The effects of hyperoxic and hypercarbic gases on tumour blood flow

Carbogen (95% O(2) and 5% CO(2)) has been used in preference to 100% oxygen (O(2)) as a radiosensitizer, because it is believed that CO(2) blocks O(2)-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 O(2) vs carbogen breathing respectively. We hypothesized that CO(2) content might cause vasoconstriction and investigated the effects of three O(2)–CO(2) 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% CO(2) + O(2). Intravital microscopy and laser Doppler flowmetry were used to measure TAD and TBF respectively. Animals breathing 1% CO(2) had increased mean arterial pressure (MAP), no change in heart rate (HR), transient reduction in TAD and no change in TBF. Rats breathing 5% CO(2) (carbogen) had transiently increased MAP, decreased HR, reduced TAD and a sustained 25% TBF decrease. Animals exposed to 10% CO(2) 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 CO(2) dose-dependent, suggesting that complex physiologic mechanisms are involved. Nevertheless, when ≥ 5% CO(2) 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. © 1999 Cancer Research Campaign