Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1997;76(9):1205–1210. doi: 10.1038/bjc.1997.534

Effect of continuous regional vasoactive agent infusion on liver metastasis blood flow.

M J Dworkin 1, P Carnochan 1, T G Allen-Mersh 1
PMCID: PMC2228129  PMID: 9365170

Abstract

Regionally administered vasopressors might increase tumour chemotherapy uptake by differentially constricting normal and tumour blood vessels, leading to a selective increase in blood flow to the tumour. In this study, we compared the effects of the vasopressors angiotensin II, vasopressin and endothelin I and the vasodilator calcitonin gene-related peptide (CGRP) by continuously measuring liver parenchymal and tumour blood flow during a 30-min regional vasoactive infusion in a rat HSN liver metastasis model. Vasopressin and angiotensin II produced a vasoconstriction that decreased despite continued infusion, while endothelin I infusion led to prolonged vasoconstriction with a more gradual onset. CGRP infusion resulted in increased vessel conductance but a reduction in blood flow due to systemic hypotension. The tumour to normal flow ratio (TNR) was transiently increased during infusion of all pressors, but only endothelin I produced sufficient change to result in a rise in average TNR throughout pressor infusion. Continuous liver and tumour blood flow measurement throughout vasoactive infusion demonstrated that the extent and the duration of blood flow change varied with the agents assessed. No vasoactive agent increased tumour blood flow, but endothelin I had the most suitable vasoactive properties for enhancing tumour uptake of continuously infused chemotherapy.

