Drug Effects on Cerebral Extracellular Ionic Derangement during Ischemic Hypoxia

  • D. Heuser
  • H. Guggenberger
  • B. Kottler
Part of the Advances in Behavioral Biology book series (ABBI, volume 35)


In the central nervous system ionic homeostasis is maintained under physiologic conditions by means of energy-dependent pumping mechanisms located in membrane structures. Under the precondition of adequate supply of oxygen and substrates, these pumps are able to reverse dynamic variations in the transmembrane ionic gradients — a phenomenon which can be observed during transistory O2 deficiency, electrical activation, and spreading depression. This homeostatic physiologic process is usually facilitated by concomitant changes in cerebrovascular resistance which may considerably improve local or global oxygen and substrate availability under conditions of increased energy demand of cerebral tissue.


Cerebral Ischemia Cerebral Perfusion Pressure Ionic Homeostasis Ischemic Hypoxia Oxygen Extraction Fraction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    B. K. Siesjö, Cell damage in the brain: A speculative synthesis, J. Cereb. Blood Flow Metabol. 1: 155 (1981).CrossRefGoogle Scholar
  2. 2.
    D. Heuser and H. Guggenberger, Ionic changes in brain ischemia and alterations produced by drugs, Br. J Anaesth. 57: 23 (1985).CrossRefGoogle Scholar
  3. 3.
    A. J. Hansen, Extracellular ion concentration in cerebral ischemia, in: The Application of Ionselective micro-electrodes, T. Zeuthen, ed., Elsevier/North Holland Biomedical Press, Amsterdam (1981) p. 239.Google Scholar
  4. 4.
    K. A. Hossmann, S. Sakaki, and V. Zimmermann, Cation activities in reversible ischemia of the cat brain, Stroke 8: 77 (1977).CrossRefGoogle Scholar
  5. 5.
    F. A. Welsh, M. D. Ginsberg, W. Reider, and W. W. Budd, Deleterious effect of glucose pretreatment on recovery from diffuse cerebral ischemia in the cat. I and II Regional metabolite levels, Stroke 11: 347 (1980).CrossRefGoogle Scholar
  6. 6.
    G. M. de Courten-Myers, S. Yamaguchi, K. R. Wagner, P. Ting, and R. E. Myers, Brain injury from marked hypoxia in cats: Role of blood pressure and glycemia, Stroke 16: 1016 (1985).CrossRefGoogle Scholar
  7. 7.
    E. Siemkowicz and A. J. Hansen, Brain extracellular ion composition and EEG activity following 10 minutes ischemia in normo-and hyperglycemic rats, Stroke 12: 236 (1981).CrossRefGoogle Scholar
  8. 8.
    E. Siemkowicz and A. J. Hansen, Clinical restitution following cerebral ischemia in hypo-, normo-, and hyperglycemic rats, Acta. Neurol. Scand. 58: 1 (1978).Google Scholar
  9. 9.
    R. E. Myers and M. Yamaguchi, Effect of serum glucose concentration on brain response to circulatory arrest, J. Neuropathol. Exp. Neurol. 35: 301 (1976).CrossRefGoogle Scholar
  10. 10.
    R. E. Myers, Lactic acid accumulation as a cause of brain edema and cerebral necrosis resulting from oxygen deprivation, in: Advances in Perinatal Neurology, R. Korobkin and C. Guilleminault, eds., Spectrum Publications, New York (1979) p. 85.Google Scholar
  11. 11.
    H. Kalimo, S. Rehncrona, B. Soderfeldt, Y. Olson, and B. K. Siesjö, Brain lactic acidosis and ischemic cell damage: 2. Histopathology, J. Cerebr. Blood Flow Metabol. 1: 313 (1981).CrossRefGoogle Scholar
  12. 12.
    W. A. Pulsinelli, S. Waldmann D. Rawlinson, and F. Plum, Moderate hyperglycemia augments ischemic brain damage: A neuropathological study in the rat, Neurology 32: 1239.Google Scholar
  13. 13.
    W. A. Pulsinelli, D. E. Levy, B. Sigsbee, P. Scherer, and F. Plum, Increased damage after ischemic stroke in patients with hyperglycemia with or without established diabetes mellitus, Am. J. Med. 74: 540 (1983).CrossRefGoogle Scholar
  14. 14.
