The effects of hyperoxic and hypercarbic gases on tumour blood flow.
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.
Dunn
T J
TJ
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Braun
R D
RD
Rhemus
W E
WE
Rosner
G L
GL
Secomb
T W
TW
Tozer
G M
GM
Chaplin
D J
DJ
Dewhirst
M W
MW
D000230:Adenocarcinoma / Q000097:blood / Q000098:blood supply*; D000280:Administration, Inhalation; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002245:Carbon Dioxide / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D017078:Laser-Doppler Flowmetry; D008962:Models, Theoretical; D009368:Neoplasm Transplantation; D010100:Oxygen / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012039:Regional Blood Flow / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014661:Vasoconstriction / Q000187:drug effects*
D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; C011700:carbogen; D010100:Oxygen