Effects of photosensitizer (hematoporphyrin derivative-HPD) and light dose on vascular targets in the albino mouse ear.
Photodynamic damage to normal tissues, including skin, appears to occur by photooxidative damage to the normal microvasculature as the primary target sensitized by HPD bound to the vascular wall or endothelial cell. Initial damage to the microvasculature was measured by the increase in vascular permeability (VP) as measured by Evans Blue dye (EB) extravasation as a function of HPD and laser light (632 nm) dose. Albino, Swiss-Webster mice (female 122-25 g, 5 mice per group) were injected intraperitoneally (IP) with incremental doses of HPD (Photofrin II, Photofrin Medical, Inc.) (1, 10, 20, 30, 40 and 50 mg/kg). After 48 hours the left ear of each mouse was masked as a control and the right ear was irradiated at 632 nm using the Aurora-Lexel Argon-dye laser (Cooper Laser Sonics, Inc.) with an intensity of 50 mW/cm2 and light doses of 0, 25, 50, 75, and 100 J/cm2 directed to a 3-mm spot on the mouse ear. No EB leakage occurred in the absence of HPD at any light dose or in the absence of light at any HPC dose. Vascular permeability increased as a function of HPD dose up to 30 mg/kg. AT 50 mg/kg HPD, there was a decrease in VP. At each HPD dose above 10 mg/kg, the VP increased as a function of light dose up to 75 J/cm2. Further increase in light dose was without effect. The amount of HPD porphyrin recovered from irradiated ears decreased as a function of light dose. There appeared to be an irreversible photo destruction of the porphyrin exposed to light.
Davis
R K
RK
Division of Otolaryngology-Head and Neck Surgery, University of Utah Medical Center, Salt Lake City 84132.
Davis
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K
Straight
R C
RC
Waner
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M
D002199:Capillary Permeability / Q000187:drug effects* / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004431:Ear, External / Q000098:blood supply*; D005070:Evans Blue; D006414:Hematoporphyrin Photoradiation; D006415:Hematoporphyrins / Q000008:administration & dosage; D010778:Photochemotherapy; D011829:Radiation Dosage
D006415:Hematoporphyrins; D005070:Evans Blue