    W. A. C. Mutch and A. J. Hansen, Extracellular pH changes during spreading depression and cerebral ischemia: Mechanisms of brain pH regulation, J. Cereb. Blood Flow Metabol. 4: 17 (1984).CrossRefGoogle Scholar
  15. 15.
    J. Astrup, P. Skovsted, F. Gjerris, and H. RahbekSorensen, Increase in extracellular potassium in the brain during circulatory arrest: effects of hypothermia, lidocaine, and thiopental, Anesthesiology 55: 256 (1981).CrossRefGoogle Scholar
  16. 16.
    W. Kuschinsky and M Wahl, Local chemical and neurogenic regulation of cerebral vascular resistance, Physiol. Rev. 58: 656 (1978).Google Scholar
  17. 17.
    E. A. Bering, Effects of profound hypothermia and circulatory arrest on cerebral oxygen metabolism and cerbrospinal fluid electrolyte composition in dogs, J. Neurosurg. 40: 199 (1974).CrossRefGoogle Scholar
  18. 18.
    K. A. Hossmann, H. Lechtape-Grüter, and V. Hossmann, The role of cerebral blood flow for the recovery of the brain after prolonged ischemia. Z. Neurol. 8: 77 (1977).Google Scholar
  19. 19.
    R. J. Harris, L. Symon, N.M. Branston, and M. Bayhan, Changes in extracellular calcium activity in cerebral ischemia, J. Cereb. Blood Flow Metabol. 2: 203 (1981).Google Scholar
  20. 20.
    R. J. Harrisand L. Symon, Extracllular pH, potassium, and calcium activities in progressive ischemia of rat cortex, J. Cereb. Blood Flow Metabol. 4: 178 (1984).CrossRefGoogle Scholar
  21. 21.
    T. Wieloch, R. J. Harris, and B. K. Siesjö, Brain metabolism and ischemia: Mechanism of cell damage and principles of protection, J. Cereb. Blood Flow Metabol. 2 (Suppl 1): 55 (1982)CrossRefGoogle Scholar
  22. 22.
    J. L. Farber, K. R. Chien, and S. jr. Mittnacht, The pathogenesis of irreversible cell injury in ischemia Am. J. Pathol. 102: 271 (1981).Google Scholar
  23. 23.
    B. Meldrum, M. Evans, T. Griffiths, and R. Symon, Ischemic brain damage: the role of excitatory activity and of calcium entry, Br. J. Anaesth. 57: 44 (1985).CrossRefGoogle Scholar
  24. 24.
    F. A. X. Schanne, A. B. Kane, E. E. Young, and J. L. Farber, Calcium dependence of toxic cell death: A final common pathway, Science 206: 700 (1979)CrossRefGoogle Scholar
  25. 25.
    R. Laas, B. Jahn, and K. Kessler, Duration versus degree of hypotension as critical conditions of brain infarction in the albino rat, J. Neurosurg. 65: 525 (1986).CrossRefGoogle Scholar
  26. 26.
    W. Heiss and G. Rosner, Duration versus severity of ischemia as critical factors of cortical damage in: Cerebrovascular Diseases. Thirteenth Research Conference (Princeton), M. Reivich and H.J. Hurtig, eds., Raven Press, New York (1983) p. 225.Google Scholar
  27. 27.
    J. Astrup, L. Symon, N. M. Branston, and N. A. Lassen, Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia, Stroke 8: 51 (1977).CrossRefGoogle Scholar
  28. 28.
    J. Astrup, B. K. Siesjö, and L. Symon, Thresholds in cerebral ischemia-the ischemic penumbra, Stroke 12: 723 (1983).CrossRefGoogle Scholar
  29. 29.
    L. Symon, Threshold concept of functional failure in the CNS in relation to ischemia., in: Pharmacology of Cerebral Ischemia, J. Krieglstein, ed., Elsevier Science Publishers, Amsterdam (1986) p. 31.Google Scholar
  30. 30.
    N. M. Branston, D. T. Hope, and L. Symon, Barbiturates in • focal ischemia of primate cortex: effects on blood flow distribution, evoked potential and extracellular potassium, Stroke 10: 647 (1979).CrossRefGoogle Scholar
  31. 31.
