Intestinal mitochondrial dysfunction in surgical stress.

BACKGROUND: Surgical stress is associated with altered intestinal function. Our earlier study using a rat model indicated that oxidative stress plays an important role in this process. Since mitochondria are crucial to cellular function and survival and are both a target as well as a source of reactive oxygen species, the present study looks at the changes in enterocyte mitochondria during surgical stress. METHODS: Surgical stress was induced by opening the abdominal wall and handling the intestine as done during laparotomy. Mitochondria were prepared from the isolated enterocytes at different time periods after surgical stress. The effect of surgical stress on enterocyte mitochondrial ultrastructure, respiration, anti-oxidant enzyme activity, thiol redox status, calcium flux, permeability, and matrix enzymes was then studied. RESULTS: Surgical stress resulted in alterations in mitochondrial respiration and thiol redox status. It was also associated with altered mitochondrial matrix enzyme activity, decreased superoxide dismutase activity, induction of mitochondrial permeability transition, and swelling, as well as impairment of mitochondrial calcium flux. These alterations were seen at a maximum of 60 min following surgical stress and were reversed by 24 h. CONCLUSIONS: Laparotomy and mild intestinal handling itself results in enterocyte mitochondrial damage. Since mitochondria are important cellular organelles, this damage can probably lead to compromised intestinal function.     

Heat preconditioning prevents enterocyte mitochondrial damage induced by surgical manipulation

BACKGROUND: The small intestine is susceptible to free radical-induced damage and our earlier work has shown that surgical manipulation of the intestine results in generation of oxygen free radicals, leading to mucosal damage. Heat preconditioning has been shown to offer protection against various stresses including oxidative stress and this study looked at the effect of heat preconditioning on surgical manipulation-induced intestinal mitochondrial alterations. METHODS: Control and rats pretreated with heat were subjected to surgical manipulation by opening the abdominal wall and handling the intestine as done during laparotomy. Mitochondria were prepared from isolated enterocytes and structural and functional alterations were assessed. RESULTS: Surgical manipulation of the intestine resulted in mitochondrial alterations as seen by ultrastructural changes and altered lipid composition. Mitochondria were functionally impaired as evidenced by altered calcium flux, decreased respiratory control ratio, and increased tetrazolium dye reduction and swelling. Along with this, biochemical alterations such as increased lipid and protein oxidation were seen following surgical manipulation. Mild heat preconditioning of the animal prevented these damaging effects. CONCLUSIONS: These studies suggest that stress in the small intestine due to surgery can affect enterocyte mitochondrial structure and function and these effects can be prevented by mild whole body hyperthermia prior to surgery.     

Heat preconditioning prevents oxidative stress-induced damage in the intestine and lung following surgical manipulation

BACKGROUND: The intestine is increasingly recognized as a primary effector of distant organ damage, such as lung, following abdominal surgery. Surgical manipulation of the intestine generates oxygen free radicals resulting in mucosal damage. Heat preconditioning has been proposed to prevent various stress-induced alterations in cells and tissues, including oxidative stress. This study examined the effect of heat preconditioning on oxidative stress-induced damage to the intestine and lung, following surgical manipulation. METHODS: Control rats and rats pretreated with heat were subjected to surgical manipulation by opening the abdominal wall and handling the intestine as done during laparotomy. Intestine and lung were assessed for damage by histology and markers of oxidative stress. RESULTS: Surgical manipulation resulted in ultrastructural changes in the intestine. Biochemical alterations in the enterocytes were evident, with increased xanthine oxidase activity resulting in production of superoxide anion and with a decrease in antioxidant status. Gut manipulation also resulted in neutrophil infiltration and oxidative stress in the lung as assessed by histology, myeloperoxidase activity, lipid peroxidation and antioxidant status. Heat conditioning before surgical manipulation had a protective effect against this intestinal and lung damage. CONCLUSION: This study suggests that mild whole-body hyperthermia before surgery might offer protection from postoperative complications.     

