Fibrin Plugging as a Cause of Microcirculatory Occlusion During Photodynamic Therapy

An experimental system that allows the white light observation of rapid changes in vessels without disturbance by red laser light was used. Mice were injected with mono-l-aspartyl chlorin-e-6 (Npe-6) i.v. via the tail vein and were immediately exposed to laser light. White emboli were observed forming on the inside of the vessel walls within seconds after commencement of light exposure. Emboli adhered to vessel walls and caused vascular obstruction. Light microscopy of the exposed material using fibrin staining was performed. Electron microscopy on the same material was also carried out. The embolisation time was influenced by both drug dose and laser power. With low laser power, it took a long time to stop the blood flow. Fibrin staining revealed the white emboli to be composed of fibrin. Electron microscopy findings revealed damage to endothelial cells and platelet aggregation. This study suggests that two main mechanisms (direct cellular damage and vascular shut-down ) might actually be complementary and synergistic in the production of vascular lesions using photodynamic therapy. Paper received 28 February 1998; accepted after revision 8 October 1998.