FLOW-MEDIATED FIBRIN THROMBUS FORMATION IN AN ENDOTHELIUM-LINED MODELOF ARTERIAL BRANCHING

In vivo arterial thrombosis occurs preferentially at curvatures and br anchings, i.e. regions of flow separation and recirculation where bloo d is retained orders of magnitude longer than within straight vessel s ections. To examine the effect of such disturbed flow on endothelial t hromboresistance glass T-branchings lined with endothelial cells from human umbilical cord veins (HUVEC) were perfused with buffered fibrino gen solution (3mg/ml). The flow was adjusted to form a large recircula tion zone and flow conditions were determined beforehand by means of f low visualization via dye injection as well as by laser ultramicroscop e anemometry. Thrombus formation, which was registered on-line by vide o and evaluated planimetrically, was induced by injection of thrombin at concentrations ranging from 0.3 to 2.0 units/ml. Fibrin thrombus gr owth always began within the flow niche at the point of flow separatio n and extended downstream along the wall and into the vessel lumen fin ally occluding up to 80% of the lumen. Light and electron microscopy r evealed that overall thrombus form as well as the orientation of singl e fibrin fibers were correlated strictly to the prevailing streamlines . Despite the integrity of the endothelial lining fibrin thrombus form ation occurred. The fibrin fibers closely contacted the endothelial su rface. These results indicate that recirculation zones promote fibrin thrombus formation sufficient to obstruct the vessel lumen and that in tact endothelium alone is insufficient in preventing adhesion of fibri n to its surface.