Perfusion changes in the RIF-1 tumour and normal tissues after carbogen and nicotinamide, individually and combined

Abstract

Summnu.aThe strategy of combining carbogen breathing and nicotinamide to overcome chronic and acute hypoxia respectively is being evaluated clinically. The effects of both agents individually and in combination on relative perfusion of 400-700 mm3 RIF-I tumours and normal tissues were measured by 'Rb extraction.Carbogen breathing alone for 6 min increased relative tumour perfusion by 50-700,<0 compared with control at flow rates of 50 to 200 ml min-'. but the effect was lost at 300 ml min-'. All flow rates also produced similar increases in relative perfusion of lung, of between 36% and 58%. and smaller increases in skin, of between 200 and 3400. The minimum breathing time at 150mlmin-' to produce a significant increase in relative tumour perfusion was 4.5 min. and the effect was maintained up to 9 min. Nicotinamide alone at 1000mgkg-' 60min before assay did not alter relative tumour perfusion. Comparing the combination of nicotinamide with 6 min carbogen breathing at 150 ml min-with carbogen breathing alone showed no difference in relative tumour perfusion: increases were of 36% and 42% respectively. Nicotinamide-induced alterations in microcirculation associated with reduction of acute hypoxia have therefore not been detected by 'Rb extraction. The perfusion-enhancing effect of carbogen in this tumour is probably an important component of its radiosensitising ability. in addition to its known ability to increase the oxvgen-carrving capacity of the blood. and should be taken into consideration in clinical studies.

The effects of host carbogen (95% oxygen/5% carbon dioxide) breathing on metabolic characteristics of Morris hepatoma 9618a

“…The studies here show that in hepatoma 9618a the flow component is probably negligible because no increase in the average microregional blood flow was shown by laser Doppler measurements after carbogen breathing. This has also been observed in several other (Dewhirst et al, 1996;Powell et al, 1996;Hill et al, 1998), but not all (Honess and Bleehen, 1995) tumour types. Both increased oxygen tension and increased flow in response to carbogen breathing appear to be a tumour (type)-specific phenomenon (Hill et al, 1998).…”

The effects of hyperoxic and hypercarbic gases on tumour blood flow

“…Allowing the mice to breathe 10% CO 2 -90% O 2 caused blood flow to increase by an average of 50% (Kruuv et al, 1966). Similarly, it was recently shown that carbogen breathing for 6 min resulted in a 50-70% increase in blood flow in RIF-1 tumours growing subcutaneously in mice (Honess and Bleehen, 1995). In another study, Grau and coworkers could show no carbogen-induced change in blood flow in C3H mammary carcinoma growing in the feet of mice (Grau et al, 1992).…”

“…Hickam and Frayser, 1966) but there is evidence that carbogen decreases flow in some other tissues (Hampson et al, 1987;Honess and Bleehen, 1995). Furthermore, the vasoactive effects of carbogen appear to be dependent on route of administration, with mechanically ventilated animals responding with vasodilation, and freely breathing animals with vasoconstriction (Kallinen et al, 1991).…”

The response to carbogen breathing in experimental tumour models monitored by gradient-recalled echo magnetic resonance imaging

“…Both these mechanisms would have to take account of the wellknown radiosensitizing effect of carbogen (Song et al, 1987) and of a recent report (Honess and Bleehen, 1995) that carbogen breathing causes an increase in RIF-l tumour blood flow. A fall in tumour blood flow lasting a few minutes would be unlikely to affect radiosensitivity unless the radiation were administered in that time window.…”