Effects of hypernatraemia in the central nervous system and its therapy in rats and rabbits.

Abstract

1. We studied the effects of acute (1 or 4 h) and chronic (1 week) hypernatraemia (plasma [Na+], 170-190 mM) on brain histology, and brain water and solute contents in rats and rabbits. 2. In rabbits with acute hypernatraemia, there was significant loss of intracelluar brain water, with increases in brain [Na+ + K+], amino acid concentration, and undetermined solute (idiogenic osmole). After 1 week of recovery, brain intracellular water content had returned to normal. 3. In hypernatraemic rats there was myelinolysis of brain white matter, with karyorrhexis and necrosis of neurons.4. Hypernatraemic rabbits were treated with 77 mm NaCl (i.v.) to normalize plasma [Nae] over 4-24 h intervals. Therapy of either acute or chronic hypernatraemia resulted in significant brain oedema because brain osmolality failed to decrease at the same rate as plasma osmolality. 5. It is concluded that: (a) untreated hypernatraemia results in brain lesions demonstrating myelinolysis and cellular necrosis; (b) normalization of hypernatraemia over 4-24 h results in cerebral oedema, due primarily to failure of brain amino acids and idiogenic osmoles to dissipate as plasma [Na+] is decreased to normal.Hypernatraemia is a common clinical condition which tends to affect individuals at the extremes of age -children and the elderly -and frequently leads to central nervous system damage or death. Plasma Na+ levels associated with brain damage in hypernatraemic patients have been in the range 160-190 mm (Zierler, 1958;Finberg, Kiley & Luttrell, 1963;Morris-Jones, Houston & Evans, 1967; Snyder, Feigal & Arieff, 1987). Previous studies on animals from both our laboratory and others suggest that central nervous system damage or death can occur as a consequence of untreated hypernatraemia (Finberg et al. 1963;Morris-Jones et al. 1967;De Villota, Cavanilles & Stein, 1973; Simmons, Adcock, Bard & Battaglia, 1974;Snyder et al. 1987), but the mechanisms responsible are unclear.Improper therapy of hypernatraemia can also produce brain dysfunction, neurological deterioration and death (Lutrell & Finberg, 1959;Hogan, Dodge & Gill, 1969 METHODS Studies in rabbitsThe experimental protocol was approved by the Animal Studies Subcommittee (Veterans Administration Medical Center, San Francisco, CA, USA). Rabbits were used to study the effects of hypernatraemia on brain water and solute content because in this species grey matter can be readily isolated, and also because of our substantial experience in brain analysis using rabbit models of fluid and electrolyte disorders (Arieff, Doerner, Zelig & Massry, 1974a;Arieff, Kleeman, Keushkerian & Bagdoyan, 1974b). Studies were carried out on New Zealand White rabbits (3-4 kg) of both genders, in which hypernatraemia was induced either acutely for periods of 1 or 4 h, or chronically for 7 days. Hypernatraemic rabbits were then treated over intervals of 4-24 h, to return the plasma [Na+] to normal values (below 150 mM). The following goups of rabbits were studied. Group I: effects of acute untreated hypernatraem...

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