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Intracranial hypertension and brain oedema in albino rabbits

Part 2: Effects of acute therapy with diuretics

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Summary

Increased intracranial pressure due to brain oedema was produced in albino rabbits by combining a cryogenic lesion in the left hemisphere with the intraperitoneal administration of 6-aminonicotinamide (cytotoxic agent).

The most effective reduction in ICP (74%) was achieved when furosemide and mannitol were used in combination. When either mannitol or furosemide was employed alone, the average ICP reduction was approximately 53%. Peak ICP reduction occurred at 45 minutes with furosemide, 30 minutes with mannitol and furosemide combined, and at 60 minutes with a combination of mannitol and acetazolamide.

Also studied simultaneously in these animals were intracranial elastance (Em), brain water content, hemispheric water volume content, electrolytes, EEG, and gross pathology. Following therapy there was a statistically significant reduction of water content in the left hemisphere (cryogenic lesion) by all therapeutic modalities except with furosemide alone. In the right hemisphere the water content was reduced by furosemide and the furosemide-mannitol combination but not by the association of mannitol with acetazolamide. A significant decrease of brain sodium was noted only for the combination of mannitol and furosemide.

This study indicates that effective reduction of cytotoxic-cryogenic brain oedema and intracranial hypertension can be obtained with a variety of diuretic agents. From the standpoint of tissue dehydration, restoration of tissue electrolyte balance, and rate of ICP reduction, the combination of furosemide-mannitol appears to offer advantages over furosemide alone, or acetazolamide-mannitol.

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References

  1. Baethmann, A., Lanksch, W., Schmiedek, P., Formation and treatment of cerebral edema. Neurochirurgia (Stuttg.)17 (1974), 37–47.

    Google Scholar 

  2. Baethmann, A., Reulen, H. J., Brendel, W., Die Wirkung des Antimetaboliten 6-Aminonicotinamid (6-ANA) auf Wasser- und Elektrolytgehalt des Rattenhirns und ihre Hemmung durch Nikotinsäure. Z. ges. exp. Med.146 (1968). 226–240.

    Google Scholar 

  3. Baethmann, A., van Harreveld, A., Water and electrolyte distribution in gray matter rendered edematous with a metabolic inhibitor. J. Neuropathol. Exp. Neurol.32 (1973), 408–423.

    PubMed  Google Scholar 

  4. Bakey, L., Haque, I. U., Morphological and chemical studies in cerebral edema: I. Cold induced edema. J. Neuropathol. Exp. Neurol.23 (1964), 393–418.

    PubMed  Google Scholar 

  5. Beks, J. W. F., ter Weeme, C. A., The influence of urea and mannitol on increased intraventricular pressure in cold-induced cerebral edema. Acta neurochir. (Wien)16 (1967), 97–107.

    Google Scholar 

  6. Bergland, R. M., Page, R. B., Howland, W. S., Furosemide: A non-osmotic diuretic for neurosurgical use. Presented at the 43rd Annual Meeting of the American Association of Neurological Surgeons, Miami Beach, Florida, April 8, 1975.

  7. Billet, R., Injectable acetazolamide in neurosurgery. Sem. Hop. Ther.38 (1962), 248–251.

    Google Scholar 

  8. Blakemore, W. F., The fate of escaped plasma protein after thermal necrosis of the rat brain: An electron microscope study. J. Neuropathol. Exp. Neurol.28 (1969), 139–152.

    PubMed  Google Scholar 

  9. Blasberg, R. G., Clearance of serum albumin from brain extracellular fluid: A possible role in cerebral edema. In: Dynamics of brain edema (Pappius, H. M., Feindel, W., eds.), pp. 98–102. New York: Springer. 1976.

    Google Scholar 

  10. Buhan, S., Effect of acetazolamide (Diamox) on the water content and distribution in various segments of the central nervous system. Acta Med. Jugosl.14 (1960), 341–352.

