Heparin coating reduces cell activation and mediator release in an in vitro venovenous bypass model for liver transplantation.
We used an in vitro model for venovenous bypass in a prospective, randomized study to analyze the effect on leukocytes cell activation after coating the total blood contact surface with covalently bound heparin. In ten experiments heparin-coated circuits were used, and in ten other experiments noncoated circuits were used. Monocyte cytokine production and neutrophil myeloperoxidase release were analyzed. Monocytes were isolated using anti-CD14 paramagnetic beads, and oligo (dT)25 beads were used to isolate mRNA before subsequent reverse transcription and semiquantitative amplification of various cytokines in order to determine time-related changes in expression during bypass. After 2 h, mRNAs for IL-1 beta and IL-6 were highly upregulated in noncoated compared to heparin-coated circuits. Little or no change was seen in the expression of other cytokines. IL-1 beta and IL-6 were measured in plasma after 12 h and reflected the upregulated mRNAs in noncoated circuits. A significantly reduced release of myeloperoxidase was observed in coated versus noncoated circuits. This indicates that heparin-coated surfaces reduce cellular activation and the release of inflammatory mediators.
Institute for Surgical Research, Rikshospitalet, National Hospital, Oslo, Norway. rigmor.solberg@basalmed.uio.no
R
R
Solberg
T
T
Scholz
V
V
Videm
C
C
Okkenhaug
A O
AO
Aasen
D000925:Anticoagulants / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D016031:Liver Transplantation; D018375:Neutrophil Activation / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis
D000925:Anticoagulants; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D006493:Heparin; D009195:Peroxidase