THE EFFECTS OF ASPIRIN ON MICROVASCULATURE AFTER PHOTODYNAMIC THERAPY

Abstract— The effects of aspirin (acetylsalicylic acid: ASA) on vessel behavior and tumor response were measured during and after photodynamic therapy (PDT). Changes to vessel constriction, macromolecular leakage, tumor interstitial pressure, and tumor response were examined. Animals were randomly placed into treatment groups and injected with 0–25 mg/kg Photofrin® and given 0 or 135 J/cm² light treatment. The light treatment was standardized to 75 mW/cm² at 630 nm over a 30 min treatment interval (135 J/cm²). The treatment groups were further subdivided to receive Photofrin® alone or Photofrin® plus 100 mg/kg ASA. A cremaster muscle model in Sprague-Dawley rats was used to directly observe microvascular response and changes in vessel permeability to macromolecules. A tumor interstitial pressure model was designed to measure pressure changes in a chondrosarcoma tumor over time. This model indirectly measures macromolecular leakage, among other factors, in the tumor tissue. Groups of 10–20 rats were implanted subcutaneously with chondrosarcoma and were subjected to PDT to assess tumor response to the various treatments. Statistically significant differences in vessel leakage and changes in interstitial pressure were observed between animals given ASA plus PDT as compared to animals given PDT alone. The administration of ASA significantly inhibited venule leakage of albumin and reduced increases in interstitial pressure after treatment. The use of ASA had no effect on vessel constriction or tumor response after PDT. These findings suggest that the increases in vessel permeability observed during and after PDT, using Photofrin®, do not significantly contribute to tumor response.