Effects of hematoporphyrin derivative and photodynamic therapy on atherosclerotic rabbits

This study was performed to demonstrate selective uptake of hematoporphyrin derivative (HPD) within actively developing atheroma, to localize the site of uptake of HPD within the atheroma, and to determine the potential for photodynamic therapy (PDT) of atherosclerosis in the rabbit model. Fifteen rabbits were rendered atherosclerotic. Five rabbits received neither HPD nor PDT and 2 rabbits received HPD, 10 mg/kg intravenously, without subsequent irradiation. Eight other rabbits received 5 to 20 mg of HPD intravenously and subsequent intravascular 636-nm laser radiation to either the thoracic aorta or the aortic arch. A total of 32 to 288 J of laser energy was delivered through a 300-mu quartz fiber. All rabbits that received in vivo HPD had red fluorescence of their aortas when placed under ultraviolet light. The pattern of fluorescence corresponded precisely to the pattern of atheroma. In segments that received PDT, light microscopic examination revealed an accumulation of smooth muscle cells at the intimal surface. Fluorescence microscopy revealed a diminishing concentration gradient of HPD from intimal surface layers towards the media. Assessment of treated thoracic aortic segments revealed quantitative and qualitative differences compared with control segments. In the arch-treated segments, however, no changes were seen. It is concluded that HPD localizes within rabbit atheroma, can be detected by fluorescence and is deposited in a diminishing concentration gradient from lumen toward media. Irradiation with 636-nm light may induce qualitative and quantitative changes in atheroma.