Photodynamic Therapy Inhibits Experimental Vein Graft Restenosis

PURPOSE: Intimal hyperplasia is a common cause of obstructive stenosis after arterial reconstructive procedures and it remains troublesome for patients after coronary artery bypass surgery. The graft anastomosis has been implicated as the major cause of restenosis and long-term graft failure. Despite the high incidence of graft failure, autologous saphenous vein grafts remain the most widely used conduits for coronary artery bypass surgery. This is because of their ready availability and ease of removal and the insufficient number of arterial grafts available to achieve complete revascularization in patients with multivessel coronary disease.Neointimal hyperplasia, whether in the balloon-injured artery or in the grafted vein, follows a similar pathogenic sequence. Initially, medial smooth muscle cells proliferate in response to a number of growth factors and cytokines released from platelets and from activated endothelial cells and macrophages. This is followed by migration of smooth muscle cells into the intima, with subsequent further proliferation. Later, synthesis and deposition of extracellular matrix by activated smooth muscle cells leads to a progressive increase in intimal fibrosis and a reduction in cellularity. Intimal thickening in the anastomosis hasbeen implicated as the major cause of restenosis and long-term graft failure.Beyond the first year after bypass surgery, atherosclerosis is the dominant process.Although advances in surgical technique and drug therapies, gene therapies, Brachytherapy and low power laser irradiation have all undoubtedly had a salutatory impact on vein graft patency, novel approaches for the prevention of accelerated vein graft intimal hyperplasia need to be explored. Photodynamic therapy (PDT) is a therapeutic modality that uses nonthermal light to activate photosensitizers that have accumulated in diseased tissue. Free radical species are produced either by the photosensitizer itself or by energy transfer to molecular oxygen to produce singlet oxygen; both processes result in cytotoxic effects on cellular and tissue structures. PDT has been demonstrated to successfully inhibit experimental IH in balloon-injured arteries. Others' data suggested that PDT of vein grafts suppresses the development of IH in the body of the vein graft but does not affect IH adjacent to the anastomoses. The artery may be the source of proliferating smooth muscle cells. So the purpose of this study is to investigate the efficacy of PDT to reduce the anastomotic vein graft IH.Methods and Results: Reversed external jugular vein bypass grafts of the common carotid artery were performed in 16 male New Zealand rabbits , and 32 anastomoses were divided into 4 groups according to different treatments , controlled group: saline treatment, HMME group: only given HMME, locally, laser irradiation group : only given laser light illumination extravascularly, PDT group: given laser light illumination after HMME treated. The animals received either HMME(15ug/ml 2.5ml ,locally) before the extravascular irradiation of thevein grafts (VG) with 30 joule/cm2 at 532nm (PDT VG) . All vein grafts were perfusion fixed at 4 weeks for the main study. Histology, and morphometric analysis of three parts of the anastomosis , which was consisited of arterial part, the veno-arterial junction, and venous part, were performed. Percent of stenoses in all three part were significantly less in PDT group compared with those in the nonphotooxidized 3 groups.Conclusions: These data suggest that HMME-induced photooxidation of vein grafts suppresses the development of IH, not only in the body of the vein graft but also affect IH adjacent to the anastomoses.