lactoferrin and Heart-Defects--Congenital

This study was undertaken to assess whether different filter types or ultrafiltration methods influence inflammatory markers in pediatric cardiac surgery.. Forty-one children younger than 5 years were prospectively randomized to groups A (polyamid filter with conventional ultrafiltration), B (polyamid filter with modified ultrafiltration), C (polysulfon filter with conventional ultrafiltration), and D (polysulfon filter with modified ultrafiltration). Interleukin 6, interleukin 10, tumor necrosis factor, terminal complement complex, and lactoferrin were measured before the operation (T0), before rewarming (T1), after ultrafiltration (T2), at 6 (T3) and 18 hours (T4) after the operation, and in the ultrafiltrate.. All markers changed with both ultrafiltration methods, both filter types, and in all groups (except tumor necrosis factor) along the T0 to T4 observation time (P <.0001). Their patterns of changes were different for terminal complement complex, with less decrease after use of the polysulfon filter (P <.05), and among groups A through D for interleukin 6 (P =.01), with more decrease in group C than group A (P <.02). Interleukin 10 decreased with the polyamid filter (P <.001) but not with the polysulfon filter. In the ultrafiltrate, tumor necrosis factor was higher with the polysulfon filter than the polyamid filter (6.8 +/- 5 pg/mL vs 4.0 +/- 3.7 pg/mL, P <.05). The ultrafiltrate/plasma ratio of interleukin 6 was higher with conventional ultrafiltration than modified ultrafiltration (0.018 +/- 0.017 vs 0.004 +/- 0.007, P <.005).. The polysulfon filter showed a filtration profile for inflammatory mediators superior to that of the polyamid filter for interleukin 6, tumor necrosis factor, and interleukin 10. Interleukin 6 was most efficiently removed by conventional ultrafiltration with a polysulfon filter, and tumor necrosis factor was best removed by modified ultrafiltration with a polysulfon filter, whereas other inflammatory mediators were not influenced by filter type or ultrafiltration method. Therefore combined conventional and modified ultrafiltration with a polysulfon filter may currently be the most effective strategy for removing inflammatory mediators in pediatric heart surgery.

Topics: Biomarkers; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Child, Preschool; Complement C3a; Complement Membrane Attack Complex; Cytokines; Female; Heart Defects, Congenital; Hemofiltration; Humans; Inflammation Mediators; Interleukin-10; Interleukin-6; Lactoferrin; Male; Micropore Filters; Monitoring, Physiologic; Postoperative Care; Postoperative Period; Probability; Prognosis; Prospective Studies; Sensitivity and Specificity; Statistics, Nonparametric; Tumor Necrosis Factor-alpha

Several CXC-chemokines, of which interleukin (IL)-8 is the prototype, are potent neutrophil chemotactic and activating cytokines, inducing the secretion of granule proteins and the generation of reactive oxygen intermediates that may cause tissue damage and amplify inflammatory responses. Here, we investigated whether chemokines play a key role in the inflammatory process following cardiac surgery with cardiopulmonary bypass (CPB) in children. We performed an observational prospective clinical study of 40 pediatric patients before, during, and after open heart surgery with CPB. Plasma levels of chemokines, myeloperoxidase (MPO), and lactoferrin were measured by immunoassays. Cell surface receptors were detected by flow cytometry. Plasma levels of IL-8 were increased after CPB, correlating strongly with a reduction of expression of the CXC-chemokine receptors (CXCR) 1 and 2 on neutrophils indicating in vivo activation of neutrophils by IL-8. Other CXC-chemokines with Glu-Leu-Arg motif showed no correlation with CXCR1 or CXCR2 expression. Two components of neutrophilic granules, MPO and lactoferrin, were strongly elevated postoperatively, and the levels of both were correlated with IL-8. Levels of monocyte chemoattractant protein (MCP)-1 were increased postoperatively, correlating with a reduction of CCR2 expression and an increase of CD11b expression on monocytes, suggesting monocyte activation by MCP-1. The early postoperative course was complicated in patients with an increase of these inflammatory parameters. Impaired cardiovascular function correlated with increased levels of IL-8 and activation of neutrophils and was most prominent in patients with a long time on CPB and in those with cyanotic heart lesions. In conclusion, MCP-1 is involved in the regulation of chemotaxis and function of monocytes during and early after the end of CPB. Activation of neutrophils and down-regulation of CXCR1 and CXCR2 were predominantly caused by IL-8. This activation implies release of components of neutrophilic granules and correlates with the need for inotropic support.

