leukotriene-b4 and Postoperative-Complications

Omega-3 fatty acids (n-3 FA) may have beneficial clinical and immune-modulating effects in surgical patients. In a randomized, double-blind, prospective, placebo-controlled trial, 148 patients referred for elective colorectal cancer surgery received an n-3 FA-enriched oral nutritional supplement (ONS) providing 2.0 g of eicosapentaenoic acid (EPA) and 1.0 g of docosahexaenoic acid (DHA) per day or a standard ONS for seven days before surgery. On the day of operation, there was a significant increase in the production of leukotriene B5 (LTB5) (p < 0.01) and 5-hydroxyeicosapentaenoic acid (5-HEPE) (p < 0.01), a significant decrease in the production of leukotriene B4 (LTB4) (p < 0.01) and a trend for a decrease in the production of 5-hydroxyeicosatetraenoic acid (5-HETE) (p < 0.1) from stimulated neutrophils in the active group compared with controls. There was no association between LTB4 values and postoperative complications. In conclusion, oral n-3 FA exerts anti-inflammatory effects in surgical patients, without reducing the risk of postoperative complications.

Topics: Adult; Aged; Aged, 80 and over; Colorectal Neoplasms; Dietary Supplements; Double-Blind Method; Eicosapentaenoic Acid; Elective Surgical Procedures; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; Humans; Leukotriene B4; Male; Middle Aged; Neutrophils; Postoperative Complications; Postoperative Period; Preoperative Period; Prospective Studies; Treatment Outcome

Compared with soybean oil, a fish oil-enriched emulsion can improve the clinical outcomes of patients requiring parenteral nutrition. However, the superiority of fish oil emulsion to medium-chain triacylglycerols/long-chain triacylglycerols for short-term administration has seldom been discussed.. Sixty-four adult patients with gastrointestinal diseases were randomly assigned to receive isocaloric and isonitrogenous total parenteral nutrition with an ω-3 fatty acid-enriched emulsion (Lipoplus; study group, n = 32) or medium-chain triacylglycerols/long-chain triacylglycerols (Lipofundin; control group, n = 32) for 5 d after surgery. Safety and efficacy parameters were assessed on postoperative days 1, 3, and 6.. Clinical outcomes including infectious complications and systemic inflammatory response syndrome were comparable between the two groups. Total bilirubin decreased over time in the study group versus an increase in the control group (P = 0.017). Activated partial thromboplastin time in the study group was prolonged significantly compared with the control group from days 1 to 3 (P = 0.002), although the prolongation stopped at the study termination. There were no differences in changes of C-reactive protein, interleukin (IL)-1, IL-8, IL-10, vascular endothelial growth factor (VEGF), and the distribution of the T-cell subpopulation between the two groups. However, fish oil consumption led to an increase in leukotriene B5/ leukotriene B4 and significant decreases in IL-6, tumor necrosis factor-α, and nuclear factor-κB. Furthermore, the overall changes in tumor necrosis factor-α and nuclear factor-κB were positively associated (R(2) = 0.295, P < 0.001).. Gastrointestinal surgery patients benefited from a fish oil-enriched emulsion rather than medium-chain triacylglycerols/long-chain triacylglycerols in the amelioration of liver function and immune status. The positive association of tumor necrosis factor-α and nuclear factor-κB might be involved in the potential anti-inflammation mechanism of fish oil.

Topics: Adult; Aged; Anti-Inflammatory Agents; Bilirubin; Cross Infection; Dietary Fats; Eicosapentaenoic Acid; Fat Emulsions, Intravenous; Fatty Acids, Omega-3; Female; Fish Oils; Gastrointestinal Diseases; Humans; Immunity; Inflammation; Inflammation Mediators; Leukotriene B4; Liver; Male; Middle Aged; NF-kappa B; Parenteral Nutrition; Partial Thromboplastin Time; Postoperative Complications; Systemic Inflammatory Response Syndrome; Triglycerides; Tumor Necrosis Factor-alpha