    Google Scholar 

  11. Buhrley, L., Reed, D. J., The effect of furosemide on sodium-22 uptake into cerebrospinal fluid and brain. Exp. Brain Res.14 (1972), 503–510.

    PubMed  Google Scholar 

  12. Clasen, R. A., Cooke, P. M., Pandolfi, S., Boyd, D., Raimondi, A. J., Experimental cerebral edema produced by focal freezing: I. An anatomic study utilizing vital dye techniques. J. Neuropathol. Exp. Neurol.21 (1962), 579–596.

    PubMed  Google Scholar 

  13. Clasen, R. A., Cooke, P. M., Pandolfi, S., Carnecki, G., Bryar, G., Hypertonic urea in experimental cerebral edema. Arch. Neurol.12 (1965), 424–434.

    PubMed  Google Scholar 

  14. Clasen, R. A., Pandolfi, S., Casey, D., Jr., Furosemide and pentobarbital in cryogenic cerebral injury and edema. Neurology (Minneap.)24 (1974), 642–648.

    Google Scholar 

  15. Cottrell, J. E., Robustelli, A., Post, K., Turndorf, H., Furosemide- and mannitol-induced changes in intracranial pressure and serum osmolality and electrolytes. Anesthesiology47 (1977), 28–30.

    PubMed  Google Scholar 

  16. Cserr, H., Cooper, D. N., Milhorat, T. H., Production, circulation, and absorption of brain interstitial fluid. In: Dynamics of brain edema (Pappius, H. M., Feindel, W., eds.), pp. 95–97. New York: Springer. 1976.

    Google Scholar 

  17. Demailly, P., Acetazolamide in intracranial hypertension. Gaz. Med. France69 (1962), 2123–2124.

    PubMed  Google Scholar 

  18. Domer, F., Effects of diuretics on cerebrospinal fluid formation and potassium movement. Exp. Neurol.24 (1969), 54–64.

    PubMed  Google Scholar 

  19. Ehrenrich, D. L., Burns, R. A., Alhman, R. W., Fazekas, J. F., Influence of acetazolamide on cerebral blood flow. Arch. Neurol.5 (1961), 227–232.

    PubMed  Google Scholar 

  20. Einspruch, B. C., Clark, K., Further studies on the effectiveness of agents used to lower intracranial pressure. J. Neurosurg.23 (1965), 45–48.

    PubMed  Google Scholar 

  21. Elliott, K. A. C., Jasper, H., Measurement of experimentally induced brain swelling and shrinkage. Amer. J. Physiol.157 (1949), 122–129.

    Google Scholar 

  22. Fenske, A., Samii, M., Reulen, H. M., Hey, O., Extracellular space and electrolyte distribution in cortex and white matter of dog brain in cold induced oedema. Acta neurochir. (Wien)29 (1973), 81–94.

    Google Scholar 

  23. Fishman, R. A., Brain edema. N. Engl. J. Med.293 (1975), 706–711.

    PubMed  Google Scholar 

  24. Fossati, P., Delandtscheer, J. M., Galibert, P., Lopez-Pinto, C. M., Linguette, C., Laine, E., Importance of acetazolamide in the resuscitation of subjects with head injuries. Lille Med.8 (1963), 501–506.

    PubMed  Google Scholar 

  25. Giacobini, E., Localization of carbonic anhydrase in the nervous system. Science134 (1961), 1524–1525.

    PubMed  Google Scholar 

  26. Goluboff, B., Shenkin, H. A., Haft, H., The effects of mannitol and urea on cerebral hemodynamics and cerebrospinal fluid pressure. Neurology (Minneap.)14 (1964), 891–898.

    Google Scholar 

  27. Gray, W. D., Rauh, C. E., Shanahan, R. W., The intracellular localization of carbonic anhydrase and a carbonic anhydrase inhibitor in the brains of mice. Biochem. Pharmacol.8 (1961), 307–316.

