The development of an in vitro flow model of human saphenous vein graft intimal hyperplasia

Abstract

Although the role of blood flow has been investigated in animal models of intimal hyperplasia, there have been no detailed studies in intact human vein owing to the difficulties in designing a suitable laboratory model. The aim of this study was to develop a flow model of human vein graft intimal hyperplasia. Organ cultures of human saphenous vein were exposed to laminar flow by culturing in a closed circulatory system under predetermined conditions of venous and arterial shear stress for 14 days. Following fixation and processing, paraffin sections were immunostained and neointimal thicknesses measured. It was found that arterial flow completely inhibited neointima formation, but venous flow only partly suppressed the response when compared with vein cultured under static conditions. These results are in agreement with previous in vivo studies in a primate graft model, where increased shear stress inhibited intimal proliferation. The endothelial cell is believed to be the key mediator of haemodynamic effects which influence smooth muscle cell proliferation, and the flow rig developed in this study offers the potential to study inter-cellular interactions within the intact vessel. Furthermore, this method provides the facility to study the effects of different flow conditions on segments of vein from the same patient. This model has scope for further development and sophistication which may ultimately lead to increasing our understanding of the aetiology of vein graft stenoses, and hence formulation of preventative strategies.