PHOTODYNAMIC THERAPY OF VEIN GRAFTS - SUPPRESSION OF INTIMAL HYPERPLASIA OF THE VEIN GRAFT BUT NOT THE ANASTOMOSIS

Purpose: There is no clinically useful therapy for the suppression of vein bypass graft intimal hyperplasia (IH). Photodynamic therapy (PDT) , a technique that uses light to activate otherwise biologically inert photosensitizers to produce cytotoxic effects, has been demonstrated to successfully inhibit experimental IH in balloon-injured arteries. T he purpose of this study was to investigate the efficacy of PDT as a m ethod to reduce vein graft IH. Methods: Reversed external jugular vein bypass grafts of the common carotid artery were performed in 28 male Sprague-Dawley rats. The animals received either chloroaluminum sulfon ated phthalocyanine (2.5 mg/kg intravenously) 24 hours before the ex v ivo irradiation of the vein grafts (VG) with 100 joule/cm(2) at 675 nm (PDT VG) or saline solution as control (CON VG). Preharvest bromodeox yuridine was administered to label proliferating cells. All vein graft s were perfusion fixed within 96 hours for a pilot study or at 2 and 4 weeks for the main study. Histology, immunohistochemistry, and morpho metric analysis were performed. Results: There was no acute thrombus f ormation in the hypocellular PDT VG with occasional platelets but no l eukocytes adherent to the luminal surface. Intimal areas of the PDT VG were 18% at 2 weeks and 53% at 4 weeks of the CON VGs (p < 0.05). Med ial areas and percent of stenoses were also significantly less in PDT than in CON VG. However, intimal hyperplasia noted in the longitudinal sections within 2 mm of the anastomoses did not demonstrate a differe nce between PDT and CON VG. Intimal hyperplasia of both PDT and CON VG consisted of smooth muscle cells, verified by immunohistochemistry. B romodeoxyuridine-labeled cells were more abundant in 2-week than in 4- week specimens, were found most frequently in the intimal areas of the CON VG body, and were equivalent in the anastomoses of PDT VG and CON VG. Conclusions: These data suggest that PDT of vein grafts suppresse s the development of IH in the body of the vein graft but does not aff ect IH adjacent to the anastomoses. The artery may be the source of pr oliferating smooth muscle cells that contribute to the anastomotic vei n graft IH.