PERFUSION CHANGES IN THE RIF-1 TUMOR AND NORMAL-TISSUES AFTER CARBOGEN AND NICOTINAMIDE, INDIVIDUALLY AND COMBINED

The strategy of combining carbogen breathing and nicotinamide to overc ome chronic and acute hypoxia respectively is being evaluated clinical ly. The effects of both agents individually and in combination on rela tive perfusion of 400-700 mm(3) RIF-1 tumours and normal tissues were measured by Rb-86 extraction. Carbogen breathing alone for 6 min incre ased relative tumour perfusion by 50-70% compared with control at Bow rates of 50 to 200 ml min(-1), but the effect was lost at 300 ml min(- 1). All flow rates also produced similar increases in relative perfusi on of lung, of between 36% and 58%, and smaller increases in skin, of between 20% and 34%. The minimum breathing time at 150 ml min(-1) to p roduce a significant increase in relative tumour perfusion was 4.5 min , and the effect was maintained up to 9 min. Nicotinamide alone at 100 0 mg kg(-1) 60 min before assay did not alter relative tumour perfusio n. Comparing the combination of nicotinamide with 6 min carbogen breat hing at 150 ml min(-1) with carbogen breathing alone showed no differe nce in relative tumour perfusion; increases were of 36% and 42% respec tively. Nicotinamide-induced alterations in microcirculation associate d with reduction of acute hypoxia have therefore not been detected by Rb-86 extraction. The perfusion-enhancing effect of carbogen in this t umour is probably an important component of its radiosensitising abili ty, in addition to its known ability to increase the oxygen-carrying c apacity of the blood, and should be taken into consideration in clinic al studies.