interleukin-8 and Heart-Defects--Congenital

Leukocyte filtration has evolved as an important technique in cardiac surgery with cardiopulmonary bypass to prevent pathogenic effector functions mediated by activated leukocytes. The underlying mechanisms that result in an improvement of laboratory variables as well as clinical outcome are not resolved yet. Moreover, the optimum strategy for the use of current filtration technology has not been systematically evaluated. This paper, therefore, reviews how activated leukocytes may lead to tissue damage, summarizes the known effects of leukocyte filtration on clinical outcome and laboratory parameters, and deals with current experimental and clinical efforts to further limit the pathogenic effects of leukocytes in cardiac surgery.

Topics: Adult; Animals; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Catheterization, Peripheral; Catheters, Indwelling; Cell Adhesion; Chemotaxis, Leukocyte; Endothelium, Vascular; Filtration; Heart Arrest, Induced; Heart Defects, Congenital; Heart-Lung Transplantation; Humans; Infant; Interleukin-8; Intraoperative Complications; Leukocytes; Lymphocyte Activation; Lymphocyte Depletion; Lymphokines; Neutrophils; Oxidative Stress; Retrospective Studies; Suction; Swine; Systemic Inflammatory Response Syndrome

Cardiopulmonary bypass is associated with ischemia-reperfusion injury to multiple organs. We aimed to evaluate whether remote ischemic preconditioning performed the day before surgery for congenital heart disease with cardiopulmonary bypass attenuates the postoperative inflammatory response and myocardial dysfunction.. This was a prospective, randomized, single-blind, controlled trial. Children allocated to remote ischemic preconditioning underwent 4 periods of 5 minutes of lower limb ischemia by a blood pressure cuff intercalated with 5 minutes of reperfusion. Blood samples were collected 4, 12, 24, and 48 hours after cardiopulmonary bypass to evaluate nuclear factor kappa B activation in leukocytes by quantification of mRNA of I kappa B alpha by real-time quantitative polymerase chain reaction and for interleukin-8 and 10 plasma concentration measurements by enzyme-linked immunosorbent assay. Myocardial dysfunction was assessed by N-terminal pro-B-type natriuretic peptide and cardiac troponin I plasma concentrations, measured by chemiluminescence, and clinical parameters of low cardiac output syndrome.. Twelve children were allocated to remote ischemic preconditioning, and 10 children were allocated to the control group. Demographic data and Risk Adjustment for Congenital Heart Surgery 1 classification were comparable in both groups. Remote ischemic preconditioning group had lower postoperative values of N-terminal pro-B-type natriuretic peptide, but cardiac troponin I levels were not significantly different between groups. Interleukin-8 and 10 concentrations and I kappa B alpha gene expression were similar in both groups. Postoperative morbidity was similar in both groups; there were no postoperative deaths in either group.. Late remote ischemic preconditioning did not provide clinically relevant cardioprotection to children undergoing cardiopulmonary bypass.

Topics: Cardiopulmonary Bypass; Female; Heart Defects, Congenital; Humans; Infant; Interleukin-10; Interleukin-8; Ischemic Preconditioning; Leg; Linear Models; Male; Natriuretic Peptide, Brain; NF-kappa B; Peptide Fragments; Prospective Studies; Single-Blind Method; Statistics, Nonparametric; Treatment Outcome; Troponin I

To investigate and compare the effects of propofol and midazolam on inflammation and oxidase stress in children with congenital heart disease undergoing cardiac surgery.. Thirty-two ASA class I-II children with congenital heart disease undergoing cardiac surgery were randomly divided into two groups: propofol combined with low dose fentanyl (PF group, n = 16) and midazolam combined with low dose fentanyl (MF group, n = 16). Tracheal extubation time and length of Intensive Care Unit (ICU) stay were recorded. Blood samples were taken before operation (T₀), at 2 h after release of the aorta cross-clamp (T₃) and at 24 h after operation (T₄) to measure interleukin 6 (IL-6), IL-8, superoxide dismutase (SOD) and malondialdehyde (MDA) levels. Myocardium samples were collected at 10-20 min after aorta cross-clamp (T₁) and at 10-20 min after the release of the aorta cross-clamp (T₂) to detect heme oxygenase-1 (HO-1) expression.. Tracheal extubation time and length of ICU stay in PF group were significantly shorter than those of the MF group (p < 0.05, respectively). After cardiopulmonary bypass, IL-6, IL-8 and MDA levels were significantly increased, and the SOD level was significantly reduced in both two groups, but PF group exhibited lower IL-6, IL-8 and MDA levels and higher SOD levels than the MF group (p < 0.05, respectively). The HO-1 expression in the PF group was significantly higher than that in MF group at the corresponding time points (p < 0.05, respectively).. Propofol is superior to midazolam in reducing inflammation and oxidase stress and in improving post-operation recovery in children with congenital heart disease undergoing cardiac surgery.

Topics: Anesthesia, Intravenous; Anesthetics, Intravenous; Cardiac Surgical Procedures; Child; Female; Heart Defects, Congenital; Heme Oxygenase-1; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Malondialdehyde; Midazolam; Oxidative Stress; Propofol; Superoxide Dismutase

Paediatric cardiac surgery is often performed under hypothermic conditions, that is, with a reduced core body temperature. Certain interventions even require the circulation to be stopped. This can only be done at a body temperature of 18 degrees C, with no risk of neurological damage and harm to the brain and other organs. Vasoconstriction is a natural reaction of the body to cold, causing the blood vessels to contract. Such a reaction would lead to a clear rise in blood pressure on cardiopulmonary bypass (CPB). Since the blood pressure is regulated in the arteriolar loop of the capillary system, there is a marked increase in blood pressure and a suppression of free water into the surrounding tissue, which, in turn, may lead to the intra-operative development of oedemas. This study aimed to investigate whether the high-flow, low-resistance (HFLR) technique offers any benefits over conventional methods.. This open, prospective, randomised study was to recruit 48 children scheduled to undergo surgery for congenital heart disease. To investigate the two different perfusion strategies, we have measured intestinal perfusion as well as skin perfusion with laser Doppler spectroscopy. To identify the effects on the immune system, selected immunologic parameters of systemic inflammation were additionally measured. Laser Doppler spectroscopy is a method that uses a glass fibre probe to determine the parameters of oxygen saturation of haemoglobin and relative haemoglobin quantity in an illuminated tissue volume, as well as the perfusion parameters of relative blood flow and blood flow velocity in the sample volume of the probe.. During the study period, the change in oxygen saturation over time was comparable in both groups. At the end of surgery, the patients of the high-flow group had significantly higher saturation levels in the intestinal mucosa (p<0.05). Over the course of intensive care, the groups did not differ in terms of fluid supply, administration of packed red blood cells, platelet concentrates or fresh frozen plasma. Analysis of urinary output revealed significant group differences. It was higher in the patients of the high-flow group than the normal-flow group (p<0.03), without differences in diuretic administration.. Laser Doppler spectroscopy is highly suited to the detection even of the slightest changes in flow characteristics and oxygenation of the skin, musculature and intestinal mucosa during surgery with extracorporeal circulation using CPB. At the same time, the technique of HFLR perfusion was found to have benefits over conventional bypass methods.

Topics: Calcitonin; Cardiopulmonary Bypass; Heart Defects, Congenital; Hemoglobins; Humans; Infant; Infant, Newborn; Interleukin-6; Interleukin-8; Intestinal Mucosa; Laser-Doppler Flowmetry; Oxygen; Oxygen Consumption; Protein Precursors; Regional Blood Flow; Skin; Tumor Necrosis Factor-alpha

Pulmonary artery perfusion during cardiopulmonary bypass (CPB) is a novel adjunctive method, which can minimize the lung ischemic-reperfusion injury and inflammatory response. This study evaluated the protective effect of pulmonary perfusion with hypothermic HTK solution in corrections of congenital heart defects with pulmonary hypertension.. Between June 2009 and December 2009, 24 consecutive infants with congenital heart defects and pulmonary hypertension were randomly divided into perfused group (n = 12) and control group (n = 12). Oxygen index, alveolar-arterial O2 gradient, serum levels of malondialchehyche (MDA), interleukin (IL)-6, -8, -10, soluble intercellular adhesion molecule-1 (sICAM-1), and P-selectin were measured before commencement and serially for 48 hours after termination of bypass.. Oxygenation values were better preserved in the perfused group than in the control group. The serum levels of IL-6 increased immediately after CPB in both groups and returned to baseline at 48 hours after CPB,but it was restored faster and earlier in the perfused group. The serum levels of IL-8, sICAM-1, and MDA remained at baseline at each point after CPB in the perfused group and elevated significantly immediately after CPB in the control group, except for sICAM-1. The serum level of IL-10 increased immediately after CPB and decreased to baseline at 48 hours after CPB in both groups, but the IL-10 level in the perfused group was significantly higher than in the control group at 12 hours after CPB. The serum P-selectin levels in the control group immediately after CPB were significantly higher than prebypass levels. Moreover, there were no significant differences in postoperative clinical characters, except for the intubated time.. In infants with congenital heart defects, pulmonary perfusion with hypothermic HTK solution during cardiopulmonary bypass could ameliorate lung function and reduce the inflammatory response.

