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

Abstract

Photodynamic therapy (PDT) has been proposed as a treatment for intimal hyperplasia (ll{). We studied the effect of PDT on the development of ill following endothelial injury, using the photosensitizer Metatetrahydroxyphenyl-chiorin (mTHPC) and 652 nm illumination. 9 minipigs were used in 3 groups of 3 . Pigs in the first group (balloon alone; BA) were anaesthetised 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 Jcm2 using a transparent PDT catheter. In the third group pigs were sensitized with 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 1 0% formal saline. 5sections were cut from the treated segments and stained for elastin. Specimens were measured by a computerised 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) IIM; b) I/(I+M) and c) JJ(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 intimal area was increased 10 fold in the LA group and 14 fold in the PDT group. The changes in the medial 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 JR and improved the overall diameter of the lumen. 390 1SPIE Vol. 2395 0-8194-1742-4/95/$6.00 Downloaded From: http://proceedings.spiedigitallibrary.org/ on 06/21/2016 Terms of Use: http://spiedigitallibrary.org/ss/TermsOfUse.aspx

Significance of Dosimetry in Photodynamic Therapy of Injured Arteries: Classification of Biological Responses

“…One paradox that relates to other vascular PDT studies where several investigators could not achieve inhibition of IH with PDT, is in fact that PDT appeared to accelerate the development of stenotic lesions (13)(14)(15)). In the present study, it is hypothesized that conflicting data with reference to the ability of PDT to inhibit M in injured arteries may be based not only on the use of divergent protocols, animal models and vessel sizes, but on the different photosensitizer and light dosimetry employed.…”

Photoangioplasty

“…The light is then delivered to the treatment site either directly or via hollow wave guides or fibers terminating in optical configurations to achieve either a circumferential, segmental, or conical beam profile. 16 Radially emitting fibers, with a variety of designs, have been used for endovascular PDT in animals, [17][18][19] and in one case, a 2-patient clinical study. 17 Another important advance in photoangioplasty is the development of compact, portable, and relatively inexpensive diode-based lasers to replace the older, large systems requiring special electrical and plumbing infrastructures; the latter are mostly dye lasers pumped by another laser (argon, 19 -21 KTP YAG) or pulse lasers (copper vapor).…”

“…17 Another important advance in photoangioplasty is the development of compact, portable, and relatively inexpensive diode-based lasers to replace the older, large systems requiring special electrical and plumbing infrastructures; the latter are mostly dye lasers pumped by another laser (argon, 19 -21 KTP YAG) or pulse lasers (copper vapor). 19 Severe cellular damage is noted in atheromatous areas after light exposure. 7 However, there is demonstrable preservation of the intact elastic lamina and of normal collagen in the adventitia, suggesting that the functional integrity of the vessel is conserved.…”