Fingar V H, Wieman T J, Doak K W
Department of Surgery, University of Louisville, KY 40292.
Photochem Photobiol. 1991 Jun;53(6):763-8. doi: 10.1111/j.1751-1097.1991.tb09890.x.
This study has examined the changes in tumor interstitial pressure exhibited during and after photodynamic therapy (PDT). The kinetics of these changes are marked by an initial decrease, followed by a rapid rise in tumor interstitial pressure. We have also employed two inhibitory agents to evaluate the different components of the pressure curve. Specially designed pressure chambers were seeded with chondrosarcoma and implanted subcutaneously in rats. Animals were injected with 0-50 mg/kg Photofrin II (i.v.) 7 days post-implantation and tumors were exposed to 0-540 J/cm2 630 nm 24 h later. Interstitial pressure was monitored via a transducer connected to the implanted chamber. Additional groups of animals were injected with either indomethacin (an inhibitor of thromboxane synthesis) or Ketanserin (a serotonin antagonist) before light treatment. Porphyrin doses of 10 mg/kg and above (135 J/cm2), or light doses of 135 J/cm2 and above (25 mg/kg Photofrin II) were effective in modifying interstitial pressure. Porphyrin doses greater than 25 mg/kg, or light doses greater than 270 J/cm2 produced no further increases in interstitial pressure. Animals given indomethacin (10 mg/kg i.p.) exhibited the initial decrease in pressure during light treatment, but showed no increase past baseline levels. Animals given Ketanserin (10 mg/kg i.p.) demonstrated no decrease in pressure during PDT, but showed the same elevations in pressure as controls. This suggests that two independent mechanisms account for the different components of the pressure curve, and that serotonin release may occur during PDT.
本研究检测了光动力疗法（PDT）期间及之后肿瘤间质压力的变化。这些变化的动力学特征是初期下降，随后肿瘤间质压力迅速上升。我们还使用了两种抑制剂来评估压力曲线的不同组成部分。将经过特殊设计的压力室接种软骨肉瘤后皮下植入大鼠体内。在植入后7天给动物静脉注射0 - 50 mg/kg的二血卟啉醚（Photofrin II），24小时后将肿瘤暴露于0 - 540 J/cm²的630 nm光线下。通过连接到植入式压力室的传感器监测间质压力。在光照治疗前，给另外几组动物注射吲哚美辛（一种血栓素合成抑制剂）或酮色林（一种血清素拮抗剂）。卟啉剂量为10 mg/kg及以上（135 J/cm²），或光照剂量为135 J/cm²及以上（25 mg/kg二血卟啉醚）可有效改变间质压力。卟啉剂量大于25 mg/kg，或光照剂量大于270 J/cm²不会使间质压力进一步升高。给予吲哚美辛（10 mg/kg腹腔注射）的动物在光照治疗期间压力初期下降，但未超过基线水平升高。给予酮色林（10 mg/kg腹腔注射）的动物在光动力疗法期间压力未下降，但压力升高情况与对照组相同。这表明压力曲线的不同组成部分由两种独立机制引起，并且血清素释放可能发生在光动力疗法期间。
