| Publications [#134070] of Mark W. Dewhirst
Papers Published
- TJ Dunn, RD Braun, WE Rhemus, GL Rosner, TW Secomb, GM Tozer, DJ Chaplin, MW Dewhirst, The effects of hyperoxic and hypercarbic gases on tumour blood flow.,
British journal of cancer, SCOTLAND, vol. 80 no. 1-2
(April, 1999),
pp. 117-26, ISSN 0007-0920
(last updated on 2004/03/30)
Abstract: 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.
Keywords: Adenocarcinoma • Administration, Inhalation • Animals • Arterioles • Carbon Dioxide • Hemodynamic Processes • Laser-Doppler Flowmetry • Models, Theoretical • Neoplasm Transplantation • Oxygen • Radiation-Sensitizing Agents • Rats • Rats, Inbred F344 • Regional Blood Flow • Tumor Cells, Cultured • Vasoconstriction • blood • blood supply* • drug effects • drug effects* • pharmacology*
|