Inhalation of carbon monoxide following resuscitation ameliorates hemorrhagic shock-induced lung injury.

Even after successful resuscitation, hemorrhagic shock frequently causes pulmonary inflammation that induces acute lung injury (ALI). We previously demonstrated that when CO is inhaled at a low concentration both prior to and following hemorrhagic shock and resuscitation (HSR) it ameliorates HSR-induced ALI in rats due to its anti-inflammatory effects. In the present study, we administered CO to the same model of ALI only after resuscitation and examined whether it exerted a therapeutic effect without adverse events on HSR-induced ALI, since treatment of animals with CO prior to HSR did not prevent lung injury. HSR were induced by bleeding animals to achieve a mean arterial pressure of 30 mmHg for 1 h followed by resuscitation with the removed blood. HSR resulted in the upregulation of inflammatory gene expression and increased the rate of apoptotic cell death in the lungs. This was determined from an observed increase in the number of cells positive for transferase-mediated dUTP-fluorescein isothiocyanate (FITC), nick-end labeling staining and activated caspase-3. HSR also resulted in prominent histopathological damage, including congestion, edema, cellular infiltration and hemorrhage. By contrast, CO inhalation for 3 h following resuscitation significantly ameliorated these inflammatory events, demonstrated by reduced histological damage, inflammatory mediators and apoptotic cell death. The protective effects of CO against lung injury were notably associated with an increase in the protein expression level of peroxisome proliferator-activated receptor (PPAR)-γ, an anti-inflammatory transcriptional regulator in the lung. Moreover, CO inhalation did not affect the hemodynamic status or tissue oxygenation during HSR. These findings suggest that inhalation of CO at a low concentration exerts a potent therapeutic effect against HSR-induced ALI and attenuates the inflammatory cascade by increasing PPAR-γ protein expression.

[Impact of beach chair position on the value of bispectral index during general anesthesia].

BACKGROUND: Although the bispectral index (BIS) has been established as a common index of anesthetic depth, there is a possibility that head-up position may influence BIS values under general anesthesia. This study examined whether beach chair position with 57 degrees head-up would cause the variation of BIS values during shoulder surgery. METHODS: Two groups of patients were scheduled for surgery, one was supine position group, and the other was beach chair position group. Anesthesia was induced with propofol and rocuronium, and maintained with sevoflurane (end-tidal concentration 1.0-1.2%). The BIS values were recorded manually until 120 minutes after the onset of positioning and evaluated at each 30 min interval. RESULTS: There was no time-dependent difference in BIS values during supine position. In contrast, BIS values in beach chair position group showed a marked downward-trend through the measurement period. End-tidal anesthetic gas concentration and mean blood pressure did not significantly differ between the groups consistently. CONCLUSIONS: To our knowledge, this is the first report of the effect of beach chair position on BIS values intraoperatively. This result indicates that the beach chair position causes a time-dependent decrease in BIS under general anesthesia.

Heme breakdown and ischemia/reperfusion injury in grafted liver during living donor liver transplantation.

Living donor liver transplantation (LDLT) requires ischemia/reperfusion (I/R), which can cause early graft injury. However, the detailed mechanism of I/R injury remains unknown. Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme catabolism and results in the production of iron, carbon monoxide (CO), and biliverdin IXα. Furthermore, in animals, HO-1 has a protective effect against oxidative stress associated with I/R injury. However, in humans, the molecular mechanism and clinical significance of HO-1 remain unclear. We previously demonstrated that exhaled CO levels increase during LDLT, and postulated that this may indicate I/R injury. In this study, we elucidate the origin of increased exhaled CO levels and the role of HO-1 in I/R injury during LDLT. We studied 29 LDLT donors and recipients each. For investigation of HO-1 gene expression by polymerase chain reaction and HO-1 localization by immunohistological staining, liver biopsies from the grafted liver were conducted twice, once before and once after I/R. Exhaled CO levels and HO-1 gene expression levels significantly increased after I/R. In addition, HO-1 levels significantly increased after I/R in Kupffer cells. Furthermore, we found a significant positive correlation between exhaled CO levels and HO-1 gene expression levels. These results indicated that increased heme breakdown in the grafted liver is the source of increased exhaled CO levels. We also found a significant relationship between HO-1 gene expression levels and alanine aminotransferase (ALT) levels; i.e., the higher the HO-1 gene expression levels, the higher the ALT levels. These results suggest that HO-1-mediated heme breakdown is caused by I/R during LDLT, since it is associated with increased exhaled CO levels and liver damage.

