Abstract

Purpose: Photodynamic therapy (PDT), the production of cytotoxic free-radical moieties by light activation of photosensitisers, is a novel approach to inhibit intimal hyperplasia and develop a vascular allograft conduit.

Methods: Tire balloon injury model of the rat carotid artery was applied for the in vivo experiments, cell cultures with bovine aortic endothelial and smooth muscle cells and endothelial cell matrix were used in the in vitro studies. The photosensitiser chloraluminum sulfonated phatlocyanine (CASPc) was used in experiments, the thermoneutral light application was performed with an Argon pumped dye laser with irradiances between 10-100 mW/cm² and fluences between 10-100 J/cm² a wavelength of 675 nm.

Results: Local eradication of vascular cells with this method is followed by expedient reendothelialization and a durable depletion of smooth muscle cells without inflammation. Local PDT treatment of vascular allografts inhibits the rejection process. The development of injury-induced intimal hyperplasia, defined as a proliferation and migration of vascular smooth muscle cells, was significantly diminished. PDT of the extracellular matrix modulates cell functions with an inhibition of smooth muscle cell migration, proliferation and attachment and a significant potentiation of these parameters in endothelial cells without structural matrix alterations. One reason for these findings may be the PDT-induced inhibition of transforming growth tactor-ß (TGF-ß) and cell- and matrix-associated basic fibroblast growth factor (bFGF) activity.

Condusions: Tills free-radical mediated vascular cell depletion and functional changes of matrix including the inhibition of biological active molecules, like TGF-ß and bFGF contribute to favorable vascular healing after PDT for the inhibition of injury-induced intimal hyperplasia. Furthermore, PDT of arterial allografts inhibits acute and chronic rejection processes.

© 1998 Optical Society of America