No abstract

Cardiopulmonary bypass (CPB) is associated with an inflammatory response, mainly caused by the trauma of surgery, contact of blood with the artificial surface of the circuit, and reperfusion injury, resulting in increased capillary permeability, respiratory distress, low cardiac output, and multiorgan failure. The inflammatory reaction includes an activation of the humoral and cellular immune system with enhanced release of cytokines. The present study focused on the effect of CPB on the time course of pro- and anti-inflammatory cytokines. In 20 patients undergoing coronary artery bypass grafting, the plasma concentration of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-2, IL-4, IL-6, IL-8, and IL-10 was investigated pre-, intra-, and postoperatively by enzyme-linked immunosorbent assay technique. With the exception of IFN-gamma, all the other cytokines could be detected in the patients plasma. However, neither TNF-alpha nor IL-1 beta and IL-2 revealed significant changes in concentration during the investigated time period. In contrast, IL-6 and IL-8 levels peaked early postoperatively, reaching median concentrations of 430 pg/ml (221 pg per ml/558 pg per ml; lower/upper quartiles, respectively) and approximately 12 pg/ml (0/17 pg/ml; lower/upper quartiles, respectively). IL-4 and IL-10, respectively, revealed maximal concentrations of approximately 2 pg/ml (0/39 pg/ml; lower/upper quartiles, respectively) and 208 pg/ml (76 pg per ml/380 pg per ml; lower/upper quartiles, respectively) immediately after protamine administration, preceding the maximal concentration of IL-6. The degree of the observed modulation of cytokine patterns during and after CPB seemed to be patient-dependent, since large interindividual variations in cytokine levels were observed, not only preoperatively, but especially during and following CPB. However, IL-6 and IL-10 showed the least interindividual variations, suggesting that these cytokines may give reliable information regarding modulation of the immune response following CPB and its consequences for the patient's outcome.

Cardiopulmonary bypass (CPB) is known to induce an inflammatory response. Previous studies reported an impairment of the cellular immune response with activation of neutrophils and changes in lymphocyte subpopulations. The objective of the present study was to investigate the effect of CPB on leukocyte activation in vivo. In 27 patients undergoing coronary artery bypass grafting, the quantitative and the qualitative response of leukocyte populations to CPB was analysed pre-, intra-, and postoperatively using flow cytometry. A significant increase in leukocyte counts was detected during CPB, resulting in a marked leukocytosis postoperatively. The total number of lymphocytes peaked in the early phase of CPB, followed by a significant decrease, mainly due to a loss in B and cytotoxic T lymphocytes. In contrast, the lymphocytopenia observed 8 h after protamin administration was mainly caused by a drop in the population of helper T lymphocytes. Activation of distinct cell populations could be detected during and following CPB. The results indicate an influence of CPB on the cellular immune system, however an immuno-suppression was detectable only transiently.

During cardiopulmonary bypass (CPB) mechanical stress and the contact of blood with artificial surfaces lead to the activation of pro- and anticoagulant systems and the complement cascade, and to changes in cellular components. This phenomenon causes the "postperfusion-syndrome", with leukocytosis, increased capillary permeability, accumulation of interstitial fluid, and organ dysfunction. In this study, we focused on the influence of the extracorporeal circulation, sternotomy, and heparin administration on the activation of coagulation and fibrinolysis. In 15 patients we investigated coagulation parameters before, during and post CPB, i.e., fibrinogen, antithrombin (AT) III, thrombin-antithrombin complex (TAT), prothrombin fragments F1 + 2 (F1 + 2), factor (F) XIIa, tissue factor (TF), and parameters of the fibrinolytic system, i.e., plasmin-antiplasmin-complex (PAP), D-dimer, tissue-plasminogen-activator (tPA), urokinase-type plasminogen activator (uPA), and plasminogen-activator inhibitor type 1 (PAI 1). The results demonstrate distinct alterations in the above mentioned parameters. Despite administration of a high dose of heparin (activated clotting time [ACT] > 450s) combined with a low dose of aprotinin, activation of the coagulation and fibrinolytic pathways was observed. We found this activation was mainly caused by CPB and not by sternotomy. The activation of coagulation was due to foreign surface contact (F XII => F XIIa) as well as to an effect of tissue factor release in the late phase of CPB. The enhanced fibrinolytic activity during CPB was, at least in part, caused by tPA and was followed by PAI 1 release.

S100B release is related to embolus and thrombin formation during CPB, indicating that thrombofibrinous embolism is involved in perioperative brain damage. Inflammatory parameters (i.e. interleukin 8 and C5a) seem to have no influence on S100B release.