Dunn T J, Braun R D, Rhemus W E, Rosner G L, Secomb T W, Tozer G M, Chaplin D J, Dewhirst M W
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Br J Cancer. 1999 Apr;80(1-2):117-26. doi: 10.1038/sj.bjc.6690330.
Carbogen (95% O2 and 5% CO2) has been used in preference to 100% oxygen (O2) as a radiosensitizer, because it is believed that CO2 blocks O2-induced vasoconstriction. However, recent work suggests that both normal and tumour arterioles of dorsal flap window chambers exhibit the opposite: no vasoconstriction vs constriction for O2 vs carbogen breathing respectively. We hypothesized that CO2 content might cause vasoconstriction and investigated the effects of three O2-CO2 breathing mixtures on tumour arteriolar diameter (TAD) and blood flow (TBF). Fischer 344 rats with R3230Ac tumours transplanted into window chambers breathed either 1%, 5%, or 10% CO2 + O2. Intravital microscopy and laser Doppler flowmetry were used to measure TAD and TBF respectively. Animals breathing 1% CO2 had increased mean arterial pressure (MAP), no change in heart rate (HR), transient reduction in TAD and no change in TBF. Rats breathing 5% CO2 (carbogen) had transiently increased MAP, decreased HR, reduced TAD and a sustained 25% TBF decrease. Animals exposed to 10% CO2 experienced a transient decrease in MAP, no HR change, reduced TAD and a 30-40% transient TBF decrease. The effects on MAP, HR, TAD and TBF were not CO2 dose-dependent, suggesting that complex physiologic mechanisms are involved. Nevertheless, when > or = 5% CO2 was breathed, there was clear vasoconstriction and TBF reduction in this model. This suggests that the effects of hypercarbic gases on TBF are site-dependent and that use of carbogen as a radiosensitizer may be counterproductive in certain situations.
曾优先使用含95%氧气（O₂）和5%二氧化碳（CO₂）的混合气（卡波金）作为放射增敏剂，而非100%氧气（O₂），因为人们认为CO₂可阻止O₂诱导的血管收缩。然而，近期研究表明，背阔肌皮瓣窗口室的正常和肿瘤小动脉表现出相反的情况：分别是在呼吸O₂时无血管收缩，而在呼吸卡波金时出现血管收缩。我们推测CO₂含量可能导致血管收缩，并研究了三种O₂-CO₂呼吸混合气对肿瘤小动脉直径（TAD）和血流量（TBF）的影响。将R3230Ac肿瘤移植到窗口室的Fischer 344大鼠分别呼吸含1%、5%或10% CO₂的O₂。采用活体显微镜和激光多普勒血流仪分别测量TAD和TBF。呼吸1% CO₂的动物平均动脉压（MAP）升高，心率（HR）无变化，TAD短暂降低，TBF无变化。呼吸5% CO₂（卡波金）的大鼠MAP短暂升高，HR降低，TAD减小，TBF持续降低25%。暴露于10% CO₂的动物MAP短暂降低，HR无变化，TAD减小，TBF短暂降低30 - 40%。对MAP、HR、TAD和TBF的影响并非CO₂剂量依赖性，提示涉及复杂的生理机制。然而，当呼吸≥5% CO₂时，该模型中出现明显的血管收缩和TBF降低。这表明高碳酸气体对TBF的影响具有部位依赖性，并且在某些情况下使用卡波金作为放射增敏剂可能会适得其反。
