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NEUROLOGY 1987;37:1870
© 1987 American Academy of Neurology

Intravenous adenosine selectively increases blood flow to xenotransplanted intracerebral gliomas

P. C. Warnke, MD, P. Molnar, MD, D. D. Bigner, MD, PhD, D. H. Heistad, MD and D. R. Groothuis, MD

Department of Neurology (Drs. Warnke, Molnar, and Groothuis), Northwestern University Medical School and Evanston Hospital, Evanston, IL; the Department of Pathology (Neuropathology) (Dr. Bigner), Duke University School of Medicine, Durham, NC; and the Department of Internal Medicine (Dr. Heistad), VA Hospital and University of Iowa College of Medicine, Iowa City, IA.

Adenosine was infused intravenously at 10 µmol/(kg·min) into athymic ("nude") rats with intracerebral D-54MG xenotransplanted brain tumors, in an attempt to increase tumor blood flow. Cerebral blood flow (F) was measured with 14C-iodoantipyrine and quantitative autoradiography. Mean arterial blood pressure was 95 ± 9.4 (SE) mm Hg in the adenosine group and 112 ± 6.0 mm Hg in the controls. Averaged mean whole tumor F was significantly higher in adenosine-treated brain tumors (117.6 ± 20.8ml/[hg · min]) than in controls (62.2 ± 9.7ml/[hg · min]). Regionally, there were significant increases of F in tumor periphery and brain around tumor, but not in tumor center or any tumor-free brain regions. Focal values of F < 5 ml/(hg · min) were present in some necrotic regions of adenosine-treated tumors. These results, obtained in unanesthetized rats with transplanted gliomas from a human cell line, confirm our earlier observations in avian sarcoma virus-induced brain sarcomas in dogs, and suggest that adenosine or perhaps other vasodilators could be used to selectively increase the delivery of lipid-soluble chemotherapeutic drugs to brain tumors.

Address correspondence and reprint requests to Dr. Groothuis, 2650 Ridge Avenue, Evanston, IL 60201.

Supported by the Richard Lilienfeld Brain Tumor Research Fund, NIH grants R01 NS12745 (Javits Neuroscience Investigator Award), K04 NS00814 (D. R. G.), R01 CA11878, P01 CA32672 (D. D. B.), R01 HL14388 (D. H. H.), PO1 NS20023 (D. R. G. and D. D. B.), and by a VA Medical Investigator Award (D. H. H.). Dr. Warnke was the recipient of an Arlene and Marshall Bennett Neuro-Oncology Fellowship. Dr. Molnar was supported by the Mark Moritz Brain Tumor Research Fund.

Received April 28, 1986. Accepted for publication in final form March 6, 1987.






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