Skip to main content

Fluctuations in red cell flux in tumor microvessels can lead to transient hypoxia and reoxygenation in tumor parenchyma.

Publication ,  Journal Article
Kimura, H; Braun, RD; Ong, ET; Hsu, R; Secomb, TW; Papahadjopoulos, D; Hong, K; Dewhirst, MW
Published in: Cancer Res
December 1, 1996

Hypoxia occurs in two forms in tumors. Chronic or diffusion-limited hypoxia is relatively well characterized. In contrast, intermittent or perfusion-limited hypoxia is not well characterized, and it is not known how common it is in tumors. The purpose of this study was to determine whether spontaneous fluctuations in tumor microvessel flow rate can modify vessel oxygen tension (pO2) sufficiently to cause intermittent hypoxia (IH; tissue pO2 < 3 mmHg) in the tumor parenchyma supplied by such vessels. Microvessel red cell flux (RCF) and perivascular pO2 were measured simultaneously and continuously in dorsal flap window chambers of Fischer-344 rats with implanted R3230Ac tumors. In all vessels, RCF was unstable, with apex/nadir ratios ranging from 1.5 to 10. RCF and pO2 were temporally coordinated, and there were linear relationships between the two parameters. Vascular pO2 was less sensitive to changes in RCF in well-vascularized tumor regions compared with poorly vascularized regions. Simulations of oxygen transport in a well-vascularized region of a tumor demonstrated that two-fold variations in RCF can produce IH in 30% of the tissue in that region. In poorly vascularized regions, such fluctuations would lead to an even greater percentage of tissue involved in transient hypoxia. These results suggest that IH is a relatively common phenomenon. It could affect binding of hypoxic cytotoxins to tumor cells, in addition to being an important source of treatment resistance. Intermittent hypoxia also could contribute to tumor progression by providing repeated exposure of tumor cells to hypoxia-reoxygenation injury.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

December 1, 1996

Volume

56

Issue

23

Start / End Page

5522 / 5528

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Skin Window Technique
  • Reperfusion
  • Rats, Inbred F344
  • Rats
  • Partial Pressure
  • Oxygen
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Microcirculation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kimura, H., Braun, R. D., Ong, E. T., Hsu, R., Secomb, T. W., Papahadjopoulos, D., … Dewhirst, M. W. (1996). Fluctuations in red cell flux in tumor microvessels can lead to transient hypoxia and reoxygenation in tumor parenchyma. Cancer Res, 56(23), 5522–5528.
Kimura, H., R. D. Braun, E. T. Ong, R. Hsu, T. W. Secomb, D. Papahadjopoulos, K. Hong, and M. W. Dewhirst. “Fluctuations in red cell flux in tumor microvessels can lead to transient hypoxia and reoxygenation in tumor parenchyma.Cancer Res 56, no. 23 (December 1, 1996): 5522–28.
Kimura H, Braun RD, Ong ET, Hsu R, Secomb TW, Papahadjopoulos D, et al. Fluctuations in red cell flux in tumor microvessels can lead to transient hypoxia and reoxygenation in tumor parenchyma. Cancer Res. 1996 Dec 1;56(23):5522–8.
Kimura, H., et al. “Fluctuations in red cell flux in tumor microvessels can lead to transient hypoxia and reoxygenation in tumor parenchyma.Cancer Res, vol. 56, no. 23, Dec. 1996, pp. 5522–28.
Kimura H, Braun RD, Ong ET, Hsu R, Secomb TW, Papahadjopoulos D, Hong K, Dewhirst MW. Fluctuations in red cell flux in tumor microvessels can lead to transient hypoxia and reoxygenation in tumor parenchyma. Cancer Res. 1996 Dec 1;56(23):5522–5528.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

December 1, 1996

Volume

56

Issue

23

Start / End Page

5522 / 5528

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Skin Window Technique
  • Reperfusion
  • Rats, Inbred F344
  • Rats
  • Partial Pressure
  • Oxygen
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Microcirculation