1
Critical Care II 113 Methods: Twenty-four Swiss male mice were randomly divided into 3 groups: Sham, IO (intestinal obstruction) and CIT. The CIT group received 30mg/day of citrulline added to the chow and the other groups ate conventional chow. Both diets were isocaloric and isoproteic. After 7 days, the groups were gavaged with 10 8 CFU/mL of E. coli labeled with technetium 99m ( 99m Tc-E. coli). Ninety minutes later, the animals were anesthetized and underwent terminal ileum ligation. The Sham group underwent only laparotomy. After 18 hours, blood and organs (mesenteric lymph nodes, liver, spleen and lungs) were removed for radioactivity determination. The intestinal fluid and serum were also collected to assess secretory IgA and cytokines by ELISA. We used Kruskal- Wallis ANOVA for bacterial translocation data analysis and one-way ANOVA for cytokines and sIgA data. Statistical significance was set at p 0.05. Results: Bacterial translocation was significantly higher in IO group than control and treated groups (p < 0.05). CIT and Sham animals demonstrated the same levels of bacterial translocation to mesenteric lymph nodes, spleen and lungs (p > 0.05). SIgA levels were raised in CIT group (2414.78±828.24 mg/mL), when compared with Sham (921.50±182.06) and IO groups (876.62±136.49) (p < 0.05). IO group presented the highest serum lev- els of IFN-g (56.86±13.03 pg/mL), considering Sham (17.08±1.92) and CIT groups (21.36±8.03)(p < 0.05). The levels of IL-10 did not differ between IO, CIT and Sham groups (69.44±11.17; 87.30±13.42 and 71.93±2.28 pg/mL) (p > 0.05). Conclusion: Citrulline might protect against bacterial translocation by increasing intestinal sIgA and decreasing the levels of pro-inflammatory cytokine (IFN-g). Disclosure of Interest: None declared PP231 ORAL GLUTAMINE REDUCES MYOCARDIAL INJURY IN PATIENTS UNDERGOING CARDIAC SURGERY A. Sufit 1 , K. Queensland 2 , C. Hamiel 2 , A. Baer 2 , P. Wischmeyer 1 . 1 Anesthesiology, 2 University of Colorado, Aurora, CO, United States Rationale: Glutamine (GLN) can protect against in vitro and in vivo myocardial cell injury following ischemia and reperfusion injury. This effect may be mediated by increased heat shock protein (HSP) expression. However, the potential for GLN to protect the myocardium in patients undergoing cardiac surgery is unknown. Thus, our objective was to perform a proof-of-concept pilot trial to determine if pre-operative GLN therapy could attenuate myocardial injury as measured by serum injury markers in patients undergoing cardiac surgery. Methods: Subjects undergoing elective cardiac surgery (CABG or heart valve replacement/repair), in which cardiopulmonary bypass was required were enrolled in a randomized, double-blinded trial to receive oral GLN (25 mg BID) (n = 7) or maltodextran control (C) (n = 7) daily for 3 days prior to surgery. Serum troponin (TROP I), creatine kinase (CK-MB), myoglobin, and white cell HSP70 level was obtained at: baseline, pre-anesthesia, and at 6, 24, 48, and 72h post-surgery. Results: Of enrolled patients, 2 withdrew (1 GLN, 1 C), 1 expired in OR (C pt), and 1 underwent non-qualifying surgery (GLN pt). No adverse effects were noted in either group. Thus, 10 patients (4 GLN and 6 C) had samples available for analysis. Our data reveals patients receiving GLN had significantly decreased TROP I, at 24, 48, and 72 h post-surgery (all p < 0.05) versus C. GLN therapy also reduced CK-MB at 24 and 48 h (p < 0.05 and p < 0.001 respectively) and myoglobin 24 h post-surgery (p < 0.05) versus C. GLN treated patients showed a non- statistically significant trend towards increased cellular HSP70 content. Conclusion: In this pilot study, GLN therapy prior to cardiac surgery reduces myocardial injury as measured by serum injury markers. This may be due to increased cellular HSP70 expression. This data indicates a larger trial of GLN therapy in cardiac surgery powered on clinical outcomes is warranted. Disclosure of Interest: A. Sufit: None declared, K. Queensland: None declared, C. Hamiel: None declared, A. Baer: None de- clared, P. Wischmeyer Grant/Research Support from: Fresenius Inc PP232 CELLULAR MECHANISMS UNDERLYING THE PROTECTIVE EFFECTS OF PREOPERATIVE CARBOHYDRATE LOADING: A RANDOMISED STUDY INVESTIGATING MITOCHONDRIAL FUNCTION, GENE AND PROTEIN EXPRESSION (NCT00662376) S. Awad 1 , D. Constantin-Teodosiu 2 , D. Constantin 2 , B.J. Rowlands 1 , K.C. Fearon 3 , I.A. Macdonald 2 , D.N. Lobo 1 . 1 Division of Gastrointestinal Surgery, Nottingham Digestive Diseases Centre NIHR Biomedical Research Unit, Queen’s Medical Centre, Nottingham University Hospitals, 2 Metabolic Physiology Group, School of Biomedical Sciences, University of Nottingham, Nottingham, 3 Clinical and Surgical Sciences, University of Edinburgh, Edinburgh, United Kingdom Rationale: Preoperative carbohydrate loading attenuates postoperative insulin resistance but the mechanisms underlying this are unclear. The effects of preopera- tive ingestion of a carbohydrate-based drink that also contained glutamine and antioxidants [Oral Nutritional Supplement (ONS), Fresenius Kabi] on mitochondrial function and the expression of key metabolic genes and proteins were studied. Methods: Two groups of 20 patients undergoing laparo- scopic cholecystectomy participated in this randomised placebo-controlled double-blind study. Patients ingested either 600 ml of ONS or placebo the evening before surgery and 300 ml 3 4 h before anaesthesia. 300 ml of ONS contained 50 g carbohydrate, 15 g glutamine and antioxidants. Rectus abdominis muscle and liver biopsies were performed intraoperatively to study mitochondrial function (complex II, II+III, IV and citrate synthase activities and ATP content), pyruvate dehydrogenase kinase-4 (PDK4), FOXO1 and Metallothionein 1A (Mt1A) gene and protein expression. Results: The mean (SE) age and BMI of the 40 patients (31 female) were 50.3 (2.1) years and 29.0 (0.9) kg/m 2 respectively. There were no differences in mitochondrial

