Intraoperative embolus formation during cardiopulmonary bypass affects the release of S100B.

BACKGROUND: Intraoperative thromboembolism and the systemic inflammatory reaction are thought to play a role in causing cerebral dysfunction following cardiopulmonary bypass (CPB). Increased levels of S100B, an astroglial protein, have been linked to neuropsychological deficits after CPB. The present study investigated whether S100B release correlates with intraoperative embolus formation, thrombin formation, or the release of inflammatory parameters. METHODS: 40 patients undergoing coronary artery bypass grafting were included. Blood samples were taken before, during, and after CPB, and levels of S100B, thrombin-antithrombin complex (TAT), complement C5a, and interleukin 8 were analysed. Embolus formation was assessed by Doppler ultrasound at the arterial line of CPB. RESULTS: The release of S100B correlated with embolus count (r = 0.42; p = 0.009) and TAT formation (r = 0.71; p = 0.0001). The correlation of S100B with interleukin 8 (r = 0.58; p = 0.0001) was due to the dependence of both parameters on bypass time (r = 0.29; p = 0.075, partial correlation). A correlation of S100B with C5a formation could not be observed. CONCLUSIONS: 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.

Influence of different autotransfusion devices on the quality of salvaged blood.

BACKGROUND: Cardiopulmonary bypass causes a systemic inflammatory response and impaired hemostasis. We investigated whether intraoperative blood salvage with the cardiotomy suction contributes to these alterations. Furthermore, an alternative autotransfusion device (Haemonetics cell-saving device) was examined. METHODS: In 10 patients, interleukin-6, interleukin-8, tumor necrosis factor-alpha, thrombin-antithrombin complex, plasmin-antiplasmin complex, free hemoglobin, and the percentage of CD62+ thrombocytes were determined in the systemic circulation during cardiopulmonary bypass, in the cardiotomy suction tube, and in the blood from the cell-saving device. Additionally, bacterial contamination was examined. RESULTS: Median levels of interleukin-6 (52 versus 10 microg/L; p = 0.005), interleukin-8 (26 versus 20 microg/L; p = 0.017), tumor necrosis factor-alpha (24 versus 1 microg/L; p = 0.005), thrombin-antithrombin complex (113 versus 43 microg/L; p = 0.005), plasmin-antiplasmin complex (566 versus 489 microg/L; p = 0.022), and free hemoglobin (61 versus 30 mg/dL; p = 0.005) were higher in the cardiotomy suction tube compared with the systemic circulation. After processing the blood from the cell-saving device, interleukin-8, thrombin-antithrombin complex, and free hemoglobin remained above reference range, and in 90% of the cases bacterial contamination was observed. CONCLUSIONS: Cardiotomy suction additionally contributes to the release of proinflammatory cytokines, activation of coagulation, and hemolysis. Because blood salvage with a Haemonetics cell-saving device led to normalization of some, but not all, parameters and bacterial contamination was common, the alternative use seems at least questionable.

Response of the cellular immune system to cardiopulmonary bypass is independent of the applied pump type and of the use of heparin-coated surfaces.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with an activation of leukocytes. The extent of this activation was thought to depend on the applied CPB-circuit set-up. The present study comparatively evaluated the effect of roller pump, centrifugal pump, and uncoated and heparin-coated surfaces. METHODS: 73 patients were included, randomly assigned to 3 groups. In group A a roller pump was used, in group B a centrifugal pump, and in group C a centrifugal pump together with Carmeda heparin-coated surfaces. The quantitative (cell count) and the qualitative changes of leukocyte populations (subpopulations and expression of the CD126-, HLA-DR-, CD45 RO-, CD71 antigens) was comparatively analysed before, during, and following CPB. RESULTS: Groups A and B did not differ in leukocyte counts and the differences between groups B and C were restricted to single time points. Neither groups A and B, nor groups B and C differed significantly in the relative distribution of lymphocyte subpopulations or in the percentage of CD126+, HLA-DR+, CD45 RO+ and CD71+ leukocyte subpopulations. CONCLUSIONS: CPB affects the cellular immune system; however, this effect seems to be a physiological reaction, independent of the applied CPB circuit system.