Protease activation during surgical stress in the rat small intestine

BACKGROUND: Surgical stress affects intestinal permeability and our earlier study using a rat model indicated that oxidative stress plays an important role in this process. Proteases are important mediators of cellular damage and are known to be activated in oxidative stress. This study looked at protease activity in enterocytes after surgical stress. METHODS: Surgical stress was induced by opening the abdominal wall and handling the intestine as done during laparotomy, in normal and xanthine oxidase-deficient rats. Enterocytes at various stages of differentiation were isolated and protease activity and protection offered by xanthine oxidase inhibitors were determined. Mitochondria and cytosol were prepared from total isolated enterocytes at different periods after surgical stress and protease activation was studied. RESULTS: Surgical stress induced activation of proteases in both the villus and crypt cells. Protease activation is seen in both mitochondria and cytosol, and similar to the other alterations in mucosal cells, protease activation was maximum 60 min after stress, returning to normal by 24 h. Thiol compounds modulate protease activity in both mitochondria and cytosol and the activation is not seen in xanthine oxidase-deficient animals. CONCLUSIONS: Surgical stress induces activation of proteases in villus and crypt cells of the small intestine. Both mitochondrial and cytosolic proteases are activated and free radicals generated by xanthine oxidase may mediate protease activation after surgical stress in the intestine.     

Effect of surgical manipulation of the rat intestine on enterocyte populations

BACKGROUND: The intestine is susceptible to operations at remote locations, and the barrier function is altered during intestinal manipulation, leading to bacterial or endotoxin translocation into the systemic circulation. One of the mainstays for the maintenance of the integrity of the barrier function is epithelial cell proliferation and migration. The present study looked at the effect of gut manipulation after laparotomy on different cell populations of the intestinal epithelium. METHODS: Surgical manipulation of the gut was performed by opening the abdominal wall and handling the intestine, as is done during laparotomy. Villus and crypt cells were isolated at different time periods after gut manipulation, and mitochondria were prepared from isolated enterocytes. The effects of surgical manipulation on enterocytes and isolated mitochondria were studied. RESULTS: Mechanical manipulation of the gut resulted in alterations in the intestinal epithelium, as shown by decreased cell viability and yield in the crypt cells. The alterations were associated with actin reorganization, as well as with altered cell proliferation and adenosine deaminase activity. At the mitochondrial level, altered mitochondrial function, such as decreased respiratory control ratio, increased 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide reduction, and induction of permeability transition in the crypt cells, was observed. These alterations were maximal 1 hour after surgical manipulation and partially recovered to normal by 24 hours. CONCLUSIONS: Mechanical manipulation of the gut that occurs during any abdominal operation induces alterations in the intestine, both at the cellular and the subcellular levels. The crypt cells bear the brunt of the damage, and the reversibility of the damage is possibly brought about by increased proliferation and movement of the cells.     

Role of xanthine oxidase in small bowel mucosal dysfunction after surgical stress

BACKGROUND: The small intestine is highly susceptible to surgical stress even at remote locations. An earlier study using a rat model indicated that oxidative stress plays an important role in this process. The enzyme xanthine oxidase is an important source of free radicals in the small intestine. The role of this enzyme in intestinal damage after surgical stress was examined. METHODS: Rats pretreated with xanthine oxidase inhibitors were subjected to surgical stress by opening the abdomen and handling the intestine, as done during laparotomy. Enterocytes at various stages of differentiation were isolated and the protection offered by xanthine oxidase inhibitors against damage due to surgical stress was determined and compared with normal controls. Protection against ultrastructural changes to the mucosa, as well as mitochondrial function was examined. RESULTS: Surgical stress affected both the villus as well as crypt cells, causing increased superoxide generation, accompanied by increased activity of xanthine oxidase. Xanthine oxidase inhibitors ameliorated the increased superoxide generation, and protected against mitochondrial damage and ultrastructural changes in the intestine. CONCLUSION: Surgical stress affects both the villus and crypt cell populations in the small intestine. The enzyme xanthine oxidase maybe an important mediator of surgical stress in the intestine.     