Full text

PDF
1205

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Acker J. C., Dewhirst M. W., Honoré G. M., Samulski T. V., Tucker J. A., Oleson J. R. Blood perfusion measurements in human tumours: evaluation of laser Doppler methods. Int J Hyperthermia. 1990 Mar-Apr;6(2):287–304. doi: 10.3109/02656739009141139. [DOI] [PubMed] [Google Scholar]
  2. Ackerman N. B., Jacobs R., Bloom N. D., Poon T. T. Increased capillary flow in intrahepatic tumors due to alpha-adrenergic effects of catecholamines. Cancer. 1988 Apr 15;61(8):1550–1554. doi: 10.1002/1097-0142(19880415)61:8<1550::aid-cncr2820610811>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  3. Allen-Mersh T. G., Earlam S., Fordy C., Abrams K., Houghton J. Quality of life and survival with continuous hepatic-artery floxuridine infusion for colorectal liver metastases. Lancet. 1994 Nov 5;344(8932):1255–1260. doi: 10.1016/s0140-6736(94)90750-1. [DOI] [PubMed] [Google Scholar]
  4. Allen-Mersh T. G. Improving survival after large bowel cancer. BMJ. 1991 Sep 14;303(6803):595–596. doi: 10.1136/bmj.303.6803.595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Almond N. E., Wheatley A. M. Measurement of hepatic perfusion in rats by laser Doppler flowmetry. Am J Physiol. 1992 Feb;262(2 Pt 1):G203–G209. doi: 10.1152/ajpgi.1992.262.2.G203. [DOI] [PubMed] [Google Scholar]
  6. Arvidsson D., Svensson H., Haglund U. Laser-Doppler flowmetry for estimating liver blood flow. Am J Physiol. 1988 Apr;254(4 Pt 1):G471–G476. doi: 10.1152/ajpgi.1988.254.4.G471. [DOI] [PubMed] [Google Scholar]
  7. Bloom N. D., Kroop E., Sadjadi M., Jacobs R., Ramaswamy G., Ackerman N. B. Enhancement of tumor blood flow and tumoricidal effect of doxorubicin by intraportal epinephrine in experimental liver metastasis. Arch Surg. 1987 Nov;122(11):1269–1272. doi: 10.1001/archsurg.1987.01400230055010. [DOI] [PubMed] [Google Scholar]
  8. Burton M. A., Gray B. N., Self G. W., Heggie J. C., Townsend P. S. Manipulation of experimental rat and rabbit liver tumor blood flow with angiotensin II. Cancer Res. 1985 Nov;45(11 Pt 1):5390–5393. [PubMed] [Google Scholar]
  9. Carter R., Cooke T. G., Hemingway D., McArdle C. S., Angerson W. The combination of degradable starch microspheres and angiotensin II in the manipulation of drug delivery in an animal model of colorectal metastasis. Br J Cancer. 1992 Jan;65(1):37–39. doi: 10.1038/bjc.1992.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Conn H. O., Ramsby G. R., Storer E. H. Hepatic arterial escape from vasopressin-induced vasoconstriction: an angiographic investigation. Am J Roentgenol Radium Ther Nucl Med. 1973 Sep;119(1):102–108. doi: 10.2214/ajr.119.1.102. [DOI] [PubMed] [Google Scholar]
  11. Currie G. A., Gage J. O. Influence of tumour growth on the evolution of cytotoxic lymphoid cells in rats bearing a spontaneously metastasizing syngeneic fibrosarcoma. Br J Cancer. 1973 Aug;28(2):136–146. doi: 10.1038/bjc.1973.131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dworkin M. J., Carnochan P., Allen-Mersh T. G. Nitric oxide inhibition sustains vasopressin-induced vasoconstriction. Br J Cancer. 1995 May;71(5):942–944. doi: 10.1038/bjc.1995.182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dworkin M. J., Zweit J., Carnochan P., Deehan B., Allen-Mersh T. G. Effect of regional angiotensin II infusion on the relationship between tumour blood flow and fluorouracil uptake in a liver metastasis animal model. Eur J Cancer. 1996 Aug;32A(9):1580–1584. doi: 10.1016/0959-8049(96)00169-4. [DOI] [PubMed] [Google Scholar]
  14. Hafström L., Nobin A., Persson B., Sundqvist K. Effects of catecholamines on cardiovascular response and blood flow distribution to normal tissue and liver tumors in rats. Cancer Res. 1980 Feb;40(2):481–485. [PubMed] [Google Scholar]
  15. Hemingway D. M., Angerson W. J., Anderson J. H., Goldberg J. A., McArdle C. S., Cooke T. G. Monitoring blood flow to colorectal liver metastases using laser Doppler flowmetry: the effect of angiotensin II. Br J Cancer. 1992 Nov;66(5):958–960. doi: 10.1038/bjc.1992.392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hemingway D. M., Cooke T. G., Chang D., Grime S. J., Jenkins S. A. The effects of intra-arterial vasoconstrictors on the distribution of a radiolabelled low molecular weight marker in an experimental model of liver tumour. Br J Cancer. 1991 Apr;63(4):495–498. doi: 10.1038/bjc.1991.118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hryniuk W. M., Figueredo A., Goodyear M. Applications of dose intensity to problems in chemotherapy of breast and colorectal cancer. Semin Oncol. 1987 Dec;14(4 Suppl 4):3–11. [PubMed] [Google Scholar]
  18. Jain R. K. Barriers to drug delivery in solid tumors. Sci Am. 1994 Jul;271(1):58–65. doi: 10.1038/scientificamerican0794-58. [DOI] [PubMed] [Google Scholar]
  19. Kemeny N., Cohen A., Bertino J. R., Sigurdson E. R., Botet J., Oderman P. Continuous intrahepatic infusion of floxuridine and leucovorin through an implantable pump for the treatment of hepatic metastases from colorectal carcinoma. Cancer. 1990 Jun 1;65(11):2446–2450. doi: 10.1002/1097-0142(19900601)65:11<2446::aid-cncr2820651107>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
  20. Sasaki Y., Imaoka S., Hasegawa Y., Nakano S., Ishikawa O., Ohigashi H., Taniguchi K., Koyama H., Iwanaga T., Terasawa T. Changes in distribution of hepatic blood flow induced by intra-arterial infusion of angiotensin II in human hepatic cancer. Cancer. 1985 Jan 15;55(2):311–316. doi: 10.1002/1097-0142(19850115)55:2<311::aid-cncr2820550202>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  21. Suzuki M., Hori K., Abe I., Saito S., Sato H. A new approach to cancer chemotherapy: selective enhancement of tumor blood flow with angiotensin II. J Natl Cancer Inst. 1981 Sep;67(3):663–669. [PubMed] [Google Scholar]
  22. Withrington P. G., de Nucci G., Vane J. R. Endothelin-1 causes vasoconstriction and vasodilation in the blood perfused liver of the dog. J Cardiovasc Pharmacol. 1989;13 (Suppl 5):S209–S210. doi: 10.1097/00005344-198900135-00060. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES