title: Simultaneous administration of glucose and hyperoxic gas achieves greater improvement in tumor oxygenation than hyperoxic gas alone.
abstract: OBJECTIVE
  To test the feasibility of hyperglycemic reduction of oxygen consumption combined with oxygen breathing (O(2)), to improve tumor oxygenation.
  
  
  METHODS
  Fischer-344 rats bearing 1 cm R3230Ac flank tumors were anesthetized with Nembutal. Mean arterial pressure, heart rate, tumor blood flow ([TBF], laser Doppler flowmetry), pH, and pO(2) were measured before, during, and after glucose (1 or 4 g/kg) and/or O(2).
  
  
  RESULTS
  Mean arterial pressure and heart rate were unaffected by treatment. Glucose at 1 g/kg yielded maximum blood glucose of 400 mg/dL, no change in TBF, reduced tumor pH (0.17 unit), and 3 mm Hg pO(2) rise. Glucose at 4 g/kg yielded maximum blood glucose of 900 mg/dL, pH drop of 0.6 unit, no pO(2) change, and reduced TBF (31%). Oxygen tension increased by 5 mm Hg with O(2). Glucose (1 g/Kg) + O(2) yielded the largest change in pO(2) (27 mm Hg); this is highly significant relative to baseline or either treatment alone. The effect was positively correlated with baseline pO(2), but 6 of 7 experiments with baseline pO(2) < 10 mm Hg rose above 10 mm Hg after combined treatment.
  
  
  CONCLUSIONS
  We demonstrated the feasibility of combining hyperglycemia with O(2) to improve tumor oxygenation. However, some cell lines are not susceptible to the Crabtree effect, and the magnitude is dependent on baseline pO(2). Additional or alternative manipulations may be necessary to achieve more uniform improvement in pO(2).
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Snyder
authors.forename: J L
authors.initials: JL
authors.lastname: Lanzen
authors.forename: R D
authors.initials: RD
authors.lastname: Braun
authors.forename: G
authors.initials: G
authors.lastname: Rosner
authors.forename: T W
authors.initials: TW
authors.lastname: Secomb
authors.forename: J
authors.initials: J
authors.lastname: Biaglow
authors.forename: D M
authors.initials: DM
authors.lastname: Brizel
authors.forename: M W
authors.initials: MW
authors.lastname: Dewhirst
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology*; D003131:Combined Modality Therapy; D005110:Extracellular Space / Q000737:chemistry; D005240:Feasibility Studies; D005260:Female; D005947:Glucose / Q000008:administration & dosage*; D005973:Glutamine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D023421:Models, Animal; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology*; D010100:Oxygen / Q000008:administration & dosage*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D012039:Regional Blood Flow; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D001786:Blood Glucose; D005973:Glutamine; D005947:Glucose; D010100:Oxygen