Plasma endotoxin concentrations during cardiac surgery may be related to atherosclerosis

Systemic endotoxemia develops during cardiopulmonary bypass, probably due to intestinal ischaemia. Differences in endotoxaemia among various cardiac operations and the relationship between endotoxemia and postoperative complications were studied in high-risk patients. Blood samples were obtained at termination of bypass in 136 adults undergoing elective cardiac surgery. Postoperative complications were registered prospectively. Plasma endotoxin was quantified by a kinetic limulus amebocyte lysate assay. Mean endotoxin concentrations were significantly lower in patients undergoing isolated valve replacement (89 ng/l) than in patients undergoing coronary artery bypass grafting alone (234 ng/l), or combined with valve replacement (278 ng/l) or carotid artery surgery (321 ng/l) (p < 0.05). In multivariate linear regression, only the number of grafts (0, 1-3, 4-5) was significantly correlated to endotoxin concentrations (p < 0.0005). Endotoxin concentrations were related to development of gastrointestinal dysfunction (p = 0.03), but not to mortality (p = 0.24) or other complications (p = 0.62).     

Functional polymorphisms in the LTF gene and risk of coronary artery stenosis

Plasma lactoferrin concentrations are increased in patients with coronary artery stenosis. We investigated the effects of LTF gene polymorphisms in 305 healthy blood donors and their associations with coronary artery stenosis in 236 patients admitted for coronary angiography. Lactoferrin concentrations were determined by enzyme immunoassay. Genotyping was performed by polymerase chain reaction and DNA sequencing of LTF exons 2 and 4. In the blood donors, the deletion variant of rs10662431 and the G allele of rs1126478 were associated with higher plasma lactoferrin concentrations. The G allele of rs1126478 was more frequent in patients with significant coronary artery stenosis (p = 0.018, p value limit for significance by permutation = 0.030). The association remained significant in logistic regression with adjustment for clinical risk factors (odds ratio 2.485 [95% confidence interval 1.116-5.536], p = 0.026), but was weakened upon the inclusion of plasma lactoferrin (odds ratio 2.295 [0.949-5.550], p = 0.064). Current evidence indicates that rs1126478 affects the antibacterial effect of lactoferrin and that lactoferrin is involved in lipid metabolism. The relationships among lactoferrin genotypes, lactoferrin concentrations, and clinical factors on the risk for atherosclerosis are not fully understood, but the G allele of rs1126478 seems to have a detrimental effect in a European population.     

Replica patterns on composite restorations performed in vitro with different acid-etch procedures and dentin adhesives

Abstract — 160 experimental Class V restorations using two chemically cured composite resins were inserted in extracted human teeth wjth conventional and modified acid-etch restorative procedures. The modifications included cavity treatment with non-composite resin, ethanol, or four different dentin adhesives. Following deemineralization of the teeth the fillings were examined in the SEM cuncerning their replica patterns 01 the etched cavity walls. In vitro conditions favored resin penetration into pretreated cnarnel and dentin; but resulted in minor variations between diltrerent acid-etch procedures compared with those previously seen on resin restorations plawd in viva in teeth with vital pulps.     

Leucocyte filtration during cardiopulmonary reperfusion in coronary artery bypass surgery.

Postoperative organ dysfunction after cardiac operations has been related to the damaging effects of cardiopulmonary bypass (CPB). These complications are considered to be mediated partly by complement activation and subsequent activation of leucocytes due to the contact between blood and the large nonendothelial surfaces in the bypass circuit. Removal of leucocytes by filtration during the reperfusion period may potentially reduce the postoperative morbidity after CPB. Forty patients undergoing elective, primary coronary artery bypass grafting were randomized to initial identical bypass circuits until the aortic crossclamp was released. Then, the ordinary arterial line filter was closed and either a leucocyte depletion filter (n = 20), or a control filter (n = 20) was incorporated in the circuits during the reperfusion period of CPB. Blood samples were drawn at fixed intervals and analysed for white blood cell and platelet counts, plasma concentration of myeloperoxidase, C3-complement activation products, the terminal complement complex, and interleukins (IL)-6 and -8. The numbers of circulating white blood cells in the leucocyte-depleted group decreased during the reperfusion period from 5.5 (4.8-6.8) to 5.3 (4.4-6.2) x 10(9)/l, and increased in the control group from 6.5 (5.1-8.0) to 7.4 (5.7-9.0) x 10(9)/l. Two hours postoperatively the total white blood cell count in the leucocyte-depleted group was 14.7 (12.1-17.2) x 10(9)/l, and in the control group 17.6 (14.5-20.7) x 10(9)/l. The differences between the groups were statistical significant (p = 0.05). There were no statistically significant differences between the groups with regard to other test parameters or clinical data. We conclude that the use of leucocyte filters during the reperfusion period in elective coronary artery bypass surgery significantly reduced the number of circulating leucocytes, whereas no effects were seen for granulocyte activation measured as myeloperoxidase release, platelet counts, complement activation, or IL-6 and -8 release. The clinical benefit of leucocyte filters in routine or high risk patients remains to be demonstrated and is suggested to be dependent on both the efficacy and the biocompatibility of the filters.     