Topics: Cardiopulmonary Bypass; Child; Child, Preschool; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Intercellular Adhesion Molecule-1; Interleukin-10; Interleukin-6; Interleukin-8; Lung Injury; Male; Organ Preservation Solutions; P-Selectin; Perfusion; Pulmonary Artery

To determine whether inhaled steroid administration after cardiopulmonary bypass will attenuate pulmonary inflammation and improve lung compliance and oxygenation.. Randomized, prospective, double-blind, placebo-controlled clinical trial.. Children's Hospital of Michigan, intensive care unit.. Thirty-two children <2 yrs of age with congenital heart disease requiring cardiopulmonary bypass.. Participants were randomly assigned to one of two groups. Group 1 (n = 16) received an inhaled steroid, Budesonide (0.25 mg/2 mL), and group 2 (n = 16) received an inhaled placebo (2 mL of inhaled 0.9% saline). The nebulizations were given at the end of cardiopulmonary bypass, 6 hrs after cardiopulmonary bypass, and 12 hrs after cardiopulmonary bypass. Two hours after each nebulization, bronchoalveolar lavage for interleukin-6 and interleukin-8 was collected.. The concentrations of interleukin-6 and interleukin-8 in the bronchoalveolar lavage increased in both groups after cardiopulmonary bypass. Interleukin-6 peaked 2 hrs after cardiopulmonary bypass and was decreasing by 14 hrs after cardiopulmonary bypass. However, administration of corticosteroid did not affect the production of interleukin-6 when compared with the placebo group (378 +/- 728 vs. 287 +/- 583 pg/mL pre-cardiopulmonary bypass, 1662 +/- 1410 vs. 1584 +/- 1645 pg/mL at the end of cardiopulmonary bypass, 2601 +/- 3132 vs. 3677 +/- 4935 pg/mL 2 hrs after cardiopulmonary bypass, and 1792 +/- 3100 vs. 1283 +/- 1344 pg/mL 14 hrs after cardiopulmonary bypass; p > .05). Likewise, interleukin-8 in the lavage fluid was similar in both the placebo and steroid groups at all time points (570 +/- 764 vs. 990 +/- 1147 pg/mL pre-cardiopulmonary bypass, 1647 +/- 1232 vs. 1394 +/- 1079 pg/mL at the end of cardiopulmonary bypass, 1581 +/- 802 vs. 1523 +/- 852 pg/mL 2 hrs after cardiopulmonary bypass, and 1652 +/- 1069 pg/mL vs. 1808 +/- 281 pg/mL 14 hrs after cardiopulmonary bypass; p > .05). Lung compliance and oxygenation were similar in both groups.. Cardiopulmonary bypass is associated with a pulmonary inflammatory response. Inhaled corticosteroid did not affect the pulmonary inflammatory response as measured by interleukin-6 and interleukin-8 concentrations in the lung lavage after cardiopulmonary bypass. Pulmonary mechanics and oxygenation were not improved by the use of inhaled corticosteroid.

Topics: Administration, Inhalation; Bronchoalveolar Lavage Fluid; Budesonide; Cardiopulmonary Bypass; Child; Double-Blind Method; Female; Glucocorticoids; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Inflammation; Inflammation Mediators; Interleukin-6; Interleukin-8; Lung; Lung Compliance; Male; Prospective Studies; Respiratory Distress Syndrome

Systemic inflammatory response and capillary leak syndrome, caused by extracorporeal circulation, have negative effects on the function of vital organs during the postoperative period. Modified ultrafiltration (MUF) has been developed as an alternative method to reduce the detrimental effects of cardiopulmonary bypass. The aim of this prospective, randomized study is to analyze the effects of MUF in a pediatric population undergoing congenital cardiac surgery.. Twenty-seven patients who underwent open-heart surgery at our institution were included in this prospective study. They were randomized into two groups as follows: Group I (n=14) of conventional ultrafiltration during bypass and Group II (n=13) receiving both conventional and modified ultrafiltration during and after the cessation of the bypass, respectively. The amount of prime volume, postoperative chest drain loss, transfusion requirements, hemodynamical parameters, duration of mechanical ventilatory support, and length of intensive care unit stay were compared between the two groups. During the postoperative period, the concentrations of hematological, biochemical and inflammatory parameters were also compared by analyzing the blood samples obtained at various time points.. MUF resulted in a significant increase in hemoglobin, hematocrit and platelet levels, and significantly reduced the amount of chest tube output and transfused blood and blood products. MUF also shortened the duration of postoperative mechanical ventilatory support, length of the intensive care unit stay and improved postoperative hemodynamical parameters. During the early postoperative hours, IL-8 is significantly reduced in patients undergoing MUF, however, the concentrations of IL-8 were similar in both groups at the end of 24 h.. MUF decreases the duration of mechanical ventilatory support, the length of intensive care unit stay, the need for blood transfusion and improves postoperative hemodynamics. It is associated with increased levels of hemoglobin, hematocrit and platelets. We can conclude that MUF attenuates the inflammatory response by decreasing the levels of inflammatory mediators.

Topics: Blood Pressure; Cardiopulmonary Bypass; Female; Heart Defects, Congenital; Hemofiltration; Humans; Infant; Interleukin-8; Male; Postoperative Period; Prospective Studies; Treatment Outcome

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

This study tests the hypothesis that a cardiopulmonary bypass system that combines complete heparin-coating, a centrifugal pump, and a closed circuit in comparison with a conventional system (uncoated system, roller pump, and hard shell venous reservoir) attenuates the inflammatory response in pediatric heart surgery.. In a prospective randomized controlled clinical study 40 consecutive children weighing 10 kg or less were included and divided into two groups. Concentrations of complement proteins (C3a, sC5b-9, C4d, and Bb), granulocyte degranulation products (polymorphonuclear [PMN] elastase), and proinflammatory cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6, and IL-8) were measured.. C3a and sC5b-9 concentrations were lower (C3a, p < 0.001; sC5b-9, p = 0.01) in the combined (heparin-coated/centrifugal pump/closed reservoir) group, the peak values being 58% and 37% of conventional group values. The Bb- and C4d-fragment values indicated activation of the complement system through the alternative pathway in both groups. PMN elastase concentrations were lower (p = 0.02) in the combined group, the peak values being 43% of conventional group values. There were no significant intergroup differences regarding TNF-alpha, IL-6, or IL-8 concentrations.. The use of a fully heparin-coated system, a centrifugal pump, and a closed circuit during CPB in children (10 kg or less) leads to a lower degree of complement activation and PMN elastase release compared with a conventional system.

Topics: Adolescent; Cardiopulmonary Bypass; Child; Child, Preschool; Coated Materials, Biocompatible; Complement Activation; Equipment Design; Female; Heart Defects, Congenital; Heparin; Humans; Infant; Inflammation Mediators; Interleukin-6; Interleukin-8; Leukocyte Elastase; Male; Postoperative Complications; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha

We performed this prospective randomized study to determine the effect of a human urinary protease inhibitor (Ulinastatin) on respiratory function in pediatric patients undergoing cardiopulmonary bypass.. Twenty-two children were included in this study. They were randomly allocated to 1 of the following groups; a control group (n=11) or a Ulinastatin group (n=11) in which patients received 5000 U/kg of Ulinastatin. Arterial blood samples were obtained before cardiopulmonary bypass (CPB), immediately after CPB, and 30 min after protamine administration, as well as 3 hours after and 18 hours after CPB, and Interleukin-8 and neutrophil elastase concentration were evaluated.. CPB time and aortic clamp time did not differ between the groups. Interleukin 8 and neutrophil elastase concentrations before CPB increased significantly immediately after CPB, these concentrations did not differ between the groups. However, neutrophil elastase concentrations of a Ulinastatin group were significantly lower than that of a control group at 30 min after protamine administration (a Ulinastatin group: 1011.3+/-539.1 mg/ml, a control group: 1619.7+/-595.7 mg/ml, p<0.05) and A-aDO2 of a Ulinastatin group was significantly lower than that of a control group at 2 hours after CPB (a Ulinastatin group: 67.1+/-70.6 mmHg, a control group: 169.2+/-116.3 g, p<0.05).. These results suggest that Ulinastatin suppresses the increase in neutrophil elastase and protects the respiratory function in pediatric patients undergoing cardiopulmonary bypass.

Topics: Cardiopulmonary Bypass; Child, Preschool; Female; Glycoproteins; Heart Defects, Congenital; Humans; Interleukin-8; Leukocyte Elastase; Male; Prospective Studies; Respiration; Trypsin Inhibitors

We sought to compare low-flow cardiopulmonary bypass with deep hypothermic circulatory arrest in respect to the influence on the systemic inflammatory response.. Twenty-three infants weighing less than 10 kg and scheduled for repair of congenital malformations were enrolled in a randomized, controlled study. Eleven patients underwent cardiac surgery with deep hypothermic circulatory arrest (the DHCA group). Low-flow cardiopulmonary bypass was used in another 12 patients (the LF group). Interleukin 6 and 8 and anaphylatoxin C3a levels were measured 6 times perioperatively. Also, perioperative weight gain and a radiologic soft-tissue index were compared.. All patients had an uneventful clinical course. Duration of deep hypothermic circulatory arrest was 40 +/- 4 minutes; the bypass time was significantly shorter in the DHCA group (85 +/- 8 vs 130 +/- 19 minutes). However, the duration of the operation was similar in both groups (245 +/- 30 vs 246 +/- 30 minutes). During cardiopulmonary bypass (rewarming), the concentration of C3a (3751 +/- 388 vs 5761 +/- 1688 ng/mL, mean +/- SEM) was significantly lower in the DHCA group than in the LF group. The interleukin 8 level was significantly lower, and the interleukin 6 level had a tendency to be lower in the DHCA group compared with levels in the LF group. There was less weight gain on the first postoperative day in the DHCA group (65 +/- 61 vs 408 +/- 118 g). The soft-tissue index suggested reduced edema formation in the DHCA group.. Deep hypothermic circulatory arrest produces less systemic inflammatory response than low-flow cardiopulmonary bypass. In addition, there is an indication of less fluid accumulation postoperatively.

