Complement activation during cardiopulmonary bypass: Effects of immobilized heparin

Pekna, Marcela; Hagman, Leif; Haldén, E.; Nilsson, Ulf; Nilsson, Bo; Thelin, Stefan

doi:10.1016/0003-4975(94)92219-5

Cited by 79 publications

(21 citation statements)

References 28 publications

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“…2,4,9 The finding that none of the inflammatory markers increased in the heparin-coated loops confirms that the activation phenomena studied indeed reflect properties of the artificial material and that coating with heparin dramatically improves the biocompatibility, presumably due to the endothelial cell like properties of this surface modification. [17][18][19][20][21] In previous clinical trials with CPB, investigation of inflammatory mediators has to a large extent focused on cytokines. Based on our results, we suggest that a broader range of mediators, including chemokines and growth factors, should be evaluated in future trials.…”

Section: Discussionmentioning

confidence: 99%

The artificial surface‐induced whole blood inflammatory reaction revealed by increases in a series of chemokines and growth factors is largely complement dependent

Lappegård

Bergseth

Riesenfeld³

et al. 2007

J Biomedical Materials Res

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Exposing blood to an artificial surface results in a systemic inflammatory response, including cytokine release and complement activation. We studied the artificial surface-induced inflammation in human whole blood using an extensive panel of inflammatory mediators including proinflammatory cytokines, chemokines and growth-factors and investigated the role of the complement system in the induction of this response. Using multiplex technology, 27 different inflammatory mediators were measured after circulating blood for 4 hours in polyvinyl chloride tubing. The C3 inhibitor compstatin was used to block complement activation. A significant (p < 0.05) increase in 14 of the 27 mediators was induced by the surface, of which 7 were chemokines (IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, eotaxin and IP-10) and 5 were growth-factors (G-CSF, GM-CSF, VEGF, PDGF and FGF). The traditional proinflammatory cytokines like IL-1β, TNFα and IL-6 were not induced, although IL-6, as well as IL-15 and IL-17 increased if the surface was coated with highly bioincompatible laminaran. Inhibition of complement activation with compstatin significantly (p < 0.05) reduced the formation of 12 of the 14 mediators. For 10 of the 12 mediators, the inhibition was by 2/3 or more, for the remaining two the inhibition was more moderate. A highly biocompatible heparin-coated PVC surface was used as negative control and completely abolished the whole inflammatory response. The artificial surface PVC markedly induced a broad spectrum of chemokines and growth-factors, which was largely dependent on activation of complement.

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Section: Discussionmentioning

confidence: 99%

The artificial surface‐induced whole blood inflammatory reaction revealed by increases in a series of chemokines and growth factors is largely complement dependent

Lappegård

Bergseth

Riesenfeld³

et al. 2007

J Biomedical Materials Res

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“…Moreover, complement activation was higher when CABG had been performed [11]–[13]. However, taking into account that the involved markers reach peak plasma levels at different clinical stages, comparisons made on inflammatory markers alone might be misinterpreted [14], [15]. For this reason it is desirable to assess perioperative immune alterations not exclusively by measuring the concentration of individually selected key mediators at different time points, but also at a functional level, by assessing the sensitivity or responsiveness of inflammatory effector cells.…”

Section: Introductionmentioning

confidence: 99%

CD62L (L-Selectin) Shedding for Assessment of Perioperative Immune Sensitivity in Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass

Erdoes

Balmer²,

Slack

et al. 2013

PLoS ONE

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ObjectiveTo investigate the suitability of blood granulocyte and monocyte sensitivity, as measured by the quantity of different agonists required to induce CD62L shedding, for assessment of perioperative immune changes in patients undergoing cardiac surgery with cardiopulmonary bypass.MethodsPatients scheduled for aortocoronary bypass grafting or for valve surgery were included in this prospective observational study. Blood samples were drawn before anesthesia induction, directly after surgery and 48 hours after anesthesia induction. We determined the concentration of two different inflammatory stimuli – lipoteichoic acid (LTA) and tumor necrosis factor alpha (TNF) - required to induce shedding of 50% of surface CD62L from blood granulocytes and monocytes. In parallel monocyte surface human leukocyte antigen (HLA)-DR, and plasma interleukin (IL)-8, soluble (s)CD62L, soluble (s)Toll-like receptor (TLR)-2 and ADAM17 quantification were used to illustrate perioperative immunomodulation.Results25 patients were enrolled. Blood granulocytes and monocytes showed decreased sensitivity to the TLR 2/6 agonist Staphylococcus aureus LTA immediately after surgery (p = 0.001 and p = 0.004 respectively). In contrast, granulocytes (p = 0.01), but not monocytes (p = 0.057) displayed a decreased postoperative sensitivity to TNF. We confirmed the presence of a systemic inflammatory response and a decreased immune sensitivity in the post-surgical period by measuring significant increases in the perioperative plasma concentration of IL-8 (p≤0.001) and sTLR (p = 0.004), and decreases in monocyte HLA-DR (p<0.001), plasma sCD62L (p≤0.001). In contrast, ADAM17 plasma levels did not show significant differences over the observation period (p = 0.401).ConclusionsMonitoring granulocyte and monocyte sensitivity using the “CD62L shedding assay” in the perioperative period in cardiac surgical patients treated with the use of cardiopulmonary bypass reveals common changes in sensitivity to TLR2/6 ligands and to TNF stimulus. Further long-term follow-up studies will address the predictive value of these observations for clinical purposes.

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“…The benefit of heparin-coated circuits appears to be in their ability to decrease the inflammatory effects of CPB [7]. What has been consistently demonstrated is the capacity of heparincoated surfaces to decrease complement activation [54] independent of the heparin dose, with consistent evidence of decreased generation of terminal complement complex [55][56][57]. Other demonstrated anti-inflammatory effects include decreased leukocyte surface activation markers [44], decreased cytokine release [45] and decreased monocyte tissue factor expression [46].…”

Section: Clinical Results With Heparin-coated Circuits In Cardiopulmomentioning

confidence: 98%

Currently available biomaterials for use in cardiopulmonary bypass

Belway¹,

Rubens²

2006

Expert Review of Medical Devices

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Cardiopulmonary bypass (CPB) represents one of the most important technical innovations in healthcare history, yet the systemic responses to CPB remain a fundamentally unresolved problem. Study of the blood-biomaterial interaction and development of biocompatible materials is intimately related to efforts to optimize patient outcome following CPB. This article reviews the design innovations in biomaterial surfaces that have been introduced into clinical practice in an attempt to ameliorate the detrimental consequences of CPB, contrasting the actual clinical improvements and patient benefits achieved against those predicted on the basis of theory and in vitro testing. Some discussion of the underlying mechanisms of action as presently understood is provided and the current limitations of biomaterial-dependent strategies to improve outcome following CPB are addressed.

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Complement activation during cardiopulmonary bypass: Effects of immobilized heparin

Cited by 79 publications

References 28 publications

The artificial surface‐induced whole blood inflammatory reaction revealed by increases in a series of chemokines and growth factors is largely complement dependent

The artificial surface‐induced whole blood inflammatory reaction revealed by increases in a series of chemokines and growth factors is largely complement dependent

CD62L (L-Selectin) Shedding for Assessment of Perioperative Immune Sensitivity in Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass

Currently available biomaterials for use in cardiopulmonary bypass

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