The effects of hyperoxic and hypercarbic gases on tumour blood flow

Carbogen (95% O-2 and 5% CO2) has been used in preference to 100% oxygen (O -2) as a radiosensitizer, because it is believed that CO2 blocks O-2-induce d vasoconstriction. However, recent work suggests that both normal and tumo ur arterioles of dorsal flap window chambers exhibit the opposite: no vasoc onstriction vs constriction for O-2 vs carbogen breathing respectively. We hypothesized that CO2 content might cause vasoconstriction and investigated the effects of three O-2-CO2 breathing mixtures on tumour arteriolar diame ter (TAD) and blood flow (TBF). Fischer 344 rats with R3230Ac tumours trans planted into window chambers breathed either 1%, 5%, or 10% CO2 + O-2. Intr avital microscopy and laser Doppler flowmetry were used to measure TAD and TBF respectively. Animals breathing 1% CO2 had increased mean arterial pres sure (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 ex posed to 10% CO2 experienced a transient decrease in MAP, no HR change, red uced TAD and a 30-40% transient TBF decrease. The effects on MAP, HR, TAD a nd TBF were not CO2 dose-dependent, suggesting that complex physiologic mec hanisms are involved. Nevertheless, when greater than or equal to 5% CO2 wa s breathed, there was clear vasoconstriction and TBF reduction in this mode l. This suggests that the effects of hypercarbic gases on TBF are site-depe ndent and that use of carbogen as a radiosensitizer may be counterproductiv e in certain situations.