CHRONIC CHANGES IN BLOOD-FLOW ALTER ENDOTHELIUM-DEPENDENT RESPONSES IN AUTOGENOUS VEIN GRAFTS IN DOGS

Purpose: Experiments were designed to determine the effects of blood flow on endothelium-dependent relaxations in canine vein grafts. Methods: Blood flow through reversed femoral vein grafts was either increased by a distal arteriovenous fistula (increased flow), unmanipulated (normal flow), or reduced by a proximal adjustable clamp (reduced flow). Six weeks after implantation, blood flow through the graft was measured. Rings cut from grafts were suspended for the measurement of isometric force in organ chambers to determine endothelial function. Results: Blood flow was significantly greater in grafts with a distal fistula compared to grafts with normal or decreased flow. Endothelium-dependent relaxations to acetylcholine were absent in all grafts. Endothelium-dependent relaxations to adenosine diphosphate, thrombin, and the calcium ionophore A23187 were less in grafts with reduced flow compared with grafts with increased flow. Relaxations to these agents in grafts with increased how were reduced by an analog of L-arginine. Neointimal hyperplasia was increased in grafts with reduced flow. Conclusions: These data demonstrate that chronic diminution of blood flow decreases receptor-mediated release of endothelium-derived relaxing factors and increases neointimal hyperplasia in canine vein grafts. The production of endothelium-derived relaxing factors, one of which is nitric oxide, may influence the development of myointimal hyperplasia in vein grafts.