Photodynamic therapy for the prevention of intimal hyperplasia in balloon-injured rabbit arteries

This study was performed to demonstrate accumulation of the photosensitizer hematoporphyrin derivative (HPD) in atherosclerosis and to determine wheth er intimal hyperplasia, the main cause of restenosis after angioplasty, can be inhibited by photodynamic therapy (PDT). Forty Japanese White rabbits w ere subjected to balloon endothelial injury in the common iliac artery. Fiv e groups of rabbits, ie, immediately after, or 3, 7, 14 or 28 days after th e balloon injury, were injected with HPD. These rabbits were sacrificed 24 h after HPD administration, and HPD fluorescence was investigated in the in jured arteries by fluorescence microscopy. Other groups of rabbits were inj ected with HPD 24 h before PDT, and they were then subjected to intravascul ar Hg-Xe flashlamp irradiation immediately after (OD-PDT), or 3 days (SD-PD T), 7 days (7D-PDT), or 14 days (14D-PDT) after the balloon injury. All rab bits were sacrificed 28 days after the balloon injury, and histological sec tions of PDT-treated arteries were examined by light microscopy. Slight, un iform HPD accumulation was observed in the injured media immediately after the balloon injury, and throughout the entire media and the neointima on da y 7. On day 14, HPD accumulation had diminished in the media and increased in the intima, and on day 28 no HPD remained in the media. In the 0D- or 3D -PDT groups, no inhibition of intimal hyperplasia was observed. In contrast , there was significant inhibition of intimal hyperplasia in the 7D- and 14 D-PDT groups, and the most effective inhibition was in the 7D-PDT group. Th is study demonstrated that PDT with HPD inhibits smooth muscle cell growth and decreases the intimal hyperplasia response in rabbits.