Nitric oxide protects the intestine from the damage induced by laparotomy and gut manipulation.

BACKGROUND: The intestine is highly susceptible to free radical-induced damage, and our earlier work has shown that surgical stress induces the generation of oxygen free radicals in enterocytes, resulting in intestinal damage along with ultrastructural changes. Since nitric oxide (NO) is an important mediator of gastrointestinal function, this study looked at the effect of NO on surgical stress-induced intestinal alterations. MATERIALS AND METHODS: Control rats and rats pretreated with the NO donor l-arginine were subjected to surgical stress by opening the abdominal wall and handling the intestine as done during laparotomy. Enterocytes were isolated and homogenate prepared, and the protection offered by l-arginine against damage due to surgical stress was determined and compared with normal controls. Protection to structural as well as functional aspects of the intestine was also examined. RESULTS: Intestinal manipulation affected intestinal structure as assessed by electron microscopy. Functional impairment of the enterocyte was also evident, with increased xanthine oxidase activity resulting in production of superoxide anion. This impairment is more dramatic in the crypt cells. Increased protease activity was also seen following laparotomy and handling. Pretreatment with the NO synthase substrate l-arginine prevented these damaging effects. Arginine protection was abolished in the presence of the NO synthase inhibitor NG-nitro-l-arginine methyl ester, indicating the role of NO. CONCLUSION: Stress in the small intestine due to any surgery can affect enterocyte structure and function. These damaging effects can be prevented by NO, an important modulator of cellular function.     

Surgical manipulation of the small intestine and its effect on the lung

BACKGROUND: Surgical manipulation of the intestine results in generation of oxygen free radicals leading to mucosal damage as evidenced by ultrastructural and biochemical changes. It is likely that the gut-derived mediators can bring about damage to distant organs such as the lung. METHODS: Surgical manipulation of the gut was performed by opening the abdominal wall and handling the intestine. Lung damage was assessed by histology, markers of oxidative stress, and protein content in bronchoalveolar lavage fluid. Protection offered by pretreatment with various compounds such as allopurinol, L-arginine, quinacrine, and indomethacin was also studied. RESULTS: Gut manipulation resulted in neutrophil infiltration, oxidative stress, and permeability changes in the lung and these changes were maximum 30 and 60 min following surgical manipulation, which recovered with time and reversed to normal by 24 h. Prior treatment with inhibitors of xanthine oxidase, phospholipase A(2), or cyclooxygenase showed a protective effect against lung damage. CONCLUSION: This study has shown that laparotomy and intestinal handling result in distant organ (lung) damage which is probably brought about by neutrophil infiltration and oxidative stress on the lung. This is likely mediated by compounds generated in the intestine and transported into the systemic circulation since inhibition of generation of chemical mediators in the intestine offers protection against lung damage.     

Nitric oxide prevents intestinal mitochondrial dysfunction induced by surgical stress

BACKGROUND: The intestine is highly susceptible to free radical-induced damage and earlier work has shown that surgical stress induces generation of oxygen free radicals in enterocytes, resulting in intestinal damage along with changes in mitochondrial structure and function. Nitric oxide is an important mediator of gastrointestinal function and this study looked at the effect of nitric oxide on surgical stress-induced intestinal mitochondrial alterations. METHODS: Controls and rats pretreated with the nitric oxide donor L-arginine were subjected to surgical stress by opening the abdominal wall and handling the intestine. Enterocytes were isolated, mitochondria prepared and the protection offered by L-arginine against damage due to surgical stress was determined. Protection to structural as well as functional aspects of mitochondria was examined. RESULTS: Mild handling of the intestine affected the enterocyte mitochondrial structure as assessed by lipid composition and electron microscopy. Mitochondria were also functionally impaired with altered calcium flux and decreased respiratory control ratio. Pretreatment with the nitric oxide synthase substrate L-arginine prevented these damaging effects of surgical stress. Protection with arginine was abolished by the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, indicating the role of nitric oxide. CONCLUSION: Surgical stress in the small intestine can affect enterocyte mitochondrial structure and function. These damaging effects can be prevented by nitric oxide, an important modulator of cellular function.     