[Case of coronary vasospasm during lumbar discectomy in prone position].

A 62-year-old man with hypertension was scheduled for discectomy at L4-5 in prone position. Anesthesia was induced with propofol 70 mg, fentanyl 0.75 mg and rocuronium 40 mg and maintained with sevoflurane 0.8-2.0% in oxygen 2 l x min(-1) and nitrous oxide 2 l x min(-1). Just before the end of surgery, ST elevation with hypotension on the ECG was observed for only a few seconds, followed by ventricular fibrillation (Vf). Immediately, lidocaine 50 mg, nitroglycerine 0.5 mg and methoxamine 6 mg were administered intravenously, and sinus rhythm and normal blood pressure returned from Vf within one minute. This case achieved a complete response to quick administration of the coronary vasodilator and antiarrhythmic agent, in this case whose coronary spasm was suspected on the basis of ST elevation in the first place. We have to be careful of various initiating factors for coronary spasm each time during anesthesia as it is difficult to assess its clinical risk, especially in prone position because actual coronary flow is much lower and cardiac resuscitation is difficult in a sudden cardiac complication.

Nonimmersive virtual reality mirror visual feedback therapy and its application for the treatment of complex regional pain syndrome: an open-label pilot study.

OBJECTIVE: Chronic pain conditions such as phantom limb pain and complex regional pain syndrome are difficult to treat, and traditional pharmacological treatment and invasive neural block are not always effective. Plasticity in the central nervous system occurs in these conditions and may be associated with pain. Mirror visual feedback therapy aims to restore normal cortical organization and is applied in the treatment of chronic pain conditions. However, not all patients benefit from this treatment. Virtual reality technology is increasingly attracting attention for medical application, including as an analgesic modality. An advanced mirror visual feedback system with virtual reality technology may have increased analgesic efficacy and benefit a wider patient population. In this preliminary work, we developed a virtual reality mirror visual feedback system and applied it to the treatment of complex regional pain syndrome. DESIGN: A small open-label case series. Five patients with complex regional pain syndrome received virtual reality mirror visual feedback therapy once a week for five to eight sessions on an outpatient basis. Patients were monitored for continued medication use and pain intensity. RESULTS: Four of the five patients showed >50% reduction in pain intensity. Two of these patients ended their visits to our pain clinic after five sessions. CONCLUSION: Our results indicate that virtual reality mirror visual feedback therapy is a promising alternative treatment for complex regional pain syndrome. Further studies are necessary before concluding that analgesia provided from virtual reality mirror visual feedback therapy is the result of reversing maladaptive changes in pain perception.

An increase in exhaled CO concentration in systemic inflammation/sepsis.

Despite recent progress in Critical Care Medicine, sepsis is still a major medical problem with a high rate of mortality and morbidity especially in intensive care units. Oxidative stress induced by inflammation associated with sepsis causes degradation of heme protein, increases microsomal free heme content, promotes further oxidative stress and results in cellular and organ damage. Heme-oxygenase-1 (HO-1) is a rate-limiting enzyme for heme breakdown. HO-1 breaks down heme to yield CO, iron and biliverdin. Measurement of CO in exhaled air may potentially be useful in monitoring changes in HO enzyme activity in vivo, which might reflect the degree of inflammation or oxidative stress in patients with systemic inflammation. The increased exhaled CO concentrations were observed after anesthesia/surgery, in critically ill patients and also in systemic inflammation/sepsis. Some reports also showed that exhaled CO concentration is related to mortality. Further studies are needed to elucidate whether increased endogenous CO production may predict a patient's morbidity and mortality. Techniques for monitoring CO are continuously being refined and this technique may find its way into the office of clinicians.

[Anesthetic management of pediatric patients with insulinoma using continuous glucose monitoring].

