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The British Journal of Cancer. Supplement logoLink to The British Journal of Cancer. Supplement
. 1996 Jul;27:S241–S246.

Arteriolar oxygenation in tumour and subcutaneous arterioles: effects of inspired air oxygen content.

M W Dewhirst 1, E T Ong 1, G L Rosner 1, S W Rehmus 1, S Shan 1, R D Braun 1, D M Brizel 1, T W Secomb 1
PMCID: PMC2149985  PMID: 8763889

Abstract

Carbogen is thought to be more effective than normobaric oxygen in reducing tumour hypoxia because it may reduce hyperoxic vasoconstriction. In this study, tumour and normal arteriolar diameters were measured simultaneously with perivascular pO2 during air breathing followed by either carbogen or 100% oxygen to determine whether the action of carbogen is the result of alterations in feeding vessel diameter. Fischer-344 rats bearing dorsal flap window chambers, with or without implanted R3230AC tumours, were the experimental subjects. Arteriolar diameters were measured using optical techniques and perivascular pO2 was measured using recessed-tip electrodes (3-6 microns tip diameter). Baseline arteriolar pO2 averaged 30-50% of blood gas pO2 (mean = 97 mmHg). Both hyperoxic gases increased blood gas pO2 by 4-to 5-fold, but relative improvements in arteriolar pO2 were < or = 2.5 for all arterioles studied. This means that these normobaric high O2 gases are not very efficient in increasing O2 delivery to tumours. In addition, improvements in tumour arteriolar pO2 were transient for both hyperoxic gases. Oxygen and carbogen caused no change and mild vasodilatory responses in tumour arterioles, respectively. Normal arterioles on the other hand, tended toward vasoconstriction by carbogen breathing. Peri-arteriolar pO2 in tumours increased within the first 5 min of breathing either hyperoxic gas, followed by a decline back toward values seen with air-breathing. These results suggest that temporal changes in tumour oxygenation after exposure to carbogen or O2 may not be due to changes in perfusion. Other factors, such as changes in O2 consumption rate may be involved.

