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Selective enhancement of intratumoural blood flow in malignant gliomas: Experimental study in rats by intracarotid administration of adenosine or adenosine triphosphate

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Summary

We studied the effect of intravenous and intracarotid infusion of adenosine and adenosine triphosphate (ATP) on the regional blood flow of intracerebrally transplanted RG-C 6 tumours in rats, using the hydrogen clearance method. The intracarotid administration of adenosine or ATP selectively increased blood flow in the tumour, but did not produce any significant change either in the regional cerebral blood flow of the extratumoural ipsilateral hemisphere or in the ipsilateral hemisphere without tumour. The intracarotid administration of ATP at a dose of 10 Μg/kg/min produced the most effective increase in the tumour blood flow (+51.5± 16.8%). In contrast, both the intravenous administration of adenosine and that of ATP failed to increase tumour blood flow. These results may possibly indicate that intracarotid administration of the adenosine or ATP might contribute in selectively enhancing the delivery of anti-cancer agents to malignant brain tumours.

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References

  1. Aukland K, Bower BF, Berliner RW (1964) Measurement of local blood flow with hydrogen gas. Circ Res 14: 164–187

    PubMed  Google Scholar 

  2. Benda P, Someda K, Messer J, Sweet WH (1971) Morphological and immunochemical studies of rat glial tumors and clonal strains propagated in culture. J Neurosurg 34: 310–323

    PubMed  Google Scholar 

  3. Berne RM, Rubio R, Curnish R (1974) Release of adenosine from ischemic brain. Effect on cerebral vascular resistance and incorporation into cerebral adenine nucleotides. Circ Res 35: 262–271

    Google Scholar 

  4. Blasberg RG, Groothuis DR (1986) Chemotherapy of brain tumors: Physiological and pharmacokinetic considerations. Semin Oncol 13: 70–82

    PubMed  Google Scholar 

  5. Bourke RS, West CR, Chheda G, Tower DB (1973) Kinetics of entry and distribution of 5-fluorouracil in cerebrospinal fluid and brain following intravenous injection in a primate. Cancer Res 33: 1735–1746

    PubMed  Google Scholar 

  6. Conforde EM, Oldendrof WH (1975) Independent blood-brain barrier transport systems for nucleic acid precursors. Biochim Biophys Acta 394: 211–219

    PubMed  Google Scholar 

  7. Drury AN, Szent-Györgyl A (1929) The physiological activity of the adenine compounds with especial reference to their action upon the mammalian heart. J Physiol 68: 213–237

    Google Scholar 

  8. Duff F, Patterson GC, Shepherd JT (1954) A quantitative study of the response to adenosine triphosphate of the blood vessels of the human hand and forearm. J Physiol 125: 581–589

    PubMed  Google Scholar 

  9. Fujiwara S, Kassel NF, Sasaki T, Nakagomi T, Lehman RM (1986) Selective hemoglobin inhibition of endothelium-dependent vasodilatation of rabbit basilar artery. J Neurosurg 64: 445–452

    PubMed  Google Scholar 

  10. Fujiwara S, Kassel NF, Sasaki T, Yamashita M, Zuccarello M (1986) Presynaptic inhibitory action of adenosine on neuromuscular transmission in the canine cavernous carotid artery. Stroke 17: 312–317

    PubMed  Google Scholar 

  11. Hiesiger EM, Voorhies RM, Basler GA, Lipschutz LE, Posner JB, Shapiro WR (1986) Opening the blood-brain and bloodtumor barriers in experimental rat brain tumors: The effect of intracarotid hyperosmolar mannitol on capillary permiability and blood flow. Ann Neurol 19: 50–59

    PubMed  Google Scholar 

  12. Hiraga S, Klubes P, Owens ES, Cysyk R, Blasberg RG (1987) Increases in brain tumors and cerebral blood flow by bloodperfluorochemical emulsion (Fluosol-DA) exchange. Cancer Res 47: 3296–3302

    PubMed  Google Scholar 

  13. Hirano A, Matsui T (1975). Vascular structures in brain tumors. Human Pathol 6: 611–621

    Google Scholar 

  14. Inoue T, Fukui M, Nishio S, Kitamura K, Nagara H (1987) Hyperosmotic blood-brain barrier disruption in brains of rats with an intracerebrally transplanted RG-C 6 tumor. J Neurosurg 66: 256–263

    PubMed  Google Scholar 

  15. Kondo A, Inoue T, Nagara H, Tateishi J, Fukui M (1987) Neurotoxity of adriamycin passed through the transiently disrupted blood-brain barrier by mannitol in the rat brain. Brain Res 412: 73–83

    PubMed  Google Scholar 

  16. Levin VA (1975) A pharmacologic basis for brain tumor chemotherapy. Semin Oncol 2: 57–61

    PubMed  Google Scholar 

  17. Lou HC, Edvinsson L, MacKenzie ET (1987) The concept of coupling blood flow to brain function: Revision required? Ann Neurol 22: 289–297

    PubMed  Google Scholar 

  18. MacKenzie ET, McCulloch J, O'Keane M, Pickard JD, Harper AM (1976) Cerebral circulation and norepinephrine: Relevance of the blood-brain barrier. Am J Physiol 231: 483–488

    PubMed  Google Scholar 

  19. Matsuura H, Ikeda Y, Imaya H, Nakazawa S (1987) Selective changes of blood flow in experimental brain tumor with induced hypertension. Surg Neurol 27: 433–436

    PubMed  Google Scholar 

  20. Mitsuhata N, Hino N, Tagusagawa Y, Suga K, Nishigaki S (1984) Intracarotid arterial infusion with CDDP in combination with Angiotensine II. Jpn J Cancer Chemother 11: 2594–2597

