8-Methoxy psoralen (8MOP) when activated by ultraviolet light (UVA) establishes DNA crosslinks which inhibit cellular replication. Inhibition of smooth muscle cell hyperplasia using 8MOP activated by UVA was studied in a porcine model of intimal hyperplasia. In 9 (15kg) pigs, 8MOP was given rectally at 5mg/kg. Bilateral femoral arteries (FA) were injured with 4mm balloons inflated x3 to 10 atm. A titanium aluminum sapphire laser emitting 365nm UVA delivered 300mJ diffusely through the balloon catheters during inflation in treated FA. Contralateral control arteries had injury and 8MOP without light activation. 8MOP levels were obtained during UVA delivery. Intraperitoneal bromodeoxyuridine (BRDU) was given at 30 hrs to label proliferating cells. Vessels were retrieved at 48 hrs., perfusion fixed, and BRDU-stained nuclei were counted by a blinded observer in two cross sections of each artery at the site of balloon injury. Mean 8MOP levels were 845±369 ng/ml. A marked decrease in BRDU-labelled nuclei were observed in arteries with 8MOP activated by UVA compared to control vessels (Mean nuclei 185 vrs 515±87), p<0.0165. There were no adverse vascular or systemic complications. We conclude that 8MOP activated by UVA reduces intimal smooth muscle cell proliferation and represents a potential site-specific therapy for intimal hyperplasia.
Gregory KW, Buckley LA, Haw TE, Grunkemeier JM, Chasteney EA, Qu Z, Bahlman Dt, Fahrenbach H, Block PC: Photochemotherapy using psoralen and UVA light in a porcine model of intimal hyperplasia. Circulation (Suppl.II) 88:II-82, 1993.