Formation of C5a during cardiopulmonary bypass: inhibition by precoating with heparin

A novel enzyme immunoassay based on direct detection of C5a by a monoclonal antibody (C17/5) specific for a neoepitope exposed in C5a/C5adesArg was used to measure in vivo and in vitro C5a formation during cardiopulmonary bypass. In vivo, we observed a significant threefold to fourfold increase in patient plasma C5a/C5adesArg levels from baseline values (5.6; 1.6 to 12.9 ng/mL) (median and range) up to 42 hours postoperatively (17.5; 6.5 to 46.0 ng/mL) when two different uncoated cardiopulmonary bypass circuits were used. Coating of the extracorporeal circuit with end-point-attached heparin completely abolished C5a formation in vitro during circulation of blood through the circuit for 120 minutes. The C5a concentration (median and range) was 3.2 (2.6 to 15.9) ng/mL at the start and 3.1 (2.7 to 15.0) ng/mL at the end of the experiment. In the uncoated setups the corresponding C5a concentrations were 10.1 (6.2 to 17.5) and 19.7 (13.1 to 24.3) ng/mL. Finally, heparin-coated cardiopulmonary bypass circuits were examined in vivo. C5a levels did not increase significantly during the cardiopulmonary bypass period in the heparin-coated group in contrast to the uncoated group, but the postoperative increase in C5a levels was similar in the two groups. We conclude that heparin coating improves biocompatibility by completely abolishing C5a formation in vitro. The discrepancy between the in vitro and the in vivo findings is probably related to the complicated biological turnover of C5a.     

Reduced complement activation with heparin-coated oxygenator and tubings in coronary bypass operations.

Complement activation after cardiopulmonary bypass is correlated with postoperative organ dysfunction. Heparin coating of the entire blood-contact surface of the cardiopulmonary bypass circuit has proved to reduce complement activation in vitro. A membrane oxygenator and tubing setup coated with functionally active heparin was compared with an uncoated, otherwise identical setup in 20 patients undergoing routine coronary bypass operations. The concentrations of C3 activation products and the terminal complement complex were measured in sensitive and specific enzyme immunoassays. Peak concentrations of C3 activation products were 90.1 (74.7 to 107.4) AU/ml (medians and 95% confidence intervals) and 52.4 (35.7 to 76.4) AU/ml with the uncoated and coated setups, respectively (p = 0.02). The corresponding concentrations of the terminal complement complex were 26.2 (20.1 to 37.5) AU/ml and 13.7 (11.1 to 25.1) AU/ml (p = 0.03). Blood loss from the mediastinal drains during the first 12 postoperative hours was 533 (416 to 975) ml in patients treated with the uncoated setup and 388 (313 to 579) ml in the coated treatment group (p = 0.06) and was significantly correlated with peak concentrations of the terminal complement complex (p = 0.01). There were no differences in neutrophil counts nor platelet numbers between the treatment groups. The approximate 45% reduction in complement activation with the heparin-coated cardiopulmonary bypass device indicates a substantial improvement of biocompatibility.     

Neutrophil dysfunction after biomaterial contact in an in vitro model of cardiopulmonary bypass.

