Importance of the Treatment Field for the Application of Vascular Photodynamic Therapy to Inhibit Intimal Hyperplasia

Abstract

Intimal hyperplasia (IH) plays a dominant role in the development of restenosis. In previous studies, photodynamic therapy (PDT) prevented IH induced by segmental balloon injury of the rat carotid. The critical elements required to control IH effectively with this technique are not fully understood. This study assessed the importance of the treatment field by studying the repair process of injured vessels, in which the PDT-treatment field did not target the entire injured area. The entire rat common carotid artery was balloon-injured to induce IH, whereas only the cervical segment below the bifurcation was subjected to PDT by external light irradiation after administration of the photosensitizer chloroaluminum sulfonated phthalocyanine. Light irradiation of injured arteries without photosensitizer served as control for PDT, and PDT of uninjured arteries was included as a control group for the balloon injury. Histologic characterization of the repair process was sequentially assessed. Balloon-injured arteries without PDT displayed rapid IH development with a peak at 2 weeks. Photodynamic therapy of balloon-injured arteries resulted in complete local depletion of medial smooth muscle cells (SMC), which was associated with a lack of IH until 2 weeks. However, at 4 and 16 weeks there was significant IH in PDT-treated arteries despite a lack of medial SMC repopulation. A wave of IH progression over the acellular media was observed in these arteries, migrating from the injured non-PDT-treated area. The PDT of uninjured arteries did not result in IH and was also associated with a persistent acellular media. Delayed IH development after PDT of injured vessels can result from IH progression from an injured site not included in the treatment field. This also indicated that the source of cells developing the intimal hyperplasia lesion can originate from an area remote from the lesion. Together with previous results and the determination that PDT itself does not induce IH, it can be reasoned that inclusion of the whole injured artery or a section of an uninjured margin in the treatment field is essential for effective PDT prevention of IH.