The effects of dexamethasone on experimental brain tumors: I. Transcapillary transport and blood flow in RG-2 rat gliomas.
Dexamethasone dramatically improves cerebral edema associated with malignant gliomas. Although the pathophysiology of this effect is not clearly understood, many investigators have postulated that tumor capillary permeability is reduced by dexamethasone. We studied blood-to-tissue transport and blood flow in 178 RG-2 transplanted gliomas in a control group and four groups given dexamethasone at doses of 3, 6, 9, and 12 mg/kg for four days. 14C-alpha aminoisobutyric acid (AIB) was used to study blood-to-tissue transport in 31 animals; in an additional 27 animals 14C-AIB and 131I-iodoantipyrine (IAP) were used in double label experiments to study blood-to-tissue transport and blood flow. Regional measurements of the transfer constant (K) of AIB and blood flow (F) were made with quantitative autoradiography. There were significant differences between the control and dexamethasone-treated groups with regard to weight loss and plasma glucose. However, there was no significant effect of dexamethasone on values of K or F, regardless of the tumor or brain region examined, and regardless of the dose of dexamethasone administered. Analysis of the profiles of the transfer constant of AIB in the brain around tumor showed that the K of AIB decreased within 0.5 mm of the tumor edge in direct relationship to the dexamethasone dose. These results do not support the hypothesis that dexamethasone reduces brain tumor capillary permeability, and suggest that dexamethasone may decrease tumor-associated cerebral edema by effects on bulk flow away from the tumor margin.
Molnar
P
P
Department of Neurology, Northwestern University Medical School, Evanston Hospital, IL 60201, USA.
Lapin
G D
GD
Groothuis
D R
DR
D000621:Aminoisobutyric Acids; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D000983:Antipyrine / Q000031:analogs & derivatives; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001932:Brain Neoplasms / Q000098:blood supply* / Q000503:physiopathology; D002196:Capillaries / Q000187:drug effects* / Q000503:physiopathology; D002250:Carbon Radioisotopes; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000098:blood supply* / Q000503:physiopathology; D006400:Hematocrit; D007457:Iodine Radioisotopes; D051381:Rats; D011916:Rats, Inbred F344; D012039:Regional Blood Flow / Q000187:drug effects
D000621:Aminoisobutyric Acids; D018931:Antineoplastic Agents, Hormonal; D001786:Blood Glucose; D002250:Carbon Radioisotopes; D007457:Iodine Radioisotopes; C100049:2-aminoisobutyric acid; D003907:Dexamethasone; D000983:Antipyrine; C008135:iodoantipyrine