Clincial and laboratory aspects of intimal hyperplasia in lower limb bypass grafts.

This thesis examines aspects of intimal hyperplasia in infrainguinal bypass grafts. There are 3 introductory chapters. Chapter 1 describes the aetiology and treatment of lower limb vascular disease, with particular reference to atherosclerosis. Chapter 2 is a review of the literature regarding the vascular biology of intimal hyperplasia. Chapter 3 is a review of the techniques of cell and organ culture used in the study of vascular disorders. Chapter 4 is composed of four clinical studies of infrainguinal grafts performed at the Leicester Royal Infirmary. There is a prospective study of the long-term benefit of vein graft surveillance. This is followed by a study of the long-term results of percutaneous transluminal angioplasty of vein graft stenoses. A retrospective review of the outcome of polytetrafluoroethylene (PTFE) grafts used in lower limb bypass surgery forms the 3rd part of the chapter. This is followed by a prospective study of the benefits of graft surveillance for synthetic grafts. The next 3 chapters are laboratory based. Chapter 5 looks at the effect of various growth factors on the proliferation of human saphenous vein smooth muscle cells, the ceils involved in the intimal hyperplasia of vein graft stenoses. Chapter 6 looks at aspects of platelet- derived growth factor on the proliferation seen in an organ culture model of human saphenous vein. Chapter 7 examines 2 different ways of incorporating flow in an organ culture of human saphenous vein and compares the effects of high and low shear rates on the development of intimal hyperplasia in the model. In the final chapter, the experimental results are summarised and possible future work relating to the thesis is discussed.