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Selected References

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  1. Bertuglia S., Colantuoni A., Coppini G., Intaglietta M. Hypoxia- or hyperoxia-induced changes in arteriolar vasomotion in skeletal muscle microcirculation. Am J Physiol. 1991 Feb;260(2 Pt 2):H362–H372. doi: 10.1152/ajpheart.1991.260.2.H362. [DOI] [PubMed] [Google Scholar]
  2. Braun R. D., Linsenmeier R. A. Retinal oxygen tension and the electroretinogram during arterial occlusion in the cat. Invest Ophthalmol Vis Sci. 1995 Mar;36(3):523–541. [PubMed] [Google Scholar]
  3. Brizel D. M., Lin S., Johnson J. L., Brooks J., Dewhirst M. W., Piantadosi C. A. The mechanisms by which hyperbaric oxygen and carbogen improve tumour oxygenation. Br J Cancer. 1995 Nov;72(5):1120–1124. doi: 10.1038/bjc.1995.474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chaplin D. J., Horsman M. R., Siemann D. W. Further evaluation of nicotinamide and carbogen as a strategy to reoxygenate hypoxic cells in vivo: importance of nicotinamide dose and pre-irradiation breathing time. Br J Cancer. 1993 Aug;68(2):269–273. doi: 10.1038/bjc.1993.326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Degner F. L., Sutherland R. M. Mathematical modelling of oxygen supply and oxygenation in tumor tissues: prognostic, therapeutic, and experimental implications. Int J Radiat Oncol Biol Phys. 1988 Aug;15(2):391–397. doi: 10.1016/s0360-3016(98)90021-9. [DOI] [PubMed] [Google Scholar]
  6. Dewhirst M. W., Ong E. T., Klitzman B., Secomb T. W., Vinuya R. Z., Dodge R., Brizel D., Gross J. F. Perivascular oxygen tensions in a transplantable mammary tumor growing in a dorsal flap window chamber. Radiat Res. 1992 May;130(2):171–182. [PubMed] [Google Scholar]
  7. Duling B. R., Berne R. M. Longitudinal gradients in periarteriolar oxygen tension. A possible mechanism for the participation of oxygen in local regulation of blood flow. Circ Res. 1970 Nov;27(5):669–678. doi: 10.1161/01.res.27.5.669. [DOI] [PubMed] [Google Scholar]
  8. Falk S. J., Ward R., Bleehen N. M. The influence of carbogen breathing on tumour tissue oxygenation in man evaluated by computerised p02 histography. Br J Cancer. 1992 Nov;66(5):919–924. doi: 10.1038/bjc.1992.386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Groebe K., Vaupel P. Evaluation of oxygen diffusion distances in human breast cancer xenografts using tumor-specific in vivo data: role of various mechanisms in the development of tumor hypoxia. Int J Radiat Oncol Biol Phys. 1988 Sep;15(3):691–697. doi: 10.1016/0360-3016(88)90313-6. [DOI] [PubMed] [Google Scholar]
  10. Hampson N. B., Jöbsis-VanderVliet F. F., Piantadosi C. A. Skeletal muscle oxygen availability during respiratory acid-base disturbances in cats. Respir Physiol. 1987 Nov;70(2):143–158. doi: 10.1016/0034-5687(87)90046-6. [DOI] [PubMed] [Google Scholar]
  11. Jackson W. F. Regional differences in mechanism of action of oxygen on hamster arterioles. Am J Physiol. 1993 Aug;265(2 Pt 2):H599–H603. doi: 10.1152/ajpheart.1993.265.2.H599. [DOI] [PubMed] [Google Scholar]
  12. Kavanagh B. D., Coffey B. E., Needham D., Hochmuth R. M., Dewhirst M. W. The effect of flunarizine on erythrocyte suspension viscosity under conditions of extreme hypoxia, low pH, and lactate treatment. Br J Cancer. 1993 Apr;67(4):734–741. doi: 10.1038/bjc.1993.134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kelleher D. K., Vaupel P. W. Nicotinamide exerts different acute effects on microcirculatory function and tissue oxygenation in rat tumors. Int J Radiat Oncol Biol Phys. 1993 Apr 30;26(1):95–102. doi: 10.1016/0360-3016(93)90178-x. [DOI] [PubMed] [Google Scholar]
  14. Kjellen E., Joiner M. C., Collier J. M., Johns H., Rojas A. A therapeutic benefit from combining normobaric carbogen or oxygen with nicotinamide in fractionated X-ray treatments. Radiother Oncol. 1991 Oct;22(2):81–91. doi: 10.1016/0167-8140(91)90002-x. [DOI] [PubMed] [Google Scholar]
  15. Martin L., Lartigau E., Weeger P., Lambin P., Le Ridant A. M., Lusinchi A., Wibault P., Eschwege F., Luboinski B., Guichard M. Changes in the oxygenation of head and neck tumors during carbogen breathing. Radiother Oncol. 1993 May;27(2):123–130. doi: 10.1016/0167-8140(93)90132-r. [DOI] [PubMed] [Google Scholar]
  16. Ono K., Masunaga S., Akuta K., Akaboshi M. Middle dose rate irradiation in combination with carbogen inhalation selectively and more markedly increases the responses of SCCVII tumors. Int J Radiat Oncol Biol Phys. 1994 Apr 30;29(1):81–85. doi: 10.1016/0360-3016(94)90229-1. [DOI] [PubMed] [Google Scholar]
  17. Papenfuss H. D., Gross J. F., Intaglietta M., Treese F. A. A transparent access chamber for the rat dorsal skin fold. Microvasc Res. 1979 Nov;18(3):311–318. doi: 10.1016/0026-2862(79)90039-6. [DOI] [PubMed] [Google Scholar]
  18. Rockwell S. Use of a perfluorochemical emulsion to improve oxygenation in a solid tumor. Int J Radiat Oncol Biol Phys. 1985 Jan;11(1):97–103. doi: 10.1016/0360-3016(85)90367-0. [DOI] [PubMed] [Google Scholar]
  19. Rojas A. ARCON: accelerated radiotherapy with carbogen and nicotinamide. BJR Suppl. 1992;24:174–178. [PubMed] [Google Scholar]
  20. Secomb T. W., Hsu R., Ong E. T., Gross J. F., Dewhirst M. W. Analysis of the effects of oxygen supply and demand on hypoxic fraction in tumors. Acta Oncol. 1995;34(3):313–316. doi: 10.3109/02841869509093981. [DOI] [PubMed] [Google Scholar]
  21. Siemann D. W., Hill R. P., Bush R. S. The importance of the pre-irradiation breathing times of oxygen and carbogen (5% CO2: 95% O2) on the in vivo radiation response of a murine sarcoma. Int J Radiat Oncol Biol Phys. 1977 Sep-Oct;2(9-10):903–911. doi: 10.1016/0360-3016(77)90188-2. [DOI] [PubMed] [Google Scholar]
  22. Siemann D. W., Horsman M. R., Chaplin D. J. The radiation response of KHT sarcomas following nicotinamide treatment and carbogen breathing. Radiother Oncol. 1994 May;31(2):117–122. doi: 10.1016/0167-8140(94)90391-3. [DOI] [PubMed] [Google Scholar]
  23. Smith T. L., Osborne S. W., Hutchins P. M. Long-term micro- and macrocirculatory measurements in conscious rats. Microvasc Res. 1985 May;29(3):360–370. doi: 10.1016/0026-2862(85)90025-1. [DOI] [PubMed] [Google Scholar]
  24. Song C. W., Lee I., Hasegawa T., Rhee J. G., Levitt S. H. Increase in pO2 and radiosensitivity of tumors by Fluosol-DA (20%) and carbogen. Cancer Res. 1987 Jan 15;47(2):442–446. [PubMed] [Google Scholar]
  25. Swain D. P., Pittman R. N. Oxygen exchange in the microcirculation of hamster retractor muscle. Am J Physiol. 1989 Jan;256(1 Pt 2):H247–H255. doi: 10.1152/ajpheart.1989.256.1.H247. [DOI] [PubMed] [Google Scholar]
  26. Thews O., Kelleher D. K., Vaupel P. W. Modulation of spatial O2 tension distribution in experimental tumors by increasing arterial O2 supply. Acta Oncol. 1995;34(3):291–295. doi: 10.3109/02841869509093977. [DOI] [PubMed] [Google Scholar]

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