Heat preconditioning attenuates oxygen free radical-mediated alterations in the intestinal brush border membrane induced by surgical manipulation

BACKGROUND: The intestine is highly susceptible to free radical-induced damage and our earlier work has shown that surgical manipulation of the intestine results in generation of oxygen free radicals and mucosal damage along with alterations in the brush border membrane (BBM). Heat preconditioning is known to offer protection against various stresses including oxidative stress and this study looked at the effect of heat preconditioning on the intestinal BBM alterations following surgical manipulation. METHODS: Control and rats heat preconditioned were subjected to surgical manipulation by opening the abdominal wall and handling the intestine. BBM were isolated from the intestine and structural and functional alterations to these membranes were assessed. RESULTS: Surgical manipulation resulted in oxidative stress suggested by a decrease in alkaline phosphatase activity and alpha-tocopherol content, accompanied by an increase in lipid peroxidation. A decrease in glucose transport by the isolated BBM vesicles suggested functional impairment. Surgical manipulation resulted in phospholipid degradation with generation of arachidonic acid along with appearance of cPLA(2) in the membrane. These changes were prevented by heat preconditioning of the animal prior to surgical manipulation. CONCLUSION: These results suggest that heat preconditioning offers protection from damage to the intestinal BBM following surgical manipulation and mild whole body hyperthermia might prevent postsurgical complications.     

Surgical manipulation of the intestine results in quantitative and qualitative alterations in luminal Escherichia coli

OBJECTIVES: To look at the qualitative and quantitative changes in the luminal bacterial flora in response to surgical manipulation of the small intestine. SUMMARY BACKGROUND DATA: The barrier function of the intestine is compromised in pathologic conditions, such as shock, trauma, or surgical stress. Our earlier work has shown that surgical manipulation results in oxidative stress in the intestinal mucosa leading to permeability alterations. METHODS: Studies were done on rats, which were randomly divided into four groups (n = 8): group I, control, group II, III, IV different time periods, such as 8, 12, and 24 hours after surgical manipulation, which was simulated by opening the abdominal wall and handling the intestine. The cecal wall and cecal luminal contents were harvested under sterile conditions and processed for quantitation for aerobes and anaerobes. Adherence assays using Hep-2 cells were carried out on Escherichia coli isolated under different experimental conditions. In addition, control E. coli were exposed to superoxide or hydrogen peroxide, followed by subculture and adherence studies. RESULTS: Surgical manipulation of the intestine resulted in qualitative and quantitative alterations in the aerobic bacteria. There was an increase in the number and relative proportion of E. coli in the cecal flora, and there was also an increase in adherence of E. coli to cecal mucosa, which was confirmed by in vitro bacterial adherence studies with HEp-2 cells. These changes were maximum at 12 hours following surgical manipulation and by 24 hours, this came back to control pattern. Control E. coli after in vitro exposure to oxidants also showed increased adherence. CONCLUSION: These studies suggest that oxidative stress in the mucosa following surgical manipulation results in alterations in the luminal bacteria leading to increased bacterial adherence onto mucosal epithelium, which may contribute to postsurgical complications.     

Oral glutamine attenuates surgical manipulation-induced alterations in the intestinal brush border membrane

BACKGROUND: Our earlier work has shown that surgical manipulation of the intestine results in oxidative stress and mucosal damage along with alterations in the brush border membrane (BBM). Glutamine feeding is known to offer protection against damage to mucosa under various conditions and this study looked at the effect of oral supplementation of glutamine or glutamic acid in the intestinal BBM alterations after surgical manipulation. MATERIALS AND METHODS: Control and rats pretreated for 7 days with 2% glutamine or glutamic acid or isonitrogenous amino acids, glycine, or alanine were subjected to surgical manipulation of the intestine. BBMs were isolated from the intestine and functional and structural alterations to these membranes were assessed and compared. RESULTS: Surgical manipulation resulted in oxidative stress in the enterocyte BBM and these changes included a decrease in alkaline phosphatase activity and alpha-tocopherol content along with an increase in lipid peroxidation parameters. A decrease in glucose transport by the isolated BBM vesicles suggested functional impairment. Surgical manipulation also resulted in phospholipid degradation possibly mediated by PLA(2) and membrane protease activation. Glutamine or glutamic acid supplementation prevented these changes but not by glycine or alanine. CONCLUSION: This study suggests that oral glutamine or glutamic acid supplementation prior to surgery can offer protection to the intestine and this might prevent postsurgical complications.     

