Photodynamic therapy inhibition of experimental intimal hyperplasia: acute and chronic effects.

Abstract

Intimal hyperplasia (IH) is a focal arterial problem that still eludes successful therapy. We have previously demonstrated the feasibility of use of photodynamic therapy (PDT) for the acute treatment of experimental IH with light to activate an otherwise biologically inert photosensitizer. The purpose of this study was to determine the acute and long-term effects of PDT inhibition of IH on the artery wall. Segmental IH was induced by balloon injury localized to the cervical common carotid artery of 33 rats. The photosensitizer chloroaluminum sulfonated phthalocyanine (5 mg/kg) for the experimental group or saline solution for the control group was administered intravenously. Twenty-four hours later, all instrumented portions of arteries were irradiated at 675 nm to induce cytotoxic injury in the PDT-treated arteries as compared with laser only-treated arteries for controls. Animals were killed at 1, 2, 4, and 16 weeks. There were no untoward side effects in either group. All PDT-treated arteries were devoid of smooth muscle or inflammatory cells in the treated media. There was no evidence of arterial degeneration of PDT-treated arteries. Only three arteries in the PDT group developed IH, whereas it was universal in all controls. In control arteries, immunocytochemistry with bromodeoxyuridine revealed maximal intimal and medial cell proliferation at 1 week, and morphometric analysis demonstrated a maximal IH at 2 weeks. Immunocytochemistry staining for smooth muscle cell actin was positive for the IH in control and when present in PDT-treated arteries, whereas the adventitia of PDT-treated arteries were positive after 2 weeks. Electron microscopy demonstrated early myofibroblast migration to the adventitia, and at 16 weeks occasional myofibroblasts were noted in the media of PDT-treated arteries. There was complete reendothelial cell covering of the intima by 4 weeks. These in vivo data demonstrate that PDT is an effective local method for the treatment of experimental IH. There is no evidence of significant recurrence of IH or arterial degeneration. Further studies with PDT may provide novel approaches to the understanding and treatment of arterial IH.