    PubMed  Google Scholar 

  28. Harbaugh, R. D., James, H. E., Marshall, L. F., Shapiro, H. M., Laurin, R., Acute therapeutic modalities for experimental vasogenic edema. Neurosurgery5 (1979), 656–665.

    PubMed  Google Scholar 

  29. Harper, A. M., Bell, R. A., The failure of intravenous urea to alter the blood flow through the cerebral cortex. J. Neurol. Neurosurg. Psychiat.26 (1963), 69–70.

    PubMed  Google Scholar 

  30. Herrmann, H. D., Neuenfeldt, D., Development and regression of a disturbance of the blood-brain barrier and of edema in tissue surrounding a circumscribed cold lesion. Exp. Neurol.34 (1972), 115–120.

    PubMed  Google Scholar 

  31. James, H. E., Bruce, D. A., Welsh, F., Cytotoxic edema produced by 6-aminonicotinamide and its response to therapy. Neurosurgery3 (1978), 196–200.

    PubMed  Google Scholar 

  32. James, H. E., Laurin, R., Intracranial hypertension and brain oedema in albino rabbits: Part I: Experimental models. Acta neurochir. (Wien)55 (1981), 213–226.

    Google Scholar 

  33. James, H. E., Langfitt, T. W., Kumar, V. S., Ghostine, S. Y., Treatment of intracranial hypertension: Analysis of 105 consecutive, continuous recordings of intracranial pressure. Acta neurochir. (Wien)36 (1977), 189–200.

    Google Scholar 

  34. Javid, M., Anderson, J., The effect of urea on cerebrospinal fluid pressure in monkeys before and after bilateral nephrectomy. J. Lab. Clin. Med.53 (1959), 484–489.

    PubMed  Google Scholar 

  35. Johnston, I. H., Harper, A. M., The effect of mannitol on cerebral blood flow: An experimental study. J. Neurosurg.36 (1973), 461–471.

    Google Scholar 

  36. Kirkendall, W. M., Stein, J. H., Clinical pharmacology of furosemide and ethacrynic acid. Amer. J. Cardiol.22 (1968), 162–167.

    PubMed  Google Scholar 

  37. Kister, S. J., Carbonic anhydrase inhibition: VI. The effect of acetazolamide on cerebrospinal fluid flow. J. Pharmacol. Exp. Ther.117 (1956), 402–405.

    PubMed  Google Scholar 

  38. Klatzo, I., Neuropathological aspects of brain edema. J. Neuropathol. Exp. Neurol.26 (1967), 1–14.

    PubMed  Google Scholar 

  39. Klatzo, I., Pathophysiological aspects of brain edema. In: Steroids and brain edema (Reulen, H. J., Schurmann, K., eds.), pp. 1–8. New York: Springer. 1972.

    Google Scholar 

  40. Klatzo, I., Piraux, A., Laskowski, E. J., The relationship between edema, blood-brain barrier and tissue elements in a local brain injury. J. Neuropathol. Exp. Neurol.17 (1958), 548–564.

    PubMed  Google Scholar 

  41. Klatzo, I., Wisniewski, H., Steinwall, O., Streicher, E., Dynamics of cold injury edema. In: Brain edema (Klatzo, I., Seitelberger, F., eds.), pp. 554–563. New York: Springer. 1967.

    Google Scholar 

  42. Knopp, L. M., Atkinson, J. R., Ward, A. A., Jr., Effect of diamox on cerebrospinal pressure of cat and monkey. Neurology (Minneap.)7 (1957), 119–123.

    Google Scholar 

  43. Koch, A., Woodbury, D. M., Carbonic anhydrase inhibition and brain electrolyte composition. Amer. J. Physiol.198 (1960), 434–440.

    PubMed  Google Scholar 

  44. Leech, P., Miller, J. D., Intracranial volume-pressure relationships during experimental brain compression in primates: I. Pressure responses to changes in ventricular volume. J. Neurol. Neurosurg. Psychiat.37 (1974), 1093–1098.

    PubMed  Google Scholar 

  45. Leech, P., Miller, J. D., Intracranial volume-pressure relationships during experimental brain compression in primates: 3. Effect of mannitol and hyperventilation. J. Neurol. Neurosurg. Psychiat.37 (1974), 1105–1111.

    PubMed  Google Scholar 

  46. Long, D., Maxwell, R., Choi, K. S., A new therapy regimen for brain edema. In: Dynamics of brain edema (Pappius, H. M., Feindel, W., eds.), pp. 293–300. New York: Springer. 1976.

    Google Scholar 

  47. Long, D. M., Maxwell, R. E., Choi, K. S., Cole, H. O., French, L. A., Multiple therapeutic approaches in the treatment of brain edema induced by a standard cold lesion. In: Steroids and brain edema (Reulen, H. J., Schurmann, K., eds.), pp. 87–94. New York: Springer. 1972.

    Google Scholar 

  48. Lopez-Pinto, C., Fosati, P., Galibert, P., Delandtsheer, J., Acetazolamide (Diamox) immediately following craniocerebral injuries. Acta Neurol. Belg.63 (1963), 298–314.

    Google Scholar 

  49. Maren, T. H., Carbonic anhydrase: Chemistry, physiology, and inhibition. Physiol. Rev.47 (1967), 595–781.

    PubMed  Google Scholar 

  50. Maren, T. H., Robinson, B., Pharmacology of acetazolamide in man, with particular reference to the cerebrospinal fluid. Amer. J. Med.27 (1959), 317 (abstr.).

    Google Scholar 

  51. Miller, J. D., Volume and pressure in the craniospinal axis. Clin. Neurosurg.22 (1974), 76–105.

    Google Scholar 

  52. Miller, J. D., Leech, P., Effects of mannitol and steroid therapy on intracranial volume-pressure relationships in patients. J. Neurosurg.42 (1975), 274–281.

    PubMed  Google Scholar 

  53. Pappius, H. M., Dayes, L. A., Hypertonic urea: Its effect on the distribution of water and electrolytes in normal and edematous brain tissue. Arch. Neurol.13 (1965), 395–402.

    PubMed  Google Scholar 

  54. Pollay, M., Formation of cerebrospinal fluid: Relations of studies of isolated choroid plexus to the standing gradient hypothesis. J. Neurosurg.42 (1975), 665–673.

    PubMed  Google Scholar 

  55. Raimondi, A. J., Evans, J. P., Mullan, S., Studies of cerebral edema: III. Alteration in the white matter: An electron microscopic study using ferritin as a labeling compound. Trans. Amer. Neurol. Assoc.87 (1962), 143–146.

    Google Scholar 

  56. Reed, D. J., The effect of furosemide on cerebrospinal fluid flow in rabbits. Arch. Int. Pharmacodyn. Ther.178 (1969), 324–330.

    PubMed  Google Scholar 

  57. Reed, D. J., Woodbury, D. M., Effect of urea and acetazolamide on brain volume and cerebrospinal fluid pressure. J. Physiol. (Lond.)164 (1962), 265–273.

    Google Scholar 

  58. Reulen, H. J., Vasogenic brain oedema: New aspects in its formation, resolution and therapy. Brit. J. Anaesth.48 (1976), 741–752.

    PubMed  Google Scholar 

  59. Reulen, H. J., Graham, R., Spatz, M., Klatzo, I., Role of pressure gradients and bulk flow in dynamics of vasogenic brain edema. J. Neurosurg.46 (1977), 24–35.

    PubMed  Google Scholar 

  60. Rose, A. L., Millac, P., The treatment of benign intracranial hypertension with furosemide. J. Neurol. Sci.3 (1966), 606–608.