Topics: Blood Pressure; Body Weight; Cardiopulmonary Bypass; Cardiotonic Agents; Complement Activation; Complement C3a; Dobutamine; Dopamine; Heart Arrest, Induced; Heart Defects, Congenital; Heart Rate; Humans; Hypothermia, Induced; Infant; Infant Welfare; Inflammation Mediators; Interleukin-6; Interleukin-8; Postoperative Complications; Systemic Inflammatory Response Syndrome; Time Factors; Treatment Outcome

The priming solution using in cardiopulmonary bypass (CPB) for infants undergoing cardiac surgery includes considerable amounts of stored blood. Our objective was to test the hypothesis that ultrafiltration (UF) of the stored blood before CPB reduces the unfavorable effects of stored blood and the production of inflammatory cytokines. Fifty pediatric patients with congenital heart defects took part in this study. The patients were randomly divided into two groups: the UF (27 pediatric patients who received UF) and control (23 pediatric patients who did not receive UF) groups. UF was performed with a polysulphone ultrafiltrator before CPB. Blood samples were collected immediately before, during, and 1 h after CPB. The levels of cytokines (TNF-alpha, IL-1beta, IL-8), NH3, and bradykinin were determined. The serum concentrations of NH3 and bradykinin decreased significantly after UF. Compared with the control group, the UF group had significantly lower cytokine production. Water balance in UF group was better than that of control group. The UF group received significantly less inotropic support and shorter duration of ventilator support and ICU stay. We conclude that removal of bradykinin and a decrease in the levels of NH3, potassium, and pH play a significant role in reducing water retention and postoperative lung injury. UF of the blood used to prime the circuit for CPB is a safe and efficient method for use in open heart surgery in small pediatric patients.

Topics: Ammonia; Bradykinin; Cardiopulmonary Bypass; Cytokines; Female; Heart Defects, Congenital; Humans; Hydrogen-Ion Concentration; Infant; Inflammation; Inflammation Mediators; Interleukin-1; Interleukin-6; Interleukin-8; Male; Postoperative Complications; Potassium; Tumor Necrosis Factor-alpha; Ultrafiltration; Water-Electrolyte Balance

This study evaluates the effect of balanced ultrafiltration, modified ultrafiltration, and balanced ultrafiltration with modified ultrafiltration on inflammatory mediators in children's open-heart surgery. Eighty children with congenital heart disease were randomly divided into four groups: control group (C group); balanced ultrafiltration group (BUF group); modified ultrafiltration group (MUF group); and balanced ultrafiltration with modified ultrafiltration group (B+M group). Clinical data of these groups were similar. Tumor necrosis factor (TNF), interleukin-8(IL-8), and E-selectin were measured at the beginning of cardiopulmonary bypass (CPB), 30 min later, at the cessation of CPB, at the cessation of MUF (MUF group and B+M group), and 2 hours postoperatively. During CPB, the concentrations of TNF, IL-8, and E-selectin increased significantly in C and MUF groups and did not change significantly in BUF and B+M groups. In the period of MUF, TNF and IL-8 increased; whereas, E-selectin did not change. The study shows that ultrafiltration can filter out the inflammatory mediators, but only BUF can decrease the concentrations of them. Moreover, MUF only can concentrate blood. Combining both techniques has both effects, but the effect of BUF was offset by MUF.

Topics: Cardiopulmonary Bypass; Child, Preschool; E-Selectin; Heart Defects, Congenital; Hemofiltration; Humans; Interleukin-8; Tumor Necrosis Factor-alpha

Cardiopulmonary bypass (CPB) induces numerous systemic reactions. This study examined the efficacy of heparin-bonded CPB circuits on inflammatory responses and postoperative status in children.. Thirty-four infants undergoing elective cardiac surgery were randomly divided into two groups: a heparin-bonded CPB group (n = 17) and a non-heparin-bonded group (n = 17). Plasma levels of the inflammatory cytokines were measured before, during, and after CPB, and postoperative status was determined by examining the respiratory index, blood loss, and the post- and preoperative body weight percent ratio.. Significant differences in tumor necrosis factor-alpha, interleukin-6, and interleukin-8 patterns were observed during and after CPB between the two groups (p < 0.01, p < 0.01, p < 0.05, respectively). All cytokines measured were significantly lower in the heparin-bonded group just after CPB (p < 0.05). There were no differences in duration of intubation, intensive care unit or hospital stay, or postoperative blood loss, but the respiratory index 3 hours after CPB and body weight percent ratio 24 and 48 hours after CPB were significantly reduced in the bonded group (p < 0.05, p < 0.01, p < 0.05, respectively).. Our findings suggest that heparin bonding of the bypass circuits affects early postoperative status and reduces cytokine responses in pediatric cardiac surgery.

Topics: Anticoagulants; Cardiopulmonary Bypass; Coated Materials, Biocompatible; Cytokines; Heart Defects, Congenital; Heparin; Humans; Infant; Interleukin-8; Oxygenators; Tumor Necrosis Factor-alpha

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

Cardiopulmonary bypass is associated with the production of both proinflammatory and anti-inflammatory cytokines, the balance of which leads to varying degrees of postoperative systemic inflammation. Arteriovenous modified ultrafiltration effectively reduces total body water and improves postoperative hemodynamic and homeostatic functions. Venovenous modified ultrafiltration is a modification of this technique, which has the potentially added advantage of eliminating the obligatory left-to-right shunt associated with arteriovenous modified ultrafiltration. We tested the hypothesis that venovenous modified ultrafiltration is a safe and effective method of achieving ultrafiltration in children after cardiopulmonary bypass.. Thirty-eight pediatric patients were randomly assigned to undergo conventional, venovenous (n = 13), or no ultrafiltration venovenous (n = 13), and controls (n = 12). Perioperative, cardiopulmonary, and cytokine (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interleukin-8, and interleukin-10) data were collected for statistical analysis.. Compared with patients in the conventional ultrafiltration and control groups, patients undergoing venovenous modified ultrafiltration had the greatest volume of ultrafiltrate removed (46. 9 +/- 8.4 mL/kg vs 20.1 +/- 5.0 mL/kg and 0 mL/kg for conventional ultrafiltration and control groups, respectively; P =.0001), least increase in total body water (1.91% +/- 1.49% vs 3.90% +/- 1.86% and 8.24% +/- 3.41%; P =.05), greatest rise in hematocrit (39.7% +/- 1. 7% vs 33.8% +/- 2.1% and 29.6% +/- 2.3%; P =.006), and shortest length of hospital stay (4.41 +/- 0.28 days vs 6.69 +/- 1.47 days and 8.38 +/- 1.11 days; P =.03, P =.03).. Venovenous modified ultrafiltration is a safe and effective method of reducing the increase in total body water and duration of postoperative convalescence after cardiopulmonary bypass.

Topics: Cardiopulmonary Bypass; Child; Child, Preschool; Female; Heart Defects, Congenital; Hemofiltration; Humans; Infant; Interleukin-1; Interleukin-10; Interleukin-6; Interleukin-8; Male; Postoperative Care; Prospective Studies; Tumor Necrosis Factor-alpha

BACKGROUND.:Contact of blood with the surfaces of the cardiopulmonary bypass (CPB) circuit has been implicated as a cause of the inflammatory response. We undertook a prospective randomized trial of 200 pediatric patients, all with a calculated total bypass flow of less than 2.3 L/min (< 0.96 L/m2/min).. Patients were randomly assigned to 1 of 4 CPB groups: (1) Nonheparin-bonded circuit with no albumin preprime; (2) Nonheparin-bonded circuit with albumin preprime; (3) Heparin-bonded circuit with no albumin preprime; (4) Heparin-bonded circuit with albumin preprime. Measurements of cytokines, (interleukin [IL]-6, IL-8) and blood cell counts were made prebypass and 6 and 24 hours after institution of cardiopulmonary bypass.. Analysis of variance showed no significant difference in any of the clinical or biochemical characteristics of the 4 groups. The interaction between heparin-bonded oxygenators and albumin preprime was not significant. No important differences in IL-6 or IL-8 concentrations were noted after CPB using either heparin or nonheparin-bonded oxygenators with albumin or albumin free preprime using two-way analysis of variance.. Albumin preprime and heparin-bonding do not attenuate the inflammatory response component attributable to the concentration of these markers.

Topics: Albumins; Cardiopulmonary Bypass; Child; Coated Materials, Biocompatible; Heart Defects, Congenital; Heparin; Humans; Interleukin-6; Interleukin-8; Oxygenators, Membrane; Postoperative Complications; Prospective Studies; Systemic Inflammatory Response Syndrome

Release of calprotectin and interleukin-8 (IL-8), changes in leukocyte counts and subsets and influence of extracorporeal ultrafiltration were evaluated during and after cardiopulmonary bypass (CPB) in 18 children undergoing open-heart surgery for congenital heart anomalies. Ultrafiltration was used in nine cases and nine were controls. Calprotectin concentration rose after start of CPB, peaking 48 hours postoperatively, with no significant intergroup difference. Positive correlation was found between duration of CPB and calprotectin (peak level and accumulated total). Circulating IL-8 was detected in all patients perioperatively, peaking at wound closure in the ultrafiltration group and at termination of bypass in the controls. CPB duration correlated significantly to peak level and accumulated total of IL-8. Seven of nine ultrafiltrate samples contained IL-8 at levels similar to the plasma concentration. Changes in white cell counts were mainly attributable to neutrophils. The two subgroups did not differ significantly in neutrophil counts. Neutropenia found after 10 minutes of CPB was replaced by neutrophilia, with maximal values postoperatively. Calprotectin and IL-8 thus were released into the circulation during CPB in children. Ultrafiltration did not affect the plasma concentrations of these substances, and only IL-8 was detected in the ultrafiltrate.