Topics: Chemokine CCL2; Chemokines, CXC; Child; Child, Preschool; Down-Regulation; Heart Defects, Congenital; Humans; Infant; Interleukin-8; Lactic Acid; Lactoferrin; Neutrophils; Peroxidase; Postoperative Care; Receptors, Interleukin-8A; Receptors, Interleukin-8B; Thoracic Surgery; Treatment Outcome

Children are sensitive to the inflammatory side effects of cardiopulmonary bypass (CPB). Our intention was to investigate if the biocompatibility benefits of heparin-coated CPB circuits apply to children. In 20 operations, 19 children were randomized to heparin-coated (group HC, n = 10) or standard (group C, n = 10) bypass circuits. Plasma levels of acute phase reactants, interleukins, granulocytic proteins and complement factors were measured. All were significantly elevated after CPB. Levels of complement factor C3a (851 (791-959)ng/ml [median with quartiles] in group C, 497 (476-573)ng/ml in group HC, p < 0.001), Terminal Complement Complex (114 (71-130) AU/ml in group C, 35.5 (28.9-51.4) AU/ml in group HC, p < 0.001), and interleukin-6 (570 (203-743) pg/ml in group C, 168 (111-206)pg/ml in group HC, p = 0.005), were significantly reduced in group HC. Heparin-coated CPB circuits improve the biocompatibility of CPB during heart surgery in the paediatric patient population, as reflected by significantly reduced levels of circulating complement factors and interleukin-6.

Topics: Anticoagulants; Antithrombin III; Biomarkers; C-Reactive Protein; Cardiopulmonary Bypass; Coated Materials, Biocompatible; Complement C3; Complement Membrane Attack Complex; Enzyme-Linked Immunosorbent Assay; Heart Defects, Congenital; Heparin; Humans; Infant; Interleukin-10; Interleukin-6; Interleukin-8; Lactoferrin; Peptide Hydrolases; Peroxidase; Prospective Studies; Treatment Outcome

Clinical studies of deep hypothermic circulatory arrest (DHCA) have focused only on the immediate postoperative period. However, experimental findings suggest impairment of cerebral oxygenation at 2 to 8 hours after reperfusion.. In 10 children who had DHCA for heart operations, transcerebral differences of hemoglobin oxygen saturation and plasma hypoxanthine, xanthine, and lactoferrin concentrations were measured in concurrently obtained cerebral venous, arterial, and mixed venous samples up to 10 hours postoperatively.. Compared with preoperative levels (57% +/- 7%), cerebral venous oxygen saturation was not significantly reduced until 2 hours (44% +/- 6%) and 6 hours (42% +/- 5%) after DHCA (p < 0.05). A statistically significant transcerebral (ie, cerebral vein versus artery) concentration difference of hypoxanthine was observed at 30 minutes (3.6 +/- 0.9 micromol/L), 1 hour (3.4 +/- 1.1 micromol/L), and 2 hours (3.1 +/- 0.8 micromol/L) after DHCA but not preoperatively (0.4 +/- 0.2 micromol/L). A transcerebral concentration difference of lactoferrin occurred 30 minutes after DHCA (196 +/- 70 microg/mL) but not preoperatively (16 +/- 20 microg/mL).. Cerebral venous oxygen saturation of hemoglobin decreased as late as 2 to 6 hours after DHCA, in association with impaired cerebral energy status. Neutrophil activation in the cerebral circulation occurred 30 minutes after reperfusion.

Topics: Brain; Female; Heart Arrest, Induced; Heart Defects, Congenital; Hemoglobins; Humans; Hypothermia, Induced; Hypoxanthine; Infant; Infant, Newborn; Lactoferrin; Male; Neutrophil Activation; Oxygen; Postoperative Period; Time Factors; Xanthine