Perfusion changes in the RIF-1 tumour and normal tissues after carbogen and nicotinamide, individually and combined.
The 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-1 tumours and normal tissues were measured by 86Rb extraction. Carbogen breathing alone for 6 min increased relative tumour perfusion by 50-70% compared with control at flow 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 perfusion 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 produce a significant increase in relative tumour perfusion was 4.5 min, and the effect was maintained up to 9 min. Nicotinamide alone at 1000 mg kg-1 60 min before assay did not alter relative tumour perfusion. Comparing the combination of nicotinamide with 6 min carbogen breathing at 150 ml min-1 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 86Rb 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 oxygen-carrying capacity of the blood, and should be taken into consideration in clinical studies.
Honess
D J
DJ
MRC Unit, MRC Centre, Cambridge, UK.
Bleehen
N M
NM
D000280:Administration, Inhalation; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000503:physiopathology; D009536:Niacinamide / Q000494:pharmacology*; D010100:Oxygen / Q000008:administration & dosage / Q000494:pharmacology*; D010477:Perfusion; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D012413:Rubidium / Q000378:metabolism
D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; D009536:Niacinamide; C011700:carbogen; D012413:Rubidium; D010100:Oxygen