Topics: Calcium-Binding Proteins; Cardiopulmonary Bypass; Child; Heart Defects, Congenital; Hemofiltration; Humans; Interleukin-8; Intraoperative Care; Leukocyte Count; Leukocyte L1 Antigen Complex; Leukocytosis; Lymphocyte Count; Neural Cell Adhesion Molecules; Neutropenia; Neutrophils; Prospective Studies; Time Factors

Infants with Down syndrome (DS) have an altered immune response. We aimed to characterise the inflammatory response in infants with DS and congenital heart disease (CHD) peri-operatively in comparison to infants with CHD and a normal chromosomal complement, and to healthy infants pre-operatively.. Infants with DS/CHD, infants without DS but with CHD (CHD only) and healthy infants were prospectively recruited and serial serum cytokines evaluated peri-operatively using multiplex ELISA: tumour necrosis factor (TNF)-α and TNF-β; interferon (IFN)-γ, interleukin (IL)-1α, IL-2, IL-6, IL-8, IL-18, IL-1β, IL-10, and IL-1ra; vascular endothelial growth factor (VEGF); granulocyte macrophage colony-stimulating factor (GM-CSF); and erythropoietin (EPO).. Ninety-four infants were recruited including age-matched controls (n = 10), DS/CHD (n = 55), and CHD only (n = 29). Children with DS/CHD had significantly lower concentrations of several cytokines (IL-10, IL-6, IL-8, IL-1β, VEGF) in the pre- and post-operatively vs CHD only and controls. EPO and GM-CSF were significantly higher in DS/CHD (p value <0.05).. Children with DS/CHD had significantly lower concentrations of several cytokines compared to controls or children with CHD only. EPO and GM-CSF were significantly higher in children with DS/CHD. The assessment of the immune response may be suitable for the predictable clinical outcomes in these children.. This study demonstrated that children with Down syndrome (DS) and congenital heart disease (CHD) have significant alterations in pro-inflammatory and anti-inflammatory immune responses peri-operatively. These changes may contribute to adverse clinical outcomes, including sepsis, chylothorax, and autoimmunity. They may impact the pathogenesis and outcome post-operatively and long term in this population. Children with DS and CHD have significantly lower cytokine concentrations, increased EPO and GM-CSF, and decreased VEGF pre- and post-operatively. Assessing their inflammatory state peri-operatively may facilitate the development of a predictive model that can inform tailored management of these infants using novel therapies including immunomodulation.

Topics: Child; Cytokines; Down Syndrome; Granulocyte-Macrophage Colony-Stimulating Factor; Heart Defects, Congenital; Humans; Immunity; Infant; Interleukin-10; Interleukin-6; Interleukin-8; Vascular Endothelial Growth Factor A

Cardiopulmonary bypass (CPB) is required during most cardiac surgeries. CBP drives systemic inflammation and multiorgan dysfunction that is especially severe in neonatal patients. Limited understanding of molecular mechanisms underlying CPB-associated inflammation presents a significant barrier to improve clinical outcomes. To better understand these clinical issues, we performed mRNA sequencing on total circulating leukocytes from neonatal patients undergoing CPB. Our data identify myeloid cells, particularly monocytes, as the major cell type driving transcriptional responses to CPB. Furthermore, IL-8 and TNF-α were inflammatory cytokines robustly upregulated in leukocytes from both patients and piglets exposed to CPB. To delineate the molecular mechanism, we exposed THP-1 human monocytic cells to CPB-like conditions, including artificial surfaces, high shear stress, and cooling/rewarming. Shear stress was found to drive cytokine upregulation via calcium-dependent signaling pathways. We also observed that a subpopulation of THP-1 cells died via TNF-α-mediated necroptosis, which we hypothesize contributes to post-CPB inflammation. Our study identifies a shear stress-modulated molecular mechanism that drives systemic inflammation in pediatric CPB patients. These are also the first data to our knowledge to demonstrate that shear stress causes necroptosis. Finally, we observe that calcium and TNF-α signaling are potentially novel targets to ameliorate post-CPB inflammation.

Topics: Animals; Animals, Newborn; Calcium Signaling; Cardiopulmonary Bypass; Cytokines; Female; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Inflammation Mediators; Interleukin-8; Male; Models, Animal; Monocytes; Necroptosis; RNA-Seq; Stress, Mechanical; Sus scrofa; Systemic Inflammatory Response Syndrome; THP-1 Cells; Tumor Necrosis Factor-alpha; Up-Regulation

In the member countries of the Organization for Economic Co-operation and Development (OECD), overweight and obesity affect the majority of the population. The use of environmental chemicals, such as the plasticizer DEHP, has largely increased simultaneously with this development. DEHP is an "obesogen" that interferes with normal adipocyte differentiation and energy homeostasis. Obesity in turn is accompanied by chronic low-grade adipose tissue inflammation, leading to metabolic disorders such as type II diabetes. The main actors in adipose tissue inflammation are adipocytes and macrophages. However, the impact of DEHP on adipose tissue inflammation and the crosstalk between adipocytes and macrophages are unknown and the subjects of the current study. The influence of DEHP on inflammation was investigated in human Simpson-Golabi-Behmel syndrome (SGBS)-derived adipocytes and human THP-1 macrophages. The proinflammatory markers IL8, MCP1, IL1β, TNFα and others were measured (qRT-PCR, ELISA) in SGBS-derived adipocytes treated with DEHP [day 0 (d0)-d4; 50 µg/ml] and THP-1 macrophages cultured with conditioned medium (CM) from DEHP-treated adipocytes (SGBS-CM) (from d4 and d8). DEHP exposure led to a proinflammatory state in SGBS-derived adipocytes (e.g., increased secretion of IL8 and MCP1). Surprisingly, exposure of THP-1 macrophages to SGBS-CM did not show DEHP-induced effects. However, we demonstrated that medium containing (pre)adipocyte-secreted factors had a significant impact on the expression and secretion of macrophage and inflammatory markers in THP-1 macrophages in general and led to the significantly increased accumulation of intracellular lipid droplets.

Topics: Adipocytes; Arrhythmias, Cardiac; Chemokine CCL2; Culture Media, Conditioned; Cytokines; Diethylhexyl Phthalate; Fluorescence; Gene Expression Regulation; Genetic Diseases, X-Linked; Gigantism; Heart Defects, Congenital; Humans; Inflammation; Intellectual Disability; Interleukin-8; Lipid Droplets; Macrophages; RNA, Messenger; THP-1 Cells

Adipocyte-macrophage crosstalk plays a critical role to regulate adipose tissue microenvironment and cause chronic inflammation in the pathogenesis of obesity. Interleukin-29 (IL-29), a member of type 3 interferon family, plays a role in host defenses against microbes, however, little is known about its role in metabolic disorders. We explored the function of IL-29 in the pathogenesis of obesity-induced inflammation and insulin resistance. We found that serum IL-29 level was significantly higher in obese patients. IL-29 upregulated IL-1β, IL-8, and monocyte chemoattractant protein-1 (MCP-1) expression and decreased glucose uptake and insulin sensitivity in human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes through reducing glucose transporter 4 (GLUT4) and AKT signals. In addition, IL-29 promoted monocyte/macrophage migration. Inhibition of IL-29 could reduce inflammatory cytokine production in macrophage-adipocyte coculture system, which mimic an obese microenvironment. In vivo, IL-29 reduced insulin sensitivity and increased the number of peritoneal macrophages in high-fat diet (HFD)-induced obese mice. IL-29 increased M1/M2 macrophage ratio and enhanced MCP-1 expression in adipose tissues of HFD mice. Therefore, we have identified a critical role of IL-29 in obesity-induced inflammation and insulin resistance, and we conclude that IL-29 may be a novel candidate target for treating obesity and insulin resistance in patients with metabolic disorders.

Topics: Adipocytes; Adipose Tissue; Animals; Arrhythmias, Cardiac; Cell Differentiation; Cell Movement; Chemokine CCL2; Diet, High-Fat; Genetic Diseases, X-Linked; Gigantism; Glucose Transporter Type 4; Heart Defects, Congenital; Inflammation; Insulin Resistance; Intellectual Disability; Interferons; Interleukin-1beta; Interleukin-6; Interleukin-8; Interleukins; Lipopolysaccharides; Macrophages; Mice, Inbred C57BL; Mice, Obese; Obesity; Phosphorylation; Proto-Oncogene Proteins c-akt; Receptors, Interleukin; Up-Regulation

Cardiopulmonary bypass causes detrimental effects on remote organs due to inflammatory response. One of these organs is kidney that is frequently affected by cardiac surgery. Acute kidney injury is a post-cardiopulmonary bypass complication, which may result in increased post-operative morbidity and mortality. Post-cardiopulmonary bypass inflammatory response may contribute to remote organ dysfunction. In the present study, we investigated the relation between cytokines including interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α, and renal function tests such as creatinine and blood urea nitrogen (BUN).. In total, 91 patients between the ages of 4 and 60 months were enrolled for elective cardiac surgery with cardiopulmonary bypass after informed consent. Data regarding renal function tests and clinical outcomes were carefully recorded until 24 hours after admission to intensive care unit and analyzed.. Our findings support that there is a direct correlation between cytokines including interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α and cardiopulmonary bypass time, duration of operation, and intensive care unit stay. Longer cardiopulmonary bypass time was associated with higher interleukin-8 at cross-clamp removal and 24 hours post- intensive care unit as well as higher interleukin-10 at declamp time. Higher interleukin-6 at declamp time was directly correlated with higher post-operative BUN. Interleukin-8 level after anesthesia induction was directly correlated with intensive care unit stay duration. Higher blood interleukin-6 and tumor necrosis factor-α levels following 24 hours of admission to intensive care unit were associated with longer mechanical ventilation time.. Higher circulatory pro-inflammatory cytokine level is associated with adverse outcomes such as increased intensive care unit stay and longer mechanical ventilation time in pediatric patients. It is also correlated with unfavorable biochemical parameter of renal function, BUN. Findings hint that proper control of the inflammatory response is vital for the control of unfavorable clinical and pathological outcomes.

