Differential Effect of Heparin Coating and Complement Inhibition on Artificial Surface- Induced Eicosanoid Production Knut Tore Lappegård, MD, Johan Riesenfeld,

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Differential Effect of Heparin Coating and Complement Inhibition on Artificial Surface- Induced Eicosanoid Production Knut Tore Lappegård, MD, Johan Riesenfeld, PhD, Ole-Lars Brekke, MD, PhD, Grethe Bergseth, BS, John D. Lambris, PhD, Tom Eirik Mollnes, MD, PhD The Annals of Thoracic Surgery Volume 79, Issue 3, Pages 917-923 (March 2005) DOI: 10.1016/j.athoracsur.2004.08.015 Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions

Fig 1 Polyvinyl chloride-induced (PVC) synthesis of leukotriene B4 (LTB4) (pg/mL) in human whole blood. Human whole blood, with or without complement inhibitors or indomethacin, was circulated for 4 hours in segments of tubing rotated as closed loops, whereupon the LTB4 concentration in plasma was measured by enzyme-linked immunosorbent assay. (T0 = baseline values; PVC = PVC loops. Heparin = heparin-coated loops; Compstatin 5 or 25 μmol/L; C5aRA = C5a receptor antagonist 1 or 5 μmol/L; indomethacin 2 or 10 μmol/L. Inhibitors were added to blood incubated in uncoated PVC only; # = p < 0.001 versus baseline; * = p < 0.05; ** = p < 0.02; *** = p < 0.01; **** = p < 0.001; all versus PVC; data are presented as mean ± standard error of the mean). The Annals of Thoracic Surgery 2005 79, 917-923DOI: (10.1016/j.athoracsur.2004.08.015) Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions

Fig 2 Polyvinyl chloride-induced (PVC) synthesis of prostaglandin E2 (PGE2) (pg/mL) in human whole blood. Human whole blood, with or without complement inhibitors or indomethacin, was circulated for 4 hours in segments of tubing rotated as closed loops, whereupon the PGE2 concentration in plasma was measured by enzyme-linked immunosorbent assay. (T0 = baseline values; PVC = PVC loops; Heparin = heparin-coated loops; Compstatin 5 or 25 μmol/L; C5aRA = C5a receptor antagonist 1 or 5 µmol/L; indomethacin 2 or 10 μmol/L. Inhibitors were added to blood incubated in uncoated PVC only; # = p < 0.001 versus baseline; * = p < 0.05; *** = p < 0.01; **** = p < 0.001; all versus PVC; data are presented as mean ± standard error of the mean). The Annals of Thoracic Surgery 2005 79, 917-923DOI: (10.1016/j.athoracsur.2004.08.015) Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions

Fig 3 Polyvinyl chloride-induced (PVC) synthesis of thromboxane B2 (TXB2) (pg/mL) in human whole blood. Human whole blood, with or without complement inhibitors or indomethacin, was circulated for 4 hours in segments of tubing rotated as closed loops, whereupon the TXB2 concentration in plasma was measured by enzyme-linked immunosorbent assay. (T0 = baseline values; PVC = PVC loops; Heparin = heparin-coated loops; Compstatin 5 or 25 μmol/L; C5aRA = C5a receptor antagonist 1 or 5 μmol/L; indomethacin 2 or 10 μmol/L. Inhibitors were added to blood incubated in uncoated PVC only; data are presented as mean ± standard error of the mean; # = p < 0.001 versus baseline; * = p < 0.05; **** = p < 0.001; both versus PVC.) The Annals of Thoracic Surgery 2005 79, 917-923DOI: (10.1016/j.athoracsur.2004.08.015) Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions

Fig 4 Polyvinyl chloride-induced (PVC) complement activation in human whole blood. Human whole blood, with or without complement inhibitors, was circulated for 4 hours in segments of tubing rotated as closed loops, whereupon the concentration of the terminal complement complex (TCC) in plasma was measured by enzyme-linked immunosorbent assay. (T0 = baseline values; PVC = PVC loops; Heparin = heparin-coated loops; Compstatin 5 or 25 μmol/L; C5aRA = C5a receptor antagonist 1 or 5 μmol/L; indomethacin 2 or 10 μmol/L. Inhibitors were added to blood incubated in uncoated PVC only; data are presented as mean ± standard error of the mean; AU = arbitrary units; # = p < 0.001 versus baseline; *** = p < 0.01 versus PVC.) The Annals of Thoracic Surgery 2005 79, 917-923DOI: (10.1016/j.athoracsur.2004.08.015) Copyright © 2005 The Society of Thoracic Surgeons Terms and Conditions