Surgical stress induces phospholipid degradation in the intestinal brush border membrane

BACKGROUND: Surgical stress can lead to translocation of bacteria from the intestine into the systemic circulation. The intestinal brush border membrane (BBM) plays an important role in defense against such invasion by luminal bacteria and endotoxin. Our earlier work has shown the development of oxidative stress in the intestine after surgical stress and since the BBM is sensitive to free radical attack, this study examined the effect of surgical stress on the structure and function of intestinal BBM. METHODS: Intestinal BBM were isolated from control and after surgical stress and compared for structural and functional alterations. Surgical stress was also carried out following pretreatment with the xanthine oxidase inhibitor allopurinol or the nitric oxide donor l-arginine, to study the protection offered by these compounds. RESULTS: Surgical stress affected intestinal BBM structure as well as function. A decrease in alkaline phosphatase activity and alpha-tocopherol content, accompanied by an increase in lipid peroxidation, was seen. Surgical stress induced phospholipid degradation with generation of arachidonic acid. Functional impairment with a decrease in glucose transport ability was also seen. These changes are prevented by inhibition of xanthine oxidase by allopurinol pretreatment but not by NO. CONCLUSION: Surgical stress in the small intestine causes structural and functional alterations in the BBM through oxidative stress. This damage could affect gut barrier integrity and generation of arachidonic acid might mediate distal organ dysfunction.     

Altered glycosylation of surfactant and brush border membrane of the small intestine in response to surgical manipulation

BACKGROUND: Surgical stress can lead to bacterial translocation from the intestine into systemic circulation. Adherence of bacteria onto the glycoconjugates of the brush border membrane (BBM) and surfactant coat (SLP) of the mucosal cells is the first step in the translocation of luminal bacteria. Our earlier study showed that surgical manipulation of the intestine results in oxidative stress leading to structural and functional alterations in the mucosa. This study looks at the effect of surgical manipulation on the glycoconjugate alterations of SLP and BBM. MATERIALS AND METHODS: SLP and BBM were isolated from control and after surgical manipulation and the sugar composition was analyzed. Bacterial adherence using E. coli isolated from cecum was compared after coating microtiter plates with SLP or BBM isolated from control and after surgical manipulation. RESULTS: An increase in various sugars was seen after surgical manipulation both in SLP and BBM and this increase was maximum at 12 h after surgery. These alterations increased bacterial adherence onto SLP and BBM. Inhibiting superoxide generation by allopurinol treatment prior to surgical manipulation prevented glycosylation alteration and bacterial adherence. CONCLUSION: Surgical manipulation results in altered glycoconjugates of SLP and BBM which leads to increased bacterial adherence. These alterations are probably brought about by oxygen-free radicals. This is clinically significant because postsurgical complications such as sepsis may be brought about by altered glycosylation.     

Surgical manipulation of the intestine and distant organ damage-protection by oral glutamine supplementation