Topics: Acute Kidney Injury; Cardiopulmonary Bypass; Child, Preschool; Cross-Sectional Studies; Female; Heart Defects, Congenital; Humans; Infant; Interleukin-10; Interleukin-6; Interleukin-8; Kidney; Male; Treatment Outcome; Tumor Necrosis Factor-alpha

High serum concentrations of TNF-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor protein family, are found in patients with increased BMI and serum lipid levels. In a model of murine obesity, both the expression of TRAIL and its receptor (TRAIL-R) is elevated in adipose tissue. Accordingly, TRAIL has been proposed as an important mediator of adipose tissue inflammation and obesity-associated diseases. The aim of this study was to investigate if TRAIL regulates inflammatory processes at the level of the adipocyte. Using human Simpson-Golabi-Behmel syndrome (SGBS) cells as a model system, we found that TRAIL induces an inflammatory response in both preadipocytes and adipocytes. It stimulates the expression of interleukin 6 (IL-6), interleukin 8 (IL-8) as well as the chemokines monocyte chemoattractant protein-1 (MCP-1) and chemokine C-C motif ligand 20 (CCL-20) in a time- and dose-dependent manner. By using small molecule inhibitors, we found that both the NFκB and the ERK1/2 pathway are crucial for mediating the effect of TRAIL. Taken together, we identified a novel pro-inflammatory function of TRAIL in human adipocytes. Our findings suggest that targeting the TRAIL/TRAIL-R system might be a useful strategy to tackle obesity-associated adipose tissue inflammation.

Topics: Adipocytes; Adult; Arrhythmias, Cardiac; Cells, Cultured; Chemokine CCL2; Chemokine CCL20; Genetic Diseases, X-Linked; Gigantism; Heart Defects, Congenital; Humans; Inflammation; Intellectual Disability; Interleukin-6; Interleukin-8; Mitogen-Activated Protein Kinases; NF-kappa B; Signal Transduction; TNF-Related Apoptosis-Inducing Ligand

Inflammation is a key component of both acute kidney injury (AKI) and response to cardiopulmonary bypass. Because AKI poses risks to children after cardiac surgery, we investigated the value of inflammatory biomarkers interleukin-8 (IL-8) and tumor necrosis factor alpha (TNFα) for predicting AKI and other complications.. We enrolled 412 children between the ages of 1 month and 18 years undergoing cardiopulmonary bypass for cardiac surgery. We collected blood both preoperatively and postoperatively (within 6 hours post-surgery) and measured plasma IL-8 and TNFα.. IL-8 and TNFα did not predict AKI in children <2 years, but were strongly associated with AKI in children ≥2 years. There were significant associations between biomarker levels and age (<2 or ≥2 years). In children ≥2 years, patients in the highest tertile of preoperative IL-8 and postoperative TNFα had 4.9-fold (95% CI: 1.8-13.2) and 3.3-fold (95% CI: 1.2-9.0) higher odds of AKI compared with those in the lowest tertile. Children <2 years with higher biomarker levels also had higher odds of AKI, but the difference was not significant. We also found that postoperative TNFα levels were significantly higher in patients with longer hospital stays, and that both postoperative IL-8 and TNFα levels were significantly higher in patients with longer ventilation lengths. There was no evidence that biomarker levels mediated the association between AKI and length of ventilation; they appear to be independent predictors.. Preoperative IL-8 and postoperative TNFα are significantly associated with higher odds of AKI and greater lengths of hospital stays and ventilator use in children 2 years and older.

Topics: Acute Kidney Injury; Adolescent; Biomarkers; Cardiac Surgical Procedures; Child; Child, Preschool; Female; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Interleukin-8; Male; Postoperative Complications; Prognosis; Prospective Studies

The generation of naive T cells is dependent on thymic output, but in adults, the naive T cell pool is primarily maintained by peripheral proliferation. Naive T cells have long been regarded as relatively quiescent cells; however, it was recently shown that IL-8 production is a signatory effector function of naive T cells, at least in newborns. How this functional signature relates to naive T cell dynamics and aging is unknown. Using a cohort of children and adolescents who underwent neonatal thymectomy, we demonstrate that the naive CD4+ T cell compartment in healthy humans is functionally heterogeneous and that this functional diversity is lost after neonatal thymectomy. Thymic tissue regeneration later in life resulted in functional restoration of the naive T cell compartment, implicating the thymus as having functional regenerative capacity. Together, these data shed further light on functional differentiation within the naive T cell compartment and the importance of the thymus in human naive T cell homeostasis and premature aging. In addition, these results affect and alter our current understanding on the identification of truly naive T cells and recent thymic emigrants.

Topics: Case-Control Studies; Cell Differentiation; Cells, Cultured; Child; Child, Preschool; Female; Follow-Up Studies; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Interleukin-8; Male; Platelet Endothelial Cell Adhesion Molecule-1; T-Lymphocytes; Thymectomy; Thymus Gland

The obesity-associated inflammation of white adipose tissue (WAT) is one of the factors leading to the development of related diseases such as insulin resistance and liver steatosis. Recently, microRNAs (miRNAs) were identified as important regulators of WAT functions. Herein, we cultured human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes with macrophage-conditioned medium (MacCM) and performed an Affimetrix miRNA array to identify miRNAs differentially expressed under inflammatory conditions. We identified 24 miRNAs differentially expressed upon inflammation in human adipocytes and miR-146a was the most up-regulated miRNA species. In subcutaneous WAT, miR-146a was elevated in both human and murine obesity. Transfection of miR-146a mimics prevented the MacCM-induced inflammatory response in SGBS adipocytes as seen by reduced levels of IL-8 and MCP-1 mRNA and protein. We identified IRAK1 and TRAF6 as targets of miR-146a in human adipocytes and detected a reduced inflammation-induced activation of JNK and p38 upon miR-146a transfection. Taken together, we could show that miR-146a reduces the inflammatory response in human adipocytes. In a negative feedback loop miR-146a might contribute to the regulation of inflammatory processes in WAT and possibly prevent an overwhelming inflammatory response.

Topics: Adipocytes, White; Adipose Tissue, White; Arrhythmias, Cardiac; Chemokine CCL2; Culture Media, Conditioned; Feedback, Physiological; Female; Gene Expression Regulation; Genetic Diseases, X-Linked; Gigantism; Heart Defects, Congenital; Humans; Inflammation; Intellectual Disability; Interleukin-1 Receptor-Associated Kinases; Interleukin-8; Intracellular Signaling Peptides and Proteins; Macrophages; MAP Kinase Kinase 4; MicroRNAs; Molecular Mimicry; Oligonucleotide Array Sequence Analysis; Oligoribonucleotides; p38 Mitogen-Activated Protein Kinases; Primary Cell Culture; RNA, Small Interfering; Signal Transduction; TNF Receptor-Associated Factor 6; Transfection

Cardiopulmonary bypass (CPB) during pediatric cardiac surgery often elicits a systemic inflammatory response followed by a compromised immune response, which has been attributed to the morbidity of postoperative infection; however, the underlying mechanism(s) has not yet been fully elucidated. We hypothesized that CPB inhibits the activation of Toll-like receptor (TLR) signal transduction pathways, thereby causing an immunosuppressive state after pediatric cardiac surgery.. We examined 20 children with congenital heart disease undergoing pediatric cardiac surgery.. Cardiopulmonary bypass differentially affected lipopolysaccharide (LPS)- or bacterial lipoprotein (BLP)-stimulated ex vivo production of proinflammatory and anti-inflammatory cytokines, with significantly diminished tumor necrosis factor α, interleukin (IL) 1β, IL-6, and IL-8, but substantially enhanced IL-10 production. Consistent with the reduced inflammatory response, CPB strongly inhibited LPS- or BLP-activated TLR signal transduction pathways in monocytes with down-regulated expression of CD14, TLR4, and TLR2 and with suppressed phosphorylation of nuclear factor κB p65, p38, and extracellular signal-regulated kinase 1/2.. These results indicate that CPB during pediatric cardiac surgery causes substantially reduced production of inflammatory cytokines in response to bacterial component LPS or BLP stimulation, which is associated with CPB-induced suppression of TLR-mediated signal transduction pathways. This reduced inflammatory response after CPB in children with congenital heart disease may predispose them to an increased risk of postoperative infection.

Topics: Cardiopulmonary Bypass; Cytokines; Female; Heart; Heart Defects, Congenital; Humans; Infant; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Lipopolysaccharide Receptors; Lipopolysaccharides; Lipoproteins; Male; Monocytes; Signal Transduction; Systemic Inflammatory Response Syndrome; Toll-Like Receptor 2; Toll-Like Receptor 4; Toll-Like Receptors; Tumor Necrosis Factor-alpha

Tobacco smoke is the main factor in the etiology of lung emphysema. Generally prolonged, substantial exposure is required to develop the disease. Humic acid is a major component of cigarette smoke that accumulates in smokers' lungs over time and induces tissue damage.. To investigate whether humic acid pre-loading potentiates the development of cigarette smoke-induced lung emphysema in mice and increases IL-8 release by human monocytes.. C57BL/6J mice received humic acid or aqueous vehicle by tracheal installation on day 0 and day 7. From day 21 to day 84, the mice were exposed to cigarette smoke or clean air for 5 days/week. Twenty-four hours after the last exposure we determined leukocytes in lung lavage, heart hypertrophy and alveolar wall destruction. Human monocytes were incubated with cigarette smoke extract (CSE), humic acid or the combination overnight.. Humic acid nor cigarette smoke caused alveolar wall destruction within two months. Interestingly, the combination did induce lung emphysema. Humic acid, cigarette smoke or the combination did not change leukocyte types and numbers in lung lavage fluid, but the combination caused peribronchiolar and perivascular lymphocyte infiltration. Humic acid treatment resulted in a high proportion of alveolar macrophages heavily loaded with intracellular granula. Humic acid also induces the release of IL-8 from human monocytes and enhances the CSE-induced IL-8 release.. Humic acid deposition in the lungs potentiates the development of cigarette smoke-induced interstitial inflammation and lung emphysema. Moreover, humic acid promotes IL-8 release from human monocytes. Since humic acid accumulates steadily in the lungs of smokers, this may provide an explanation for the natural history on late onset of this disease. The model described here offers a novel way to study emphysema and may direct the search for new therapeutic approaches.