Previous work of our group showed that lipoxygenase (LOX) pathways become activated upon surgical manipulation of the bowel wall and revealed a beneficial immune modulating role of the LOX-derived anti-inflammatory mediator protectin DX in postoperative ileus (POI). While we found a particular role of 12/15-LOX in the anti-inflammatory LOX action during POI, the role of 5-LOX, which produces the pro-inflammatory leukotriene B4 (LTB4), remained unknown. The purpose of this study was to investigate the role of 5-LOX within the pathogenesis of POI in a mouse model.. POI was induced by intestinal manipulation (IM) of the small bowel in C57BL/6, 5-LOX-/-, and CX3CR1GFP/+. Mice were either treated with a vehicle or with the synthetic 5-LOX antagonist zileuton or were left untreated. Cellular localization of 5-LOX and LTB4 release were visualized by immunofluorescence or ELISA, respectively. POI severity was quantified by gastrointestinal transit (GIT) and leukocyte extravasation into the muscularis externa (ME) by immunohistochemistry.. 5-LOX expression was detected 24 h after IM within infiltrating leukocytes in the ME. LTB4 levels increased during POI in wild type but not in 5-LOX-/- after IM. POI was ameliorated in 5-LOX-/- as shown by decreased leukocyte numbers and normalized GIT. Zileuton normalized the postoperative GIT and reduced the numbers of infiltrating leukocytes into the ME.. Our data demonstrate that 5-LOX and its metabolite LTB4 play a crucial role in POI. Genetic deficiency of 5-LOX and pharmacological antagonism by zileuton protected mice from POI. 5-LOX antagonism might be a promising target for prevention of POI in surgical patients.

Topics: Animals; Arachidonate 5-Lipoxygenase; Ileus; Leukotriene B4; Mice; Mice, Inbred C57BL; Postoperative Complications

Cardiac surgery using cardiopulmonary by-pass and, to a greater extent, lung resection, causes acute lung injury that is usually subclinical. Analysis of mediators in exhaled breath condensate is a promising means of monitoring inflammation in a variety of airway diseases but the contribution of the airway lining fluid from the lower respiratory tract is uncertain. We compared the analysis of markers of lung injury in exhaled breath condensate and bronchoalveolar lavage in endotracheally intubated patients before and after coronary artery bypass graft surgery with cardiopulmonary bypass and lobectomy. The neutrophil count and leukotriene B4 concentration in bronchoalveolar lavage fluid rose after coronary artery bypass graft surgery (p < 0.05), but there was no significant change in leukotriene B4, hydrogen peroxide, or hydrogen ion concentrations in exhaled breath condensate. By contrast, after lobectomy, the concentration in exhaled breath condensate of leukotriene B4, hydrogen peroxide and hydrogen ions rose significantly (p < 0.05). Exhaled breath condensate is a safe, noninvasive method of sampling the milieu of the distal lung and is sufficiently sensitive to detect markers of inflammation and oxidative stress in patients after lobectomy, but not after the milder insult associated with cardiac surgery.

Topics: Aged; Breath Tests; Bronchoalveolar Lavage Fluid; Cohort Studies; Coronary Artery Bypass; Dinoprost; F2-Isoprostanes; Female; Humans; Inflammation Mediators; Leukotriene B4; Male; Mass Spectrometry; Middle Aged; Pneumonia; Postoperative Complications; Probability; Prognosis; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric

