PHOTODYNAMIC THERAPY INHIBITION OF EXPERIMENTAL INTIMAL HYPERPLASIA -ACUTE AND CHRONIC EFFECTS

Purpose: Intimal hyperplasia (IH) is a focal arterial problem that sti ll eludes successful therapy. We have previously demonstrated the feas ibility of use of photodynamic therapy (PDT) for the acute treatment o f experimental IH with light to activate an otherwise biologically ine rt photosensitizer. The purpose of this study was to determine the acu te and long-term effects of PDT inhibition of IH on the artery wall. M ethods: Segmental IH was induced by balloon injury localized to the ce rvical common carotid artery of 33 rats. The photosensitizer chloroalu minum sulfonated phthalocyanine (5 mg/kg) for the experimental group o r 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 art eries as compared with laser only-treated arteries for controls. Anima ls were killed at 1, 2, 4, and 16 weeks. Results: There were no untowa rd 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 th ree arteries in the PDT group developed IH, whereas it was universal i n all controls. In control arteries, immunocytochemistry with bromodeo xyuridine 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, where as the adventitia of PDT-heated arteries were positive after 2 weeks. Electron microscopy demonstrated early myofibroblast migration to the adventitia, and at 16 weeks occasional myofibroblasts were noted in th e media of PDT-treated arteries. There was complete reendothelial cell covering of the intima by 4 weeks. Conclusions: These in vivo data de monstrate that PDT is an effective local method for the treatment of e xperimental IH. There is no evidence of significant recurrence of IH o r arterial degeneration. Further studies with PDT may provide novel ap proaches to the understanding and treatment of arterial IH.