Topics: Animals; Female; Heart Defects, Congenital; Heart Ventricles; Humic Substances; Interleukin-8; Lung; Mice; Mice, Inbred C57BL; Monocytes; Nicotiana; Pulmonary Emphysema; Reactive Oxygen Species; Smoke

Cardiopulmonary bypass (CPB) induces a systemic inflammatory response. The magnitude and consequences in infants remain unclear. We assessed the relationship between inflammatory state and clinical outcomes in infants undergoing CPB.. Plasma concentrations of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor α, IL-1β, and C-reactive protein (CRP) were measured pre-CPB and immediately post-CPB, and at 6, 12, and 24 hours post-CPB in infants ≤9 months old. Perioperative clinical data were collected prospectively.. Diagnoses of 93 patients included transposition of the great arteries (40), tetralogy of Fallot (28), ventricular septal defect (21), truncus arteriosus (2), and complete atrioventricular canal (2). The median age was 37 days (range = 2 to 264). Pre-CPB IL-6 and CRP were higher in younger infants but were not associated with postoperative inflammatory mediator concentrations or measured clinical outcomes. IL-6 increased post-CPB (median 3.2 pg/mL pre-CPB, 24.2 post-CPB, 95.4 at 6 hours, and 90.3 at 24 hours; all P < 0.001). CRP increased post-CPB, peaking at 24 hours (median 27.5 at 24 hours, 0.3 pre-CPB; P < 0.001). IL-10 and IL-8 increased immediately post-CPB. After adjusting for age and diagnosis, postoperative IL-6 and IL-8 correlated with intensive care unit length of stay and postoperative blood product administration and, for IL-8, 24-hour lactate.. Greater preoperative cytokine and CRP production in younger infants did not correlate with postoperative outcomes; correlation between postoperative inflammatory mediator production and clinical course was statistically significant but clinically modest. We conclude that in infants undergoing low-to-moderate-complexity cardiac surgery in a single high-volume center, the contribution of inflammatory mediator production to postoperative morbidity is relatively limited.

Topics: Biomarkers; Boston; C-Reactive Protein; Cardiopulmonary Bypass; Heart Defects, Congenital; Hematocrit; Humans; Infant; Infant, Newborn; Inflammation; Inflammation Mediators; Intensive Care Units, Neonatal; Intensive Care Units, Pediatric; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Lactic Acid; Length of Stay; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Transfusion Reaction; Treatment Outcome; Tumor Necrosis Factor-alpha

We evaluated the effects of thyroid hormone levels and interleukin-8 levels on prognosis in patients undergoing congenital heart surgery under cardiopulmonary bypass (CPB).. The study included 41 consecutive children (19 boys, 22 girls; mean age 3.4 ± 3.1 years; range 0.3 to 12 years). The patients were divided into two groups based on the presence or absence of postoperative low cardiac output state (LCOS). The definition of LCOS included oliguria, tachycardia, metabolic acidosis, and increased plasma lactate level. Plasma total (tT4) and free (fT4) thyroxine, total (tT3) and free (fT3) triiodothyronine, thyroid stimulating hormone (TSH), and interleukin-8 (IL-8) levels were measured preoperatively and at 48 hours postoperatively.. Postoperatively, nine patients (22%) developed LCOS. While the two groups were similar with respect to preoperative levels of thyroid hormones, lactate, and IL-8, postoperative tT3 and fT3 levels were significantly lower, and lactate and IL-8 levels were significantly higher in the LCOS group (p<0.05). In correlation analysis, postoperative IL-8 level showed significant correlations with CPB time (r=0.66), duration of mechanical ventilation (r=0.68), and inotropic requirement (r=0.59) (for all p<0.001). On the other hand, LCOS was significantly correlated with the following: preoperative tT4 (r=-0.32, p=0.043) and postoperative fT3 (r=-0.44, p=0.004) levels, duration of mechanical ventilation (r=0.56, p<0.001), intensive care unit stay (r=0.45, p=0.003), and cross-clamp time (r=0.43, p=0.005). Regression analysis showed preoperative level of tT4 as the independent predictor of LCOS (t=-2.092, p=0.045). Mortality occurred in four patients (9.8%) in the early postoperative period, all of whom were in the LCOS group.. Our findings suggest that the development of LCOS after congenital heart surgery is associated with decreased total and free T3, and increased IL-8 levels at 48 hours, and preoperative tT4 level is an independent predictor of LCOS.

Topics: Cardiopulmonary Bypass; Child; Child, Preschool; Female; Heart Defects, Congenital; Humans; Infant; Interleukin-8; Male; Postoperative Complications; Prognosis; Thyroid Hormones; Treatment Outcome

Long-term neurodevelopmental sequelae are commonly detectable in children after open-heart surgery with cardiopulmonary bypass (CPB). The objective of the study was to determine the neurodevelopmental outcome in these children in relation to postoperative inflammatory reaction. This is a prospective, observational study on children with congenital heart defects (n = 32) undergoing elective open-heart surgery in a tertiary pediatric cardiac center. Neurodevelopmental outcome was assessed in the median 6 months after CPB. Neurological examination was done in all children before the operation and, additionally, complete neurodevelopmental status was assessed preoperatively in 14 children. Three hours after the end of CPB, plasma concentrations of interleukin (IL)-6 and IL-8 were strongly elevated (p < 0.001). Moreover, there was a rise of neutrophils and C-reactive protein at 24 h postoperatively (p < 0.001). Intellectual performance after surgery was correlated with preoperative performance, r ( S ) = 0.83, p < 0.001 (mean IQ scores after CPB = 90.4 +/- 18.4 and before CPB = 87.5 +/- 14.5, p = 0.20). Multiple regression analysis demonstrated that preoperative IQ scores accounted for 83.8% of the variance of postoperative IQ scores (p < 0.0001). Inflammatory variables were not significant predictors of postoperative IQ scores. The frequency of neuromotor abnormalities at 6 months after CPB was influenced by the presence of a cyanotic heart defect, duration of CPB and aortic clamp time, and plasma levels of IL-6 shortly after CPB (R (2) = 67.8%, p = 0.002). In conclusion, in the examined population, preexisting neurodevelopmental impairment is frequent and predicts postoperative outcome. The high frequency of postoperative neuromotor disabilities seems to be associated with the type of congenital heart defect but also with the procedure and possible complications of CPB.

Topics: Biomarkers; C-Reactive Protein; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Child; Child, Preschool; Female; Follow-Up Studies; Heart Defects, Congenital; Humans; Infant; Inflammation; Intelligence; Interleukin-6; Interleukin-8; Male; Motor Activity; Postoperative Complications; Prospective Studies; Time Factors

Cardiac surgery with cardiopulmonary bypass (CPB) in children with congenital heart disease induces a systemic inflammatory response. This inflammatory response is thought to be produced by exposing patients to proinflammatory factors.. To explore the role of cytokines and proteolytic enzymes in inflammatory complications after cardiac surgery in children.. We investigated the dynamics of concentrations of IL-6, IL-8 and IL-10, and metalloproteinases (MMPs) MMP-2 and MMP-9, and their inhibitors - tissue inhibitors of metalloproteinases (TIMPs) TIMP-1 and TIMP-2. These investigations were carried out in 28 children, aged 4-34 months, who underwent a cardiac operation with CPB. Serum concentrations of proteins were sequentially measured before induction of anaesthesia, at the initiation of CPB, after 30 minutes of CPB, at the end of CPB, and 4 and 48 hours after CPB.. The serum levels of IL-6 increased dramatically 4 hours after CPB compared with the level before anaesthesia (141.83+/-25.49 vs. 10.68+/-5.01 ng/ml, p=0.00004) and correlated with duration of CPB (r=0.74, p=0.00028). The serum levels of IL-8 increased 4 hours after CPB compared with the level before anaesthesia (267.1+/-41.3 vs. 8.5+/-6.3 ng/ml, p=0.00002). A significant increase of IL-10 concentration at the end of surgery and 4 hours after CPB was detected (95.12+/-23.57 vs. 10.34+/-6.45 ng/ml, p=0.000004 and 59.41+/-21.4 vs. 10.34+/-6.45 ng/ml, p=0.00004, respectively ). The MMP-9 concentration increased at the end of CPB and remained elevated for a period of 48 hours (44.40+/-13.95 vs. 19.53+/-7.58, p=0.000004 and 38.97+/-10.76 vs. 19.53+/-7.58, p=0.00004, respectively). The concentration of MMP-9 detected at the end of CPB positively correlated with duration of CPB (r=0.68, p=0.0045). The TIMP-1 concentration decreased significantly after 30 minutes of CPB, and remained lowered to the end of CPB (respectively 52.68+/-17.72 vs. 83.29+/-17.06 ng/ml, p=0.000006 and 34.94+/-10.58 vs. 83.29+/-17.06 ng/ml, p=0.00004,respectively).. Cardiac surgery causes an increase of IL-6 and IL-8 concentrations in peripheral blood 4 hours after CPB termination. The concentration of anti-inflammatory IL-10 cytokine increases immediately after the end of CPB. We showed an increase of the MMP-2 and MMP-9 concentrations during and after CPB and simultaneous decrease of TIMP-1 inhibitor. We demonstrated a link between CPB duration and IL-6 and MMP-9 concentrations.

