The effect of flunarizine on erythrocyte suspension viscosity under conditions of extreme hypoxia, low pH, and lactate treatment.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kavanagh, BD; Coffey, BE; Needham, D; Hochmuth, RM; Dewhirst, MW

Published Date

  • April 1993

Published In

Volume / Issue

  • 67 / 4

Start / End Page

  • 734 - 741

PubMed ID

  • 8471430

Pubmed Central ID

  • 8471430

International Standard Serial Number (ISSN)

  • 0007-0920

Digital Object Identifier (DOI)

  • 10.1038/bjc.1993.134

Language

  • eng

Conference Location

  • England