Svein Tore Baksaas

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) × 109/l, and increased in the control group from 6.5 (5.1-8.0) to 7.4 (5.7-9.0) × 109/l. Two hours postoperatively the total white blood cell count in the leucocyte-depleted group was 14.7 (12.1-17.2) × 109/l, and in the control group 17.6 (14.5-20.7) × 109/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.

Sternal wound infections in patients undergoing open heart surgery: randomized study comparing intracutaneous and transcutaneous suture techniques

BACKGROUNDnIntracutaneous suture technique has been our standard method for closing sternal wounds in cardiac surgery, mainly for cosmetic reasons. However, an increased rate of postoperative infections has been reported in cosmetic surgery with this method compared with the percutanous or transcutaneous closure technique. A comparison of these two techniques in cardiac surgery is presented.nnnMETHODSnIn a randomized study, 300 patients were selected to intracutaneous suture (n = 150) or percutanous suture (n = 150). The endpoints were superficial and deep sternal wound infections within 6 weeks postoperatively.nnnRESULTSnThe total infection rate was lower in the percutanous group compared with the intracutaneous group (3% versus 8%) (p = 0.007). The superficial infection rate was lower in the percutaneous group (2.3% versus 6.7%) (p = 0.01), whereas there was no statistically significant difference in the deep infection rate between the groups.nnnCONCLUSIONSnThe percutaneous suture technique reduces the incidence of superficial wound infections, but not the deep infection rate in open heart surgery. There was no difference in the cosmetic results on a visual scale, assessed by the patients.

Leucocyte filtration during cardiopulmonary bypass hardly changed leucocyte counts and did not influence myeloperoxidase, complement, cytokines or platelets

In some patients, coronary artery bypass surgery induces postoperative organ dysfunction despite an apparently adequate revascularization and good haemodynamic performance. This complication may be caused by activation of the body’s inflammatory systems on blood contact with large foreign surfaces in the extracorporeal circuit. Activated leucocytes may play an important role in organ damage, and it is conceivable that leucocyte removal by filtration may decrease the potential side-effects of cardiopulmonary bypass (CPB). The aim of the present study was to investigate possible effects of leucocyte filtration during the whole CPB period in elective coronary artery bypass surgery on biochemical and clinical parameters. Forty patients were randomized to extracorporeal circulation using a leucocyte-depleting filter (group L, n = 20) or to extracorporeal circulation with no leucocyte filter (group C, n = 20). In the leucocyte-depleted group, the mean total white blood cell counts increased from 6.3 (95% confidence interval, 5.5 - 7.0) × 109/l to 7.0 (5.7 - 8.3) × 109/l during extracorporeal circulation and in the control group from 6.3 (5.2 - 7.3) × 109/l to 8.5 (7.2 - 9.8) × 109/l. The intergroup difference was not statistically significant (p = 0.84). A substantial increase in concentrations of interleukin-6, myeloperoxidase and complement activation products were observed in both groups without statistically significant intergroup differences. It is concluded that the leucocyte-depletion filter did not cause a significant reduction of circulating white blood cells during CPB, and there were no significant differences between the groups with respect to the inflammatory markers studied.

