A comparison of the effects of photodynamic therapy on normal and tumor blood vessels in the rat microcirculation.
The effects of light activation of the tumor photosensitizer dihematoporphyrin ether (DHE) were studied in the microcirculation of the rat cremaster muscle. Arterioles and venules in an implanted chondrosarcoma were studied by in vivo television microscopy and were compared to normal vessels of the same size elsewhere in the preparation and in control preparations. Activation with green light (530-560 nm, 200 mW/cm2, 120 J/cm2) 48 h after intraperitoneal injection of DHE (10 mg/kg body wt) resulted in significant narrowing of diameters of red blood cell columns in tumor arterioles and venules. The response in normal and control arterioles and venules was not significantly different from that seen in the tumor vessels except that the control arterioles did not remain significantly constricted during the treatment period. Treatment resulted in stasis of blood flow in 90% of tumor and normal arterioles at the completion of light activation. In venules, stasis of blood flow was observed in 75% of tumor and 70% of normal vessels. Vasoconstriction was the primary response in arterioles, while thrombosis predominated in venules. Morphologic assessment of light-activated vessels in the cremaster preparation by transmission electron microscopy revealed platelet aggregation with damage to endothelial cells and smooth muscle cells. Perivascular effects observed included interstitial edema and damage to skeletal muscle cells. In the tumor-bearing preparation, no direct cytotoxic effect on the tumor cells was shown. The surrounding vessels exhibited similar vascular stasis, but the lining cells appeared minimally affected. Photoactivation of DHE results in significant changes in the microcirculation which lead to stasis of blood flow. In this model, the response was similar for the normal microvasculature and for the microcirculation of an implanted chondrosarcoma. These effects may account, in part, for the mechanism of action of photodynamic therapy.
Department of Surgery, University of Louisville, Kentucky 40292.
M W
MW
Reed
T J
TJ
Wieman
D A
DA
Schuschke
M T
MT
Tseng
F N
FN
Miller
D000818:Animals; D002813:Chondrosarcoma / Q000098:blood supply / Q000188:drug therapy*; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D009132:Muscles / Q000098:blood supply; D009368:Neoplasm Transplantation; D010778:Photochemotherapy; D051381:Rats; D011919:Rats, Inbred Strains