Temporary intestinal hypoxia induced by degradable microspheres

Abstract

IN all mammalian cells and tissues studied, the adequate presence of molecular oxygen during irradiation enhances the effects of ionising radiations of low linear energy transfer (LET), such as X rays, γ rays or electrons, by a factor of 2 or 3, compared with the effects seen after irradiation in poor oxygenation conditions^1,2. In radiotherapy, this oxygen enhancement ratio (OER) is assumed to be generally effective in all healthy tissues, whereas in poorly oxygenated tumour cells the partial radioprotection through hypoxia is believed to be efficient to an extent that the probability of tumour sterilisation may be affected critically^3,4. It has been suggested that the relative concentration of oxygen in healthy and tumour tissues could be changed to improve the relative probability of curing the disease and of reducing clinical complications caused by radiation damage of healthy tissues. To this end, the introduction of ‘high LET’ radiations for which the oxygen effect is of little importance, is presently being attempted⁵. Attempts are also being made to increase the oxygen tension in poorly oxygenated areas by treatment of patients with hyperbaric oxygen during irradiation⁶. In experiments in our laboratories, we have tried various means of changing the oxygen concentrations in tissues to be irradiated by chemical removal of oxygen⁷ or by mechanical obstruction of the blood flow (K.E.A., J.O.F., C. Clintenberg, B.L., B.R. and S.Ö., unpublished). We are now investigating, in experiments on pigs, the possibility of attaining temporary local hypoxia in intestinal segments by obstructing the blood flow at the level of the arterioles by intra-arterial injection of cross-linked starch microspheres, 43 µm in diameter, that are degraded by the amylase activity of the serum⁸. With a proper choice of the degree of cross linking and of particle concentration, a hypoxic period of about 5 min duration, followed by rapid normalisation, was achieved.