In vitro evaluation of new surface coatings for extracorporeal circulation

Cardiopulmonary bypass (CPB) exposes blood to large, foreign surfaces. This exposure may activate the cellular and humoral inflammatory systems, resulting in inflammatory reactions and organ dysfunction. Coating the inner surfaces of the bypass circuit may help alleviate these side-effects. The objective of this study was to determine the influence of two new surface treatments on blood cell and complement activation. Oxygenator and tubing sets coated with synthetic polymers (n = 7) or heparin (n = 7) were compared to uncoated sets (n = 7) in an in vitro model of CPB. The circuits were run at 4 l/min and recirculated for 120 min. The inflammatory response was assessed at regular intervals by platelet counts, and activation of complement, leucocytes and platelets. We found that the median platelet counts decreased from 127 to 122 × 109/l (not significant, NS) in the synthetic polymer sets, from 96 to 88 × 109/l (NS) in the heparin-coated sets, and from 93 to 54 × 109/l (p < 0.01) in the uncoated sets after 2 h of recirculation. There were significant differences in platelet counts between the coated sets and the uncoated set at end of experiments (p < 0.05). Beta-thromboglobulin (BTG) concentrations increased in the synthetic polymer sets from 166 to 352 ng/ml (p < 0.01), in the heparin coated sets from 336 to 1168 ng/ml (p < 0.01), and in the uncoated sets from 301 to 3149 ng/ml (p < 0.01) after 2 h of recirculation. The differences in BTG at termination of the experiments were significant among all three sets (p < 0.05). Myeloperoxidase (MPO) concentrations in the synthetic polymer sets increased from 63 to 86 μg/l (p < 0.01), in the heparin-coated sets from 90 to 208 μg/l (p < 0.01), and in the uncoated sets from 122 to 513 μg/l (p < 0.01) after 2 h of recirculation. The differences in MPO at termination of the experiments were significant among all three groups (p < 0.01). There were no significant differences at termination of the experiments among the three sets regarding complement activation as measured by C3 activation products and the terminal complement complex. We conclude that in the current in vitro model of a CPB circuit, the synthetic polymer coating and the heparin coating caused significantly less platelet loss and granulocyte and platelet activation than the uncoated surface (p < 0.05). The synthetic polymer coating caused significantly less granulocyte and platelet activation than the heparin coating (p < 0.05). There was moderate complement activation within each group, but no significant differences among the three groups.

Comparison of three oxygenator-coated and one total-circuit-coated extracorporeal devices

The present study was designed to compare the biocompatibility of three cardiopulmonary bypass setups with different surface coatings, and to determine if coating of the whole circuit with one of the coatings was more beneficial than coating of the oxygenator only. Extracorporeal devices entirely coated with synthetic polymers (Avecor, n = 6) were compared to oxygenators coated with synthetic polymers (Avecor, n = 6), end-point, covalently attached heparin (CBAS, n = 6) or absorbed heparin (Duraflo 2, n = 6) in an in vitro model of a heart-lung machine. The circuits were primed with fresh human whole blood and Ringer’s acetate and recirculated at 4 l/min at 30°C for 2 h. Test samples were obtained at regular intervals and analysed for myeloperoxidase (MPO), platelet counts, β-thromboglobulin, heparin, prothrombin fragment 1+2, plasmin-anti-plasmin complexes, and complement activation products. The mean MPO concentrations increased in the Avecor-coated oxygenator group (AV) from 247 at the start to 671 μg/l at the termination of the experiments, in the Avecor-coated total circuit group (AV-T) from 116 to 288 μg/l, in the Duraflo 2 coated oxygenator group (DU) from 160 to 332 μg/l, and in the CBAS-coated oxygenator (CA) group from 172 to 311 μg/l. The MPO concentrations increased significantly in all groups (p < 0.03). The increase in group A was significantly higher than in the other three groups (p = 0.007). The mean platelet counts decreased in the Avecor-coated total circuit group from 117 at start to 99 × 109/l at termination of the experiments, in the Avecor-coated oxygenator group from 119 to 103 × 109/l, in the Duraflo 2 group from 96 to 86 × 109/l, and in the CBAS group from 132 to 123 × 109/l. The platelet counts decreased significantly in all groups (p < 0.01), but the intergroup differences were not significant (p = 0.15). The mean β-thromboglobulin concentrations increased in the Avecor-coated total circuit group from 193 at the start to 754 ng/ml at the termination of the experiments, in the Avecor-coated oxygenator group from 474 to 1654 ng/l, in the Duraflo 2 group from 496 to 1280 ng/l, and in the CBAS group from 418 to 747 ng/l. The β-thromboglobulin increase was significant in each group (p < 0.01), but not between the groups (p = 0.49). The mean heparin concentrations in the Duraflo 2 group increased from 2460 at the start to 2897 IU/l at termination of the experiments, in the CBAS group from 2468 to 2518 IU/l. In the Avecor-coated oxygenator group heparin concentrations decreased from 2010 to 1968 IU/l, and in the Avecor-coated total circuit group from 2002 to 1927 IU/l. The differences in heparin concentrations were significant between the Duraflo 2 group and the other groups (p < 0.05). The mean prothrombin fragment 1+2 concentrations increased in the CBAS group from 0.4 at the start to 2.1 nmol/l at the end of the experiments, in the Avecor-coated oxygenator group from 0.4 to 0.6 nmol/l, in the Avecor-coated total circuit group from 0.3 to 0.4 nmol/l, and in the Duraflo 2 group from 1.2 to 1.3 nmol/l. The prothrombin fragment 1+2 increase was significant in all groups (p < 0.05), but there were no significant intergroup differences (p = 0.54). There were no significant differences at the termination of the experiments among the four groups regarding complement activation as measured by C3 activation products and the terminal complement complex. In the present in vitro model of a heart-lung machine, none of the three specific setups with different coatings was superior with regard to all test parameters. The CBAS group generated the highest levels of prothrombin fragment 1+2 formation, but least complement activation. The increasing plasma heparin concentrations in the Duraflo 2 group indicated more unstable heparin bonding. The Avecor-coated total circuit group were superior to the Avecor-coated oxygenator group regarding plasma concentrations of MPO, but not compared to the CBAS and Duraflo 2-coated oxygenator groups.