OBJECTIVE: Cardiopulmonary bypass (CPB) induces neutrophil degranulation and superoxide anion production in vivo. We hypothesized that CPB-associated neutrophil dysregulation alters neutrophil adhesion to vascular endothelial cells and the extracellular matrix. METHODS: We, therefore, recirculated neutrophils in polyvinyl chloride (PVC) tubing using a roller pump model and thereafter measured adhesion to cultured microvascular endothelial cells and gelatin-coated surfaces. Recirculation-induced neutrophil priming or exhaustion was tested by boosting with phorbol myristate-acetate (PMA) or N-formyl-methiolyl-leucyl-phenylalanine (FMLP) before quantification of adhesion. RESULTS AND CONCLUSION: After recirculation, neutrophils retained their adhesive capability to vascular endothelial cells, whereas adhesion to gelatin increased. This increase was not seen when the neutrophils were recirculated with a rotator instead of a roller pump, indicating that not only the pump mode but also foreign surface contact was of significance. The neutrophil PMA response after recirculation was not altered compared to resting neutrophils prestimulated with PMA. Recirculated neutrophils adhered less to cultured vascular endothelial cells after FMLP activation and more to gelatin compared to resting neutrophils prestimulated with FMLP. It is conceivable that dysregulation of neutrophil adhesive capability may play a part in the development of tissue damage after CPB.     

Time for new concepts about measurement of complement activation by cardiopulmonary bypass?

Fifty-one patients admitted for routine coronary bypass operations were randomized to cardiopulmonary bypass with a membrane oxygenator (Capiox) or a bubbler (Polystan or William Harvey). Complement activation was measured using enzyme immunoassays for concentrations of C3 activation products and the terminal complement complex. From 5.8 to 8.1 arbitrary units (AU)/mL (medians), the plasma concentrations of C3 activation products increased by 119.9 AU/mL (Capiox), 124.6 AU/mL (Polystan), and 79.5 AU/mL (William Harvey) to a peak at closure of the sternum (not significant when related to baseline concentrations). The increase in C3 activation products and baseline C3 activation were linearly correlated (R2 = 0.30; p less than 0.0001). From 5.5 to 6.1 AU/mL, the plasma terminal complement complex concentrations increased by 45.2 AU/mL (Capiox), 15.4 AU/mL (Polystan), and 17.4 AU/mL (William Harvey) to a peak before termination of cardiopulmonary bypass. Maximal terminal (C5-C9) activation was significantly higher in the membrane oxygenator group (p less than 0.0001) and showed no relationship to C3 activation. Measurement of C3 activation only gives no information about C5-C9 activation. At present, terminal complement complex quantitation is probably the best index of C5-C9 activation during cardiopulmonary bypass.     

Pattern of periodontal breakdown in adult Tanzanians

Abstract – A total of 170 adult Tanzanians aged 30- 691 yr were examined for loss of attachment, gingival recession, plaque, calculus and gingival bleeding on all surfaces, of all teeth. The severity of loss of attachment varied considerably between tooth types. Irrespective of age, mandibular incisors and first and second molars were the teeth most affected by loss of attachment. In all age groups heavy plaque deposits and gingival bleeding occurred more frequently in posterior than in anterior teeth, Dental calculus was most frequently observed in the maxillary posterior and mandibular anterior teeth. The distribution of calculus within the dentition showed a close resemblance with the patterns of loss of attachment and gingival recession. The variation of the severity of periodontal breakdown within individuals indicates that the use of mean values to describe periodontal breakdown may give the impression of a greater uniformity than really exists.     

Staphylococcus aureus Bacteremia in Patients with Hematological Malignancies and/or Agranulocytosis

ABSTRACT. A total of 6 253 cases of Staphylococcus aureus bacteremia, including 274 (4.4%) endocarditis cases, were registered in Denmark in the period 1975–1984. Patients with hematological malignancies and/or agranulocytosis accounted for 479 of the bacteremia cases. The incidence of endocarditis in this group of patients was only 0.4% as compared to 4.7% in other patients with staphylococcal bacteremia (p<0.01). The lower incidence of endocarditis complicating bacteremia in these patients may justify a shorter course of therapy than usually recommended for suspected endocarditis. Patients with hematological malignancies and other patients with agranulocytosis had a higher mortality (49 and 46%, respectively) than other patients with S. aureus bacteremia (33%). The highest mortality was found in patients with multiple myeloma (71%, p<0.01), the lowest in patients with acute lymphocytic leukemia (28%, p<0.01). The higher mortality in these patients may indicate that empiric antibiotic regimens in granulocytopenic patients should include a specific anti-staphylococcal agent.