Insulinomas are rare tumors, the incidence of which is 1-2 per million. Patients with insulinomas present with symptoms of hypoglycemia secondary to insulin hypersecretion. Surgical resection is a treatment of choice and offers the only chance of cure. The important points in anesthesia are the precaution against hypoglycemia until tumor resection and the control of rebound hyperglycemia soon after tumor resection. We report the anesthetic management of a 5-year-old patient with insulinoma. Soon after the induction of anesthesia, the continuous glucose monitoring was commenced. Until the tumor resection, 10% glucose infusion was required to avoid hypoglycemia. Then, insulin infusion was continued to maintain blood glucose level around 150 mg x dl(-1). All glucose management was guided with continuous glucose monitoring. This is a first case report to show the feasibility and usefulness of continuous glucose monitoring in management of pediatric insulinoma patients. As the blood glucose was dramatically altered during perioperative period, frequent blood glucose measurements or continuous glucose monitoring is mandatory during perioperative period of insulinoma resection.

Heme Oxygenase-1 is an Essential Cytoprotective Component in Oxidative Tissue Injury Induced by Hemorrhagic Shock.

Hemorrhagic shock causes oxidative stress that leads to tissue injuries in various organs including the lung, liver, kidney and intestine. Excess amounts of free heme released from destabilized hemoproteins under oxidative conditions might constitute a major threat because it can catalyze the formation of reactive oxygen species. Cells counteract this by rapidly inducing the rate-limiting enzyme in heme breakdown, heme oxygenase-1 (HO-1), which is a low-molecular-weight stress protein. The enzymatic HO-1 reaction removes heme. As such, endogenous HO-1 induction by hemorrhagic shock protects tissues from further degeneration by oxidant stimuli. In addition, prior pharmacological induction of HO-1 ameliorates oxidative tissue injuries induced by hemorrhagic shock. In contrast, the deletion of HO-1 expression, or the chemical inhibition of increased HO activity ablated the beneficial effect of HO-1 induction, and exacerbates tissue damage. Thus, HO-1 constitutes an essential cytoprotective component in hemorrhagic shock-induced oxidative tissue injures. This article reviews recent advances in understanding of the essential role of HO-1 in experimental models of hemorrhagic shock-induced oxidative tissue injuries with emphasis on the role of its induction in tissue defense.

[Central pontine myelinolysis after living donor liver transplantation].

Central pontine myelinolysis (CPM) is the most serious central nervous system complication that could be seen after liver transplantation and represents an important source of mortality early after liver transplantation. CPM following liver transplantation was reported more and more in literatures, but the true incidence of CPM after living related liver transplantation (LDLT) remains unknown. However, with the introduction of magnetic resonance imaging (MRI), early recognition has become possible. In this report, we present a case of rapid resolution of CPM followed by MRI examinations.

Increased exhaled carbon monoxide concentration during living donor liver transplantation.

Exhaled carbon monoxide concentration (ExCO-C) has been reported to increase in oxidative tissue injuries such as systemic inflammation, and is thought to reflect increased heme breakdown in the affected organ. As a transplanted liver undergoes ischemia-reperfusion, we hypothesized that ExCO-C might also increase following liver transplantation and might serve as a measure of the severity of the graft tissue injury. We prospectively studied 67 living donor liver transplantation (LDLT) patients in a consecutive fashion. During anesthesia, ExCO-C was determined at 6 time points, ranging from anesthesia induction, to admission to the intensive care unit. We also measured two markers of endothelial cellular injury, i.e., serum soluble thrombomodulin (sTM) and intercellular adhesion molecule (ICAM)-1. At 5 min after reperfusion of the grafted liver, ExCO-C markedly increased from 5.69+/-2.34 ppm at baseline, to 9.79+/-4.72 ppm (p<0.0001). There was an excellent correlation among an increase in CO concentration, arterial carboxyhemoglobin levels at the time of reperfusion (r(2)=0.19, p=0.0003), and postoperative total bilirubin levels (day 1, 2, and 3; r(2)=0.102, 0.109 and 0.100; p=0.008, 0.007 and 0.010, respectively). Serum sTM and ICAM-1 levels were also significantly increased after reperfusion (sTM: 3.3+/-0.8 to 5.1+/-1.7 FU/ml, p=0.0001; ICAM-1: 271.9+/-86.3 to 515.0+/-157.8 FU/ml, p=0.0001). ExCO-C had a positive relationship with sTM (r(2)=0.16, p=0.035) and ICAM-1 (r(2)=0.12, p=0.08). There was however, no correlation of ExCO-C with serum AST/ALT levels or clinical outcomes. This study demonstrated that ExCO-C significantly increased after reperfusion during LDLT. The increased ExCO-C may likely reflect increased heme breakdown and endothelial cell injury in the grafted liver.