Topics: Cardiopulmonary Bypass; Child, Preschool; Cytokines; Female; Heart Defects, Congenital; Humans; Infant; Interleukin-10; Interleukin-6; Interleukin-8; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Time Factors; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2

Oxidative stress seems to contribute to cardiopulmonary bypass (CPB)-related postoperative complications. Pediatric patients are particularly prone to these complications. With this in mind, we measured oxidative stress markers in blood plasma of 20 children undergoing elective heart surgery before, during, and up to 48 h after cessation of CPB, along with inflammatory parameters and full analysis of iron status. Ascorbate levels were decreased by approximately 50% (P < 0.001) at the time of aorta cross-clamp removal (or pump switch-off in 4 patients with partial CPB), and associated with corresponding increases in dehydroascorbate (P < 0.001, r = -0.80) and malondialdehyde (P < 0.01, r = -0.59). In contrast to the immediate oxidative response, peak levels of IL-6 and IL-8 were not observed until 3-12 h after CPB cessation. The early loss of ascorbate correlated with duration of CPB (P < 0.002, r = 0.72), plasma hemoglobin after cross-clamp removal (P < 0.001, r = 0.70), and IL-6 and IL-8 levels at 24 and 48 h after CPB (P < 0.01), but not with postoperative lactate levels, strongly suggesting that hemolysis, and not inflammation or ischemia, was the main cause of early oxidative stress. The correlation of ventilation time with early changes in ascorbate (P < 0.02, r = 0.55), plasma hemoglobin (P < 0.01, r = 0.60), and malondialdehyde (P < 0.02, r = 0.54) suggests that hemolysis-induced oxidative stress may be an underlying cause of CPB-associated pulmonary dysfunction. Optimization of surgical procedures or therapeutic intervention that minimize hemolysis (e.g., off-pump surgery) or the resultant oxidative stress (e.g., antioxidant treatment) should be considered as possible strategies to lower the rate of postoperative complications in pediatric CPB.

Topics: Ascorbic Acid; C-Reactive Protein; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Child; Child, Preschool; Dehydroascorbic Acid; Heart Defects, Congenital; Hemolysis; Humans; Infant; Interleukin-6; Interleukin-8; Iron; Ischemia; Malondialdehyde; Neutrophils; Oxidative Stress; Pneumonia; Postoperative Complications; Prospective Studies

Cytokine dysregulation contributes to the systemic inflammatory response after cardiopulmonary bypass. Clearance of cytokine binding proteins may be important in the resolution of inflammation. Our aim was to determine whether the cytokine binding protein alpha 2 -macroglobulin and its soluble receptor were upregulated in endotracheal aspirates from infants and children undergoing cardiopulmonary bypass.. Seventy tracheal aspirates were collected before and after cardiopulmonary bypass from 35 infants and children undergoing surgical correction of congenital heart defects. alpha 2 -Macroglobulin and the soluble alpha 2 -macroglobulin receptor were identified by Western blot. With the use of multi-analyte cytokine profiling, pro-inflammatory and anti-inflammatory cytokines were quantified, normalized to total protein, and expressed as ratios. Paired t tests and Wilcoxon signed-rank tests were performed between prebypass and postbypass samples. Correlations were examined among alpha 2 -macroglobulin, soluble alpha 2 -macroglobulin receptor, cytokine ratios, and the clinical variables of cardiopulmonary bypass, aortic crossclamp, and circulatory arrest times.. alpha 2 -Macroglobulin increased by 50% (mean densitometry increase 82,683 +/- 184,594, P = .012), and soluble alpha 2 -macroglobulin receptor increased by 17% (mean densitometry increase 506,148 +/- 687,037, P = .0001) after cardiopulmonary bypass. The ratio of interleukin-8/interleukin-4 increased by 136% ( P = .0001), and interleukin-8/interleukin-10 increased by 102% ( P = .001). The increase in soluble alpha 2 -macroglobulin receptor was positively correlated with the ratios of interleukin-8/interleukin-4 and interleukin-8/interleukin-10. There were no statistically significant positive correlations between the increase in alpha 2 -macroglobulin or soluble alpha 2 -macroglobulin receptor and measured clinical variables.. We report for the first time the upregulation of alpha 2 -macroglobulin and soluble alpha 2 -macroglobulin receptor in tracheal aspirates after cardiopulmonary bypass in infants and children. Soluble alpha 2 -macroglobulin receptor correlates with increased alpha 2 -macroglobulin and a disproportionate increase in pro-inflammatory to anti-inflammatory cytokine ratios.

Topics: Age Factors; alpha-Macroglobulins; Blotting, Western; Bronchoalveolar Lavage Fluid; Cardiopulmonary Bypass; Child; Child, Preschool; Cytokines; Densitometry; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Inflammation; Interleukin-10; Interleukin-4; Interleukin-8; Low Density Lipoprotein Receptor-Related Protein-1; Metabolic Clearance Rate; Metalloproteases; Proteins; Systemic Inflammatory Response Syndrome; Time Factors; Up-Regulation

Pediatric cardiac surgery with cardiopulmonary bypass (CPB) is frequently associated with neurologic deficits. We describe the postoperative EEG changes, assess their possible causes, and evaluate their relevance to neurologic outcome. Thirty-one children and five neonates with congenital heart disease were included. EEG recording started after intubation and continued until 22-96 h after CPB. In addition to conventional analysis, spectral analysis was performed for occipital and frontal electrodes, and differences between pre- and postoperative delta power (delta-deltaP) were calculated. Maximum values of occipital delta-deltaP that occurred within 48 h after CPB were correlated with clinical variables and with perioperative markers of oxidative stress and inflammation. Occipital delta-deltaP correlated with frontal delta-deltaP, and maximum delta-deltaP correlated with conventional rating. Distinct rise of deltaP was detected in 18 of 21 children without any acute or long-term neurologic deficits but only in five of 10 children with temporary or permanent neurologic deficits. Furthermore, maximally registered delta-deltaP was inversely associated with duration of CPB and postoperative ventilation. Maximal delta-deltaP was also inversely associated with the loss of plasma ascorbate (as an index of oxidative stress) and plasma levels of IL-6 and IL-8. Slow wave activity frequently occurs within 48 h after CPB. However, our data do not support the notion that EEG slowing is associated with adverse neurologic outcome. This is supported by the fact that EEG slowing was associated with less oxido-inflammatory stress.

Topics: Ascorbic Acid; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Child, Preschool; Electroencephalography; Female; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Inflammation; Interleukin-6; Interleukin-8; Male; Monitoring, Physiologic; Neurons; Oxidative Stress; Postoperative Period; Time Factors

Inflammatory processes seem to be involved in pulmonary arterial hypertension (PAH). CD40 ligand (L) may promote inflammation and thrombus formation, and we hypothesized that CD40L could be involved in the pathogenesis of PAH.. Several significant findings were revealed when examining the possible role of CD40L in PAH. (1) Patients with primary (n=13) and secondary (n=11) PAH but not those with chronic thromboembolic pulmonary hypertension (n=8) had increased plasma levels of soluble (s) CD40L compared with control subjects (n=8). (2) PAH patients using warfarin had markedly lower sCD40L levels than those without such therapy. (3) sCD40L levels were higher in arterial (femoral artery) compared with mixed venous blood (pulmonary artery), suggesting enhanced release or reduced clearance in the pulmonary vasculature. (4) Platelets from PAH patients showed enhanced spontaneous and SFLLRN-stimulated release of sCD40L compared with control subjects. (5) In vitro, recombinant sCD40L induced monocyte chemoattractant protein (MCP)-1 and interleukin-8 gene expression in endothelial cells, and plasma levels of these chemokines were raised in all PAH groups, significantly correlated to sCD40L and hemodynamic parameters. (6) Although prostacyclin therapy (3 months) showed clinical benefit, this therapy had no effect on sCD40L and increased MCP-1 levels in PAH patients, and prostacyclin enhanced MCP-1 in CD40L-stimulated endothelial cells.. Our findings suggest a role for CD40L in the pathogenesis of PAH, possibly operating through an interaction between platelets and endothelial cells involving chemokine-related mechanisms.

Topics: Aged; Anticoagulants; Blood Platelets; CD40 Ligand; Cells, Cultured; Chemokine CCL2; Collagen Diseases; Endothelial Cells; Endothelium, Vascular; Epoprostenol; Female; Femoral Artery; Gene Expression Regulation; Heart Defects, Congenital; HIV Infections; Humans; Hypertension, Pulmonary; Interleukin-8; Liver Cirrhosis; Male; Middle Aged; Peptide Fragments; Pulmonary Artery; Recombinant Proteins; Solubility; Thromboembolism; Umbilical Veins; Warfarin

The balance between systemic oxygen consumption (VO2) and delivery (DO2) is impaired after cardiopulmonary bypass (CPB) and is related to systemic inflammatory response syndrome. We sought to assess VO2 and DO2 and their relationship with proinflammatory cytokines after CPB with the use of modified ultrafiltration (MUF) in infants.. Sixteen infants, aged 1-11.5 months (median, 6.3 months), undergoing hypothermic CPB with MUF were studied during the first 12 hours after arrival in the intensive care unit (ICU). The central temperature was maintained at 36.8-37.1 degrees C using external cooling or warming. VO2 was continuously measured using respiratory mass spectrometry. Arterial blood samples for the tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-8 (IL-8) were taken and DO2 was calculated using the Fick principle on arrival at the ICU, and 2, 4, 8, and 12 hours postoperatively. Cytokines were additionally measured after induction of anesthesia and at the end of MUF.. VO2 significantly decreased by 18.8% during the study period. DO2 was depressed throughout this period and reached a nadir at 8 hours (357.1 +/- 136.2 ml x min(-1) x m(-2)). The decrease in cytokines was accompanied with the decrease in VO2 despite varied relationships between the levels of each of the cytokines and VO2 measurements.. Our data indicate an unusual continuous decrease in VO2 during the first 12 hours after CPB in infants. Control of body temperature to maintain euthermia in addition to the use of MUF may be beneficial to the balance between VO2 and DO2 in the early postoperative period.