PP231 ORAL GLUTAMINE REDUCES MYOCARDIAL INJURY IN PATIENTS UNDERGOING CARDIAC SURGERY

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Critical Care II 113

Methods: Twenty-four Swiss male mice were randomlydivided into 3 groups: Sham, IO (intestinal obstruction)and CIT. The CIT group received 30 mg/day of citrullineadded to the chow and the other groups ate conventionalchow. Both diets were isocaloric and isoproteic. After7 days, the groups were gavaged with 108 CFU/mL ofE. coli labeled with technetium 99m (99mTc-E. coli).Ninety minutes later, the animals were anesthetizedand underwent terminal ileum ligation. The Sham groupunderwent only laparotomy. After 18 hours, blood andorgans (mesenteric lymph nodes, liver, spleen andlungs) were removed for radioactivity determination. Theintestinal fluid and serum were also collected to assesssecretory IgA and cytokines by ELISA. We used Kruskal-Wallis ANOVA for bacterial translocation data analysis andone-way ANOVA for cytokines and sIgA data. Statisticalsignificance was set at p� 0.05.Results: Bacterial translocation was significantly higherin IO group than control and treated groups (p < 0.05).CIT and Sham animals demonstrated the same levelsof bacterial translocation to mesenteric lymph nodes,spleen and lungs (p > 0.05). SIgA levels were raised inCIT group (2414.78±828.24 mg/mL), when compared withSham (921.50±182.06) and IO groups (876.62±136.49)(p < 0.05). IO group presented the highest serum lev-els of IFN-g (56.86±13.03 pg/mL), considering Sham(17.08±1.92) and CIT groups (21.36±8.03)(p < 0.05). Thelevels of IL-10 did not differ between IO, CIT andSham groups (69.44±11.17; 87.30±13.42 and 71.93±2.28pg/mL) (p > 0.05).Conclusion: Citrulline might protect against bacterialtranslocation by increasing intestinal sIgA and decreasingthe levels of pro-inflammatory cytokine (IFN-g).