Plasma thromboxane B2 (TXB2), leukotriene B4 (LTB4), and endothelin-1 (ET-1) levels increase on cardiopulmonary bypass (CPB). Elevated levels of TXB2 and ET-1 have been correlated with postoperative pulmonary hypertension in infants undergoing repair of congenital heart defects. LTB4 is a potent chemotactic cytokine whose levels correlate with leukocyte-mediated injury. Modified ultrafiltration (MUF) has been associated with improved hemodynamics and pulmonary function, in addition to its beneficial effects on fluid balance and blood conservation. Recent investigations have suggested that removal of cytokines may be the cause of the improved cardiopulmonary function seen with MUF.. Plasma TXB2, ET-1, and LTB4 levels were measured in 34 infants undergoing CPB: 22 underwent MUF (group 1), and 12 did not (group 2). Samples were obtained at various time points. All patients underwent conventional ultrafiltration during the rewarming phase of cardiopulmonary bypass.. In group 1, mean end-CPB TXB2 level was 101.2 pg/mL versus 46.9 pg/mL post-MUF (p < 0.05). The mean TXB2 level 1 hour post-CPB (54.1 pg/mL) was not significantly different from the post-MUF level. In group 2, the mean end-CPB TXB2 level was 123.6 pg/mL versus 53.2 pg/mL 1 hour post-CPB. Hence, TXB2 levels decreased by similar amounts and to similar levels by 1 hour post-CPB in both groups. ET-1 levels increased after CPB and were unaffected by MUF: 1.45, 1.80, 2.55 pg/mL at end-CPB, post-MUF, and 1 hour post-CPB, respectively, in group 1; and 1.51, and 2.73 pg/mL at end-CPB and 1 hour post-CPB in group 2. LTB4 levels post-MUF were 119% of pre-MUF values, and were similar at 1 hour post-CPB in both groups.. Despite reduction in TXB2 by MUF, values were similar and approached baseline 1 hour post-CPB in both groups. LTB4 levels increased slightly with MUF. ET-1 levels increased during and post-CPB and were unaffected by MUF. MUF does not appear to have a significant effect on post-CPB levels of TXB2, ET-1, and LTB4. Therefore, the improved hemodynamics observed with MUF do not appear to be related to removal of these cytokines.

Topics: Cardiopulmonary Bypass; Endothelin-1; Female; Heart Defects, Congenital; Hemofiltration; Humans; Hypertension, Pulmonary; Infant; Leukotriene B4; Male; Postoperative Complications; Risk Factors; Thromboxane B2; Treatment Outcome

In order to evaluate its possible role in the pathogenesis of pouchitis we measured the release, into the incubation medium of leukotriene B4 from mucosal samples from patients with ileal pouch-anal anastomosis and correlated release with clinical, endoscopic and histological features.. Leukotriene B4 release was significantly elevated in patients with active pouchitis in comparison to those with a normal pouch mucosa (P < 0.007). No overlap was observed between leukotriene B4 levels from patients with active pouchitis samples and those obtained from individuals without pouchitis. Effective treatment of pouchitis was associated with a significant reduction in leukotriene B4 mucosal release to the incubation medium (P < 0.03). However, even in remission, levels of leukotriene B4 release remained significantly increased in these patients in comparison to people who never experienced pouchitis (P < 0.003). A modest correlation was observed between pouchitis disease activity index and leukotriene B4 release (r = 0.596; P < 0.01).. These results suggest that the increased production of leukotriene B4 may be implicated in the pathogenesis of pouchitis. The persistence of an increased mucosal release of leukotriene B4 in pouchitis patients during clinical remission suggests the presence of a chronic, ongoing, underlying inflammatory process.

Topics: Adult; Case-Control Studies; Colitis, Ulcerative; Female; Humans; Ileal Diseases; Inflammatory Bowel Diseases; Intestinal Mucosa; Leukotriene B4; Male; Middle Aged; Postoperative Complications; Proctocolectomy, Restorative; Severity of Illness Index; Statistics, Nonparametric

We experienced a case of reexpansion pulmonary edema (RPE) after surgical treatment of pneumothorax. In this case, protein leakage and polymorphonuclear leukocyte (PMN) accumulation were observed in the reexpanded lung. Interleukin-8 and leukotriene B4 in edema fluid were increased at the onset of RPE. PMN elastase was also increased, though its peak was delayed. The plasma level of P-selectin, which mediates adhesion between PMN and endothelium, was elevated. We speculate that some of these fluid mediators may play important roles in chemotaxis and activation of PMN in the development of RPE.

Topics: Adult; Bronchoalveolar Lavage Fluid; Extravascular Lung Water; Exudates and Transudates; Humans; Interleukin-8; Leukotriene B4; Male; Pneumothorax; Postoperative Complications; Pulmonary Edema; Time Factors