Topics: Body Temperature; Cardiac Output, Low; Cardiopulmonary Bypass; Cytokines; Female; Heart Defects, Congenital; Humans; Hypothermia, Induced; Infant; Infant, Newborn; Interleukin-6; Interleukin-8; Lactates; Male; Organophosphates; Oxygen; Oxygen Consumption; Postoperative Complications; Postoperative Period; Premedication; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha; Ultrafiltration

To promote further improvement of surgical results in the longer terms after the Fontan procedure, we have paid attention to age at operation. Establishment of a non-cyanotic circulation at younger stage, for example around 1 year of age, could have potential advantages in postoperative cardiac performance and functional status. In order to commence the Fontan circulation safe and sound, in turn, the surgical intervention ought to be arranged in a less invasive fashion. In this respect, we introduced off-pump Fontan procedure. Since April 1996, 77 patients have undergone the off-pump Fontan procedure. Its less invasive nature was demonstrated in terms of inflammatory reaction immediately after the operation. Further devices are being sought. These include an alternative off-pump procedure even without a temporary bypass for drainage through the inferior caval vein, which has been thus far applied in 14 patients. This option proved to provide readily an excellent surgical field when an extracardiac conduit is to be anastomosed to the orifice of the inferior caval vein. Another device can be a cordial preparation of the extracardiac channel at the time of the bidirectional Glenn procedure when the staged approach is chosen.

Topics: Age Factors; Blood Vessel Prosthesis Implantation; Cardiopulmonary Bypass; Coronary Circulation; Fontan Procedure; Heart Bypass, Right; Heart Defects, Congenital; Humans; Interleukin-6; Interleukin-8; Pulmonary Circulation; Tumor Necrosis Factor-alpha

Leptin may be involved in the acute stress response, regulating inflammatory parameters of major importance after cardiopulmonary bypass (CPB) surgery. Critically ill patients demonstrated significant increases in leptin levels in response to stress-related cytokines (tumor necrosis factor, interleukin [IL]-1) and abolishment of the circadian rhythm of leptin secretion. We characterized the pattern of leptin secretion in the acute postoperative period in children undergoing cardiac surgery and compared the changes in leptin levels with concomitantly occurring changes in cortisol levels, IL-8, and clinical parameters.. Investigative study.. University-affiliated tertiary care hospital.. Twenty-nine consecutive patients, aged 6 days to 15 yrs, operated upon for the correction of congenital heart defects were studied. Surgery in 20 patients (group 1) involved conventional CPB techniques, and 9 (group 2) underwent closed-heart surgery. The time courses of leptin, cortisol, and IL-8 levels were determined. Serial blood samples were collected preoperatively, on termination of CPB, and at six time points postoperatively. Plasma was recovered immediately, aliquoted, and frozen at -70 degrees C until use.. The leptin levels in group 1 decreased during CPB to 51% of baseline (p <.001), then gradually increased, reaching 120% of baseline levels at 12-18 hrs postoperatively (p <.001), returning to baseline levels at 24 hrs (p <.01). In patients undergoing closed-heart surgery (group 2), leptin levels displayed a pattern resembling the first group: they decreased during surgery to 71% of baseline levels (p =.002) and showed a tendency to return to baseline thereafter. All group 1 patients' cortisol levels increased significantly during the first hour of surgery, then decreased, returning to baseline levels at 18-24 hrs postoperatively. There was a significant negative correlation between leptin and cortisol levels (r = -2.8, p <.01). In group 2, cortisol levels increased during and after surgery, peaking 4 hrs postoperatively and decreasing thereafter. IL-8 levels determined in 15 group 1 patients increased significantly during CPB, peaked at the end of surgery, and then decreased but remained slightly elevated even at 48 hrs postoperatively. There was a significant correlation between cortisol and IL-8 levels (r = 2.55, p <.05). Children with leukocytosis, tachycardia, and hypotension had lower leptin levels and less variation over time as opposed to those with an uncomplicated course.. CPB is associated with acute changes in circulating leptin levels. These changes parallel those in cortisol, demonstrating an inverse relationship between leptin and cortisol. Further studies of the prognostic and therapeutic roles of leptin after CPB should be investigated.

Topics: Adolescent; Analysis of Variance; Cardiopulmonary Bypass; Case-Control Studies; Child; Child, Preschool; Heart Defects, Congenital; Humans; Hydrocortisone; Infant; Infant, Newborn; Interleukin-8; Leptin; Stress, Physiological

The aim of the present study was to evaluate the systemic inflammatory response to CPB in paediatric patients undergoing surgical correction of congenital heart diseases.. comparative investigation.. paediatric cardiology hospital. ICAM-1, IL-8, and IL-6 production were analysed before and during CPB, and after surgery in 9 paediatric patients, submitted to cardiocirculatory arrest (Group A); and in 11 without cardiocirculatory arrest (Group B).. ICAM-1, IL-8, and IL-6 production were analysed from arterial samples before and during CPB, and after surgery.. In group A vs group B a significant increase of IL-8 was detected during (297+/-250 vs 11+/-19 pg x ml(-1), p<0.001) and after (100+/-230 vs n.d. pg x ml(-1)) surgery and was correlated with the duration of operation (r=0.759; p=0.0001) and clamping time (r=0.738; p<0.05). After surgery in group A, IL-6 levels (35+/-43 pg x ml) were higher than those in group B (2+/-5 pg x ml), and a good correlation was observed between IL-6 and duration of aortic clamping (r=0.714; p=0.048), cardiac arrest, (r=0.714; p=0.048), and length of surgery (r=0.867; p=0.04).. In children who underwent CPB with cardiocirculatory arrest cytokine production seems related to duration of operation and amplified by ischemia-reperfusion phenomena.

Topics: Cardiopulmonary Bypass; Child; Child, Preschool; Female; Heart Arrest, Induced; Heart Defects, Congenital; Humans; Infant; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Male; Postoperative Complications; Risk Factors; Systemic Inflammatory Response Syndrome

Cardiopulmonary bypass (CPB) causes significant morbidity in paediatric patients, yet the mechanisms involved in the related inflammatory processes (resulting in capillary leak and edema) are poorly understood. Moreover, earlier palliative and corrective intervention in neonates and infants has provided the cohorts of patients about whom little is known of their proinflammatory response.. In the present two group study, 14 neonates (age 1-28 days, 2.5-4.5 kg) and 13 infants (2-12 months, 3-7 kg), undergoing CPB for congenital heart disease were consecutively recruited. The two cohorts were well matched in terms of CPB and aortic cross-clamp times (P > 0.1). Blood samples were collected on induction of anaesthesia, 5 min following onset of CPB, at the end of CPB, and 30 min, 2 and 24 h post-protamine (PP) administration. Plasma concentration of cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8), terminal complement complex (C5b-9) neutrophil counts and leucocyte elastase were measured.. Plasma levels of all inflammatory markers significantly increased in both groups during and following CPB as compared to baseline. During and following CPB the change in IL-8 level was more pronounced in neonates (peak 30 min PP, median(range): 1062 (182-3872) pg/ml) than in infants 568 (172-1368) pg/ml), P = 0.01. Changes in IL-6 level were indistinguishable between groups intraoperatively, but remained significantly higher at 24 h in neonates (P = 0.02). Peri and postoperative levels of C5b-9 were significantly higher in infants than in neonates (peak 30 min PP, median (range): 984 (118-1142) ng/ml vs 458 (22 1340) ng/ml in neonates respectively, P = 0.01) but were similar at 24 h. Despite this, leucocyte elastase profiles did not differ significantly between the respective cohorts.. These results indicate that there may be differences between neonates and infants with regard to the inflammatory response to CPB and neonatal patients merit further investigation in order to elucidate whether the pathophysiology of their CPB related inflammatory response and its clinical sequelae differs from their older counterparts.

Topics: Cardiopulmonary Bypass; Complement Membrane Attack Complex; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Inflammation; Interleukin-6; Interleukin-8; Leukocyte Count; Leukocyte Elastase; Neutrophils; Prospective Studies

Capillary leak after cardiopulmonary bypass operations for correction of congenital heart defects is universally seen in children and often causes significant morbidity and mortality. Since neutrophil-mediated endothelial injury has been implicated as a pathogenetic mechanism, a prospective controlled descriptive study was performed to investigate possible activation pathways during and after the bypass procedure. Eighteen children undergoing operations, nine with cardiopulmonary bypass and nine neurosurgical craniotomy (i.e., operations without bypass), had samples of arterial blood collected at intervals before, during, and after operations. In six of nine cardiac patients circulating interleukin-8 concentrations rose from less than 30 pg/ml to very high concentrations (> 500 pg/ml); in the remaining three patients small rises (peak 57 to 81 pg/ml) were also seen. In all nine, the rise commenced at the time of rewarming, toward the end of bypass, and peaked 1 to 3 hours thereafter. Interleukin-8 release correlated significantly with length of bypass. Interleukin-1 alpha and interleukin-1 beta were not found, and traces of tumor necrosis factor-alpha were detected in one patient only. Circulating elastase alpha 1-antitrypsin concentrations rose simultaneously and correlated significantly with interleukin-8 (p < 0.001) in patients with cardiac disease, as did absolute neutrophil counts (p < 0.001). In contrast, only one of nine patients with neurosurgical disease (undergoing an unusually long operation and exchange transfusion) had a rise in circulating interleukin-8 to levels greater than 500 pg/ml (p < 0.01). The two samples from this patient with elevated interleukin-8 were the only neurosurgical samples with elevated elastase. This study demonstrates the release of interleukin-8 into the circulation after pediatric hypothermic cardiopulmonary bypass and supports the suggestion that this cytokine plays a role in the pathophysiology of capillary leak through neutrophil degranulation.

Topics: alpha 1-Antitrypsin; Cardiopulmonary Bypass; Cell Degranulation; Child; Child, Preschool; Female; Heart Defects, Congenital; Humans; Infant; Interleukin-1; Interleukin-8; Leukocyte Count; Leukocyte Elastase; Male; Neutrophils; Pancreatic Elastase; Prospective Studies; Tumor Necrosis Factor-alpha