Prostanoid antagonists inhibit the response of the microcirculation to "early" photodynamic therapy.
Microcirculatory shutdown appears to be of central importance in the mechanisms of action of photodynamic therapy (PDT). Traditionally 24-48 h are allowed between the administration of the photosensitizer and light to allow for tumor localization. However, previous studies have shown that the effects of PDT on the microcirculation are maximal soon after administration of the photosensitizer when serum levels are highest. This study involved the use of television video microscopy of the cremaster muscle microcirculation of male Sprague-Dawley rats to study the involvement of prostanoids in the effects of PDT on the microcirculation 30 min after administration of photofrin II. Pretreatment with topical indomethacin resulted in an altered response to PDT with arteriolar dilation and delay in vessel shutdown. The thromboxane A2 antagonist SQ29548 (100 mg/kg/min iv) resulted in a significant delay in platelet thrombus formation in arterioles and venules. These results indicate that prostanoids are involved in the mediation of the response of the normal microcirculation to PDT.
Reed
M W
MW
Department of Surgery, University of Sheffield, United Kingdom.
Schuschke
D A
DA
Miller
F N
FN
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects* / Q000502:physiology; D009132:Muscles / Q000098:blood supply; D010778:Photochemotherapy; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011448:Prostaglandin Antagonists; D013928:Thromboxane A2; C045749:SQ 29548; D007213:Indomethacin