Monocytes, Tissue Factor and Heparin-coated Surfaces : Clinical and Experimental Studies

• Cardiopulmonary bypass (CPB) is associated with inflammatory response and activation of coagulation. Heparin coating of the CPB circuit is shown to improve the biocompatibility of the surface. The biological effects of a new heparin surface, the Corline Heparin Surface (CHS), prepared according to a new principle, have been studied. The CHS used during coronary artery bypass grafting with CPB in sixty patients prevented adhesion of cells to the extracorporeal device. The activation of inflammation, coagulation, and fibrinolysis was significantly reduced by the use of CHS. Both a reduced and an increased dose of systemic heparin in combination with the heparin-coated surface resulted in more activation of inflammation and coagulation. Photoelectron spectroscopy studies of the molecular structure of the CHS demonstrated that a single layer of the heparin surface, equivalent to what was used in the in vivo studies, did not completely cover the substrate surface. Additional layer of immobilized heparin has resulted in a complete coverage. We examined the biological effects, i.e. activation of inflammation and coagulation, by CHS in one and two layers in an in vitro-study. The data from this study clearly demonstrated that a uniform surface coating of the CHS results in only minor activation of coagulation, inflammation and cell activation. Monocytes do not normally express tissue factor (TF), initiator of the coagulation in vivo, but can be induced upon adhesion to artificial surfaces. TF is receptor for coagulation factor VIIa (FVIIa) and binding subsequently leads to formation of thrombin. Other biological effects beyond coagulation, as inflammation and angiogenesis, has recently been associated with the formation of TF·FVIIa. The TF∙FVIIa signal transduction induced an increased sensitivity to PDGF-BB-stimulated migration and an increased production of IL-8 and TNF-α in monocytes. These could be important mechanisms for continued recruitment of cells to sites of inflammation.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)

Nyckelord

Medicine

monocytes

tissue factor

heparin-coated surfaces

coagulation

inflammation

thrombin

cytokines

cardiopulmonary bypass

biocompatibility

migration

chemotaxis

Medicin

Dermatology and venerology,clinical genetics, internal medicine

Dermatologi och venerologi, klinisk genetik, invärtesmedicin

Publikations- och innehållstyp

vet (ämneskategori)

dok (ämneskategori)