    Google Scholar 

  61. Schaul, N., Ball, G., Gloor, P., Pappius, H. M., The EEG in cerebral edema. In: Dynamics of brain edema (Pappius, H. M., Feindel, W., eds.), pp. 144–149. New York: Springer. 1976.

    Google Scholar 

  62. Shenkin, H. A., Goluboff, B., Haft, H., The use of mannitol for the reduction of intracranial pressure in intracranial surgery. J. Neurosurg.19 (1962), 897–901.

    PubMed  Google Scholar 

  63. Steicher, E., Ferris, P. J., Prokop, J. D., Klatzo, I., Brain volume and thiocyanate space in local cold injury. Arch. Neurol.11 (1964), 444–448.

    PubMed  Google Scholar 

  64. Thilmann, J., Zeumer, H., Untersuchungen zur Behandlung des Hirnödems mit hohen Dosen Furosemid. Dtsch. Med. Wochenschr.99 (1974), 932–935.

    PubMed  Google Scholar 

  65. Torack, R. M., Terry, R. D., Zimmerman, H. M., The fine structure of cerebral fluid accumulation. I. Swelling secondary to cold injury. Amer. J. Pathol.35 (1959), 1135–1147.

    Google Scholar 

  66. Trotot, R., Remarks on the action of acetazolamide on certain closed cranial injuries. Gaz. Med. France68 (1961), 945–949.

    PubMed  Google Scholar 

  67. Tschirgi, R. D., Frost, R. W., Taylor, J. L., Inhibition of cerebrospinal fluid formation by a carbonic anhydrase inhibitor, 2-acetylamino-1,3,4-thiadiazole-5-sulfonamide (Diamox). Proc. Soc. Exp. Biol. Med.87 (1954), 373–376.

    PubMed  Google Scholar 

  68. Tutt, H. P., Pappius, H. M., Studies on the mechanisms of action of steroids in traumatized brain. In: Steroids and brain edema (Reulen, H. J., Schurmann, K., eds.), pp. 147–151. New York: Springer. 1972.

    Google Scholar 

  69. Vassallo, A., Cioffi, F., Strukelj, S., Il fursemid nel trattamento dell'edema cerebrale durante l'intervento chirurgico. Minerva Neurochir.15 (1971), 165–167.

    PubMed  Google Scholar 

  70. Vernadakis, A., Woodbury, D. M., Electrolyte and amino avid changes in rat brain during maturation. Amer. J. Physiol.203 (1962), 748–752.

    PubMed  Google Scholar 

  71. Weed, L. H., McKibben, P. S., Pressure changes in the cerebrospinal fluid following intravenous injection of solutions of various concentrations. Amer. J. Physiol.48 (1919), 512–530.

    Google Scholar 

  72. Wilkinson, H. A., Wepsic, J. G., Austin, G., Diuretic synergy in the treatment of acute experimental cerebral edema. J. Neurosurg.34 (1971), 203–208.

    PubMed  Google Scholar 

  73. Wise, B. L., Effects of infusion on hypertonic mannitol on electrolyte balance and on osmolarity of serum and cerebrospinal fluid. J. Neurosurg.20 (1963), 961–967.

    PubMed  Google Scholar 

  74. Wise, B. L., Chater, N., The value of hypertonic mannitol solution in decreasing brain mass and lowering cerebrospinal fluid pressure. J. Neurosurg.19 (1962), 1038–1043.

    PubMed  Google Scholar 

  75. Wistrand, P., Nechay, B. R., Maren, T. H., Effects of carbonic anhydrase inhibition on cerebrospinal and intraocular fluids in the dog. Acta Pharmacol. (Kbh.)17 (1961), 315–336.

    Google Scholar 

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Millson, C., James, H.E., Shapiro, H.M. et al. Intracranial hypertension and brain oedema in albino rabbits. Acta neurochir 56, 167–181 (1981). https://doi.org/10.1007/BF01407228

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