Arterial flow induces changes in venous endothelium which are modified by calcium channel blockers

Introduction: adaptation of saphenous vein to arterial flow may be critical to the results of bypass. The present paper summarizes work recently presented as a Hunterian Lecture. Work includes in vitro investigation of the response of saphenous vein endothelium to arterial flow and assessment of its clinical importance using a cohort of patients undergoing vein bypass surgery. Methods: freshly excised human saphenous vein segments were placed in an in vitro flow circuit to simulate arterial and venous flow conditions. Changes in the endothelial expression of proteins were assessed using a combination of immunohistochemistry and Western blotting. The role of ion channels in the changes seen induced by arterial flow in the saphenous vein endothelium was assessed by addition of ion channel blocking medication to the medium perfusing vein segments. A cohort of patients undergoing vein bypass surgery were followed to assess graft patency and the influence of prescribed medication on its outcome. Results: after arterial flow conditions, the staining area for the endothelial adhesin ICAM-1 and nitric oxide synthase were increased, while that of the anticoagulant protein thrombomodulin was decreased. The concentration of the important stimulant of the clotting cascade tissue factor was unaffected by arterial flow. These changes were modulated by the addition of ion channel blocking drugs to the vein perfusate. In particular, nifedipine abolished the reduction in thrombomodulin, but increased the amount of tissue factor. In a series of 236 patients undergoing primary infra-inguinal vein grafts, prescription of calcium channel blocker was associated with improved primary patency. Conclusions: important changes in the venous endothelium are induced by arterial flow. Ion channel blocking drugs have the potential to modulate these responses