    D. Heuser and H. Guggenberger, Recovery from disturbed ion cerebral homeostasis following severe incomplete ischemia and modification by the metabolic depressant drug etomidate, in: Brain Protection, K. Wiedemann and S. Hoyer, eds., Springer Berlin Heidelberg New York Tokyo (1983) p. 38.Google Scholar
  32. 32.
    E. M. Nemoto and B. S: Stanely Frinak, Brain tissue pH after global brain ischemia and barbiturate loading in rats, Stroke 12: 77 (1981).CrossRefGoogle Scholar
  33. 33.
    L.A. Newberg and J. D. Mitchenfelder, Cerebral protection by isoflurane during hypoxemia or ischemia, Anesthesiology 59: 29 (1983).CrossRefGoogle Scholar
  34. 34.
    R. E. Anderson and T. M. Sundt, Brain pH in focal cerebral ischemia and the protective effect of barbiturate anesthesia, J Cereb. Blood Flow Metabol. 3: 493 (1983).CrossRefGoogle Scholar
  35. 35.
    G. Strichartz, Molecular mechanisms of nerve block by local anesthetics, Anesthesiology 45: 421 (1976).CrossRefGoogle Scholar
  36. 36.
    A. A. Artru and J. D. Michenfelder, Anoxic cerebral potassium accumulation reduced by phenytoin: mechanism of cerebral protection ?, Anesth. Analg. 60: 41 (1981).Google Scholar
  37. 37.
    J. P. Cullen, J. A. Aldrete, L. Jankowski, and F. RomoSalas, Protective action of phenytoin in cerebral ischemia, Anesth. Analg. 58: 165 (1979).Google Scholar
  38. 38.
    V. Heinemann and H. D. Lux, Effects of diphenylhydanzoin on extracellular [K+] in rat cortex, Electroencephalogr. Clin. Neurophysiol. 34: 735 (1973).Google Scholar
  39. 39.
    B. W. Festoff and S. H. Appel, Effect of diphenylhydantoin on synaptosome sodium-potassium-ATPase, J. Clin. Inves.t 47: 2752 (1968).CrossRefGoogle Scholar
  40. 40.
    A. P. Ferbiger, S. E. Liuzzi, and P. B. Dunham, Diphenylhydantoin: Stimulation of potassium influx in lobster axons, Brain. Res. 47: 2752 (1971).Google Scholar
  41. 41.
    J. H. Pincus, Diphenylhydantoin and ion flux in lobster nerve, Arch. Neurol. 26: 4 (1972).CrossRefGoogle Scholar
  42. 42.
    J. H. Pincus, J. Grove, and B.B. Marino, Studies on the mechanism of action of diphenylhydantoin, Arch. Neurol. 22: 566 (1970).Google Scholar
  43. 43.
    L. M. Auer, Prophylaxis of cerebral ischemic damage from vasospasm after subarachnoid hemorrhage in: Brain Protection, K. Wiedemann and S. Hoyer, eds., Springer, Berlin Heidelberg New York Tokyo (1983) p. 124.CrossRefGoogle Scholar
  44. 44.
    L. M. Auer, Z. Ito, A. Suzuki, and H. Ohta, Prevention of symptomatic vasospasm by topically applied nimodipine, Acta Neurochir. 63: 297 (1982)CrossRefGoogle Scholar
  45. 45.
    L. Symon, R. J. Harris and N. M. Branston, Calcium ions and calcium antagonists in ischemia, Acta Neurochir. 63: 267CrossRefGoogle Scholar
  46. 46.
    M. Höller, H. Dierking, K. Dengler, F. Tegtmeier, and T. Peters, Effect of flunarizine on extracellular ion concentration in the rat brain under hypoxia and ischemia, in: Acute Brain Ischemia, Medical and Surgical Therapy, N. Battistini, P. Fiorini, R. Courbier, F. Plum, and C. Fiesci, eds., Serono Symposia Publication,32, Raven Press, New York (1986) p. 229Google Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • D. Heuser
    • 1
  • H. Guggenberger
    • 1
  • B. Kottler
    • 1
  1. 1.Clinic of AnaesthesiologyEberhard-Karls-UniversityTübingenGermany

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