The effect of flunarizine on erythrocyte suspension viscosity under conditions of extreme hypoxia, low pH, and lactate treatment (original) (raw)

British Journal of Cancer volume 67, pages 734–741 (1993)Cite this article

Abstract

Flunarizine is a class IV calcium channel blocker which increases oxygen delivery to hypoxic regions in solid tumours, exerting a radiosensitising effect in vivo in animal tumour models. Precisely how the drug improves oxygenation is not well understood. We hypothesised that metabolic conditions present within solid tumours reduce red blood cell (RBC) deformability and that flunarizine exerts its in vivo effect by preventing this loss of RBC deformability. A microrheometer was used to compare the viscosity of rat and human RBC suspensions in conditions of hypoxia (pO2 < 10 mmHg), acidic environment (pH 6.8), and elevated lactate concentration (lactate 5 mMol l-1), without or with flunarizine at concentrations of 5, 10, and 50 mg l-1. The effects of flunarizine on RBC density and morphology were also recorded. Hypoxia, low pH, and lactate exposure together increased both human and rat RBC suspension viscosity. Flunarizine at concentrations of 5 and 10 mg l-1 prevented the increases in viscosity. The drug caused dose-dependent shifts toward lower cell density while inducing a characteristic cupped shape (stomatcytic morphology), suggesting a mechanism involving calmodulin inhibition. The results support the hypothesis that flunarizine improves tumour blood flow and oxygenation by enhancing flow properties of RBC's in solid tumours.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 24 print issues and online access

$259.00 per year

only $10.79 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Duke University Medical Center, Durham, 27710, NC
    BD Kavanagh

Authors

  1. BD Kavanagh
    You can also search for this author inPubMed Google Scholar
  2. BE Coffey
    You can also search for this author inPubMed Google Scholar
  3. D Needham
    You can also search for this author inPubMed Google Scholar
  4. RM Hochmuth
    You can also search for this author inPubMed Google Scholar
  5. MW Dewhirst
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Kavanagh, B., Coffey, B., Needham, D. et al. The effect of flunarizine on erythrocyte suspension viscosity under conditions of extreme hypoxia, low pH, and lactate treatment.Br J Cancer 67, 734–741 (1993). https://doi.org/10.1038/bjc.1993.134

Download citation