The influence of different heparin surface concentrations and antithrombin-binding capacity on inflammation and coagulation

被引:44
作者
Johnell, M
Larsson, R
Siegbahn, A [1 ]
机构
[1] Uppsala Univ, Akad Hosp, Lab Coagulat Res, Dept Med Sci, SE-75185 Uppsala, Sweden
[2] Akad Hosp, Dept Oncol Radiol & Clin Immunol, Clin Immunol Sect, Rudbeck Lab C5, SE-75185 Uppsala, Sweden
关键词
heparin; biomaterial; biocompatibility; cell activation;
D O I
10.1016/j.biomaterials.2004.05.029
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
The corline heparin surface (CHS) used in the extracorporeal circuit during coronary artery bypass grafting is shown to decrease the activation of inflammation and coagulation. Synchrotron radiation studies have shown that a single layer of the CHS may not completely cover the substrate surface. However, a double layer of CHS results in a uniform surface. We investigated the effect of surfaces with different surface concentrations of heparin on cell activation and coagulation compared to an uncoated surface. The CHS is prepared by a conditioning layer of polymeric amine onto which a macromolecular heparin conjugate is attached. We used PVC tubing, uncoated or modified with a single or double layer of the CHS, and circulated fresh whole blood from healthy volunteers in a loop model system at 37degreesC up to 4h. Blood was drawn from the loops at different times and activation of inflammation and coagulation was studied by real-time PCR, flow cytometry and ELISA. The activation of leukocytes and platelets and formation of leukocyte-platelet aggregates were reduced by use of the single-layered CHS compared to the uncoated surface. Use of double-layered CHS resulted in significantly reduced cell activation and thrombin generation. Development of the CHS obtained by the double layer of the coating has improved the biocompatibility of the surface. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1731 / 1739
页数:9
相关论文
共 28 条
[21]   Role of platelet P-selectin and CD40 ligand in the induction of monocytic tissue factor expression [J].
Lindmark, E ;
Tenno, T ;
Siegbahn, A .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2000, 20 (10) :2322-2328
[22]   A quantitative real-time PCR method for tissue factor mRNA [J].
Mälarstig, A ;
Tenno, T ;
Jossan, S ;
Åberg, M ;
Siegbahn, A .
THROMBOSIS RESEARCH, 2003, 112 (03) :175-183
[23]  
Morrissey JH, 2001, THROMB HAEMOSTASIS, V86, P66
[24]   Induction of cytokine expression in leukocytes by binding of thrombin-stimulated platelets [J].
Neumann, FJ ;
Marx, N ;
Gawaz, M ;
Brand, K ;
Ott, I ;
Rokitta, C ;
Sticherling, C ;
Meinl, C ;
May, A ;
Schomig, A .
CIRCULATION, 1997, 95 (10) :2387-2394
[25]   Active site-inhibited seven: Mechanism of action including signal transduction [J].
Petersen, LC .
SEMINARS IN HEMATOLOGY, 2001, 38 (04) :39-42
[26]   FIBRIN(OGEN) MEDIATES ACUTE INFLAMMATORY RESPONSES TO BIOMATERIALS [J].
TANG, LP ;
EATON, JW .
JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 178 (06) :2147-2156
[27]   The role of RAR and RXR activation in retinoid-induced tissue factor suppression [J].
Tenno, T ;
Botling, J ;
Öberg, F ;
Jossan, S ;
Nilsson, K ;
Siegbahn, A .
LEUKEMIA, 2000, 14 (06) :1105-1111
[28]   Coating-techniques to improve the hemocompatibility of artificial devices used for extracorporeal circulation [J].
Wendel, HP ;
Ziemer, G .
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY, 1999, 16 (03) :342-350