Effect of Hydralazine on Blood Flow, Oxygenation, and Interstitial Fluid Pressure in Subcutaneous Tumors

  • Tomaž Jarm
  • Blaž Podobnik
  • Damijan Miklavčič
  • Gregor Serša
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 510)

Abstract

Many experimental and clinical solid tumors are known to exhibit poor oxygenation and high interstitial fluid pressure (IFP) in comparison to normal surrounding tissues. Oxygenation and IFP in addition to abnormal blood flow influence the response of tumors to various therapies and are also important for development and progression of malignant growth.“ Hydralazine (HYZ) is an arteriolar vasodilating drug which is used for treatment of hypertension in humans. HYZ can decrease both tumor blood flow and tumor IFP. These two changes may have opposite effects on drug delivery and oxygenation in tumors. In our study we evaluated the effect of HYZ on blood flow, oxygenation, and IFP in a murine tumor model. Oxygenation was measured by a relatively new method which has recently become available, the OxyLite system.

Keywords

Convection Macromolecule Ruthenium Isoflurane Hydralazine 

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References

  1. 1.
    M. R. Horsman, Measurement of tumor oxygenation, Int..1. Radiat. Oncol. Biol. Phys. 42 701–704 (1998).CrossRefGoogle Scholar
  2. 2.
    M. Höckel, B. Vomdran, K. Schienger, E. Baußmann, and P. G. Knapstein, Tumor oxygenation: a new predictive parameter in locally advanced cancer of the uterine cervix, Gynecol. Oncol. 51 141–149 (1993).PubMedCrossRefGoogle Scholar
  3. 3.
    P. Vaupel, D.K. Kelleher, and O. Thews, Modulation of tumor oxygenation, Int. J. Radial. Oncol. Biol. Phys. 42 843–848 (1998).CrossRefGoogle Scholar
  4. 4.
    L. T. Baxter and R. K. Jain, Transport of fluid and macromolecules in tumors 1. Role of interstitial fluid pressure and convection, Microvasc. Res. 37 77–104 (1989).PubMedCrossRefGoogle Scholar
  5. 5.
    M. F. Milosevic, A. W. Fyles, and R. P. Hill, The relationship between elevated interstitial fluid pressure and blood flow in tumors: a bioengineering analysis, Int. J. Radial. Oncol. Biol. Phys. 43 1111–1123 (1999).CrossRefGoogle Scholar
  6. 6.
    R. F. Albrecht, E.T. Toyooka, S. L. H. Polk, and B. Zahed, Hydralazine therapy for hypertension during the anesthetic and postanesthetic periods, Int. Anesthesiol. Clin. 16 299–312 (1978).PubMedCrossRefGoogle Scholar
  7. 7.
    M. J. Trotter, B. D. Acker, and D. J. Chaplin, Histological evidence for nonperfused vasculature in a murine tumor following hydralazine administration, Int. J. Radial. Oncol. Biol. Phys. 17 785–789 (1989).CrossRefGoogle Scholar
  8. 8.
    J. Kalmus, P. Okunieff, and P. Vaupel, Dose-dependent effects of hydralazine on microcirculatory fuction and hyperthermic response of murine FSaII tumors, Cancer Res. 50 15–19 (1990).PubMedGoogle Scholar
  9. 9.
    R. A. Zlotecki, L. T. Baxter, Y. Boucher, and R. K. Jain, Pharmacologic modification of tumor blood flow and interstitial fluid pressure in a human tumor xenograft: network analysis and mechanistic interpretation, Microvasc. Res. 50 429–443 (1995).PubMedCrossRefGoogle Scholar
  10. 10.
    M. R. Horsman, K. L. Christensen, and J. Overgaard, Relationship between the hydralazine-induced changes in murine tumor blood supply and mouse blood pressure, Int. J. Radial. Oncol. Biol. Phys. 22 455–458 (1992).CrossRefGoogle Scholar
  11. 11.
    B. Podobnik and D. Miklav6i6, Influence of hydralazine on interstitial fluid pressure in experimental tumors — a preliminary study, Radio!. Oncol. 34 59–65 (2000).Google Scholar
  12. 12.
    D. R. Collingridge, W. K. Young, B. Vojnovic, P. Wardman, E. M. Lynch, S. A. Hill, and D. J. Chaplin, Measuremen of tumor oxygenation: a comparison between polarographic needle electrodes and a time-resolved luminescence-based optical sensor, Radial. Res. 147 329–334 (1997).CrossRefGoogle Scholar
  13. 13.
    J. R. Griffiths and S. P. Robinson, The OxyLite: a fibre-optic oxygen sensor, Br. J. Radio!. 72 627–630 (1999).Google Scholar
  14. 14.
    H. O. Fadnes, R. K. Reed, and K. Aukland, Interstitial fluid pressure in rats measured with a modified wick technique, Microvasc. Res. 14 27–36 (1977).PubMedCrossRefGoogle Scholar
  15. 15.
    B. M. Seddon, D. J. Honess, B. Vojnovic, G. M. Tozer, and P. Workman, Measurement of tumor oxygenation: in vivo comparison of a luminescence fiber-optic sensor and a polarographic sensor and a polarographic electrode in the P22 tumor, Radial. Res. 155 837–846 (2001).CrossRefGoogle Scholar
  16. 16.
    P. Okunieff, C. S. Walsh, P. Vaupel, F. Kallinowski, B. M. Hitzig, L. J. Neuringer, and H. D. Suit, Effects of hydralazine on in vivo tumor energy metabolism, hematopoietic radiation sensitivity, and cardiovascular parameters, Int. J. Radiar. Oncol. Biol. Phys. 16 1145–1148 (1989).CrossRefGoogle Scholar
  17. 17.
    D. J. Chaplin and B. Acker, The effect of hydralazine on the tumor cytotoxicity of the hypoxic cell cytotoxin RSU-1069: evidence for therapeutic gain, Int. J. Radial. Oncol. Biol. Phys. 13 579–585 (1987).CrossRefGoogle Scholar
  18. 18.
    F. Steinberg, E. Hildenhagen-Brüggemann, and M. A. Konerding, Oxygen electrode injury in tumour tissue, in: Tumor oxygenation, edited by O. Thews, D. K. Kelleher, and P. W. Vaupel (Gustav Fischer Verlag, Stuttgart, 1995), pp. 186–193.Google Scholar
  19. 19.
    U. Schramm, W. Fleckenstein, and C. Weber, Morphological assessment of skeletal muscular injury caused by pO2 measurements with hypodermic needle probes, in: Clinical oxygen measurement II, edited by A. M. Ehrly, W. Fleckenstein, J. Hauss, and R. Huch (Blackwell Ueberreuter Wissenschaft, Berlin, 1990), pp. 38–50.Google Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Tomaž Jarm
    • 1
  • Blaž Podobnik
    • 1
  • Damijan Miklavčič
    • 1
  • Gregor Serša
    • 2
  1. 1.Faculty of Electrical EngineeringUniversity of LjubljanaLjubljanaSlovenia
  2. 2.Institute of OncologyLjubljanaSlovenia

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