Prevention of vein graft intimal hyperplasia with photochemical tissue passivation

Abstract

Saphenous vein is the conduit of choice for bypass grafting. Saphenous vein grafts have poor long-term patency rates because of intimal hyperplasia (IH) and subsequent accelerated atherosclerosis. One of the primary triggers of IH is endothelial injury resulting from excessive dilation of the vein after exposure to arterial pressures. Photochemical tissue passivation (PTP) is a technology that cross-links adventitial collagen by a light-activated process, which limits dilation by improving vessel compliance. The objective of this study was to investigate whether PTP limits the development of IH in a rodent venous interposition graft model. PTP is accomplished by coating venous adventitia with a photosensitizing dye and exposing it to light. To assess the degree of collagen cross-linking after PTP treatment, a biodegradation assay was performed. Venous interposition grafts were placed in the femoral artery of Sprague-Dawley rats. Rats were euthanized after 4weeks, and intimal thickness was measured histologically. Vein dilation at the time of the initial procedure was also measured. Time to digestion was 63± 7minutes for controls, 101± 2.4minutes for rose bengal (RB), and 300± 0minutes for PTP (P< .001 PTP vs control). A total of 37 animals underwent the procedure: 12 PTP, 12 RB only, and 13 untreated controls. Dilation of the graft after clamp release was 99% for control, 65% for RB only, and 19% for PTP-treated (P< .001 PTP vs control). Intimal thickness was 77± 59μm in controls, 60± 27μm in RB only, and 33± 28μm in PTP-treated grafts. There was a statistically significant 57% reduction in intimal thickness after treatment with PTP compared with untreated controls (P= .03). PTP treatment of venous interposition grafts in a rat model resulted in significant collagen cross-linking, decreased vessel compliance, and significant reduction in IH.