The lower intestinal tract-specific induction of heme oxygenase-1 by glutamine protects against endotoxemic intestinal injury.

OBJECTIVE: The aim of the present study was to investigate whether glutamine pretreatment improves intestinal injury in rats with endotoxemia by its heme oxygenase-1 induction in the lower intestinal tract. DESIGN: Randomized, blinded, controlled animal study. SETTING: University-based animal research facility. SUBJECTS: Sprague-Dawley male rats, weighing 220-250 g (n = 201). INTERVENTIONS: Rats were treated with glutamine (0.75 g/kg) dissolved in lactated Ringer's solution via the tail vein. Endotoxemia was induced in rats by intraperitoneal injection of lipopolysaccharide (10 mg/kg or 20 mg/kg for survival study). Lipopolysaccharide-treated animals were pretreated with glutamine or lactated Ringer's solution 9 hrs before lipopolysaccharide treatment. Some of the glutamine-pretreated animals further received tin mesoporphyrin (1 micromol/kg), a specific inhibitor of heme oxygenase activity, 1 hr before lipopolysaccharide treatment. MEASUREMENTS AND MAIN RESULTS: Glutamine treatment markedly induced heme oxygenase-1 messenger RNA and protein in the mucosal epithelial cells as well as in the lamina propria cells in the ileum and the colon, whereas its expression in the duodenum and the jejunum was not influenced by the treatment. Glutamine treatment before lipopolysaccharide administration significantly ameliorated lipopolysaccharide-induced mucosal injury, inflammation, and apoptotic cell death in the ileum and the colon, as judged by significant decreases in tumor necrosis factor-alpha gene expression, histologic damage scores, and expression of activated caspase-3 and by an increase in gene expression of Bcl-2. In addition, glutamine treatment markedly decreased lipopolysaccharide-induced mortality. In contrast, treatment with tin mesoporphyrin abolished the beneficial effect of glutamine pretreatment. CONCLUSIONS: Glutamine pretreatment significantly ameliorated intestinal tissue injury of rats following lipopolysaccharide treatment. The same treatment also improved the survival of animals from endotoxemia. The protective effect of glutamine is mediated by its lower intestine-specific induction of heme oxygenase-1, since its inhibition by tin mesoporphyrin completely abolished the beneficial effect of glutamine.

Increased heme oxygenase-1 and decreased delta-aminolevulinate synthase expression in the liver of patients with acute liver failure.

Acute liver failure (ALF) remains a serious problem in critical care with a high rate of mortality. Although the pathophysiology of ALF has not been fully elucidated, oxidative stress has been in part implicated in its pathogenesis. Heme oxygenase-1 (HO-1) is known to be induced not only by its substrate, heme, but also by various oxidative stresses, and thought to play an important role in the protection of the host from oxidative tissue injuries. In the present study, we examined expression of HO-1 as well as the non-specific delta-aminolevulinate synthase (ALAS-N, or ALAS1), the rate-limiting enzyme in heme catabolism and biosynthesis, respectively, in the livers of patients with ALF. Compared with livers from control subjects who had various disorders, but normal hepatic function, HO-1 in the liver of ALF patients was highly up-regulated at both transcriptional and protein levels. Immunohistochemical studies demonstrated that HO-1 expression occurred predominantly in hepatocytes, but not in non-parenchymal cells. In contrast to HO-1, ALAS1 gene expression was markedly down-regulated in ALF patients compared with controls. These findings suggest that, in the liver of ALF patients, there may be an increase in free heme concentration which up-regulates HO-1 gene expression, while down-regulating ALAS1 gene expression, resulting in markedly altered heme metabolism and liver function.

[Severe acute pulmonary edema during living related liver transplantation surgery].

We report a case of severe intraoperative pulmonary edema during living related liver transplantation (LRLT) surgery. A 60-year-old woman with end-stage primary biliary cirrhosis underwent LRLT. After administration of several units of packed red blood cells and fresh frozen plasma, a gradual decline in oxygen saturation was observed. After an unexpectedly prolonged ahepatic phase, she developed severe pulmonary edema and critical hypoxemia. Further deterioration of hypoxemia was observed after reperfuion of the portal vein. We conclude that this severe pulmonary edema was caused by transfusion related acute lung injury, and prolonged ahepatic phase with reperfusion injury deteriorated the lung condition.