BACKGROUND: The intestine is increasingly recognized as a primary effector of distant organ damage, such as the lung, after any abdominal surgery. Earlier studies have shown that surgical manipulation of the intestine induces generation of reactive oxygen species in the intestine, resulting in mucosal and lung damage. Because glutamine is preferentially used by the small intestine as an energy source, this study examined the effect of glutamine and glutamic acid on intestinal and lung damage after surgical manipulation. METHODS: Controls and rats were pretreated for 7 days with 2% glutamine or glutamic acid, or the isonitrogenous amino acids glycine or alanine in the diet and subjected to surgical manipulation of the intestine. The intestine and lung were assessed for damage, and protection offered by various amino acids was studied. RESULTS: Surgical manipulation resulted in oxidative stress in the intestine as evidenced by increased xanthine oxidase activity and decreased antioxidant status. Enterocyte mitochondria were also functionally impaired with altered calcium flux, decreased respiratory control ratio, and increased swelling. Gut manipulation also resulted in neutrophil infiltration and oxidative stress in the lung as assessed by an increase in myeloperoxidase activity, lipid peroxidation, and antioxidant status. Glutamine or glutamic acid supplementation for 7 days before surgical manipulation showed a protective effect against the intestinal and lung damage. CONCLUSIONS: This study suggests that preoperative enteral glutamine or glutamic acid supplementation attenuates intestinal and lung damage in rats during surgical manipulation and that this effect might offer protection from postsurgical complications.     

Regional intestinal blood flow and nitric oxide synthase inhibition during sepsis in the rat.

OBJECTIVE: Regional circulatory changes in intestinal mucosa were evaluated after the onset of septic shock and the effect of nitric oxide (NO) inhibition on mucosal blood flow was investigated at different locations along the intestine. SUMMARY BACKGROUND DATA: The response of intestinal blood flow to different physiologic and pharmacologic stimuli is known to vary along the intestine, but limited data are available on regional alterations in intestinal blood flow during septic shock. These regional variations in intestinal blood flow could become important because NO inhibition might restore the circulation of one segment of the gut or exacerbate ischemia that may be occurring concomitantly in another segment of the intestine. METHODS: Mucosal blood flow was studied with fluorescent microspheres in conscious unrestrained rats before and 2, 4, and 6 hours after lipopolysaccharide (LPS, 20 mg/kg intraperitoneally) induced sepsis in the presence and absence of the nitric oxide synthase inhibitor N(G)-nitro-L-argininemethylester (L-NAME, 5 mg/kg subcutaneously). RESULTS: Control mucosal blood flow was significantly higher in the ileum than in the duodenum, jejunum, or colon. During LPS-induced sepsis, mucosal blood flow to the ileum decreased and perfusion to the remaining gut was preserved. This was accompanied by hypotension throughout the experiment. L-NAME administration during sepsis prevented hypotension and decreased mucosal blood flow to all segments of small intestine at 2 hours. In this group, mucosal blood flow to the proximal small intestine but not to the ileum returned to baseline levels at 4 and 6 hours. L-NAME alone decreased mucosal blood flow to the small intestine throughout the experiment. CONCLUSIONS: This study indicates that mucosal blood flow alterations during septic shock vary along the intestine, with a significant change only in the ileum, suggesting that perfusion in the small intestine is dependent on physiologic NO production.     

Effect of tumor necrosis factor alpha,interferon gamma,and interleukin-4 on bacteria-enterocyte interactions

BACKGROUND: Little is known about the mechanisms involved in bacterial translocation from the intestinal lumen to extraintestinal sites. Because the cytokine cascade associated with sepsis, inflammation, and trauma has been shown to affect intestinal epithelial permeability, experiments were designed to clarify the effects of selected cytokines on bacterial adherence to and internalization by cultured HT-29 and Caco-2 enterocytes. METHODS: Mature, confluent enterocytes were pretreated 48 to 72 h with tumor necrosis factor alpha (TNF-alpha), interferon gamma, (IFN-gamma), or interleukin-4 (IL-4). Adherence of Listeria monocytogenes, Salmonella typhimurium, Proteus mirabilis, and Escherichia coli was measured by enzyme-linked immunosorbent assay and bacterial internalization was quantified by the gentamicin protection assay. Enterocyte permeability was measured by transepithelial electrical resistance and by flux of 40-kDa fluorescent dextran. Bacterial transmigration across confluent enterocytes was measured using enterocytes cultivated on permeable supports. RESULTS: TNF-alpha, IFN-gamma, and IL-4 had variable effects on bacterial adherence to HT-29 and Caco-2 enterocytes, although the most consistent finding was increased bacterial adherence associated with INF-gamma. However, none of these cytokines had a noticeable effect on bacterial internalization by either Caco-2 or HT-29 enterocytes. In addition, none of these cytokines had a noticeable effect on the permeability of confluent enterocytes as measured by transepithelial electrical resistance or dextran flux. Bacterial transmigration across confluent HT-29 enterocytes was not altered by TNF-alpha, IFN-gamma, or IL-4; however, IL-4 consistently decreased bacterial transmigration across confluent Caco-2 enterocytes. CONCLUSIONS: IFN-gamma may augment the epithelial adherence of selected species of enteric bacteria, and IL-4 may act as a barrier-sustaining agent to decrease bacterial migration across the intestinal epithelium.     

