Perioperative GLY-GLN Infusion Diminishes the Surgery-Induced Period of Immunosuppression: Accelerated Restoration of the Lipopolysaccharide-Stimulated Tumor Necrosis Factor-Alpha Response

Surgical Research Laboratories, University of Vienna, Austria.
Annals of Surgery (Impact Factor: 8.33). 02/2003; 237(1):110-5. DOI: 10.1097/01.SLA.0000041040.98684.CB
Source: PubMed


To investigate whether the administration of different glutamine-containing dipeptides, glycyl-l-glutamine (GLY-GLN) and l-alanyl-l-glutamine, has a differing impact on perioperative immunomodulation.
Surgery leads to transitory immunosuppression, which is associated with decreased plasma glutamine (GLN) levels and increased susceptibility to infection and sepsis. A useful tool to detect immunocompetence is the ex vivo lipopolysaccharide (LPS)-stimulated tumor necrosis factor alpha (TNF-alpha) secretion in whole blood.
Forty-five patients undergoing major abdominal surgery were randomized prospectively to receive 0.5 g/kg/24 h GLN dipeptides administered as GLY-GLN or as ALA-GLN or isonitrogenous Vamin (a GLN-free amino acid solution; control group) as a continuous infusion over 72 hours, starting 24 hours before surgery. Blood samples were collected before infusion, at the end of surgery, and 48 hours postoperatively to determine the TNF-alpha release into whole blood stimulated with LPS. Groups were compared by analysis of variance.
The groups were comparable in age, gender distribution, and length of operative time. At the end of surgery a significant reduction in ex vivo LPS-stimulated TNF-alpha production was observed in all groups. In patients who received GLY-GLN, the induced TNF-alpha production was restored after 48 hours.
In this study perioperative infusion of GLY-GLN reduced immunosuppression. The effect of GLN-containing dipeptides seems to be different when administered in glycine or alanine form.

Download full-text


Available from: Thomas Sautner
  • [Show abstract] [Hide abstract]
    ABSTRACT: Surgery and immunotherapy are mainstays of the treatment of renal cell carcinoma. Disease confined to the kidney can be cured by surgery alone. However, up to 19% of patients with histopathologically organ-confined disease (i.e., tumor stage pT1-2N0M0 or ROBSON I) die from tumor recurrence in the first 5 years after tumor nephrectomy (Lam et al. 2007). Some reasons and histopathological considerations were reviewed by the authors (Böhm et al., 2002, 2003). Even if one considers the methodological hazards of using different systems of tumor classi­fication (ROBSON versus UICC-TNM classification, modifications of the TNM clas­-sification in 1987, 1997, and 2002) it appears that more patients die from recurrent disease after surgically complete resection than can be expected from the frequency of undetected micrometastases at the time of operation. For this and other reasons the suggestion by (Robson et al. 1969) that the renal artery be ligated first and then the specimen be resected and removed en bloc is still valued in many surgical departments. Surgery, including renal surgery is associated with complex perioperative immunodysfunction (Böhm et al. 2001). This involves both cellular and humoral components of the immune system. It was noted that less surgical trauma is associated with less perioperative immunodysfunction and hence better outcome (Whitson et al. 2007), but this association has been challenged (Landman et al. 2004).
    No preview · Article ·
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: l " Transplantation l " fast-track-Chirurgie l " postoperative Ernährung " parenteral nutrition l " surgery l " transplantation l " fast track surgery
    Full-text · Article ·
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: During sepsis and critical illness, a systemic inflammatory response can significantly produce reactive oxygen and nitrogen species, which can damage host tissues. Usually, several different antioxidant defences protect host cells from these reactive species. One of the important antioxidant defences is glutathione, a tripeptide synthesised from the precursor amino acids cysteine, glutamate and glycine. The aim of this study was to measure glutathione synthesis in vivo, using deuterated glycine as a tracer. Firstly, a new method for analysis of glutathione and glycine using both gas chromatography-mass spectrometry (GC-MS) and gas chromatography-isotope ratio mass spectrometry (GC-IRMS) was developed. The derivatives of both compounds were measured in a single chromatographic analysis, and the method was compatible with both GC-MS and GC-IRMS, and capable of measuring low carbon-13 or deuterium enrichment of glutathione in 50μl of erythrocytes. Erythrocyte glutathione synthesis was measured, using GC-IRMS, in critically ill infants and children who had been infused with deuterated glycine. Glutathione fractional synthesis rate (FSR) was not statistically different between septic and non-septic patients. In order to determine whether glutamine is able to increase GSH synthesis by acting as a glutamate precursor, erythrocyte GSH synthesis was measured using GC-IRMS in septic infants and children randomised to receive glutamine dipeptide or placebo. There was no significant difference in glutathione FSR between those given glutamine and those given placebo. Intestinal glutathione depletion is known to occur following intestinal ischaemia-reperfusion injury. I measured glutathione synthesis in a rat model of intestinal ischaemia-reperfusion injury, and found that hypothermic rats with ischaemia-reperfusion injury had a higher intestinal glutathione synthesis than normothermic rats, providing a potential mechanism by which hypothermia may maintain intestinal glutathione levels. In conclusion, the newly developed method of glutathione analysis using GC-IRMS was useful for compound specific isotope analysis of biological samples.
    Preview · Article ·
Show more