Changes in the cytokine network and complement parameters during open heart surgery

OBJECTIVESnDuring cardiac surgery with cardiopulmonary bypass (CBP) there is a systemic inflammatory reaction, involving enhanced release of inflammatory cytokines and complement. However, few studies have analysed the levels of anti-inflammatory mediators and chemokines after CPB. In this study we investigated the complexity of the cytokine network particularly focusing on the balance between interleukin (IL)-10 and inflammatory cytokines and chemokines.nnnMETHODSnBlood samples from 20 patients (seven females; 13 males, age 30-81 (median 65) years) who underwent CPB, were collected before, and at several time points after surgery ,and analyzed for plasma levels of inflammatory and anti-inflammatory cytokines and parameters of complement activation.nnnRESULTSnA marked increase in the anti-inflammatory cytokine IL-10, rather than in inflammatory cytokines, characterized the initial phase after CBP. As for the early inflammatory response the most prominent feature was a rise in the inflammatory chemokines IL-8 and monocyte chemoattractant protein-1, while the increase in tumor necrosis factor-alpha was rather modest. In contrast to the rapid rise and fall in most of the markers, significantly raised IL-6 levels persisted throughout the study. Immediately after CPB there was also a marked increase in complement activation, with return to baseline levels on the first postoperative day.nnnCONCLUSIONnThe present study shows a complex pattern of changes in the cytokine network and complement parameters during CBP with a marked rise in both inflammatory and anti-inflammatory mediators. However, in contrast to cytokine pattern during various infections, the initial phase after CPB was dominated by a marked rise in anti-inflammatory cytokines (i.e. IL-10).

Leg Wound Closure after Saphenous Vein Harvesting in Patients Undergoing Coronary Artery Bypass Grafting: A Prospective Randomized Study Comparing Intracutaneous, Transcutaneous and Zipper Techniques

Objective : Two prospective randomized studies were undertaken to compare different suture closure techniques with respect to postoperative wound infection rates and cosmetic results after saphenous vein harvesting in patients undergoing coronary artery bypass surgery. Design : A total of 166 patients were included in the first study, in which 85 had their leg wounds closed with transcutaneous and 81 with intracutaneous suture. In the second study, 168 patients were selected to a non-invasive surgical zipper ( n = 78) or intracutaneous suture ( n = 90). Results : In the first study the overall infection rate was 20.5%, 17.6% in the transcutaneous group compared with 23.5% in the intracutaneous group ( p = 0.35). In the second study the infection rate was 19.3%, 15.3% in the zipper group vs 23.3% in the intracutaneous group ( p = 0.20). On a cosmetic scale from 1 to 10, an average score of 8.0 was obtained in the percutaneous (p.c.) group vs 8.3 in the intracutaneous (i.c.) group ( p = 0.35), and 9.0 in the zipper group vs 8.4 in the i.c. group ( p = 0.003). Conclusion : The incidence of leg wound infection after saphenous vein harvesting in coronary artery bypass graft surgery is high. The zipper closing method may give a lower infection rate and a better cosmetic result compared with the intracutaneous suture.

