ENHANCEMENT OF TISSUE FACTOR EXPRESSION BY VEIN SEGMENTS EXPOSED TO CORONARY ARTERIAL HEMODYNAMICS

Purpose: Although saphenous vein is the most reliable conduit for arte rial interposition procedures in the coronary circulation, graft throm bosis remains a clinical problem. We hypothesized that an important fa ctor in early graft thrombosis is sudden change in the hemodynamic env ironment of the vein as it is placed in the coronary circulation. Meth ods: We used an ex vivo perfusion system to study freshly excised segm ents of human saphenous vein (HSV) and pig internal jugular vein. For coronary graft (CAVG) simulation, sections of HSV were subjected to ar terial pulsatile pressure and now and twisting and stretching to mimic deformations caused by the beating heart. Using functional and immuno histochemical assays, we investigated the effect of these conditions o n expression of tissue factor (TF), an important prothrombotic surface molecule. Results: In each of 11 experiments (6 human, 5 porcine), ve in segments from a single donor were subjected to venous conditions (V EN), CAVG perfusion, or no perfusion. Expression of TF was measured as the amount of factor Xa generated per unit area of luminal vein surfa ce. VEN perfusion did not cause a significant change in mean TF expres sion over nonperfused control values (human: 14.3 +/- 1.5 versus 11.4 +/- 2.3 U/cm(2), p = 0.31; pig: 11.6 +/- 1.5 versus 12.5 +/- 1.4 U/cm( 2), p = 0.70). CAVG perfusion led to significant enhancement of TF exp ression over VEN perfusion (human: 36.8 +/- 6.2 versus 14.3 +/- 1.5 U/ cm(2), p < 0.05; pig: 40.0 +/- 9.9 versus 11.6 +/- 1.5 U/cm(2), p < 0. 05). Immunohistochemical analysis showed positive TF staining on the l uminal side of a CAVG-stimulated HSV segment, but not on a VEN-stimula ted segment. In four additional studies, HSV segments were subjected t o arterial perfusion without twist and stretch to mimic lower extremit y arterial interposition grafts. TF expression for lower extremity ven ous graft perfusion was significantly higher than for VEN perfusion (2 5.3 +/- 2.5 versus 14.3 +/- 1.5, p < 0.01) but not significantly diffe rent from CAVG perfusion. Conclusions: Our studies in a unique perfusi on system suggest that exposure of vein to coronary arterial hemodynam ic conditions results in elevated expression of the important prothrom botic molecule TF. This phenomenon may contribute to early graft throm bosis.