Reduced release of tissue factor by application of a centrifugal pump during cardiopulmonary bypass.

The application of a centrifugal pump might lead to a reduced release of tissue factor (TF) due to less blood cell damage. This could result in a decrease in activation of the extrinsic pathway of coagulation and embolus formation. In the present study, 60 patients undergoing coronary artery bypass grafting were randomly assigned to a centrifugal or a roller pump. Plasma concentrations of TF, thrombin-antithrombin complex (TAT), and prothrombin fragments F1 + 2 were investigated before, during, and after cardiopulmonary bypass (CPB). Embolus detection was performed at the arterial line of CPB and transcranially by Doppler ultrasound. The centrifugal pump group revealed a lower TF release (area under the curve during CPB) when compared with the roller pump group [5661 (696-10359) vs 12681 (6383-17538) microg x min/l; median (lower - upper quartiles); P = 0.009]. In contrast, TAT and F1 + 2 formation did not differ between the groups, and neither did the total embolus count of both Doppler systems. Embolus counts did not correlate with TAT or F1 + 2 formation. In conclusion, the reduction in TF release by the application of a centrifugal pump seems to have little consequence on total thrombin formation. Since the applied Doppler systems seem to detect mainly microbubbles, conclusions regarding differences between the two pumps in the formation of thrombofibrinous clots cannot be drawn.

Response of the cellular immune system to cardiopulmonary bypass in vivo.

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.

Interindividual variations in cytokine levels following cardiopulmonary bypass.

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.

A comparative evaluation of the effect of pump type and heparin-coated surfaces on platelets during cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) is associated with hemostatic disorders, mainly due to platelet function defects. In the present prospective study, platelet count and GMP-140 expression on platelets were investigated to comparatively evaluate the impact of different CPB-circuit systems on platelets. The study included 61 patients undergoing coronary artery bypass grafting, randomly assigned to 3 groups. In group A a roller pump, in group B a centrifugal pump, and in group C a centrifugal pump with a Carmeda heparin-coated CPB circuit was applied. Platelet count and GMP-140 expression were analysed pre, during, and following CPB. None of the tested CPB systems did affect platelet count. The percentage of GMP-140-positive platelets increased slightly early during CPB, whereas it decreased significantly postoperatively; group differences were observed between B and C after protamin administration. An advantage of the use of centrifugal pumps and heparin-coated circuits could not be proven with the present set-up. The results suggest that the benefit of the tested systems might depend on the operative procedure and management.

Effect of CO2 on the fermentation capacities of the acetogen Peptostreptococcus productus U-1.

The fermentative capacities of the acetogenic bacterium Peptostreptococcus productus U-1 (ATCC 35244) were examined. Although acetate was formed from all the substrates tested, additional products were produced in response to CO2 limitation. Under CO2-limited conditions, fructose-dependent growth yielded high levels of lactate as a reduced end product; lactate was also produced under CO2-enriched conditions when fructose concentrations were elevated. In the absence of supplemental CO2, xylose-dependent growth yielded lactate and succinate as major reduced end products. Although supplemental CO2 and acetogenesis stimulated cell yields on fructose, xylose-dependent cell yields were decreased in response to CO2 and acetogenesis. In contrast, glycerol-dependent growth yielded high levels of ethanol in the absence of supplemental CO2, and pyruvate was subject to only acetogenic utilization independent of CO2. CO2 pulsing during the growth of CO2-limited fructose cultures stopped lactate synthesis immediately, indicating that CO2-limited cells were nonetheless metabolically poised to respond quickly to exogenous CO2. Resting cells that were cultivated at the expense of fructose without supplemental CO2 readily consumed fructose in the absence of exogenous CO2 and formed only lactate. Although the specific activity of lactate dehydrogenase was not appreciably influenced by supplemental C02 during cultivation, cells cultivated on fructose under CO2-enriched conditions displayed minimal capacities to consume fructose in the absence of exogenous CO2. These results demonstrate that the utilization of alternative fermentations for the conservation of energy and growth of P. productus U-1 is augmented by the relative availability of CO2 and growth substrate.

Changes in coagulation and fibrinolytic parameters caused by extracorporeal circulation.

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.