Effects on Complement, Granulocytes and Platelets of a Leukocyte-Depletion Filter During in vitro Extracorporeal Circulation

In an in vitro study, extracorporeal circuits equipped with either a leukocyte-depleting filter (n = 5) or a standard arterial-line filter (n = 5) were perfused for 120 minutes with fresh human whole blood. Leukocyte activation, leukocyte and platelet counts and complement activation were studied. Significant reduction of leukocyte and platelet counts and significant activation of leukocytes and of platelets were found in both groups, but without significant intergroup difference for any parameter after 120 minutes of perfusion. The leukocyte-depleting filters, however, were somewhat more effective in removing leukocytes during the initial 30 minutes of circulation.

Complement activation and cytokine and chemokines release during mediastinitis.

BACKGROUNDnMediastinitis after open heart operation is an infrequent, but life-threatening complication with a reported incidence rate between 1% and 4%. Hospital mortality is estimated at 10% to 35%. The aim of the present work was to study the systemic inflammatory reaction as judged by complement activation and cytokine and chemokines release in patients with mediastinitis after open heart operation.nnnMETHODSnSeven patients with clinical signs of mediastinitis were included. Three patients had undergone coronary artery bypass grafting, whereas 4 patients had combined coronary artery bypass grafting, valve replacement, or valvuloplasty. Blood samples were drawn before induction of anesthesia and at the time of reoperation, and thereafter daily during the hospital stay. Controls comprised similar patients with an uneventful postoperative course.nnnRESULTSnThe terminal SC5b-9 complement complex concentration in the mediastinitis patients was substantially higher compared with the controls (p < 0.001), and the terminal SC5b-9 complement complex values showed no overlap between the two groups. Interleukin-8, stromal cell-derived factor-1alpha and IL-6 concentrations were also significantly higher in the mediastinitis group than in the control group (p < 0.001), but with considerable overlap between the groups. Interleukin-1beta, interleukin-10, and monocyte chemoattractant protein-1 concentrations were slightly higher in the mediastinitis group, and no differences were seen for the tumor necrosis factor-alpha.nnnCONCLUSIONSnDuring mediastinitis, the complement is activated and the cytokines and chemokines, interleukin-6, interleukin-8, and stromal cell-derived factor-1alpha are released. These proteins may be involved in the pathogenesis of this complication. Terminal SC5b-9 complement complex may be an indicator to discriminate mediastinitis patients from those with uneventful course.

Comparison of a Duraflo II-coated cardiopulmonary bypass circuit and a trillium-coated oxygenator during open-heart surgery:

Background: Cardiopulmonary bypass (CPB) evokes a systemic inflammatory response. In attempting to improve the biocompatibility of the equipment, various methods to coat the inner surfaces of the CPB systems have been developed. The present study compares a Trillium Biopassive surface-coated Affinity oxygenator with a Duraflo II totally heparin-coated CPB system. Methods: Low-risk patients admitted for primary coronary artery bypass grafting or aortic valve replacement were randomized to operation using the Trillium- or the Duraflo II-coated setups. Heparin concentration, complement activation (C3bc activation products and terminal complement complex (TCC)), platelet activation (platelet numbers and beta-thromboglobulin (BTG)), leukocyte activation (leukocyte numbers and myeloperoxidase (MPO)), coagulation (thrombin/antithrombin complexes (TAT)) and fibrinolytic activity (plasmin/a2-antiplasmin complexes (PAP)) were measured during CPB and two hours postoperatively. Results: Platelet counts decreased during CPB, without significant intergroup differences. The median BTG concentration increased moderately in both groups and were slightly higher in the Trillium group during CPB (p B-0.05), but not postoperatively. Complement activation products (C3bc and TCC), leukocyte counts, MPO, TAT and PAP activity showed no differences between the two groups. Conclusions: There were small differences in the inflammatory response between the two extracorporeal circulation devices compared in this study.