    Google Scholar 

  21. Mitsuhata N, Matsumura Y (1986) Intraarterial DDP and angiotensine II infusion chemotherapy. Jpn J Cancer Chemother 13: 1429–1438

    Google Scholar 

  22. Muramatsu I, Fujiwara M, Miura A, Shibata S (1980) Reactivity of isolated canine cerebral arteries to adenine nucleotides and adenosine. Pharmacology 21: 198–205

    PubMed  Google Scholar 

  23. Neuwelt EA, Frenkel EP, Diehhl J, Vu LH, Rapoport S, Hill S (1980) Reversible osmotic blood-brain barrier disruption in humans: Implications for the chemotherapy of malignant brain tumors. Neurosurgery 7: 44–52

    PubMed  Google Scholar 

  24. Neuwelt EA, Barnett PA, Binger DD, Frenkel EP (1982) Effects of adrenal cortical steroids and osmotic blood-brain barrier opening on methotrexate delivery to gliomas in the rodent: The factor of the blood-brain barrier. Proc Natl Acad Sci USA 79: 4420–4423

    PubMed  Google Scholar 

  25. Nishio S, Ohta M, Abe M, Kitamura K (1983) Microvascular abnormalities in ethylnitrosourea (ENU)-induced rat brain tumors: Structural basis for altered blood-brain barrier function. Acta Neuropathol (Berl) 59: 1–10

    Google Scholar 

  26. Nishio S, Egami H, Fukui M, Kitamura K, Sawa H (1986) Ultrastructural and cytochemical study of microvascular enzyme activity in experimental brain tumors of rat. Neurol Med Chir (Tokyo) 26: 527–533

    Google Scholar 

  27. Panther LA, Baumbach GL, Bigner DD, Piegors D, Groothuis DR, Heistad DD (1985) Vasoactive drugs produce selective changes in flow to experimental brain tumors. Ann Neurol 18: 712–715

    PubMed  Google Scholar 

  28. Rowe GG, Afonso S, Gurtner HP, Chelius CJ, Lowe WC, Castillo CA, Crumpton CW (1962) The systemic and coronary hemodynamic effects of adenosine triphosphate and adenosine. Am Heart J 64: 228–234

    PubMed  Google Scholar 

  29. Sadoshima S, Fujii K, Yao H, Kusuda K, Ibayashi S, Fujishima M (1986) Regional cerebral blood flow autoregulation in normotensive and spontaneously hypertensive rats: Effects of sympathetic denervation. Stroke 17: 981–984

    PubMed  Google Scholar 

  30. Shapiro WR, Voorhies RM, Hiesiger EM, Sher PB, Basler GA, Lipschutz LE (1988) Pharmacokinetics of tumor cell exposure to [14C] Methotrexate after intracarotid administration without and with hyperosmotic opening of the blood-tumor barriers in rat brain tumors: A quantitative autoradiographic study. Cancer Res 48: 694–701

    PubMed  Google Scholar 

  31. Shulman K (1965) Small artery and vein pressures in the subarachnoid space of the dog. J Surg Res 5: 56–61

    Google Scholar 

  32. Sollevi A (1986) Cardiovascular effect of adenosine in man: possible clinical implications. Prog Neurobiol 27: 319–349

    PubMed  Google Scholar 

  33. Tomura N, Uemura K, Shishido F, Inugami A, Higano S, Fujita H, Kanno I, Kato T (1987) Vascular response in brain tumor. Investigation by positron emission tomography. Nippon Acta Radiol 47: 1314–1316

    PubMed  Google Scholar 

  34. Vanhoutte PM, Rubanyi GM, Miller VM, Houston DS (1986) Modulation of vascular smooth muscle contraction by the endothelium. Ann Rev Phisiol 48: 307–320

    Google Scholar 

  35. Vriesendorp FJ, Pasternak JF, Groothuis DR (1987) The effect of systemic arterial hypertension on blood-to tissue transport in experimental gliomas. J Neuro-Oncol 5: 289–297

    Google Scholar 

  36. Warnke PC, Blasberg RG, Groothuis DR (1987) The effect of hyperosmotic blood-brain barrier disruption on blood-to-tissue transport in ENU-induced gliomas. Ann Neurol 22: 300–305

    PubMed  Google Scholar 

  37. Warnke PC, Molnar P, Bigner DD, Heistad DH, Groothuis DR (1987) Intravenous adenosine selectively increases blood flow to xenotransplanted intracerebral gliomas. Neurology 37: 1870–1873

    PubMed  Google Scholar 

  38. Winn HR, Rubio GR, Berne RM (1981) The role of adenosine in the regulation of cerebral blood flow. J Cereb Blood Flow Metabol 1: 239–244

    Google Scholar 

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Authors and Affiliations

  1. Department of Neurosurgery, Neurological Institute, Faculty of Medicine, Kyushu University, Fukuoka, Japan

    T. Baba, M. Fukui, S. Sakata, T. Tashima, I. Takeshita, T. Nakamura & T. Inoue

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  1. T. Baba
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  2. M. Fukui
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  4. T. Tashima
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  5. I. Takeshita
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  6. T. Nakamura
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  7. T. Inoue
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Baba, T., Fukui, M., Sakata, S. et al. Selective enhancement of intratumoural blood flow in malignant gliomas: Experimental study in rats by intracarotid administration of adenosine or adenosine triphosphate. Acta neurochir 101, 66–74 (1989). https://doi.org/10.1007/BF01410072

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