Local photodynamic action of methylene blue favorably modulates the postinterventional vascular wound healing response

Purpose: Photodynamic therapy (PDT), the light activation of photosensitize rs to produce free radicals, is known to inhibit experimental intimal hyper plasia (IH). However, its clinical application has been limited by the lack of a suitable approach and a clinically appropriate photosensitizer. The a im of this study was to determine the effectiveness of a clinical approach for PDT, while testing its ability to favorably modulate the vascular wound healing response. Methods: Rat carotid arteries were balloon-injured (BI), and for PDT, the a rteries were irradiated with thermoneutral laser light (lambda = 660 nm, 10 0 J/cm(2)) after the photosensitizer methylene blue (MB) was delivered loca lly. Control rats included BT alone and MB after BI alone. Arteries were an alyzed after 2 weeks with morphometric evaluation (n = 6) and in situ hybri dization for versican and procollagen type I gene expression (digitized ima ge pixel analyses, n = 3). Results: No IH developed in PDT-treated arteries (0 +/- 0 mm(2); compared w ith BI, 0.192 +/- 0.006 mm(2); P < .0001). The diameters remained unchanged (PDT, 0.95 +/- 0.04 mm; BI, 0.94 +/- 0.05 mm; uninjured artery, 0.91 +/- 0 .06 mm). Arterial injury resulted in an increase of versican and procollage n type I messenger RNA (mRNA) in the adventitia and neointima. In the repop ulating cells of the adventitia after PDT, there was a significant decrease in versican mRNA (% of positive pixels per high-power field: PET, 1.13% +/ - 0.39%; BI, 2.93% +/- 0.61%; P < .02), but not in procollagen type I mRNA. Conclusion: The decrease of versican mRNA expression of repopulating cells after PDT reflects favorable healing on a molecular level. Site-specific de livery of MB, a clinically appropriate photosensitizer, followed by PDT rep resents a suitable method to promote favorable healing after balloon interv ention and further supports its role for inhibiting postinterventional rest enosis.