Inhibition of intimal hyperplasia by photodynamic therapy using photofrin

Photodynamic therapy using photofrin and light energy inhibits human myofibroblast proliferation in cell culture. The purpose of this study is to evaluate its influence on intimal hyperplasia in vivo. Twenty New Zealand White rabbits underwent a standardized intimal injury to both common carotid arteries with a 2 Fr balloon catheter. One week later, half of the animals received photofrin (5 mg/kg) intravenously. The remaining 10 rabbits received no photofrin. Two days later, all neck incisions were reopened and a 1-cm segment of each of the 40 carotid arteries was exposed for 5 min to 80 mW of 630 nm light energy from a continuous wave tunable dye laser (fluence = 7.6 J/cm2). All vessels were harvested 5 weeks post-laser treatment following in vivo fixation with formalin. From each artery, separate cross-sections taken from both the lasered and non-lasered regions of each vessel were mounted and stained for histologic evaluation. Analyzed segments were then divided into four different treatment groups: group I segments consisted of arterial cross-sections which were taken from vessel regions that were injured but received neither photofrin nor laser treatment (group I, n = 20); group II segments also did not receive photofrin but were exposed to light energy (group II, n = 20); group III segments received photofrin but no light energy (group III, n = 20); and cross-sections in group IV were taken from those segments which received both photofrin and laser treatment. Using planimetry, the ratio of the area of intimal hyperplasia (IH) to the area enclosed by the internal elastic lamina (IEL) was measured for each specimen (IH/IEL). Results were averaged and statistically evaluated using an ANOVA and differences between groups determined by Student t test. The mean ± SEM IH/IEL ratio, expressed as a percent, for control group I segments was 28.1 ± 3.9. Regions exposed to light energy or photofrin alone had a mean value of 22.2 ± 3.2 and 22.3 ± 2.8, respectfully. Finally, those segments which received both photofrin and laser treatment had a IH/IEL ratio of 15.9 ± 2.1. The difference between the arterial segments which were exposed to both photofrin and laser treatment, and those which received neither, is statistically significant (P < 0.01). We conclude that photodynamic therapy using photofrin and 630 nm light, administered 1 week following a carotid endothelial injury, inhibits intimal hyperplasia in rabbits.