Disclosure of Interest: None declared

PP231ORAL GLUTAMINE REDUCES MYOCARDIAL INJURY INPATIENTS UNDERGOING CARDIAC SURGERYA. Sufit1, K. Queensland2, C. Hamiel2, A. Baer2,P. Wischmeyer1. 1Anesthesiology, 2University ofColorado, Aurora, CO, United States

Rationale: Glutamine (GLN) can protect against in vitroand in vivo myocardial cell injury following ischemiaand reperfusion injury. This effect may be mediated byincreased heat shock protein (HSP) expression. However,the potential for GLN to protect the myocardium inpatients undergoing cardiac surgery is unknown. Thus, ourobjective was to perform a proof-of-concept pilot trial todetermine if pre-operative GLN therapy could attenuatemyocardial injury as measured by serum injury markersin patients undergoing cardiac surgery.Methods: Subjects undergoing elective cardiac surgery(CABG or heart valve replacement/repair), in whichcardiopulmonary bypass was required were enrolled ina randomized, double-blinded trial to receive oral GLN(25 mg BID) (n = 7) or maltodextran control (C) (n = 7) dailyfor 3 days prior to surgery. Serum troponin (TROP I),creatine kinase (CK-MB), myoglobin, and white cell HSP70level was obtained at: baseline, pre-anesthesia, and at 6,24, 48, and 72 h post-surgery.

Results: Of enrolled patients, 2 withdrew (1 GLN, 1 C),1 expired in OR (C pt), and 1 underwent non-qualifyingsurgery (GLN pt). No adverse effects were noted ineither group. Thus, 10 patients (4 GLN and 6 C) hadsamples available for analysis. Our data reveals patientsreceiving GLN had significantly decreased TROP I, at 24,48, and 72 h post-surgery (all p < 0.05) versus C. GLNtherapy also reduced CK-MB at 24 and 48 h (p < 0.05 andp < 0.001 respectively) and myoglobin 24 h post-surgery(p < 0.05) versus C. GLN treated patients showed a non-statistically significant trend towards increased cellularHSP70 content.Conclusion: In this pilot study, GLN therapy prior tocardiac surgery reduces myocardial injury as measuredby serum injury markers. This may be due to increasedcellular HSP70 expression. This data indicates a largertrial of GLN therapy in cardiac surgery powered on clinicaloutcomes is warranted.

Disclosure of Interest: A. Sufit: None declared, K. Queensland:None declared, C. Hamiel: None declared, A. Baer: None de-clared, P. Wischmeyer Grant/Research Support from: FreseniusInc

PP232CELLULAR MECHANISMS UNDERLYING THE PROTECTIVEEFFECTS OF PREOPERATIVE CARBOHYDRATE LOADING:A RANDOMISED STUDY INVESTIGATING MITOCHONDRIALFUNCTION, GENE AND PROTEIN EXPRESSION(NCT00662376)

S. Awad1, D. Constantin-Teodosiu2, D. Constantin2,B.J. Rowlands1, K.C. Fearon3, I.A. Macdonald2,D.N. Lobo1. 1Division of Gastrointestinal Surgery,Nottingham Digestive Diseases Centre NIHR BiomedicalResearch Unit, Queen’s Medical Centre, NottinghamUniversity Hospitals, 2Metabolic Physiology Group,School of Biomedical Sciences, University of Nottingham,Nottingham, 3Clinical and Surgical Sciences, Universityof Edinburgh, Edinburgh, United Kingdom

Rationale: Preoperative carbohydrate loading attenuatespostoperative insulin resistance but the mechanismsunderlying this are unclear. The effects of preopera-tive ingestion of a carbohydrate-based drink that alsocontained glutamine and antioxidants [Oral NutritionalSupplement (ONS), Fresenius Kabi] on mitochondrialfunction and the expression of key metabolic genes andproteins were studied.Methods: Two groups of 20 patients undergoing laparo-scopic cholecystectomy participated in this randomisedplacebo-controlled double-blind study. Patients ingestedeither 600 ml of ONS or placebo the evening beforesurgery and 300 ml 3 4 h before anaesthesia. 300 ml ofONS contained 50 g carbohydrate, 15 g glutamine andantioxidants. Rectus abdominis muscle and liver biopsieswere performed intraoperatively to study mitochondrialfunction (complex II, II+III, IV and citrate synthaseactivities and ATP content), pyruvate dehydrogenasekinase-4 (PDK4), FOXO1 and Metallothionein 1A (Mt1A)gene and protein expression.Results: The mean (SE) age and BMI of the 40 patients(31 female) were 50.3 (2.1) years and 29.0 (0.9) kg/m2

respectively. There were no differences in mitochondrial