[Living-related liver transplantation in a patient with hepatopulmonary syndrome].

We experienced the perioperative management of the living related liver transplantation (LRLT) in a patient with hepatopulmonary syndrome (HPS). HPS is seen in 15% of patients of the endstage liver failure, and it accompanies the various types of hypoxia. The diagnostic standards of HPS are chronic liver disease usually complicated by portal hypertension with or without cirrhosis, arterial hypoxemia (PaO2 < 70 mmHg or A-aDO2 gradient > 20 mmHg), and intrapulmonary vascular dilation. The present case conformed to the diagnostic standard. But this case was of a mild type of HPS, because PaO2 was elevated after O2 inhalation and extrapulmonary uptake of 99mTcMAA after lung perfusion was lower than 40%. During perioperative period of LRLT, there were no complications such as hypoxia, acute rejection, bleeding and infection. Therefore HPS would be improved after LRLT. In the management of perioperative period it is important to be aware of hypoxia and to evaluate preoperatively the condition of the patient properly.

Increased carbon monoxide concentration in exhaled air after surgery and anesthesia.

Heme oxygenase-1 (HO-1) is induced by oxidative stress and is thought to confer protection against oxidative tissue injuries. HO-1 catalyzes the conversion of the heme moiety of hemeproteins, such as hemoglobin, myoglobin, and cytochrome P450, to biliverdin, liberating carbon monoxide (CO) in the process. CO reacts with hemoglobin to form carboxyhemoglobin. In this study, to examine the effect of anesthesia and/or surgery on endogenous CO production, we measured the amount of exhaled CO and the arterial carboxyhemoglobin concentration of patients who underwent surgery under general or spinal anesthesia. Both CO and carboxyhemoglobin concentrations were significantly larger on the day after surgery than during the preoperative period (P < 0.05) and in the recovery room (P < 0.05), regardless of anesthesia. However, neither index differed between general and spinal anesthesia. These results suggest that oxidative stress caused by anesthesia and/or surgery may induce HO-1, which catalyzes heme to produce CO, leading to increased exhaled CO concentration.

Correlation between the distribution of contrast medium and the extent of blockade during epidural anesthesia.

BACKGROUND: If the epidural spread of contrast medium can be well correlated with the spread of local anesthetics, epidurography can predict the dermatomal distribution of the anesthetic block. The authors evaluated the relation between radiographic and analgesic spread. METHODS: An epidural catheter was inserted in 90 patients, and predicted catheter tip position was recorded. The analgesic area was determined by pinprick after a 5-ml injection of 1.5% lidocaine, and epidurography was performed after a 5-ml injection of 240 mg I/ml iotrolan. Patients were assigned to three groups according to catheter tip position (group C: C-T4; group T: T5-T10; group L: T11-L), and patterns of spread were compared. In 16 of 90 subjects, radiographic and analgesic spread was further investigated after an additional 5-ml injection of iotrolan and lidocaine. RESULTS: The total radiographic spread correlated well with analgesic spread (right side: Y = 0.84 X + 0.16, r = 0.92, P < 0.01; left side: Y = 0.78 X + 0.45, r = 0.91, P < 0.01). The mean radiographic spread in the cephalad and caudal directions from the catheter tip also correlated well with mean analgesic spread (r = 0.97, P < 0.01, each direction). The mean distance between the predicted catheter tip and radiographically determined positions was 1.0 +/- 0.8 segments: the value in group T was significantly larger than that in groups C (P < 0.05) and L (P < 0.01). Although the correlation of radiographic spread with age was statistically significantly (r = 0.39, P < 0.01), great individual variation in spreading pattern was seen. In 16 subjects, mean radiographic spread correlated well with analgesic spread after 5- and 10-ml injections of iotrolan and lidocaine. CONCLUSIONS: Epidurography is useful to indicate epidural catheter position and can help to predict the exact dermatomal distribution of analgesic block.

[Massive bleeding due to hyperfibrinolysis during living-related liver transplantation for terminal liver cirrhosis; report of two cases].

