Induction or prevention of intimal hyperplasia by photodynamic therapy in a porcine model

Photodynamic therapy (PDT) has been proposed as a treatment for intimal hyperplasia (IH). We studied the effect of PDT on the development of IH following endothelial injury, using the photosensitizer Metatetrahydroxyphenyl-chlorin (m-THPC) and 652 nm illumination. 9 mini- pigs were used in 3 groups of 3. Pigs in the first group (balloon alone; BA) were anaesthetized and the lower 4 cm of abdominal aorta was denuded using a balloon catheter through the right femoral artery. In the second group (light alone; LA) the procedure was repeated, followed by illumination of the denuded area at an energy density of 20 Jcm-2 using a transparent PDT catheter. In the third group pigs were sensitized and an intravenous injection of 0.3 mg/kg of m-THPC 4 hours prior to balloon injury and illumination (PDT Group). Animals were allowed to recover for 8 weeks before being killed and perfusion fixed with 10% formal saline. 5 sections were cut from the treated segments and stained for elastin. Specimens were measured by a computerized morphometry system and the areas of the lumen (L), intima (I) and media (M) were measured. The degree of intimal hyperplasia was expressed as (a) I/M; (b) I/(I+M) and (c) I/(I+L) to take account of changes that could have occurred to the media and the overall diameter of the vessel. We found that when compared to BA controls, the lumenal area was decreased by 46% in LA group and increased by 44% in PDT group. The changes in the medical areas were minimal. These results show that both light alone and PDT produced more intimal hyperplasia than balloon injury alone (P < 0.002 for both groups, Student's t test). When allowance is made for the large increase in lumenal area associated with PDT the degree of intimal hyperplasia I/(I+L) was significantly reduced in PDT treated vessels when compared to those treated with light and balloon alone in spite of the greater absolute area of the intima in the PDT group. We conclude that PDT under the above conditions not only failed to prevent IH, but was associated with a significant increase of intimal area. The increase in the dimensions of the PDT treated vessels reduced the detrimental effect of IH and improved the overall diameter of the lumen.