Effects of Intestinal Surgery on Pulmonary,Glomerular, and Intestinal Permeability,and its Relation to the Hemodynamics and Oxidative Stress

Purpose. To investigate the pattern of changes of gut mucosal, glomerular, and pulmonary permeability in response to major resectional intestinal surgery, and to evaluate whether these changes are related to oxidative stress. Methods. Eight patients undergoing elective intestinal surgery. Lactulose/mannitol ratio (LMR), urinary albumin/creatinine ratio (MACR), and extravascular lung water and its ratio to intrathoracic blood volume (EVLW/ITBV) were measured preoperatively and at different time points postsurgery. The oxidant/antioxidant balance was assessed by measuring thiobarbituric acid-reactive species, reduced glutathione, plasma total antioxidant capacity, superoxide dismutase, and glutathione peroxidase. Results. Uncomplicated intestinal surgery was associated with early increase in LMR and MACR. The EVLW/ITBV ratio increased, but still remained within the normal range. The amount of EVLW was not affected. While renal permeability changes resolved rapidly, increased intestinal permeability persisted longer postoperatively. There was no evidence for any marked disturbances in the oxidant/antioxidant balance. Conclusions. This pilot study indicated that a moderate increase in gut and renal permeability, even in the absence of clinical sequelae, is an early feature of uncomplicated intestinal surgical trauma. These alterations are not accompanied by any clinically detectable changes in pulmonary permeability.Presented in part at the 14th Annual Congress of the European Society of Intensive Care Medicine, Geneva, October 2001     

Relationship between disruption of the unstirred mucus layer and intestinal restitution in loss of gut barrier function after trauma hemorrhagic shock

BACKGROUND: The factors involved in shock-induced loss of gut barrier function remain to be defined fully and studies investigating gut injury have focused primarily on the systemic side of the intestine. METHODS: Male Sprague-Dawley rats were subjected to a laparotomy (trauma) and 90 minutes of trauma sham shock (T/SS) or actual trauma (laparotomy) hemorrhagic shock (T/HS) (30 mm Hg). At 0, 30, 60, or 180 minutes after the end of shock and volume resuscitation (reperfusion), the animals were killed and samples of the ileum were collected for intestinal morphologic analysis, analysis of the unstirred mucus layer, and for barrier function by measuring permeability to flourescein dextran. RESULTS: T/HS-induced morphologic evidence of mucosal injury as well as epithelial apoptosis was present at the end of the shock period and maximal after 60 minutes of reperfusion. At 3 hours after reperfusion, the degree of villous injury and enterocyte apoptosis had decreased. In contrast to the morphologic appearance of the villi, disruption of the mucus layer became progressively more severe over time and was manifest as a decrease in mucus thickness, progressive loss of coverage of the luminal surface by the mucus layer, and a change in mucus appearance from a dense to a loose structure. Studies of intestinal permeability documented that T/HS-induced loss of gut barrier function persisted throughout the 3-hour reperfusion period and were associated with injury to the mucus layer as well as the villi. CONCLUSIONS: T/HS leads to changes in the intestinal mucus layer as well as increased villous injury, apoptosis, and gut permeability. Additionally, increased gut permeability was associated with loss of the intestinal mucus layer suggesting that T/HS-induced injury to the mucus layer may contribute to the loss of gut barrier function.