rates of nucleic acid and protein synthesis, in vivo incorporation of thymidine, uridine, and leucine into small intestinal deoxyribonucleic acid, ribonucleic acid, and proteins were measured. Deoxyribonucleic acid synthesis was markedly decreased with the lowest thymidine incorporation in the jejunum (p less than 0.01); these findings were confirmed by autoradiographic identification of radiolabeled nuclei in the intestinal crypts. Protein synthesis was decreased by 6 h postinjury (p less than 0.01) but had returned to normal by 48 h. Consistent with a decreased rate of protein synthesis, ribonucleic acid synthesis was also decreased 18 h postinjury (p less than 0.01). These decreased deoxyribonucleic acid, ribonucleic acid, and protein synthesis rates are not likely a result of ischemia because in other studies of this injury model, intestinal blood flow was not significantly changed by the burn injury. Potentially, factors initiating the acute inflammatory reaction may directly inhibit nucleic acid and protein synthesis and lead to alterations in nutrient absorption and intestinal barrier function after injury.

The intestinal epithelium normally provides a barrier function that prevents absorption of potentially harmful materials from the intestinal lumen. It has been postulated but never demonstrated that a cutaneous thermal injury will result in increased small-intestinal permeability. In a standardized 20% body surface area full-thickness scald injury, with polyethylene glycol 3350 and horseradish peroxidase used as permeability probes, small-intestinal permeability was examined regionally in an everted intestinal sac model. In the normal animals, the upper (proximal) and lower (distal) small intestine were less permeable to these probes than the middle segment. Within 6 hours after the injury, an increase in the mucosal uptake and transmural permeability was seen in all three small-intestinal segments; the most dramatic increase in permeability occurred in the ileum, p less than 0.01. The maximum increase in permeability was seen at 18 hours, and permeability was normal by 72 hours after the injury. This increase in intestinal permeability may represent a transient failure of the intestinal barrier function and may allow absorption of potentially toxic macromolecules from the intestinal lumen into the portal circulation early after thermal injury. Absorption of these macromolecules, such as endotoxin, may be potentially harmful by direct toxic actions or potentially helpful by activation of the immune system.

Because cardiac output decreases after burn injuries, investigators have assumed, based upon dye clearance techniques, that hepatic and intestinal blood flow are also decreased following these injuries. Blood flow to the liver, stomach, small intestine, and kidney was determined by the uptake of 201thallium and 125I-labeled fatty acid (para-125I-phenyl-3-methyl pentanoic acid) in a 20% body surface area scald injury that also included plasma volume replacement resuscitation. Uptake of these radioisotopes was determined 15 minutes, 18 hours, and 72 hours after injury. The uptake of the 201thallium and 125I-labeled fatty acid by the gastrointestinal tissues was not statistically different at any of the time periods after comparison of the injured and control (sham-treated) animals. 201Thallium uptake by the kidney was significantly diminished 15 minutes after the burn injury (P less than 0.01). Based on these blood flow measurement techniques, the data suggest that the 20% body surface area scald injury did not alter blood flow to the liver or gastrointestinal tract within the initial 72 hours after the burn injury even though a decrease in renal blood flow was easily detected. These results suggest that the dysfunction of the gastrointestinal system or hepatic system observed after an acute burn injury is not simply the result of hypovolemic shock, which reduces both renal and mesenteric blood flow. These gastrointestinal and hepatic alterations may be related to a factor or factors other than intestinal ischemia.

The effect of acute burn trauma, produced by scalding hot water, on rat small intestinal nutrient absorption and DNA synthesis has been examined. Burned rats showed decreased small-intestine mucosal weight and altered small-intestine transport of nutrients (calcium, glucose, or amino acid) in vitro. In addition, there was decreased 3H-thymidine incorporation into intestinal DNA in vivo and decreased intestinal thymidine kinase activity in vitro 18 hours after acute burn. These data suggest that after the severe stress produced by acute burn trauma, there is altered small-intestine nutrient absorption and DNA synthesis. These alterations may affect delivery of nutrients by the gut to the burn patient.

The acute phase protein response following inflammation is associated with an increased total protein-bound carbohydrate content in plasma in the form of glycoproteins. Glycosyltransferases in liver may serve as a regulator of this increased glycosylation activity in the plasma and may also serve as a marker for the acute phase response. Sialyltransferase is an example of a glycosyltransferases in which sialic acid is transferred to oligosaccharides of glycopeptides in the Golgi prior to glycopeptide secretion. In this study, sialyltransferase activities were determined in plasma, liver, and intestinal mucosa following a standardized 25% body surface area thermal injury in the rat. A statistically significant increase in sialyltransferase activity was found in liver and small intestine which were maximal at 24 hours after the injury. These increased sialyltransferase activities were accompanied by a statistically significant 2 to 4 fold elevation in plasma sialyltransferase activity at 24 hours. The plasma and liver elevations in these activities were similar to elevations seen in other models of acute inflammation using turpentine injections and bacterial infections. The increased sialyltransferase activity within the rat intestine was comparable to increases in intestinal sialyltransferase activity following colchicine treatment and may represent a similar mechanism(s).

The effect of hot- and cold-burn trauma on small intestinal mass in mice has been examined. Hot-burn but not cold-burn caused a significant reduction in the intestinal mass 24 hours after application of the trauma. These data may suggest that the alterations produced in the small intestine associated with hot-burn injury, are related, in part, to factors released from the skin.