Laboratory Investigation

Kidney International (1994) 45, 193–200; doi:10.1038/ki.1994.23

Prevention of brain demyelination in rats after excessive correction of chronic hyponatremia by serum sodium lowering

Alain Soupart1, Raymond Penninckx1, Laurent Crenier1, Alain Stenuit1, Olivier Perier1 and Guy Decaux1

1Research Unit for the Study of Hydromineral Metabolism, Department of Internal Medicine and Laboratory of Clinical Biology, Erasmus University Hospital, and Department of Neuroanatomy, School of Medicine, Free University of Brussels, Brussels, Belgium

Correspondence: Dr A Soupart, Service de Médicine Interne, Hôpital Universitaire Erasme, route de Lennik, 808, B-1070 Brussels, Belgium.

Received 4 September 1992; Revised 17 August 1993; Accepted 19 August 1993.

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Abstract

Prevention of brain demyelination in rats after excessive correction of chronic hyponatremia by serum sodium lowering. Brain myelinolysis occurs after correction of chronic hyponatremia in rats when the magnitude of increase in serum sodium (DeltaSNa) exceeds 20 to 25 mEq/liter/24 hr (the critical threshold for brain). We tested the hypothesis that after a sustained excessive correction, brain lesions (BL) could be prevented by subsequently decreasing the serum sodium below the critical threshold for brain through the administration of hypotonic fluids. After three days of severe (< 115 mEq/liter) chronic (3 days) hyponatremia, 55 rats were submitted to an excessive correction (DeltaSNa > 25 mEq/liter) by a single i.p. infusion of hypertonic saline (NaCl). This osmotic stress was maintained during 12 hours before the serum sodium decrease was initiated. Thirty-two rats reached the twelfth post-correction hour without symptoms. In group 1 after a large (DeltaSNa 32 mEq/liter) and sustained (12 hr) osmotic stress, the natremia was rapidly (2 hr) decreased by the administration of oral tap water and, at the end of the first 24 hours, the magnitude of correction was maintained below 20 mEq/liter/24 hr. All the rats fared well in this group and were free of neurologic symptoms. Mild BL were noticed in only 20% of them. On the contrary, in controls (no hypotonic fluids administration at the twelfth hour) whose serum sodium was left overcorrected, all the rats became symptomatic and 57% of them died rapidly. Brain damage developed in 100% of the surviving rats. In group 2, despite hypotonic fluids administration, the serum sodium decreased insufficiently and the correction was > 20 mEq/liter at the end of the first 24 hours (DeltaSNa 25 mEq/liter). The majority of these rats also presented a poor outcome. Finally, a group of rats developed very early (< 12 hr) neurologic symptoms (N = 23, 42%), and all of them died rapidly (< 24 hr) if the natremia was not decreased. Hypotonic fluids administration in some of these rats allowed them a longer survival, and brain analysis also demonstrated severe demyelination. This work demonstrates that the process leading to brain demyelination remains reversible in hyponatremic rats despite a sustained (12 hr) exposure to an excessive correction. Indeed, subsequent brain damage can be completely prevented in asymptomatic rats by early (12 hr) serum sodium lowering provided that the final correction was maintained below 20 mEq/liter/24 hr. Our results also show that the osmotic stress must be maintained a minimum period of time to induce brain lesions.

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