We reported two cases of massive bleeding due to critical hyperfibrinolysis during living-related liver transplantation (LRLT) for end stage liver cirrhosis. The total volume of bleeding amounted to 57930 ml with the case 1, and amounted to 55980 ml with the case 2. TEG was useful for diagnosis of the hyperfibrinolysis. We administrated large amounts of FFPs, MAPs, PLTs, and gabexate mesilate. By rapid transfusion, we could manage to finish the procedures without hypotension, and complications were not observed at the early postoperative stage. We thought that the cause of the hyperfibrinolysis is the increasing blood tissue plasminogen activator (t-PA) due to long-anhepatic stage and small graft size. During anesthesia, since the functional start of a transplant liver is indispensable to it, in order to support a transplant liver for an improvement of hyperfibrinolysis, it is important to keep the homeostasis, such as body temperature, blood pressure.

[Changes of urinary tripsin inhibitor in blood and urine, as well as serum cytokines in living related liver transplantation].

BACKGROUND: Living related liver transplantation induces the production of many inflammatory and anti-inflammatory cytokines. Urinary tripsin inhibitor (UTI) is produced in the liver and wellknown as one of the markers of surgical stress. METHODS: To clarify the significance of UTI in blood and urine and serum cytokines in living related liver transplantation, we examined the changes of UTI, polymorphonuclear elastase (PMNE), interleukin (IL)-6, IL-1 ra and IL-10 perioperatively. RESULTS: UTI in blood increased gradually after operation. It increased from 5.2 +/- 2.2 U.ml-1 at the end of operation to 19.4 +/- 7.5 U.ml-1 on the 10 th postoperative day (POD). Similarly, UTI in urine increased after operation and the peak was on the 7th POD. Cytokines including IL-6, IL-1 ra and IL-10 showed similar changes in general gastrointestinal surgery, but the peak values in liver transplantation were lower. CONCLUSION: These results demonstrate that the recovery of the transplanted liver function require certain time after operation and UTI in urine could be an important marker whether the liver is working or not. The immunosuppressive drugs, like steroid, administered during and after operation would suppress the production of cytokines.

Protective role of heme oxygenase-1 in the intestinal tissue injury in an experimental model of sepsis.

OBJECTIVE: The aim of this study was to examine the role of heme oxygenase-1 induction in the intestinal tissue injury in a rat model of sepsis. DESIGN: Randomized, masked, controlled animal study. SETTING: University-based animal research facility. SUBJECTS: Sprague-Dawley male rats, weighing 220-250 g (n = 126). INTERVENTIONS: Rats were injected with lipopolysaccharide (10 mg/kg) intraperitoneally. Another group of rats was injected with interleukin-6 (10 microg/kg) intravenously. In some rats, tin mesoporphyrin (1 micromol/kg) was administered intravenously 1 hr before lipopolysaccharide treatment. MEASUREMENTS AND MAIN RESULTS: Following lipopolysaccharide treatment, expression of heme oxygenase-1 and nonspecific delta-aminolevulinate synthase (ALAS-N), the rate-limiting enzymes of heme catabolism and biosynthesis, respectively, was examined in various regions of the intestine. Lipopolysaccharide treatment markedly increased heme oxygenase-1 messenger RNA and protein concentrations in the mucosal epithelial cells in the duodenum and the jejunum, whereas its expression in the ileum and the colon was hardly detectable and was not influenced by the treatment. ALAS-N messenger RNA was also more markedly increased in the duodenum, the jejunum, and the ileum than in the colon following lipopolysaccharide treatment. Interleukin-6 administration also induced heme oxygenase-1 and ALAS-N gene expression in a pattern similar to that following lipopolysaccharide treatment. In contrast to the marked heme oxygenase-1 expression in the upper intestine, lipopolysaccharide-induced mucosal injury and inflammation in the upper intestine were far less than observed in the lower intestine as judged both by tumor necrosis factor-alpha gene expression and by histologic analysis. Of note, inhibition of heme oxygenase activity by tin mesoporphyrin produced a significant tissue injury in the upper intestine of the lipopolysaccharide-treated animals. CONCLUSIONS: Intestinal heme oxygenase-1 and ALAS-N gene expression was regulated in a site-specific manner in a rat model of sepsis. Our findings also suggest that heme oxygenase-1 induction may play a fundamental role in protecting mucosal epithelial cells of the intestine from oxidative damages that occur in sepsis.