title: The mechanisms by which hyperbaric oxygen and carbogen improve tumour oxygenation.
abstract: Hyperbaric oxygen (HBO) has been proposed to reduce tumour hypoxia by increasing the amount of dissolved oxygen in the plasma. That this actually occurs has not been verified experimentally. This study was performed to explore changes in tumour oxygenation induced by treatment with normobaric and hyperbaric oxygen and carbogen. R3230Ac mammary adenocarcinomas were implanted into Fisher 344 rats. Arterial blood gases, blood pressure and heart rate were monitored. Tumour oxygenation was measured polarographically in five sets of animals. They received either normobaric 100% oxygen, hyperbaric (3 atmospheres; atm) 100% oxygen, normobaric carbogen or hyperbaric (3 atm) carbogen (HBC) +/- bretylium. HBO reduced the mean level of low pO2 values (< 5 mmHg) from 0.49 to 0.07 (P = 0.0003) and increased the average median pO2 from 8 mmHg to 55 mmHg (P = 0.001). HBC reduced the level of low pO2 values from 0.82 to 0.51 (P = 0.002) an increased median pO2 from 2 mmHg to 6 mmHg (P = 0.05). Normobaric oxygen and carbogen did not change tumour oxygenation significantly. Sympathetic blockade with bretylium before HBC exposure improved oxygenation significantly more than HBC alone (low pO2 0.55-0.17, median pO2 4-17 mmHg). HBO and hyperbaric carbogen improved tumour oxygenation in this model, while normobaric oxygen or carbogen had no effect. Sympathetic-mediated vasoconstriction during hyperbaric carbogen caused it to be less effective than HBO. This mechanism also appeared to operate during normobaric carbogen breathing.
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Brizel
authors.forename: S
authors.initials: S
authors.lastname: Lin
authors.forename: J L
authors.initials: JL
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Brooks
authors.forename: M W
authors.initials: MW
authors.lastname: Dewhirst
authors.forename: C A
authors.initials: CA
authors.lastname: Piantadosi
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D001340:Autonomic Nerve Block; D001950:Bretylium Tosylate; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015687:Cell Hypoxia; D005260:Female; D006931:Hyperbaric Oxygenation; D007279:Injections, Subcutaneous; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000378:metabolism / Q000628:therapy*; D009368:Neoplasm Transplantation; D010100:Oxygen / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use*; D010101:Oxygen Consumption; D051381:Rats; D011916:Rats, Inbred F344; D013565:Sympatholytics; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014666:Vasomotor System / Q000187:drug effects
chemical_list: D013565:Sympatholytics; D002245:Carbon Dioxide; D001950:Bretylium Tosylate; C011700:carbogen; D010100:Oxygen