The effects of hyperoxic and hypercarbic gases on tumour blood flow

Abstract

Summary 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.

Issues in flow and oxygenation dependent contrast (FLOOD) imaging of tumours

“…We must also consider carefully how both glucose and oxygen are utilised by the tumor. Information obtained using 31 …”

“…Non-localized 31 P spectra were acquired with repetition time TR = 3 s. 2,5 Tumour energetic status was then assessed from the ratio of bNTP/P i and intracellular pH (pH I ) was calculated from the chemical shift difference between P i and aNTP.…”

“…To investigate the use of the FLOOD technique to study tumour oxygenation we have compared the effects of various vasomodulators in subcutaneously implanted tumours in the rat using GRE and SE imaging, in conjunction with 31 P MRS and blood analysis. [2][3][4][5][6][7][8] In this paper we report on these observations, and describe how they relate to our understanding of the FLOOD phenomenon in tumours.…”

“…Unlike in the GH3 prolactinoma tumour model, there are other tumour types in which carbogen breathing produces vasoconstriction and reduced tumor blood flow. 31 The response to hypercapnia appears to be very dependent on tumour type and site of implantation, and is likely to be a balance between the local effects of CO 2 on the vascular endothelium and that mediated by the sympathetic nervous system. 32 When vasoconstriction occurs, interpretation of R 2 * changes is again confounded, because reduced blood volume masks the effect of increased blood deoxygenation.…”

Monitoring of hemodynamic changes induced in the healthy breast through inspired gas stimuli with MR-guided diffuse optical imaging

“…We investigated the physiological response in normal tissue in order to understand the physiological response to inspired gases. This purpose was encouraged by conflicting reports in the literature on the vascular effects of carbogen breathing, including both increased 25,26 and decreased blood flow 25,27,26 compared to air breathing. This technique allowed us to determine whether the oxygenation and hemoglobin changes are due to vascular tone or to the loading and unloading of oxygen from hemoglobin.…”