The ultrastructure of photochemically induced thrombi with embolization in a rat model.

Abstract

Photochemical techniques, currently used in stroke and cancer research, produce endothelial damage and thrombosis. To further characterize these thrombi and to determine whether they embolize, we studied the ultrastructure of photochemically damaged carotid arteries and small vessels distal to the irradiated carotid. The right carotid artery of 9 Wistar rats was irradiated with a laser (632 nm, 200 mW/cm2, 15 minutes) after the injection of the photosensitizing dye Photofrin II, 12.5 mg/kg. There were 6 additional control rats: laser only, 2 rats; dye only, 2; carrier only (5% dextrose), 1; and normal, 1. The carotid artery and cerebral arterioles were studied using scanning and transmission electron microscopy. Endothelial damage was present in all irradiated carotid arteries, and consisted of exposure of the subendothelium and the formation of a nonocclusive thrombus. Although most cerebral arterioles were normal, 32 of these vessels contained peripheral blood elements, with platelet or red blood cell aggregates present in 15. The endothelium adjacent to the aggregates was intact. A few scattered endothelial cells had been lost in the carotid artery of control animals (compatible with normal cell turnover), with a few platelets adhering to the exposed subendothelium. Aggregates of blood cells and platelets in cerebral vessels in the absence of endothelial denudation verifies embolism as the mechanism for cerebral vascular occlusion in this experimental model. The possibility of embolization distal to the site of photochemical irradiation has implications for potential applications of photochemistry for cancer treatment and the ablation of vascular malformations and/or aneurysms.